Original Research

Guttate psoriasis (GP) typically occurs abruptly following an acute infection such as streptococcal pharyngitis. It is thought to have a good prognosis and show rapid resolution; however, there are limited studies addressing long-term outcomes of GP, particularly the probability of developing chronic plaque psoriasis (PP) following a single episode of acute GP.

Ko et al¹ reported a long-term follow-up study of Korean patients with acute GP. The investigators determined that 19 of 36 participants (38.9%) with acute GP went on to develop chronic PP over a mean follow-up period of 6.3 years. Martin et al² reported a smaller follow-up study of 15 patients in England; 5 of 15 patients (33.3%) developed chronic PP within 10 years.

Methods

A retrospective cohort study was performed using data from the Geisinger Medical Center (Danville, Pennsylvania) electronic medical records from January 2000 to September 2012 to identify medical records that showed a specific clinical diagnosis of GP or a diagnosis of either dermatitis or psoriasis with a positive molecular probe for streptococci or antistreptolysin O (ASO) titer. (A molecular probe is used in place of culture for streptococcal pharyngeal specimens at our institution.) A separate search of the Co-Path database for biopsy-proven GP also was performed. Each medical record was reviewed by one of the authors (L.F.P.) to confirm the true diagnosis of GP. Exclusion criteria included a prior diagnosis of PP or a follow-up period of less than 1 year. Based on this chart review, the prevalence of developing chronic PP in patients with GP was determined. The patients were split into 2 cohorts: those who had a single episode of GP with resolution versus those who developed PP. We compared the clinical characteristics to those who developed chronic PP. The clinical characteristics that were recorded included patient age; whether or not the patient developed PP; length of time for clearance of GP; molecular probe or ASO results; family history; GP treatment used; smoking status; and comorbid conditions such as hyperlipidemia, hypertension, diabete mellitus, and obesity, which were lumped under the category of metabolic syndrome due to their low prevalence individually.

The study group data set contained 79 patients with GP who had a history of at least 1 year of follow-up. Descriptive statistics of the patients were provided for continuous and categorical variables in the study. Continuous variables were described using the mean and SD or, for skewed distributions, the median and interquartile range (25th-75th percentiles), while categorical variables were presented using frequency counts and percentages. Comparisons between groups were tested using 2-sample t tests or Wilcoxon rank sum tests, or Pearson χ² or Fisher exact tests, as appropriate.

Results

A total of 79 patients were included in the study. Descriptive statistics for the total patient population as well as those who did and did not develop PP are shown in Table 1. The median age of patients was 37 years. The median follow-up time was 5 years. The majority of patients were female (68.4%). There were 20 patients (25.3%) who developed PP and 59 (74.7%) who did not (95% CI, 0.1-0.36).

Molecular probes for streptoccoci were obtained from 31 patients (39.2%) during the workup for GP. Patients who had a molecular probe and developed PP were less likely to have had a molecular probe that was positive for streptococci versus patients who did not develop PP (0% vs 61.5%; P=.0177)(Table 2). Patients who developed PP were more likely to have persistent GP at 12 months than patients who did not develop PP (26.3% vs 6.8%, respectively; P=.0414). At the end of the observation period, 4 patients (5.1%) did not yet show GP clearance. The patients who developed PP were more likely to have had a case of GP that never cleared than patients who did not develop PP (15.8% vs 1.7%; P=.0505)(Table 3).

No significant differences were detected among those who developed PP compared to those who did not with respect to any degree of family history of psoriasis (22.2% vs 26.4%; P=1.0000)(Table 4). There were no significant differences in the value of a positive ASO titer between groups (Table 2), but it should be noted that the small number of patients with positive values in each group impacts a test’s power to detect statistically significant differences. There were no significant differences in the likelihood of developing PP if a patient was treated with systemic steroids or antibiotics (data not shown). Additionally, smoking status, hyperlipidemia, hypertension, diabetes mellitus, and obesity were not predictive of evolution of GP into PP (data not shown).

 

Comment

Ryan et al³ noted in a report on research gaps in psoriasis that studies are needed to validate frequency and characteristic factors associated with spontaneous remission for different phenotypes of psoriasis, including disease severity, patient age, morphologic attributes of plaques, and comorbidities. Our analysis attempts to bridge this gap in reference to type, specifically GP, and factors associated with development of chronic PP.

Our study showed that 20 of 79 patients (25.3%) with GP went on to develop chronic PP. The incidence is slightly lower than in prior smaller studies from Korea and England, which reported incidence rates of 38.9% and 33.3%, respectively.^1,2 Although Ko et al¹ noted that a younger age of onset was more frequently found in the cohort with complete remission of GP, this finding was not observed in our study. Although only a minority of patients underwent a molecular probe for streptococci, of those who were tested and had positive results, they were significantly less likely to develop chronic PP (P=.0177). This finding supports the classic teaching that GP originates after an episode of a streptococcal infection. Of those who developed PP, only one-fourth had been tested for streptococci via molecular probe and all were negative. Interestingly, there was no difference noted in those that had ASO titers drawn (P=1.0000). Although the data were too low to achieve statistical significance, this finding contrasts with Ko et al¹ who reported that a high ASO titer correlated with a good prognosis (ie, GP did not evolve into PP). There was no difference in the likelihood of developing PP seen in patients that were treated with antibiotics (P=.1651), suggesting that obtaining a molecular probe that is positive for streptococci may be predictive of prognosis (ie, resolution) and thus is a reasonable diagnostic test to obtain. We do recognize that nonpharyngeal sources for streptococci may occur (ie, perianal), but these data were not captured in our patient population.

In our study, patients were more likely to develop chronic PP if they had a GP history that was longer than 12 months. Ko et al¹ also showed that GP patients who did not develop PP were typically cleared after 8 months. There were no statistical differences noted when comparing the different treatments used to treat GP. It appears that the rapidity with which the episode clears is more predictive than the method used to clear it.

There were several limitations to this study including the small number of patients, the median 5-year follow-up time, and the retrospective design.

Conclusion

Based on our cohort study, we have concluded that GP evolves into chronic PP in approximately 25% of cases. Obtaining a group A streptococcal molecular probe or culture may serve as a prognostic tool, as physicians should recognize that GP flares associated with a positive result indicate a favorable prognosis. Additionally, GP flares that resolve within the first year of an outbreak, regardless of treatment choice, are less likely to be followed by chronic PP.

Guttate psoriasis (GP) typically occurs abruptly following an acute infection such as streptococcal pharyngitis. It is thought to have a good prognosis and show rapid resolution; however, there are limited studies addressing long-term outcomes of GP, particularly the probability of developing chronic plaque psoriasis (PP) following a single episode of acute GP.

Ko et al¹ reported a long-term follow-up study of Korean patients with acute GP. The investigators determined that 19 of 36 participants (38.9%) with acute GP went on to develop chronic PP over a mean follow-up period of 6.3 years. Martin et al² reported a smaller follow-up study of 15 patients in England; 5 of 15 patients (33.3%) developed chronic PP within 10 years.

Methods

A retrospective cohort study was performed using data from the Geisinger Medical Center (Danville, Pennsylvania) electronic medical records from January 2000 to September 2012 to identify medical records that showed a specific clinical diagnosis of GP or a diagnosis of either dermatitis or psoriasis with a positive molecular probe for streptococci or antistreptolysin O (ASO) titer. (A molecular probe is used in place of culture for streptococcal pharyngeal specimens at our institution.) A separate search of the Co-Path database for biopsy-proven GP also was performed. Each medical record was reviewed by one of the authors (L.F.P.) to confirm the true diagnosis of GP. Exclusion criteria included a prior diagnosis of PP or a follow-up period of less than 1 year. Based on this chart review, the prevalence of developing chronic PP in patients with GP was determined. The patients were split into 2 cohorts: those who had a single episode of GP with resolution versus those who developed PP. We compared the clinical characteristics to those who developed chronic PP. The clinical characteristics that were recorded included patient age; whether or not the patient developed PP; length of time for clearance of GP; molecular probe or ASO results; family history; GP treatment used; smoking status; and comorbid conditions such as hyperlipidemia, hypertension, diabete mellitus, and obesity, which were lumped under the category of metabolic syndrome due to their low prevalence individually.

The study group data set contained 79 patients with GP who had a history of at least 1 year of follow-up. Descriptive statistics of the patients were provided for continuous and categorical variables in the study. Continuous variables were described using the mean and SD or, for skewed distributions, the median and interquartile range (25th-75th percentiles), while categorical variables were presented using frequency counts and percentages. Comparisons between groups were tested using 2-sample t tests or Wilcoxon rank sum tests, or Pearson χ² or Fisher exact tests, as appropriate.

Results

A total of 79 patients were included in the study. Descriptive statistics for the total patient population as well as those who did and did not develop PP are shown in Table 1. The median age of patients was 37 years. The median follow-up time was 5 years. The majority of patients were female (68.4%). There were 20 patients (25.3%) who developed PP and 59 (74.7%) who did not (95% CI, 0.1-0.36).

Molecular probes for streptoccoci were obtained from 31 patients (39.2%) during the workup for GP. Patients who had a molecular probe and developed PP were less likely to have had a molecular probe that was positive for streptococci versus patients who did not develop PP (0% vs 61.5%; P=.0177)(Table 2). Patients who developed PP were more likely to have persistent GP at 12 months than patients who did not develop PP (26.3% vs 6.8%, respectively; P=.0414). At the end of the observation period, 4 patients (5.1%) did not yet show GP clearance. The patients who developed PP were more likely to have had a case of GP that never cleared than patients who did not develop PP (15.8% vs 1.7%; P=.0505)(Table 3).

No significant differences were detected among those who developed PP compared to those who did not with respect to any degree of family history of psoriasis (22.2% vs 26.4%; P=1.0000)(Table 4). There were no significant differences in the value of a positive ASO titer between groups (Table 2), but it should be noted that the small number of patients with positive values in each group impacts a test’s power to detect statistically significant differences. There were no significant differences in the likelihood of developing PP if a patient was treated with systemic steroids or antibiotics (data not shown). Additionally, smoking status, hyperlipidemia, hypertension, diabetes mellitus, and obesity were not predictive of evolution of GP into PP (data not shown).

 

Comment

Ryan et al³ noted in a report on research gaps in psoriasis that studies are needed to validate frequency and characteristic factors associated with spontaneous remission for different phenotypes of psoriasis, including disease severity, patient age, morphologic attributes of plaques, and comorbidities. Our analysis attempts to bridge this gap in reference to type, specifically GP, and factors associated with development of chronic PP.

Our study showed that 20 of 79 patients (25.3%) with GP went on to develop chronic PP. The incidence is slightly lower than in prior smaller studies from Korea and England, which reported incidence rates of 38.9% and 33.3%, respectively.^1,2 Although Ko et al¹ noted that a younger age of onset was more frequently found in the cohort with complete remission of GP, this finding was not observed in our study. Although only a minority of patients underwent a molecular probe for streptococci, of those who were tested and had positive results, they were significantly less likely to develop chronic PP (P=.0177). This finding supports the classic teaching that GP originates after an episode of a streptococcal infection. Of those who developed PP, only one-fourth had been tested for streptococci via molecular probe and all were negative. Interestingly, there was no difference noted in those that had ASO titers drawn (P=1.0000). Although the data were too low to achieve statistical significance, this finding contrasts with Ko et al¹ who reported that a high ASO titer correlated with a good prognosis (ie, GP did not evolve into PP). There was no difference in the likelihood of developing PP seen in patients that were treated with antibiotics (P=.1651), suggesting that obtaining a molecular probe that is positive for streptococci may be predictive of prognosis (ie, resolution) and thus is a reasonable diagnostic test to obtain. We do recognize that nonpharyngeal sources for streptococci may occur (ie, perianal), but these data were not captured in our patient population.

In our study, patients were more likely to develop chronic PP if they had a GP history that was longer than 12 months. Ko et al¹ also showed that GP patients who did not develop PP were typically cleared after 8 months. There were no statistical differences noted when comparing the different treatments used to treat GP. It appears that the rapidity with which the episode clears is more predictive than the method used to clear it.

There were several limitations to this study including the small number of patients, the median 5-year follow-up time, and the retrospective design.

Conclusion

Based on our cohort study, we have concluded that GP evolves into chronic PP in approximately 25% of cases. Obtaining a group A streptococcal molecular probe or culture may serve as a prognostic tool, as physicians should recognize that GP flares associated with a positive result indicate a favorable prognosis. Additionally, GP flares that resolve within the first year of an outbreak, regardless of treatment choice, are less likely to be followed by chronic PP.

Guttate psoriasis (GP) typically occurs abruptly following an acute infection such as streptococcal pharyngitis. It is thought to have a good prognosis and show rapid resolution; however, there are limited studies addressing long-term outcomes of GP, particularly the probability of developing chronic plaque psoriasis (PP) following a single episode of acute GP.

Ko et al¹ reported a long-term follow-up study of Korean patients with acute GP. The investigators determined that 19 of 36 participants (38.9%) with acute GP went on to develop chronic PP over a mean follow-up period of 6.3 years. Martin et al² reported a smaller follow-up study of 15 patients in England; 5 of 15 patients (33.3%) developed chronic PP within 10 years.

Methods

A retrospective cohort study was performed using data from the Geisinger Medical Center (Danville, Pennsylvania) electronic medical records from January 2000 to September 2012 to identify medical records that showed a specific clinical diagnosis of GP or a diagnosis of either dermatitis or psoriasis with a positive molecular probe for streptococci or antistreptolysin O (ASO) titer. (A molecular probe is used in place of culture for streptococcal pharyngeal specimens at our institution.) A separate search of the Co-Path database for biopsy-proven GP also was performed. Each medical record was reviewed by one of the authors (L.F.P.) to confirm the true diagnosis of GP. Exclusion criteria included a prior diagnosis of PP or a follow-up period of less than 1 year. Based on this chart review, the prevalence of developing chronic PP in patients with GP was determined. The patients were split into 2 cohorts: those who had a single episode of GP with resolution versus those who developed PP. We compared the clinical characteristics to those who developed chronic PP. The clinical characteristics that were recorded included patient age; whether or not the patient developed PP; length of time for clearance of GP; molecular probe or ASO results; family history; GP treatment used; smoking status; and comorbid conditions such as hyperlipidemia, hypertension, diabete mellitus, and obesity, which were lumped under the category of metabolic syndrome due to their low prevalence individually.

The study group data set contained 79 patients with GP who had a history of at least 1 year of follow-up. Descriptive statistics of the patients were provided for continuous and categorical variables in the study. Continuous variables were described using the mean and SD or, for skewed distributions, the median and interquartile range (25th-75th percentiles), while categorical variables were presented using frequency counts and percentages. Comparisons between groups were tested using 2-sample t tests or Wilcoxon rank sum tests, or Pearson χ² or Fisher exact tests, as appropriate.

Results

A total of 79 patients were included in the study. Descriptive statistics for the total patient population as well as those who did and did not develop PP are shown in Table 1. The median age of patients was 37 years. The median follow-up time was 5 years. The majority of patients were female (68.4%). There were 20 patients (25.3%) who developed PP and 59 (74.7%) who did not (95% CI, 0.1-0.36).

Molecular probes for streptoccoci were obtained from 31 patients (39.2%) during the workup for GP. Patients who had a molecular probe and developed PP were less likely to have had a molecular probe that was positive for streptococci versus patients who did not develop PP (0% vs 61.5%; P=.0177)(Table 2). Patients who developed PP were more likely to have persistent GP at 12 months than patients who did not develop PP (26.3% vs 6.8%, respectively; P=.0414). At the end of the observation period, 4 patients (5.1%) did not yet show GP clearance. The patients who developed PP were more likely to have had a case of GP that never cleared than patients who did not develop PP (15.8% vs 1.7%; P=.0505)(Table 3).

No significant differences were detected among those who developed PP compared to those who did not with respect to any degree of family history of psoriasis (22.2% vs 26.4%; P=1.0000)(Table 4). There were no significant differences in the value of a positive ASO titer between groups (Table 2), but it should be noted that the small number of patients with positive values in each group impacts a test’s power to detect statistically significant differences. There were no significant differences in the likelihood of developing PP if a patient was treated with systemic steroids or antibiotics (data not shown). Additionally, smoking status, hyperlipidemia, hypertension, diabetes mellitus, and obesity were not predictive of evolution of GP into PP (data not shown).

 

Comment

Ryan et al³ noted in a report on research gaps in psoriasis that studies are needed to validate frequency and characteristic factors associated with spontaneous remission for different phenotypes of psoriasis, including disease severity, patient age, morphologic attributes of plaques, and comorbidities. Our analysis attempts to bridge this gap in reference to type, specifically GP, and factors associated with development of chronic PP.

Our study showed that 20 of 79 patients (25.3%) with GP went on to develop chronic PP. The incidence is slightly lower than in prior smaller studies from Korea and England, which reported incidence rates of 38.9% and 33.3%, respectively.^1,2 Although Ko et al¹ noted that a younger age of onset was more frequently found in the cohort with complete remission of GP, this finding was not observed in our study. Although only a minority of patients underwent a molecular probe for streptococci, of those who were tested and had positive results, they were significantly less likely to develop chronic PP (P=.0177). This finding supports the classic teaching that GP originates after an episode of a streptococcal infection. Of those who developed PP, only one-fourth had been tested for streptococci via molecular probe and all were negative. Interestingly, there was no difference noted in those that had ASO titers drawn (P=1.0000). Although the data were too low to achieve statistical significance, this finding contrasts with Ko et al¹ who reported that a high ASO titer correlated with a good prognosis (ie, GP did not evolve into PP). There was no difference in the likelihood of developing PP seen in patients that were treated with antibiotics (P=.1651), suggesting that obtaining a molecular probe that is positive for streptococci may be predictive of prognosis (ie, resolution) and thus is a reasonable diagnostic test to obtain. We do recognize that nonpharyngeal sources for streptococci may occur (ie, perianal), but these data were not captured in our patient population.

In our study, patients were more likely to develop chronic PP if they had a GP history that was longer than 12 months. Ko et al¹ also showed that GP patients who did not develop PP were typically cleared after 8 months. There were no statistical differences noted when comparing the different treatments used to treat GP. It appears that the rapidity with which the episode clears is more predictive than the method used to clear it.

There were several limitations to this study including the small number of patients, the median 5-year follow-up time, and the retrospective design.

Conclusion

Based on our cohort study, we have concluded that GP evolves into chronic PP in approximately 25% of cases. Obtaining a group A streptococcal molecular probe or culture may serve as a prognostic tool, as physicians should recognize that GP flares associated with a positive result indicate a favorable prognosis. Additionally, GP flares that resolve within the first year of an outbreak, regardless of treatment choice, are less likely to be followed by chronic PP.

Psoriasis is a common immune-mediated papulosquamous skin disease with a generally chronic course. Impairments in quality of life (QOL) and psychological morbidity in the form of anxiety and depression have been reported.¹ Because psoriasis is not known to directly affect the central nervous system, the associated psychiatric morbidity is likely caused by the complex interplay of the stress, physical discomfort, and possible disfigurement inherent to psoriasis, as well as the emotional response to the condition mediated by the patient’s personality, emotional and cognitive state, and other social factors (eg, self-stigma and perceived stigma, lack of knowledge about the illness in the patient and in the community and family, lack of resources and support).² Because a variety of methodologies have been used in research on the association of psoriasis with psychiatric morbidity, it is not easy to compare findings. Most studies have assessed psychiatric symptoms rather than findings from psychiatric diagnostic instruments.³ The diagnosis of psychiatric disorders in patients with psoriasis rather than focusing on symptoms alone is likely to be more useful in generating scientific epidemiologic data and also would serve as a guide in making treatment and policy decisions. Validated clinician-rated instruments are useful in generating these data. However, psychiatric diagnoses are often missed by dermatologists, which may have an adverse impact on eventual outcomes in psoriasis patients.^4,5 Patient-assessed diagnostic instruments may help dermatologists overcome this problem.

This study investigated the prevalence and determinants of psychiatric disorders in a cohort of psoriasis patients in North India using both patient self-assessment and clinician-administered instruments.

Methods

Study Participants

The study was conducted from January 2013 to November 2013 at the Postgraduate Institute of Medical Education and Research, a tertiary-level teaching hospital in Chandigarh, India, which serves the population of a large geographic area in North India. Clearance for this study was obtained from the institute ethics committee.

Patients with chronic plaque psoriasis who presented consecutively to the outpatient clinic of the Departments of Dermatology, Venereology, and Leprology during the study period were approached for participation. Written informed consent was obtained from all participants. Inclusion criteria were the ability to read the self-assessment questionnaires, and no financial compensation was offered for inclusion in the study. Patients with psoriatic arthritis as well as erythrodermic and pustular variants of psoriasis were excluded. Exclusion criteria also included patients with known diabetes mellitus, cardiovascular disease, chronic respiratory ailments, or other notable systemic comorbidities; however, patients did not undergo biochemical testing.

Assessments

A 2-stage methodology was employed. In the first stage of the assessment, sociodemographic and clinical data were recorded. Thereafter, psychiatric symptoms and morbidity were assessed using the patient health questionnaire (PHQ).⁶ Quality of life was assessed using the dermatology life quality index (DLQI).⁷ Both tools were based on patient self-assessment. Study participants could seek assistance from the clinician in completing the questionnaires, if needed. Psoriasis severity was evaluated by the clinician using the psoriasis area severity index (PASI) score.⁸

In the second stage of the assessment, participants underwent subsequent evaluation by a psychiatrist who was blinded to the results of the first assessments. All participants were screened using the Mini international neuropsychiatric interview (MINI)⁹ and a formal psychiatric diagnosis was made. In subsequent analyses, we considered psychiatric diagnoses as generated with MINI as the gold standard against which other results were compared.

A participant was considered positive for psychiatric morbidity if he/she was positive for at least 1 PHQ or MINI diagnosis.

To assess for concordance between the 2 diagnostic instruments, the following diagnostic groups were compared against each other: (1) MINI depressive disorders (DDs)(ie, major depressive episode, current and recurrent; dysthymia) versus PHQ depressive disorders (ie, major DDs and other DDs); (2) MINI anxiety disorders (ie, panic disorder and generalized anxiety disorder) versus PHQ anxiety disorders (ie, panic syndrome and other anxiety syndromes); (3) MINI alcohol abuse (ie, alcohol dependence and abuse) versus PHQ alcohol abuse; (4) comorbid disorders if more than 1 diagnosis was made; and (5) any positive score on the MINI suicide module with a response other than not at all on PHQ depression module item 2(i), which deals with thoughts of self-harm and wishing that one was dead. The MINI depressive disorders and PHQ depressive disorders indicate the presence of a clinically significant depressive state and a need for assessment and treatment.

The PHQ can be used to diagnose somatoform disorders, while the MINI cannot be used. Because the somatoform disorders diagnosed were few in number and comorbid with DDs (n=3) and anxiety disorders (n=1), we included these cases with DDs and anxiety disorders, respectively, for purposes of statistical analysis. All data were analyzed using SPSS software.

 

Results

One hundred four participants were included in this study. The sociodemographic, clinical, and diagnostic profiles, as well as the determinants of MINI diagnosis, are provided in Tables 1 through 4. The PASI and DLQI scores indicated that most participants had mild to moderate psoriasis severity.¹⁰ The prevalence of alcohol-related disorders was only found in the male subpopulation, which is consistent with the sociocultural context of North India. Psoriasis severity (ie, PASI score) was not found to be a determinant of psychiatric diagnoses in the study population. There was no statistical difference in measures of current clinical status and treatment modality when those with or without any psychiatric diagnoses were compared. When the variables of disease duration, treatment duration, and DLQI were entered into a binary logistic regression with positive status for a MINI diagnosis as a dependent variable indicating the presence of a psychiatric disorder, it was found that the DLQI score was a significant predictor (b=0.19; SE=0.47; χ2=17.92; P<.05). This finding was the same for regression analyses for males and females separately and also for DD as a dependent variable.

Mean DLQI and PASI scores were positively correlated with each other (Pearson r=0.23; P=.01). This relationship was maintained in males (Pearson r=0.24; P=.03) but not in females (Pearson r=0.14; P=.30). The correlations between DLQI and PASI scores and both disease duration and treatment duration were not significant. The Cohen κ values for the interrater reliability analyses done to assess the concordance of the PHQ and MINI diagnostic groups were modest (0.31-0.42), which was true even when MINI depressive disorders without dysthymia and PHQ depressive disorders were compared.
 

 

Comment

Studies investigating psychiatric morbidity in psoriasis have varying methodologies, mostly assessing psychiatric symptoms rather than screening for psychiatric disorders.³ In chronic diseases such as psoriasis, there often is an overlap between disease symptoms and common psychiatric disorders (eg, depression).¹¹ Therefore, assessment of symptoms can be misleading. The current study was designed to detect psychiatric disorders in psoriasis patients using both patient self-assessment and clinician-administered instruments. We also investigated the contribution of sociodemographic and clinical variables (eg, psoriasis severity, impairment in QOL) on psychiatric morbidity.

An increased risk for depression, anxiety, and suicidality associated with greater psoriasis severity has been reported.¹² The results of the current study indicate that even in a patient population with predominantly mild to moderate psoriasis, psychiatric morbidity, particularly DDs, is common. This finding was seen both on patient self-assessment and clinician-administered evaluations. Earlier studies from this institution and region have reported a lower prevalence of psychiatric disorders in patients with psoriasis (24.7%–36.7%).^13-16 However, prior studies were based on assessment of specific symptoms and clinical diagnoses derived from history and mental status examination rather than the administration of more rigorous research diagnostic assessment tools. A systematic review and meta-analysis also revealed a lower prevalence of clinical depression using International Classification of Diseases, Tenth Revision, and Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) codes.³ A possible reason for this apparent discrepancy is the fact that psychiatric morbidity in a majority of participants in the current study was constituted by the diagnosis of dysthymia. If the diagnosis of dysthymia is removed from the current analysis, the prevalence of clinical major depressive syndromes is similar to other data. We found that chronic low-grade depression (dysthymia) was the most common diagnosis from the MINI. Lower prevalence was noted in a prior study, but methodology using clinical interviewing may have resulted in an underestimated prevalence.¹³ It also is possible that chronic low-grade depression in psoriasis patients may be missed or underestimated in comparison to more readily diagnosed and severe depressive syndromes in other studies. However, there is enough evidence to suggest that dysthymia is clinically relevant in the causation of morbidity and disability (eg, physical, psychological, or cognitive impairment) in patients with chronic physical disorders.¹⁷ This distinction between clinical major depressive syndrome and dysthymia is important because different treatment methods may be required; the former may warrant treatment with antidepressants in addition to psychosocial treatment modalities (eg, learning to cope with stress, problem-solving techniques), while the latter may benefit predominantly from psychosocial treatment modalities alone.^18,19 In the current study, most of the participants who were diagnosed with dysthymia refused treatment with any psychotropic medications but perceived benefit from discussing their problems with a professional. Our results indicated that chronic low-grade depression is more common than more severe major depressive states, and mental health professionals who are well versed in psychosocial treatment modalities should play an integral role in treatment planning for patients with psoriasis.

In the current study, there was only a modest correlation between the results of the patient self-assessment and clinician-administered evaluations, which indicated that psychiatric disorders may not be obvious to clinicians unless specifically investigated, even for some severely depressed and suicidal patients. Given the high prevalence of clinically relevant psychiatric morbidity among psoriasis patients, dermatology professionals should be more sensitive to the possible presence of psychiatric disorders in this patient population and should consider the use of formal screening or other diagnostic tools for detection of depression and anxiety in psoriasis patients.

The main determinant of psychiatric morbidity in our study population was impairment in QOL. Interestingly enough, psoriasis severity was not associated with psychiatric morbidity in our study. Depressive states in patients with chronic physical illnesses are well known and could be due to the chronic stress of illness or impaired QOL, or depression may be a direct effect of the illness and/or treatment on the central nervous system. Psoriasis is not known to have any direct effect on the central nervous system. Our findings suggest that QOL impairment plays an important role in psychiatric morbidity in patients with psoriasis. Even though the DLQI is designed to measure QOL over the preceding week, our findings suggest that impairment in QOL in psoriasis is a manifestation of a more long-term effect of interplay between many factors; the impairment in activities of daily living, disease-related physical discomfort and impaired self-esteem and self-perception, impairments in interpersonal relationships, and the stress of chronicity of illness seem to play an important role. Additionally, variables such as emotional dysfunction, magnitude and site of the area of involvement, nature and magnitude of comorbidities, and complications of illness and coping also may be relevant.²⁰ Although these factors are common in other chronic disorders, psoriasis in particular may predisposepatients to depression due to its unpredictable and relapsing nature, lack of any curative therapy, and the stigmatizing prominent lesions that often are impossible to camouflage. In chronic diseases such as psoriasis, the amelioration of impairment of different aspects of QOL may be more important than mere symptom control.

Our study was limited in that the study population was predominantly male. Fewer females may have consented to participate in the study due to time constraints associated with domestic responsibilities, reluctance to discuss psychological distress, or inability to meet the inclusion criteria (eg, level of education required to read questionnaires). However, there was no significant difference between males and females for sociodemographic variables or diagnoses other than alcohol-related disorders. Our study also had a cross-sectional design and there was no control group, without which it is difficult to assess the true prevalence and determinants of these psychiatric morbidities. Moreover, the sample size was small and did not include enough participants with moderate to severe psoriasis (ie, PASI score ≥10) to be able to detect a correlation between psychiatric morbidities and psoriasis severity. Our findings underline the need for effective screening and integrated management of psychiatric disorders in patients with psoriasis.

Psoriasis is a common immune-mediated papulosquamous skin disease with a generally chronic course. Impairments in quality of life (QOL) and psychological morbidity in the form of anxiety and depression have been reported.¹ Because psoriasis is not known to directly affect the central nervous system, the associated psychiatric morbidity is likely caused by the complex interplay of the stress, physical discomfort, and possible disfigurement inherent to psoriasis, as well as the emotional response to the condition mediated by the patient’s personality, emotional and cognitive state, and other social factors (eg, self-stigma and perceived stigma, lack of knowledge about the illness in the patient and in the community and family, lack of resources and support).² Because a variety of methodologies have been used in research on the association of psoriasis with psychiatric morbidity, it is not easy to compare findings. Most studies have assessed psychiatric symptoms rather than findings from psychiatric diagnostic instruments.³ The diagnosis of psychiatric disorders in patients with psoriasis rather than focusing on symptoms alone is likely to be more useful in generating scientific epidemiologic data and also would serve as a guide in making treatment and policy decisions. Validated clinician-rated instruments are useful in generating these data. However, psychiatric diagnoses are often missed by dermatologists, which may have an adverse impact on eventual outcomes in psoriasis patients.^4,5 Patient-assessed diagnostic instruments may help dermatologists overcome this problem.

This study investigated the prevalence and determinants of psychiatric disorders in a cohort of psoriasis patients in North India using both patient self-assessment and clinician-administered instruments.

Methods

Study Participants

The study was conducted from January 2013 to November 2013 at the Postgraduate Institute of Medical Education and Research, a tertiary-level teaching hospital in Chandigarh, India, which serves the population of a large geographic area in North India. Clearance for this study was obtained from the institute ethics committee.

Patients with chronic plaque psoriasis who presented consecutively to the outpatient clinic of the Departments of Dermatology, Venereology, and Leprology during the study period were approached for participation. Written informed consent was obtained from all participants. Inclusion criteria were the ability to read the self-assessment questionnaires, and no financial compensation was offered for inclusion in the study. Patients with psoriatic arthritis as well as erythrodermic and pustular variants of psoriasis were excluded. Exclusion criteria also included patients with known diabetes mellitus, cardiovascular disease, chronic respiratory ailments, or other notable systemic comorbidities; however, patients did not undergo biochemical testing.

Assessments

A 2-stage methodology was employed. In the first stage of the assessment, sociodemographic and clinical data were recorded. Thereafter, psychiatric symptoms and morbidity were assessed using the patient health questionnaire (PHQ).⁶ Quality of life was assessed using the dermatology life quality index (DLQI).⁷ Both tools were based on patient self-assessment. Study participants could seek assistance from the clinician in completing the questionnaires, if needed. Psoriasis severity was evaluated by the clinician using the psoriasis area severity index (PASI) score.⁸

In the second stage of the assessment, participants underwent subsequent evaluation by a psychiatrist who was blinded to the results of the first assessments. All participants were screened using the Mini international neuropsychiatric interview (MINI)⁹ and a formal psychiatric diagnosis was made. In subsequent analyses, we considered psychiatric diagnoses as generated with MINI as the gold standard against which other results were compared.

A participant was considered positive for psychiatric morbidity if he/she was positive for at least 1 PHQ or MINI diagnosis.

To assess for concordance between the 2 diagnostic instruments, the following diagnostic groups were compared against each other: (1) MINI depressive disorders (DDs)(ie, major depressive episode, current and recurrent; dysthymia) versus PHQ depressive disorders (ie, major DDs and other DDs); (2) MINI anxiety disorders (ie, panic disorder and generalized anxiety disorder) versus PHQ anxiety disorders (ie, panic syndrome and other anxiety syndromes); (3) MINI alcohol abuse (ie, alcohol dependence and abuse) versus PHQ alcohol abuse; (4) comorbid disorders if more than 1 diagnosis was made; and (5) any positive score on the MINI suicide module with a response other than not at all on PHQ depression module item 2(i), which deals with thoughts of self-harm and wishing that one was dead. The MINI depressive disorders and PHQ depressive disorders indicate the presence of a clinically significant depressive state and a need for assessment and treatment.

The PHQ can be used to diagnose somatoform disorders, while the MINI cannot be used. Because the somatoform disorders diagnosed were few in number and comorbid with DDs (n=3) and anxiety disorders (n=1), we included these cases with DDs and anxiety disorders, respectively, for purposes of statistical analysis. All data were analyzed using SPSS software.

 

Results

One hundred four participants were included in this study. The sociodemographic, clinical, and diagnostic profiles, as well as the determinants of MINI diagnosis, are provided in Tables 1 through 4. The PASI and DLQI scores indicated that most participants had mild to moderate psoriasis severity.¹⁰ The prevalence of alcohol-related disorders was only found in the male subpopulation, which is consistent with the sociocultural context of North India. Psoriasis severity (ie, PASI score) was not found to be a determinant of psychiatric diagnoses in the study population. There was no statistical difference in measures of current clinical status and treatment modality when those with or without any psychiatric diagnoses were compared. When the variables of disease duration, treatment duration, and DLQI were entered into a binary logistic regression with positive status for a MINI diagnosis as a dependent variable indicating the presence of a psychiatric disorder, it was found that the DLQI score was a significant predictor (b=0.19; SE=0.47; χ2=17.92; P<.05). This finding was the same for regression analyses for males and females separately and also for DD as a dependent variable.

Mean DLQI and PASI scores were positively correlated with each other (Pearson r=0.23; P=.01). This relationship was maintained in males (Pearson r=0.24; P=.03) but not in females (Pearson r=0.14; P=.30). The correlations between DLQI and PASI scores and both disease duration and treatment duration were not significant. The Cohen κ values for the interrater reliability analyses done to assess the concordance of the PHQ and MINI diagnostic groups were modest (0.31-0.42), which was true even when MINI depressive disorders without dysthymia and PHQ depressive disorders were compared.
 

 

Comment

Studies investigating psychiatric morbidity in psoriasis have varying methodologies, mostly assessing psychiatric symptoms rather than screening for psychiatric disorders.³ In chronic diseases such as psoriasis, there often is an overlap between disease symptoms and common psychiatric disorders (eg, depression).¹¹ Therefore, assessment of symptoms can be misleading. The current study was designed to detect psychiatric disorders in psoriasis patients using both patient self-assessment and clinician-administered instruments. We also investigated the contribution of sociodemographic and clinical variables (eg, psoriasis severity, impairment in QOL) on psychiatric morbidity.

An increased risk for depression, anxiety, and suicidality associated with greater psoriasis severity has been reported.¹² The results of the current study indicate that even in a patient population with predominantly mild to moderate psoriasis, psychiatric morbidity, particularly DDs, is common. This finding was seen both on patient self-assessment and clinician-administered evaluations. Earlier studies from this institution and region have reported a lower prevalence of psychiatric disorders in patients with psoriasis (24.7%–36.7%).^13-16 However, prior studies were based on assessment of specific symptoms and clinical diagnoses derived from history and mental status examination rather than the administration of more rigorous research diagnostic assessment tools. A systematic review and meta-analysis also revealed a lower prevalence of clinical depression using International Classification of Diseases, Tenth Revision, and Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) codes.³ A possible reason for this apparent discrepancy is the fact that psychiatric morbidity in a majority of participants in the current study was constituted by the diagnosis of dysthymia. If the diagnosis of dysthymia is removed from the current analysis, the prevalence of clinical major depressive syndromes is similar to other data. We found that chronic low-grade depression (dysthymia) was the most common diagnosis from the MINI. Lower prevalence was noted in a prior study, but methodology using clinical interviewing may have resulted in an underestimated prevalence.¹³ It also is possible that chronic low-grade depression in psoriasis patients may be missed or underestimated in comparison to more readily diagnosed and severe depressive syndromes in other studies. However, there is enough evidence to suggest that dysthymia is clinically relevant in the causation of morbidity and disability (eg, physical, psychological, or cognitive impairment) in patients with chronic physical disorders.¹⁷ This distinction between clinical major depressive syndrome and dysthymia is important because different treatment methods may be required; the former may warrant treatment with antidepressants in addition to psychosocial treatment modalities (eg, learning to cope with stress, problem-solving techniques), while the latter may benefit predominantly from psychosocial treatment modalities alone.^18,19 In the current study, most of the participants who were diagnosed with dysthymia refused treatment with any psychotropic medications but perceived benefit from discussing their problems with a professional. Our results indicated that chronic low-grade depression is more common than more severe major depressive states, and mental health professionals who are well versed in psychosocial treatment modalities should play an integral role in treatment planning for patients with psoriasis.

In the current study, there was only a modest correlation between the results of the patient self-assessment and clinician-administered evaluations, which indicated that psychiatric disorders may not be obvious to clinicians unless specifically investigated, even for some severely depressed and suicidal patients. Given the high prevalence of clinically relevant psychiatric morbidity among psoriasis patients, dermatology professionals should be more sensitive to the possible presence of psychiatric disorders in this patient population and should consider the use of formal screening or other diagnostic tools for detection of depression and anxiety in psoriasis patients.

The main determinant of psychiatric morbidity in our study population was impairment in QOL. Interestingly enough, psoriasis severity was not associated with psychiatric morbidity in our study. Depressive states in patients with chronic physical illnesses are well known and could be due to the chronic stress of illness or impaired QOL, or depression may be a direct effect of the illness and/or treatment on the central nervous system. Psoriasis is not known to have any direct effect on the central nervous system. Our findings suggest that QOL impairment plays an important role in psychiatric morbidity in patients with psoriasis. Even though the DLQI is designed to measure QOL over the preceding week, our findings suggest that impairment in QOL in psoriasis is a manifestation of a more long-term effect of interplay between many factors; the impairment in activities of daily living, disease-related physical discomfort and impaired self-esteem and self-perception, impairments in interpersonal relationships, and the stress of chronicity of illness seem to play an important role. Additionally, variables such as emotional dysfunction, magnitude and site of the area of involvement, nature and magnitude of comorbidities, and complications of illness and coping also may be relevant.²⁰ Although these factors are common in other chronic disorders, psoriasis in particular may predisposepatients to depression due to its unpredictable and relapsing nature, lack of any curative therapy, and the stigmatizing prominent lesions that often are impossible to camouflage. In chronic diseases such as psoriasis, the amelioration of impairment of different aspects of QOL may be more important than mere symptom control.

Our study was limited in that the study population was predominantly male. Fewer females may have consented to participate in the study due to time constraints associated with domestic responsibilities, reluctance to discuss psychological distress, or inability to meet the inclusion criteria (eg, level of education required to read questionnaires). However, there was no significant difference between males and females for sociodemographic variables or diagnoses other than alcohol-related disorders. Our study also had a cross-sectional design and there was no control group, without which it is difficult to assess the true prevalence and determinants of these psychiatric morbidities. Moreover, the sample size was small and did not include enough participants with moderate to severe psoriasis (ie, PASI score ≥10) to be able to detect a correlation between psychiatric morbidities and psoriasis severity. Our findings underline the need for effective screening and integrated management of psychiatric disorders in patients with psoriasis.

Psoriasis is a common immune-mediated papulosquamous skin disease with a generally chronic course. Impairments in quality of life (QOL) and psychological morbidity in the form of anxiety and depression have been reported.¹ Because psoriasis is not known to directly affect the central nervous system, the associated psychiatric morbidity is likely caused by the complex interplay of the stress, physical discomfort, and possible disfigurement inherent to psoriasis, as well as the emotional response to the condition mediated by the patient’s personality, emotional and cognitive state, and other social factors (eg, self-stigma and perceived stigma, lack of knowledge about the illness in the patient and in the community and family, lack of resources and support).² Because a variety of methodologies have been used in research on the association of psoriasis with psychiatric morbidity, it is not easy to compare findings. Most studies have assessed psychiatric symptoms rather than findings from psychiatric diagnostic instruments.³ The diagnosis of psychiatric disorders in patients with psoriasis rather than focusing on symptoms alone is likely to be more useful in generating scientific epidemiologic data and also would serve as a guide in making treatment and policy decisions. Validated clinician-rated instruments are useful in generating these data. However, psychiatric diagnoses are often missed by dermatologists, which may have an adverse impact on eventual outcomes in psoriasis patients.^4,5 Patient-assessed diagnostic instruments may help dermatologists overcome this problem.

This study investigated the prevalence and determinants of psychiatric disorders in a cohort of psoriasis patients in North India using both patient self-assessment and clinician-administered instruments.

Methods

Study Participants

The study was conducted from January 2013 to November 2013 at the Postgraduate Institute of Medical Education and Research, a tertiary-level teaching hospital in Chandigarh, India, which serves the population of a large geographic area in North India. Clearance for this study was obtained from the institute ethics committee.

Patients with chronic plaque psoriasis who presented consecutively to the outpatient clinic of the Departments of Dermatology, Venereology, and Leprology during the study period were approached for participation. Written informed consent was obtained from all participants. Inclusion criteria were the ability to read the self-assessment questionnaires, and no financial compensation was offered for inclusion in the study. Patients with psoriatic arthritis as well as erythrodermic and pustular variants of psoriasis were excluded. Exclusion criteria also included patients with known diabetes mellitus, cardiovascular disease, chronic respiratory ailments, or other notable systemic comorbidities; however, patients did not undergo biochemical testing.

Assessments

A 2-stage methodology was employed. In the first stage of the assessment, sociodemographic and clinical data were recorded. Thereafter, psychiatric symptoms and morbidity were assessed using the patient health questionnaire (PHQ).⁶ Quality of life was assessed using the dermatology life quality index (DLQI).⁷ Both tools were based on patient self-assessment. Study participants could seek assistance from the clinician in completing the questionnaires, if needed. Psoriasis severity was evaluated by the clinician using the psoriasis area severity index (PASI) score.⁸

In the second stage of the assessment, participants underwent subsequent evaluation by a psychiatrist who was blinded to the results of the first assessments. All participants were screened using the Mini international neuropsychiatric interview (MINI)⁹ and a formal psychiatric diagnosis was made. In subsequent analyses, we considered psychiatric diagnoses as generated with MINI as the gold standard against which other results were compared.

A participant was considered positive for psychiatric morbidity if he/she was positive for at least 1 PHQ or MINI diagnosis.

To assess for concordance between the 2 diagnostic instruments, the following diagnostic groups were compared against each other: (1) MINI depressive disorders (DDs)(ie, major depressive episode, current and recurrent; dysthymia) versus PHQ depressive disorders (ie, major DDs and other DDs); (2) MINI anxiety disorders (ie, panic disorder and generalized anxiety disorder) versus PHQ anxiety disorders (ie, panic syndrome and other anxiety syndromes); (3) MINI alcohol abuse (ie, alcohol dependence and abuse) versus PHQ alcohol abuse; (4) comorbid disorders if more than 1 diagnosis was made; and (5) any positive score on the MINI suicide module with a response other than not at all on PHQ depression module item 2(i), which deals with thoughts of self-harm and wishing that one was dead. The MINI depressive disorders and PHQ depressive disorders indicate the presence of a clinically significant depressive state and a need for assessment and treatment.

The PHQ can be used to diagnose somatoform disorders, while the MINI cannot be used. Because the somatoform disorders diagnosed were few in number and comorbid with DDs (n=3) and anxiety disorders (n=1), we included these cases with DDs and anxiety disorders, respectively, for purposes of statistical analysis. All data were analyzed using SPSS software.

 

Results

One hundred four participants were included in this study. The sociodemographic, clinical, and diagnostic profiles, as well as the determinants of MINI diagnosis, are provided in Tables 1 through 4. The PASI and DLQI scores indicated that most participants had mild to moderate psoriasis severity.¹⁰ The prevalence of alcohol-related disorders was only found in the male subpopulation, which is consistent with the sociocultural context of North India. Psoriasis severity (ie, PASI score) was not found to be a determinant of psychiatric diagnoses in the study population. There was no statistical difference in measures of current clinical status and treatment modality when those with or without any psychiatric diagnoses were compared. When the variables of disease duration, treatment duration, and DLQI were entered into a binary logistic regression with positive status for a MINI diagnosis as a dependent variable indicating the presence of a psychiatric disorder, it was found that the DLQI score was a significant predictor (b=0.19; SE=0.47; χ2=17.92; P<.05). This finding was the same for regression analyses for males and females separately and also for DD as a dependent variable.

Mean DLQI and PASI scores were positively correlated with each other (Pearson r=0.23; P=.01). This relationship was maintained in males (Pearson r=0.24; P=.03) but not in females (Pearson r=0.14; P=.30). The correlations between DLQI and PASI scores and both disease duration and treatment duration were not significant. The Cohen κ values for the interrater reliability analyses done to assess the concordance of the PHQ and MINI diagnostic groups were modest (0.31-0.42), which was true even when MINI depressive disorders without dysthymia and PHQ depressive disorders were compared.
 

 

Comment

Studies investigating psychiatric morbidity in psoriasis have varying methodologies, mostly assessing psychiatric symptoms rather than screening for psychiatric disorders.³ In chronic diseases such as psoriasis, there often is an overlap between disease symptoms and common psychiatric disorders (eg, depression).¹¹ Therefore, assessment of symptoms can be misleading. The current study was designed to detect psychiatric disorders in psoriasis patients using both patient self-assessment and clinician-administered instruments. We also investigated the contribution of sociodemographic and clinical variables (eg, psoriasis severity, impairment in QOL) on psychiatric morbidity.

An increased risk for depression, anxiety, and suicidality associated with greater psoriasis severity has been reported.¹² The results of the current study indicate that even in a patient population with predominantly mild to moderate psoriasis, psychiatric morbidity, particularly DDs, is common. This finding was seen both on patient self-assessment and clinician-administered evaluations. Earlier studies from this institution and region have reported a lower prevalence of psychiatric disorders in patients with psoriasis (24.7%–36.7%).^13-16 However, prior studies were based on assessment of specific symptoms and clinical diagnoses derived from history and mental status examination rather than the administration of more rigorous research diagnostic assessment tools. A systematic review and meta-analysis also revealed a lower prevalence of clinical depression using International Classification of Diseases, Tenth Revision, and Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) codes.³ A possible reason for this apparent discrepancy is the fact that psychiatric morbidity in a majority of participants in the current study was constituted by the diagnosis of dysthymia. If the diagnosis of dysthymia is removed from the current analysis, the prevalence of clinical major depressive syndromes is similar to other data. We found that chronic low-grade depression (dysthymia) was the most common diagnosis from the MINI. Lower prevalence was noted in a prior study, but methodology using clinical interviewing may have resulted in an underestimated prevalence.¹³ It also is possible that chronic low-grade depression in psoriasis patients may be missed or underestimated in comparison to more readily diagnosed and severe depressive syndromes in other studies. However, there is enough evidence to suggest that dysthymia is clinically relevant in the causation of morbidity and disability (eg, physical, psychological, or cognitive impairment) in patients with chronic physical disorders.¹⁷ This distinction between clinical major depressive syndrome and dysthymia is important because different treatment methods may be required; the former may warrant treatment with antidepressants in addition to psychosocial treatment modalities (eg, learning to cope with stress, problem-solving techniques), while the latter may benefit predominantly from psychosocial treatment modalities alone.^18,19 In the current study, most of the participants who were diagnosed with dysthymia refused treatment with any psychotropic medications but perceived benefit from discussing their problems with a professional. Our results indicated that chronic low-grade depression is more common than more severe major depressive states, and mental health professionals who are well versed in psychosocial treatment modalities should play an integral role in treatment planning for patients with psoriasis.

In the current study, there was only a modest correlation between the results of the patient self-assessment and clinician-administered evaluations, which indicated that psychiatric disorders may not be obvious to clinicians unless specifically investigated, even for some severely depressed and suicidal patients. Given the high prevalence of clinically relevant psychiatric morbidity among psoriasis patients, dermatology professionals should be more sensitive to the possible presence of psychiatric disorders in this patient population and should consider the use of formal screening or other diagnostic tools for detection of depression and anxiety in psoriasis patients.

The main determinant of psychiatric morbidity in our study population was impairment in QOL. Interestingly enough, psoriasis severity was not associated with psychiatric morbidity in our study. Depressive states in patients with chronic physical illnesses are well known and could be due to the chronic stress of illness or impaired QOL, or depression may be a direct effect of the illness and/or treatment on the central nervous system. Psoriasis is not known to have any direct effect on the central nervous system. Our findings suggest that QOL impairment plays an important role in psychiatric morbidity in patients with psoriasis. Even though the DLQI is designed to measure QOL over the preceding week, our findings suggest that impairment in QOL in psoriasis is a manifestation of a more long-term effect of interplay between many factors; the impairment in activities of daily living, disease-related physical discomfort and impaired self-esteem and self-perception, impairments in interpersonal relationships, and the stress of chronicity of illness seem to play an important role. Additionally, variables such as emotional dysfunction, magnitude and site of the area of involvement, nature and magnitude of comorbidities, and complications of illness and coping also may be relevant.²⁰ Although these factors are common in other chronic disorders, psoriasis in particular may predisposepatients to depression due to its unpredictable and relapsing nature, lack of any curative therapy, and the stigmatizing prominent lesions that often are impossible to camouflage. In chronic diseases such as psoriasis, the amelioration of impairment of different aspects of QOL may be more important than mere symptom control.

Our study was limited in that the study population was predominantly male. Fewer females may have consented to participate in the study due to time constraints associated with domestic responsibilities, reluctance to discuss psychological distress, or inability to meet the inclusion criteria (eg, level of education required to read questionnaires). However, there was no significant difference between males and females for sociodemographic variables or diagnoses other than alcohol-related disorders. Our study also had a cross-sectional design and there was no control group, without which it is difficult to assess the true prevalence and determinants of these psychiatric morbidities. Moreover, the sample size was small and did not include enough participants with moderate to severe psoriasis (ie, PASI score ≥10) to be able to detect a correlation between psychiatric morbidities and psoriasis severity. Our findings underline the need for effective screening and integrated management of psychiatric disorders in patients with psoriasis.

The prevalence of diabetes mellitus (DM) is growing at epidemic proportions in the U.S. and has been reported as the most common reason for hospital admissions in western countries.¹ There continues to be an alarmingly steady increase in the incidence of type 2 DM (T2DM), especially among the young and obese. Long-term diabetes-related complications also are likely to rise in prevalence. In particular, the diabetic foot is associated with morbidity and disability, leading to a significant impairment of quality of life.² People with DM develop foot ulcers because of neuropathy (sensory, motor, and autonomic deficits), ischemia, or both.³ The initiating injury may be from acute mechanical or thermal trauma or from repetitively or continuously applied mechanical stress.⁴

From foot ulcerations to neuropathy to peripheral vascular disease, the challenges are significant and can result in amputations and even premature death. To address these challenges, early diagnosis and a multidisciplinary team approach should be employed. Managing the numerous comorbidities is essential for treatment.^1,2,5

Due to the longevity of patients with DM, diabetes-associated complications are expected to rise in prevalence.⁶ The American Diabetes Association recently reported that T2DM accounts for about 90% to 95% of all persons with DM.^7,8 Today, many hospitalizations for patients with DM are for lower extremity conditions, such as ulceration, infection, or gangrene. Diabetic foot ulcerations (DFUs) are painful and costly for both the patient and the health care system. Every year, more than 1 million people with DM worldwide lose a leg as a consequence of this disease.⁹ Most DM-related amputations are preceded by a foot ulcer.

Diabetic foot ulcerations are the most common foot condition leading to lower extremity amputation (Figure 1).¹⁰ About 14 million individuals in the U.S. with diagnosed and undiagnosed DM will experience pathologic changes of their lower extremities that, when combined with minor trauma and infection, may lead to serious foot problems.¹¹ Although the triad of vasculopathy, neuropathy, and susceptibility to infection are the primary permissive factors in its pathogenesis, DFU can also be attributed to other important risk factors. The presence of peripheral neuropathy and peripheral arterial disease (PAD) are considered to be the most significant risk factors for all types of diabetic foot complications.¹²

Related: A Combined Treatment Protocol for Patients With Diabetic Peripheral Neuropathy

Optimal care of foot ulceration depends on the treating physician’s understanding of the pathophysiology involved, familiarity with accepted principles of treatment, and the knowledge that a coordinated, multidisciplinary team approach will best accomplish the goal of limb salvage. All efforts should be made to prevent foot lesions, and when present, existing ulcers should be treated promptly and aggressively, which can often prevent an exacerbation of the problem and decrease the incidence of amputations. Even when ulcers have healed, patients with DM and a history of a lower extremity ulcer should consider it a lifelong condition that requires monitoring to prevent recurrence.^13,14

This review provides a brief overview of DFU, including etiology, evaluation, treatment, and prevention, to provide clinicians with the clinical markers, evidence, and DFU treatment recommendations.

Etiologies

Multiple risk factors contribute to the development and pathogenesis of DFUs.^5,6,15,16 Neuropathy and PAD are major factors in the pathogenesis of diabetic foot ulcers.¹⁷ However, there are several additional factors leading to the occurrence of foot complications. Reiber and colleagues have determined that 63% of their patients’ ulcers were attributed to the critical triad of peripheral sensory neuropathy, trauma, and deformity.¹⁵

Other factors also implicated in the causal pathway to ulceration were ischemia, callus, and edema. Infection was rarely implicated in the etiology of these lesions, although once an ulcer has developed, infection and PAD were found to be the major causes for amputation.^10,18,19 Many of the risk factors for foot ulcer are also predisposing factors for amputation, because ulcers are primary antecedent events leading to amputation.^20-23

Other contributing causes for ulceration that have been identified are gender (male), duration of DM longer than 10 years, advanced age, high body mass index, prior ulceration, and other comorbidities, such as retinopathy, glycated hemoglobin level, limited joint mobility, foot deformity (Charcot foot, prior partial foot amputation, etc), high plantar pressures, and inappropriate foot self-care habits (Table 1).^3-6,22,24,25

Evaluation

The clinical evaluation must include a thorough and systematic lower extremity examination when starting DFU treatment. It is important to have a thorough assessment of the ulcer’s size and depth, and the evaluation should include a description of its appearance and measurement of its diameter at each visit. Evaluation for the presence of local and systemic infection and potential for osteomyelitis, using a small sterile blunt probe, is critical in determining depth of penetration and tracking along tendon sheaths (Figure 2).

Directly probing to bone (positive probe to bone test) has a high predictive value for underlying osteomyelitis even without acute signs of infection.²⁶ In addition, inspecting the wound for gangrene, necrosis, cellulitis, or infection and inspection of shoes for proper fit, foreign objects, and wear patterns can provide insight into other complications and underlying issues.

 

Peripheral arterial disease is directly linked to lower extremity disorders, such as intermittent claudication, pain on exertion, pain at rest, and, in severe cases, critical limb ischemia and gangrene.¹ Bilateral lower extremity pulses should routinely be palpated. When dorsalis pedis or posterior tibial artery pulses are absent or diminished, Doppler segmental pressures to the toes, pulse volume recording, skin perfusion pressure, or transcutaneous oxygen evaluation is indicated, and vascular consultation should be sought.³ Ischemia is caused by peripheral arterial occlusive disease of larger vessels, not by microangiopathy.¹³ Poor arterial inflow is associated not only with impaired ulcer healing, but also subsequent infection, gangrene, and amputation.¹³

Diabetic peripheral neuropathy is characterized by loss of protective sensation, allowing ulceration in areas of high pressure. Peripheral sensory neuropathy as measured by vibration perception thresholds can impart a 3.4-fold to 32-fold risk of ulceration.^19,21 Patients insensitive to a 10-g monofilament, commonly used to assess peripheral neuropathy, has been shown in several studies to convey a 2.2-fold to18-fold risk of ulceration.^6,19,27,28 In the large, population-based North-West Diabetes Foot Care Study, loss of protective sensation to the 10-g monofilament increased the risk of ulceration 80%, whereas abnormal ankle reflexes increased this risk 55%.²⁹

Peripheral neuropathy has been demonstrated as a strong risk factor for foot ulceration in many cross-sectional studies and is present in > 80% of affected patients.²⁹ Recent studies suggested that impaired sensation makes the foot increasingly vulnerable to damage caused by mechanical, thermal, or pressure-related injury.³⁰ Autonomic neuropathy by virtue of subsequent anhidrosis causes dryness of the skin and, therefore, vulnerability to fissuring.¹³

Unhealed cracks in the skin can easily lead to infection, especially in the presence of PAD. Neuropathy has an insidious and nonhomogeneous manifestation, making it difficult to identify its onset and a challenge for patients and clinicians.^31,32

Sacco and colleagues reviewed current literature and the International Consensus on the Diabetic Foot recommendation and concluded that most attention is given to patients with imminent foot ulceration rather than attempting to develop and improve assessment techniques that detect early impairments.^31,33 They propose that effort should be made that detect patients at risk of developing diabetic polyneuropathy. Although the 10-g monofilament pressure perception threshold is a common screening technique for early detection, tests of the vibration perception threshold may be more sensitive.

The authors propose that different monofilament sizes could probably better help determine the disease status, as the vibration tests do. In addition to the considerable subjectivity of both methods of assessing sensitivity, they are unquestionably clinical resources that can contribute to early detection of DPN. Future studies should focus on developing assessment strategies and tools that better detect early neuropathic changes. Early diagnosis of impending problems will aid in preventing further limb-threatening complications.

Treatment

The management of diabetic foot disease is focused primarily on avoiding lower extremity amputation and should be carried out through 3 main strategies: identification of the at risk foot, treatment of the acutely diseased foot, and prevention of further complications.³⁴ The primary goal in the treatment of DFUs is to obtain wound closure. Prompt, aggressive treatment of DFUs can often prevent an exacerbation of the problem and the potential need for amputation. The aim of therapy, therefore, should be early intervention to allow prompt healing of the lesion and, once healed, prevent its recurrence.^3,20,25,35

Management of the foot ulcer is largely determined by its severity (grade), vascularity, and presence of infection.^3,14,36 A multidisciplinary team approach should be used due to the multifaceted nature of foot ulcers, as well as for managing the numerous comorbidities attendant with these patients. The choice of treatment methods is determined by patient and ulcer characteristics. Equally important is the ability of patients to comply with the treatment as well as with the location and severity of the ulcer.⁴

Rest, elevation, and removal of pressure (off-loading) are essential components of treatment and should be initiated at first presentation. Recent studies provided evidence that indicated proper off-loading promotes more rapid DFU healing.^37,38 Ill-fitting footwear should be discarded and replaced with an appropriate off-loading device for mitigating pressure at the site of the ulceration. Although many off-loading modalities are currently in use, only a few studies describe the frequency and rate of wound healing associated with their use.

The total contact cast (TCC) is considered the superior standard therapy in management for neuropathic ulcers due to its proven ability to redistribute pressure, thereby promoting expeditious wound closure. Another inherent benefit is to ensure patient adherence with off-loading as well as reducing activity levels.^24,39 Previous randomized controlled trials have demonstrated that patients treated with TCC healed a higher percentage of plantar ulcers at a faster rate than did patients in the control groups. One unique study demonstrated histologic evidence of more rapid angiogenesis with formation of granulation tissue in the casted group compared with the standard treatment group.^40,41

 

Potential disadvantages of the TCC include the need for expertise in its proper application, the need for weekly cast changes, and related costs.^24,35 Although a number of new devices have been introduced as alternatives to the TCC, only several clinical studies demonstrating their efficacy have been published.^5,14,25,36 If nonweight bearing with crutches, wheelchair, or more effective devices are not feasible, even a pressure-attenuating insert can be used in a simple postoperative shoe until specialty referral is made.

Debridement of necrotic, callus, fibrous, and senescent tissues is a mainstay of ulcer therapy.^42,43 It is considered the first and the most important therapeutic step leading to wound closure in patients with DFU.^42-44 Unhealthy tissue must be sharply debrided back to bleeding tissue to fully visualize the extent of the ulcer as well as to detect any underlying abscesses or sinuses. It has been reported that regular (weekly) sharp debridement is associated with more rapid healing of ulcers compared with less frequent debridement.^45-47 Wilcox and colleagues indicated that frequent debridement healed more wounds in a shorter time (P < .001).⁴⁶ The more frequent the debridement, the better the healing outcome. There are different types of debridement methods, including surgical, enzymatic, autolytic, mechanical, and biologic.⁴⁸ Surgical or sharp debridement can convert a chronic ulcer into an acute wound that is more likely to heal.²⁴ Adequate debridement must always precede the application of topical wound healing agents, dressings, or wound closure procedures.²⁴ Conversely, a wound that does not receive the necessary debridement is one that has not been adequately treated.

There are numerous types of dressings that have been developed over the past decade that promote wound healing. Few have undergone any formal clinical studies to determine efficacy or effectiveness to help guide clinicians in their use.

Yazdanpanah and colleagues argued that dressings should confer moisture balance, protease sequestration, growth factor stimulation, antimicrobial activity, oxygen permeability, and the capacity to promote autolytic debridement to facilitate the production of granulation tissues and the re-epithelialization process.²⁴ In addition, it should have a prolonged time of action, high efficiency, and protection against contamination or infection.¹⁷ The group noted that no single dressing fulfills all the requirements of a diabetic patient with a foot ulcer. The choice of dressing is largely determined by the causes of DFU, wound location, depth, amount of scar or slough, exudates, condition of wound margins, presence of infection and pain, need for adhesiveness, and conformability of the dressing (Table 2).

Advanced Therapies

In 2003, Sheehan and colleagues reported that a 50% change in foot ulcer area after 4 weeks of observation is a robust predictor of healing at 12 weeks.⁴⁹ In addition, wounds failing to achieve a 50% reduction in area after 4 weeks need to be reassessed and considered for advanced treatment modalities if there are no otherwise identified impediments to wound healing.^6,9,38 These findings have served as a pivotal clinical decision point in the care of DFUs over the past several years for early identification of patients who may not respond to the standard of care. Today, most wound care protocols advocate use of standard therapies for at least 4 weeks before advanced therapies are considered.

Significant improvements have been achieved in the treatment of ulcerations, and today clinicians have several advanced therapeutic options for management of chronic DFUs. These new technologies have been shown to increase the probability of complete wound closure in difficult-to-heal foot ulcerations in patients with diabetes. Among these are recombinant platelet-derived growth factors, a human living skin equivalent, and a human fibroblast-derived dermal substitute.^49-51 Tissue-engineered skin equivalent (Apligraf) and human dermis (Dermagraft) are types of biologically active dressings that are derived from fibroblasts of neonatal foreskins.

The most recent advancements for wound care therapies is that of stem cell therapies, primarily bone marrow-derived and, most recently, placental-derived stem cells, including dehydrated human amnion chorion (Epifix) and amniotic matrix with mesenchymal stem cells (Grafix).^52,53 Because of the expense of these products, they cannot be used universally in the treatment of DFUs but rather are used and reserved for difficult-to-heal wounds. In addition, negative pressure therapy has assumed a major role in the management of traumatic, acute, and chronic wounds and has shown efficacy in healing DFUs.^54-57 Hyperbaric oxygen therapy and several biophysical modalities have been studied and found to be efficacious in healing a wide variety of chronic wounds over the past decade as well, although results vary by study, and no advanced modality has become universal in its application.^58-64

 

Table 3 lists most of the wound care technologies commonly used in current clinical practice. Although randomized controlled trials have been published supporting the use of most of these modalities, a lack of strong data proving efficacy for use of such treatment options remains.

Treatment of any underlying ischemia is critical in achieving a successful outcome. Vascular surgical consultation should be obtained on presentation of an ischemic wound and in cases where ulcers show no sign of progress despite appropriate management.^4,13 Revascularization is commonly performed in patients with critical limb ischemia and DFUs but is also performed in patients with less severe arteriopathy. The goal is to restore a palpable pulse on the affected foot.⁶⁵ The postrevascularization ulcer-healing rate ranges from 46% to 91% at 1 year and seems to be improved in those patients with distal arterial reconstruction and restoration of pulsatile flow.⁶⁶

Endovascular approaches are becoming increasingly common in patients whose arterial disease is more limited or morbidity is a significant concern.^67,68 Studies report that the exact role of isolated endovascular procedures is still to be determined, although such interventions are frequently performed in concert with angiography preceding vascular reconstructive procedures.^69,70 However, in many such studies, healing was often a secondary criterion, and there was no description of the initial wound or its management.⁷¹

Challenges

Within the VA setting there is a wide range of patient comorbidities that frequently present clinicians with unique challenges. Often these patients are older with many social and mental health conditions, including self-abuse, drug-abuse, nonadherence, psychological issues and lack of financial and/or educational resources or support. Many of these patients have comorbidities associated with diabetes that can delay healing of their ulcerations.

Systemwide VA mandates have implemented multidisciplinary foot care teams. The teams identify veterans at risk for lower limb complications; provide preventive care; track high-risk foot care across the continuum of outpatient, inpatient, and rehabilitative care; and provide education, orthoses, and social support.^72,73 In the late 1990s, the VHA implemented a national program of foot risk screening and referral, conducted largely in primary care.²⁹ By 1998 as determined from medical record reviews, 95% of veterans had a visual examination, 84% had palpation of pulses, and 78% had undergone a sensory examination. In addition, about 83% of patients had a monofilament examination, and 85% of individuals with risk factors were referred to foot specialists in 2004.^72,74 Veterans at higher risk for lower extremity complications routinely receive subsequent preventive foot care, such as education or prescription of therapeutic shoes in the VHA.

Tseng and colleagues evaluated risk-adjusted trends in amputations among veterans with diabetes during a 5-year period and reported a decrease in amputation rates observed for all types of lower extremity amputations (LEA) and among all racial groups.⁷⁴ Implementation of such universal programs for foot screening, tracked through performance measures, may have contributed to a decrease in LEAs and improved outcomes in the VA patient population.

Prevention

A healthy, intact diabetic foot is best maintained by a consistent and recurrent preventive treatment strategy. Prevention of ulcer recurrence remains to be a major clinical challenge. Andrews and colleagues demonstrated that recurrence rates range from 28% at 12 months to 100% at 40 months.⁷⁵ They report that the highest incidence of reulceration is in the site of a previous ulceration, noting that a newly healed ulcer is covered with fragile skin and after complete healing, there is an area of higher density tissue (scar). Shearing between the different tissue densities often contributes to new ulcers.

After the ulcer heals, the patient and their caregivers must incorporate preventative measures in care plans to reduce the risk of wound reoccurrence. A study reported by Barshes and colleagues demonstrated that a majority of people with diabetes do not receive guideline-recommended foot care, including regular foot examinations.⁷⁶ Identifying the patients with diabetes at risk for ulceration requires foot examination,including the vascular and neurologic systems, skin conditions, and foot structure.⁷⁷ Among the complications of diabetes, lower limb amputation is considered to be preventable.^78,79 Because there is a great beneficial effect of patient education on reducing LEAs, a flexible schedule for diabetes education, that offers education at any time for the maximum convenience of patients rather than focusing on health care provider’s convenience is critical.^79,80 Conservative management of foot problems also has reduced the risk of amputation by simple procedures, such as appropriate foot wear, cleanliness, aggressive surgical debridement, and evidence-based ulcer management.³⁴ This is best accomplished through a multidisciplinary approach involving a team of specialists and personnel who provide a coordinated process of care, including a patient motivated to ensure its success.⁶

 

Conclusions

The authors have described the components of assessment and treatment that can help ensure successful healing of foot ulcers in diabetic patients. These approaches should be used whenever feasible to reduce the high morbidity and risk of serious complications resulting from foot ulcers. Advances in treating chronic diabetic wounds are promising; however, the intrinsic pathophysiologic abnormalities that lead to ulcers in the first place cannot be ignored. No known therapy will be effective without concomitant management of ischemia, infection, and adequate off-loading.^6,75

Not all diabetic foot complications can be prevented, but it is possible to dramatically reduce their incidence through appropriate management and prevention programs. The multidisciplinary team approach that combines the expertise of many types of health care providers for diabetic foot disorders has been demonstrated as the optimal method to achieve favorable rates of limb salvage in the high-risk diabetic patient.

The prevalence of diabetes mellitus (DM) is growing at epidemic proportions in the U.S. and has been reported as the most common reason for hospital admissions in western countries.¹ There continues to be an alarmingly steady increase in the incidence of type 2 DM (T2DM), especially among the young and obese. Long-term diabetes-related complications also are likely to rise in prevalence. In particular, the diabetic foot is associated with morbidity and disability, leading to a significant impairment of quality of life.² People with DM develop foot ulcers because of neuropathy (sensory, motor, and autonomic deficits), ischemia, or both.³ The initiating injury may be from acute mechanical or thermal trauma or from repetitively or continuously applied mechanical stress.⁴

From foot ulcerations to neuropathy to peripheral vascular disease, the challenges are significant and can result in amputations and even premature death. To address these challenges, early diagnosis and a multidisciplinary team approach should be employed. Managing the numerous comorbidities is essential for treatment.^1,2,5

Due to the longevity of patients with DM, diabetes-associated complications are expected to rise in prevalence.⁶ The American Diabetes Association recently reported that T2DM accounts for about 90% to 95% of all persons with DM.^7,8 Today, many hospitalizations for patients with DM are for lower extremity conditions, such as ulceration, infection, or gangrene. Diabetic foot ulcerations (DFUs) are painful and costly for both the patient and the health care system. Every year, more than 1 million people with DM worldwide lose a leg as a consequence of this disease.⁹ Most DM-related amputations are preceded by a foot ulcer.

Diabetic foot ulcerations are the most common foot condition leading to lower extremity amputation (Figure 1).¹⁰ About 14 million individuals in the U.S. with diagnosed and undiagnosed DM will experience pathologic changes of their lower extremities that, when combined with minor trauma and infection, may lead to serious foot problems.¹¹ Although the triad of vasculopathy, neuropathy, and susceptibility to infection are the primary permissive factors in its pathogenesis, DFU can also be attributed to other important risk factors. The presence of peripheral neuropathy and peripheral arterial disease (PAD) are considered to be the most significant risk factors for all types of diabetic foot complications.¹²

Related: A Combined Treatment Protocol for Patients With Diabetic Peripheral Neuropathy

Optimal care of foot ulceration depends on the treating physician’s understanding of the pathophysiology involved, familiarity with accepted principles of treatment, and the knowledge that a coordinated, multidisciplinary team approach will best accomplish the goal of limb salvage. All efforts should be made to prevent foot lesions, and when present, existing ulcers should be treated promptly and aggressively, which can often prevent an exacerbation of the problem and decrease the incidence of amputations. Even when ulcers have healed, patients with DM and a history of a lower extremity ulcer should consider it a lifelong condition that requires monitoring to prevent recurrence.^13,14

This review provides a brief overview of DFU, including etiology, evaluation, treatment, and prevention, to provide clinicians with the clinical markers, evidence, and DFU treatment recommendations.

Etiologies

Multiple risk factors contribute to the development and pathogenesis of DFUs.^5,6,15,16 Neuropathy and PAD are major factors in the pathogenesis of diabetic foot ulcers.¹⁷ However, there are several additional factors leading to the occurrence of foot complications. Reiber and colleagues have determined that 63% of their patients’ ulcers were attributed to the critical triad of peripheral sensory neuropathy, trauma, and deformity.¹⁵

Other factors also implicated in the causal pathway to ulceration were ischemia, callus, and edema. Infection was rarely implicated in the etiology of these lesions, although once an ulcer has developed, infection and PAD were found to be the major causes for amputation.^10,18,19 Many of the risk factors for foot ulcer are also predisposing factors for amputation, because ulcers are primary antecedent events leading to amputation.^20-23

Other contributing causes for ulceration that have been identified are gender (male), duration of DM longer than 10 years, advanced age, high body mass index, prior ulceration, and other comorbidities, such as retinopathy, glycated hemoglobin level, limited joint mobility, foot deformity (Charcot foot, prior partial foot amputation, etc), high plantar pressures, and inappropriate foot self-care habits (Table 1).^3-6,22,24,25

Evaluation

The clinical evaluation must include a thorough and systematic lower extremity examination when starting DFU treatment. It is important to have a thorough assessment of the ulcer’s size and depth, and the evaluation should include a description of its appearance and measurement of its diameter at each visit. Evaluation for the presence of local and systemic infection and potential for osteomyelitis, using a small sterile blunt probe, is critical in determining depth of penetration and tracking along tendon sheaths (Figure 2).

Directly probing to bone (positive probe to bone test) has a high predictive value for underlying osteomyelitis even without acute signs of infection.²⁶ In addition, inspecting the wound for gangrene, necrosis, cellulitis, or infection and inspection of shoes for proper fit, foreign objects, and wear patterns can provide insight into other complications and underlying issues.

 

Peripheral arterial disease is directly linked to lower extremity disorders, such as intermittent claudication, pain on exertion, pain at rest, and, in severe cases, critical limb ischemia and gangrene.¹ Bilateral lower extremity pulses should routinely be palpated. When dorsalis pedis or posterior tibial artery pulses are absent or diminished, Doppler segmental pressures to the toes, pulse volume recording, skin perfusion pressure, or transcutaneous oxygen evaluation is indicated, and vascular consultation should be sought.³ Ischemia is caused by peripheral arterial occlusive disease of larger vessels, not by microangiopathy.¹³ Poor arterial inflow is associated not only with impaired ulcer healing, but also subsequent infection, gangrene, and amputation.¹³

Diabetic peripheral neuropathy is characterized by loss of protective sensation, allowing ulceration in areas of high pressure. Peripheral sensory neuropathy as measured by vibration perception thresholds can impart a 3.4-fold to 32-fold risk of ulceration.^19,21 Patients insensitive to a 10-g monofilament, commonly used to assess peripheral neuropathy, has been shown in several studies to convey a 2.2-fold to18-fold risk of ulceration.^6,19,27,28 In the large, population-based North-West Diabetes Foot Care Study, loss of protective sensation to the 10-g monofilament increased the risk of ulceration 80%, whereas abnormal ankle reflexes increased this risk 55%.²⁹

Peripheral neuropathy has been demonstrated as a strong risk factor for foot ulceration in many cross-sectional studies and is present in > 80% of affected patients.²⁹ Recent studies suggested that impaired sensation makes the foot increasingly vulnerable to damage caused by mechanical, thermal, or pressure-related injury.³⁰ Autonomic neuropathy by virtue of subsequent anhidrosis causes dryness of the skin and, therefore, vulnerability to fissuring.¹³

Unhealed cracks in the skin can easily lead to infection, especially in the presence of PAD. Neuropathy has an insidious and nonhomogeneous manifestation, making it difficult to identify its onset and a challenge for patients and clinicians.^31,32

Sacco and colleagues reviewed current literature and the International Consensus on the Diabetic Foot recommendation and concluded that most attention is given to patients with imminent foot ulceration rather than attempting to develop and improve assessment techniques that detect early impairments.^31,33 They propose that effort should be made that detect patients at risk of developing diabetic polyneuropathy. Although the 10-g monofilament pressure perception threshold is a common screening technique for early detection, tests of the vibration perception threshold may be more sensitive.

The authors propose that different monofilament sizes could probably better help determine the disease status, as the vibration tests do. In addition to the considerable subjectivity of both methods of assessing sensitivity, they are unquestionably clinical resources that can contribute to early detection of DPN. Future studies should focus on developing assessment strategies and tools that better detect early neuropathic changes. Early diagnosis of impending problems will aid in preventing further limb-threatening complications.

Treatment

The management of diabetic foot disease is focused primarily on avoiding lower extremity amputation and should be carried out through 3 main strategies: identification of the at risk foot, treatment of the acutely diseased foot, and prevention of further complications.³⁴ The primary goal in the treatment of DFUs is to obtain wound closure. Prompt, aggressive treatment of DFUs can often prevent an exacerbation of the problem and the potential need for amputation. The aim of therapy, therefore, should be early intervention to allow prompt healing of the lesion and, once healed, prevent its recurrence.^3,20,25,35

Management of the foot ulcer is largely determined by its severity (grade), vascularity, and presence of infection.^3,14,36 A multidisciplinary team approach should be used due to the multifaceted nature of foot ulcers, as well as for managing the numerous comorbidities attendant with these patients. The choice of treatment methods is determined by patient and ulcer characteristics. Equally important is the ability of patients to comply with the treatment as well as with the location and severity of the ulcer.⁴

Rest, elevation, and removal of pressure (off-loading) are essential components of treatment and should be initiated at first presentation. Recent studies provided evidence that indicated proper off-loading promotes more rapid DFU healing.^37,38 Ill-fitting footwear should be discarded and replaced with an appropriate off-loading device for mitigating pressure at the site of the ulceration. Although many off-loading modalities are currently in use, only a few studies describe the frequency and rate of wound healing associated with their use.

The total contact cast (TCC) is considered the superior standard therapy in management for neuropathic ulcers due to its proven ability to redistribute pressure, thereby promoting expeditious wound closure. Another inherent benefit is to ensure patient adherence with off-loading as well as reducing activity levels.^24,39 Previous randomized controlled trials have demonstrated that patients treated with TCC healed a higher percentage of plantar ulcers at a faster rate than did patients in the control groups. One unique study demonstrated histologic evidence of more rapid angiogenesis with formation of granulation tissue in the casted group compared with the standard treatment group.^40,41

 

Potential disadvantages of the TCC include the need for expertise in its proper application, the need for weekly cast changes, and related costs.^24,35 Although a number of new devices have been introduced as alternatives to the TCC, only several clinical studies demonstrating their efficacy have been published.^5,14,25,36 If nonweight bearing with crutches, wheelchair, or more effective devices are not feasible, even a pressure-attenuating insert can be used in a simple postoperative shoe until specialty referral is made.

Debridement of necrotic, callus, fibrous, and senescent tissues is a mainstay of ulcer therapy.^42,43 It is considered the first and the most important therapeutic step leading to wound closure in patients with DFU.^42-44 Unhealthy tissue must be sharply debrided back to bleeding tissue to fully visualize the extent of the ulcer as well as to detect any underlying abscesses or sinuses. It has been reported that regular (weekly) sharp debridement is associated with more rapid healing of ulcers compared with less frequent debridement.^45-47 Wilcox and colleagues indicated that frequent debridement healed more wounds in a shorter time (P < .001).⁴⁶ The more frequent the debridement, the better the healing outcome. There are different types of debridement methods, including surgical, enzymatic, autolytic, mechanical, and biologic.⁴⁸ Surgical or sharp debridement can convert a chronic ulcer into an acute wound that is more likely to heal.²⁴ Adequate debridement must always precede the application of topical wound healing agents, dressings, or wound closure procedures.²⁴ Conversely, a wound that does not receive the necessary debridement is one that has not been adequately treated.

There are numerous types of dressings that have been developed over the past decade that promote wound healing. Few have undergone any formal clinical studies to determine efficacy or effectiveness to help guide clinicians in their use.

Yazdanpanah and colleagues argued that dressings should confer moisture balance, protease sequestration, growth factor stimulation, antimicrobial activity, oxygen permeability, and the capacity to promote autolytic debridement to facilitate the production of granulation tissues and the re-epithelialization process.²⁴ In addition, it should have a prolonged time of action, high efficiency, and protection against contamination or infection.¹⁷ The group noted that no single dressing fulfills all the requirements of a diabetic patient with a foot ulcer. The choice of dressing is largely determined by the causes of DFU, wound location, depth, amount of scar or slough, exudates, condition of wound margins, presence of infection and pain, need for adhesiveness, and conformability of the dressing (Table 2).

Advanced Therapies

In 2003, Sheehan and colleagues reported that a 50% change in foot ulcer area after 4 weeks of observation is a robust predictor of healing at 12 weeks.⁴⁹ In addition, wounds failing to achieve a 50% reduction in area after 4 weeks need to be reassessed and considered for advanced treatment modalities if there are no otherwise identified impediments to wound healing.^6,9,38 These findings have served as a pivotal clinical decision point in the care of DFUs over the past several years for early identification of patients who may not respond to the standard of care. Today, most wound care protocols advocate use of standard therapies for at least 4 weeks before advanced therapies are considered.

Significant improvements have been achieved in the treatment of ulcerations, and today clinicians have several advanced therapeutic options for management of chronic DFUs. These new technologies have been shown to increase the probability of complete wound closure in difficult-to-heal foot ulcerations in patients with diabetes. Among these are recombinant platelet-derived growth factors, a human living skin equivalent, and a human fibroblast-derived dermal substitute.^49-51 Tissue-engineered skin equivalent (Apligraf) and human dermis (Dermagraft) are types of biologically active dressings that are derived from fibroblasts of neonatal foreskins.

The most recent advancements for wound care therapies is that of stem cell therapies, primarily bone marrow-derived and, most recently, placental-derived stem cells, including dehydrated human amnion chorion (Epifix) and amniotic matrix with mesenchymal stem cells (Grafix).^52,53 Because of the expense of these products, they cannot be used universally in the treatment of DFUs but rather are used and reserved for difficult-to-heal wounds. In addition, negative pressure therapy has assumed a major role in the management of traumatic, acute, and chronic wounds and has shown efficacy in healing DFUs.^54-57 Hyperbaric oxygen therapy and several biophysical modalities have been studied and found to be efficacious in healing a wide variety of chronic wounds over the past decade as well, although results vary by study, and no advanced modality has become universal in its application.^58-64

 

Table 3 lists most of the wound care technologies commonly used in current clinical practice. Although randomized controlled trials have been published supporting the use of most of these modalities, a lack of strong data proving efficacy for use of such treatment options remains.

Treatment of any underlying ischemia is critical in achieving a successful outcome. Vascular surgical consultation should be obtained on presentation of an ischemic wound and in cases where ulcers show no sign of progress despite appropriate management.^4,13 Revascularization is commonly performed in patients with critical limb ischemia and DFUs but is also performed in patients with less severe arteriopathy. The goal is to restore a palpable pulse on the affected foot.⁶⁵ The postrevascularization ulcer-healing rate ranges from 46% to 91% at 1 year and seems to be improved in those patients with distal arterial reconstruction and restoration of pulsatile flow.⁶⁶

Endovascular approaches are becoming increasingly common in patients whose arterial disease is more limited or morbidity is a significant concern.^67,68 Studies report that the exact role of isolated endovascular procedures is still to be determined, although such interventions are frequently performed in concert with angiography preceding vascular reconstructive procedures.^69,70 However, in many such studies, healing was often a secondary criterion, and there was no description of the initial wound or its management.⁷¹

Challenges

Within the VA setting there is a wide range of patient comorbidities that frequently present clinicians with unique challenges. Often these patients are older with many social and mental health conditions, including self-abuse, drug-abuse, nonadherence, psychological issues and lack of financial and/or educational resources or support. Many of these patients have comorbidities associated with diabetes that can delay healing of their ulcerations.

Systemwide VA mandates have implemented multidisciplinary foot care teams. The teams identify veterans at risk for lower limb complications; provide preventive care; track high-risk foot care across the continuum of outpatient, inpatient, and rehabilitative care; and provide education, orthoses, and social support.^72,73 In the late 1990s, the VHA implemented a national program of foot risk screening and referral, conducted largely in primary care.²⁹ By 1998 as determined from medical record reviews, 95% of veterans had a visual examination, 84% had palpation of pulses, and 78% had undergone a sensory examination. In addition, about 83% of patients had a monofilament examination, and 85% of individuals with risk factors were referred to foot specialists in 2004.^72,74 Veterans at higher risk for lower extremity complications routinely receive subsequent preventive foot care, such as education or prescription of therapeutic shoes in the VHA.

Tseng and colleagues evaluated risk-adjusted trends in amputations among veterans with diabetes during a 5-year period and reported a decrease in amputation rates observed for all types of lower extremity amputations (LEA) and among all racial groups.⁷⁴ Implementation of such universal programs for foot screening, tracked through performance measures, may have contributed to a decrease in LEAs and improved outcomes in the VA patient population.

Prevention

A healthy, intact diabetic foot is best maintained by a consistent and recurrent preventive treatment strategy. Prevention of ulcer recurrence remains to be a major clinical challenge. Andrews and colleagues demonstrated that recurrence rates range from 28% at 12 months to 100% at 40 months.⁷⁵ They report that the highest incidence of reulceration is in the site of a previous ulceration, noting that a newly healed ulcer is covered with fragile skin and after complete healing, there is an area of higher density tissue (scar). Shearing between the different tissue densities often contributes to new ulcers.

After the ulcer heals, the patient and their caregivers must incorporate preventative measures in care plans to reduce the risk of wound reoccurrence. A study reported by Barshes and colleagues demonstrated that a majority of people with diabetes do not receive guideline-recommended foot care, including regular foot examinations.⁷⁶ Identifying the patients with diabetes at risk for ulceration requires foot examination,including the vascular and neurologic systems, skin conditions, and foot structure.⁷⁷ Among the complications of diabetes, lower limb amputation is considered to be preventable.^78,79 Because there is a great beneficial effect of patient education on reducing LEAs, a flexible schedule for diabetes education, that offers education at any time for the maximum convenience of patients rather than focusing on health care provider’s convenience is critical.^79,80 Conservative management of foot problems also has reduced the risk of amputation by simple procedures, such as appropriate foot wear, cleanliness, aggressive surgical debridement, and evidence-based ulcer management.³⁴ This is best accomplished through a multidisciplinary approach involving a team of specialists and personnel who provide a coordinated process of care, including a patient motivated to ensure its success.⁶

 

Conclusions

The authors have described the components of assessment and treatment that can help ensure successful healing of foot ulcers in diabetic patients. These approaches should be used whenever feasible to reduce the high morbidity and risk of serious complications resulting from foot ulcers. Advances in treating chronic diabetic wounds are promising; however, the intrinsic pathophysiologic abnormalities that lead to ulcers in the first place cannot be ignored. No known therapy will be effective without concomitant management of ischemia, infection, and adequate off-loading.^6,75

Not all diabetic foot complications can be prevented, but it is possible to dramatically reduce their incidence through appropriate management and prevention programs. The multidisciplinary team approach that combines the expertise of many types of health care providers for diabetic foot disorders has been demonstrated as the optimal method to achieve favorable rates of limb salvage in the high-risk diabetic patient.

The prevalence of diabetes mellitus (DM) is growing at epidemic proportions in the U.S. and has been reported as the most common reason for hospital admissions in western countries.¹ There continues to be an alarmingly steady increase in the incidence of type 2 DM (T2DM), especially among the young and obese. Long-term diabetes-related complications also are likely to rise in prevalence. In particular, the diabetic foot is associated with morbidity and disability, leading to a significant impairment of quality of life.² People with DM develop foot ulcers because of neuropathy (sensory, motor, and autonomic deficits), ischemia, or both.³ The initiating injury may be from acute mechanical or thermal trauma or from repetitively or continuously applied mechanical stress.⁴

From foot ulcerations to neuropathy to peripheral vascular disease, the challenges are significant and can result in amputations and even premature death. To address these challenges, early diagnosis and a multidisciplinary team approach should be employed. Managing the numerous comorbidities is essential for treatment.^1,2,5

Due to the longevity of patients with DM, diabetes-associated complications are expected to rise in prevalence.⁶ The American Diabetes Association recently reported that T2DM accounts for about 90% to 95% of all persons with DM.^7,8 Today, many hospitalizations for patients with DM are for lower extremity conditions, such as ulceration, infection, or gangrene. Diabetic foot ulcerations (DFUs) are painful and costly for both the patient and the health care system. Every year, more than 1 million people with DM worldwide lose a leg as a consequence of this disease.⁹ Most DM-related amputations are preceded by a foot ulcer.

Diabetic foot ulcerations are the most common foot condition leading to lower extremity amputation (Figure 1).¹⁰ About 14 million individuals in the U.S. with diagnosed and undiagnosed DM will experience pathologic changes of their lower extremities that, when combined with minor trauma and infection, may lead to serious foot problems.¹¹ Although the triad of vasculopathy, neuropathy, and susceptibility to infection are the primary permissive factors in its pathogenesis, DFU can also be attributed to other important risk factors. The presence of peripheral neuropathy and peripheral arterial disease (PAD) are considered to be the most significant risk factors for all types of diabetic foot complications.¹²

Related: A Combined Treatment Protocol for Patients With Diabetic Peripheral Neuropathy

Optimal care of foot ulceration depends on the treating physician’s understanding of the pathophysiology involved, familiarity with accepted principles of treatment, and the knowledge that a coordinated, multidisciplinary team approach will best accomplish the goal of limb salvage. All efforts should be made to prevent foot lesions, and when present, existing ulcers should be treated promptly and aggressively, which can often prevent an exacerbation of the problem and decrease the incidence of amputations. Even when ulcers have healed, patients with DM and a history of a lower extremity ulcer should consider it a lifelong condition that requires monitoring to prevent recurrence.^13,14

This review provides a brief overview of DFU, including etiology, evaluation, treatment, and prevention, to provide clinicians with the clinical markers, evidence, and DFU treatment recommendations.

Etiologies

Multiple risk factors contribute to the development and pathogenesis of DFUs.^5,6,15,16 Neuropathy and PAD are major factors in the pathogenesis of diabetic foot ulcers.¹⁷ However, there are several additional factors leading to the occurrence of foot complications. Reiber and colleagues have determined that 63% of their patients’ ulcers were attributed to the critical triad of peripheral sensory neuropathy, trauma, and deformity.¹⁵

Other factors also implicated in the causal pathway to ulceration were ischemia, callus, and edema. Infection was rarely implicated in the etiology of these lesions, although once an ulcer has developed, infection and PAD were found to be the major causes for amputation.^10,18,19 Many of the risk factors for foot ulcer are also predisposing factors for amputation, because ulcers are primary antecedent events leading to amputation.^20-23

Other contributing causes for ulceration that have been identified are gender (male), duration of DM longer than 10 years, advanced age, high body mass index, prior ulceration, and other comorbidities, such as retinopathy, glycated hemoglobin level, limited joint mobility, foot deformity (Charcot foot, prior partial foot amputation, etc), high plantar pressures, and inappropriate foot self-care habits (Table 1).^3-6,22,24,25

Evaluation

The clinical evaluation must include a thorough and systematic lower extremity examination when starting DFU treatment. It is important to have a thorough assessment of the ulcer’s size and depth, and the evaluation should include a description of its appearance and measurement of its diameter at each visit. Evaluation for the presence of local and systemic infection and potential for osteomyelitis, using a small sterile blunt probe, is critical in determining depth of penetration and tracking along tendon sheaths (Figure 2).

Directly probing to bone (positive probe to bone test) has a high predictive value for underlying osteomyelitis even without acute signs of infection.²⁶ In addition, inspecting the wound for gangrene, necrosis, cellulitis, or infection and inspection of shoes for proper fit, foreign objects, and wear patterns can provide insight into other complications and underlying issues.

 

Peripheral arterial disease is directly linked to lower extremity disorders, such as intermittent claudication, pain on exertion, pain at rest, and, in severe cases, critical limb ischemia and gangrene.¹ Bilateral lower extremity pulses should routinely be palpated. When dorsalis pedis or posterior tibial artery pulses are absent or diminished, Doppler segmental pressures to the toes, pulse volume recording, skin perfusion pressure, or transcutaneous oxygen evaluation is indicated, and vascular consultation should be sought.³ Ischemia is caused by peripheral arterial occlusive disease of larger vessels, not by microangiopathy.¹³ Poor arterial inflow is associated not only with impaired ulcer healing, but also subsequent infection, gangrene, and amputation.¹³

Diabetic peripheral neuropathy is characterized by loss of protective sensation, allowing ulceration in areas of high pressure. Peripheral sensory neuropathy as measured by vibration perception thresholds can impart a 3.4-fold to 32-fold risk of ulceration.^19,21 Patients insensitive to a 10-g monofilament, commonly used to assess peripheral neuropathy, has been shown in several studies to convey a 2.2-fold to18-fold risk of ulceration.^6,19,27,28 In the large, population-based North-West Diabetes Foot Care Study, loss of protective sensation to the 10-g monofilament increased the risk of ulceration 80%, whereas abnormal ankle reflexes increased this risk 55%.²⁹

Peripheral neuropathy has been demonstrated as a strong risk factor for foot ulceration in many cross-sectional studies and is present in > 80% of affected patients.²⁹ Recent studies suggested that impaired sensation makes the foot increasingly vulnerable to damage caused by mechanical, thermal, or pressure-related injury.³⁰ Autonomic neuropathy by virtue of subsequent anhidrosis causes dryness of the skin and, therefore, vulnerability to fissuring.¹³

Unhealed cracks in the skin can easily lead to infection, especially in the presence of PAD. Neuropathy has an insidious and nonhomogeneous manifestation, making it difficult to identify its onset and a challenge for patients and clinicians.^31,32

Sacco and colleagues reviewed current literature and the International Consensus on the Diabetic Foot recommendation and concluded that most attention is given to patients with imminent foot ulceration rather than attempting to develop and improve assessment techniques that detect early impairments.^31,33 They propose that effort should be made that detect patients at risk of developing diabetic polyneuropathy. Although the 10-g monofilament pressure perception threshold is a common screening technique for early detection, tests of the vibration perception threshold may be more sensitive.

The authors propose that different monofilament sizes could probably better help determine the disease status, as the vibration tests do. In addition to the considerable subjectivity of both methods of assessing sensitivity, they are unquestionably clinical resources that can contribute to early detection of DPN. Future studies should focus on developing assessment strategies and tools that better detect early neuropathic changes. Early diagnosis of impending problems will aid in preventing further limb-threatening complications.

Treatment

The management of diabetic foot disease is focused primarily on avoiding lower extremity amputation and should be carried out through 3 main strategies: identification of the at risk foot, treatment of the acutely diseased foot, and prevention of further complications.³⁴ The primary goal in the treatment of DFUs is to obtain wound closure. Prompt, aggressive treatment of DFUs can often prevent an exacerbation of the problem and the potential need for amputation. The aim of therapy, therefore, should be early intervention to allow prompt healing of the lesion and, once healed, prevent its recurrence.^3,20,25,35

Management of the foot ulcer is largely determined by its severity (grade), vascularity, and presence of infection.^3,14,36 A multidisciplinary team approach should be used due to the multifaceted nature of foot ulcers, as well as for managing the numerous comorbidities attendant with these patients. The choice of treatment methods is determined by patient and ulcer characteristics. Equally important is the ability of patients to comply with the treatment as well as with the location and severity of the ulcer.⁴

Rest, elevation, and removal of pressure (off-loading) are essential components of treatment and should be initiated at first presentation. Recent studies provided evidence that indicated proper off-loading promotes more rapid DFU healing.^37,38 Ill-fitting footwear should be discarded and replaced with an appropriate off-loading device for mitigating pressure at the site of the ulceration. Although many off-loading modalities are currently in use, only a few studies describe the frequency and rate of wound healing associated with their use.

The total contact cast (TCC) is considered the superior standard therapy in management for neuropathic ulcers due to its proven ability to redistribute pressure, thereby promoting expeditious wound closure. Another inherent benefit is to ensure patient adherence with off-loading as well as reducing activity levels.^24,39 Previous randomized controlled trials have demonstrated that patients treated with TCC healed a higher percentage of plantar ulcers at a faster rate than did patients in the control groups. One unique study demonstrated histologic evidence of more rapid angiogenesis with formation of granulation tissue in the casted group compared with the standard treatment group.^40,41

 

Potential disadvantages of the TCC include the need for expertise in its proper application, the need for weekly cast changes, and related costs.^24,35 Although a number of new devices have been introduced as alternatives to the TCC, only several clinical studies demonstrating their efficacy have been published.^5,14,25,36 If nonweight bearing with crutches, wheelchair, or more effective devices are not feasible, even a pressure-attenuating insert can be used in a simple postoperative shoe until specialty referral is made.

Debridement of necrotic, callus, fibrous, and senescent tissues is a mainstay of ulcer therapy.^42,43 It is considered the first and the most important therapeutic step leading to wound closure in patients with DFU.^42-44 Unhealthy tissue must be sharply debrided back to bleeding tissue to fully visualize the extent of the ulcer as well as to detect any underlying abscesses or sinuses. It has been reported that regular (weekly) sharp debridement is associated with more rapid healing of ulcers compared with less frequent debridement.^45-47 Wilcox and colleagues indicated that frequent debridement healed more wounds in a shorter time (P < .001).⁴⁶ The more frequent the debridement, the better the healing outcome. There are different types of debridement methods, including surgical, enzymatic, autolytic, mechanical, and biologic.⁴⁸ Surgical or sharp debridement can convert a chronic ulcer into an acute wound that is more likely to heal.²⁴ Adequate debridement must always precede the application of topical wound healing agents, dressings, or wound closure procedures.²⁴ Conversely, a wound that does not receive the necessary debridement is one that has not been adequately treated.

There are numerous types of dressings that have been developed over the past decade that promote wound healing. Few have undergone any formal clinical studies to determine efficacy or effectiveness to help guide clinicians in their use.

Yazdanpanah and colleagues argued that dressings should confer moisture balance, protease sequestration, growth factor stimulation, antimicrobial activity, oxygen permeability, and the capacity to promote autolytic debridement to facilitate the production of granulation tissues and the re-epithelialization process.²⁴ In addition, it should have a prolonged time of action, high efficiency, and protection against contamination or infection.¹⁷ The group noted that no single dressing fulfills all the requirements of a diabetic patient with a foot ulcer. The choice of dressing is largely determined by the causes of DFU, wound location, depth, amount of scar or slough, exudates, condition of wound margins, presence of infection and pain, need for adhesiveness, and conformability of the dressing (Table 2).

Advanced Therapies

In 2003, Sheehan and colleagues reported that a 50% change in foot ulcer area after 4 weeks of observation is a robust predictor of healing at 12 weeks.⁴⁹ In addition, wounds failing to achieve a 50% reduction in area after 4 weeks need to be reassessed and considered for advanced treatment modalities if there are no otherwise identified impediments to wound healing.^6,9,38 These findings have served as a pivotal clinical decision point in the care of DFUs over the past several years for early identification of patients who may not respond to the standard of care. Today, most wound care protocols advocate use of standard therapies for at least 4 weeks before advanced therapies are considered.

Significant improvements have been achieved in the treatment of ulcerations, and today clinicians have several advanced therapeutic options for management of chronic DFUs. These new technologies have been shown to increase the probability of complete wound closure in difficult-to-heal foot ulcerations in patients with diabetes. Among these are recombinant platelet-derived growth factors, a human living skin equivalent, and a human fibroblast-derived dermal substitute.^49-51 Tissue-engineered skin equivalent (Apligraf) and human dermis (Dermagraft) are types of biologically active dressings that are derived from fibroblasts of neonatal foreskins.

The most recent advancements for wound care therapies is that of stem cell therapies, primarily bone marrow-derived and, most recently, placental-derived stem cells, including dehydrated human amnion chorion (Epifix) and amniotic matrix with mesenchymal stem cells (Grafix).^52,53 Because of the expense of these products, they cannot be used universally in the treatment of DFUs but rather are used and reserved for difficult-to-heal wounds. In addition, negative pressure therapy has assumed a major role in the management of traumatic, acute, and chronic wounds and has shown efficacy in healing DFUs.^54-57 Hyperbaric oxygen therapy and several biophysical modalities have been studied and found to be efficacious in healing a wide variety of chronic wounds over the past decade as well, although results vary by study, and no advanced modality has become universal in its application.^58-64

 

Table 3 lists most of the wound care technologies commonly used in current clinical practice. Although randomized controlled trials have been published supporting the use of most of these modalities, a lack of strong data proving efficacy for use of such treatment options remains.

Treatment of any underlying ischemia is critical in achieving a successful outcome. Vascular surgical consultation should be obtained on presentation of an ischemic wound and in cases where ulcers show no sign of progress despite appropriate management.^4,13 Revascularization is commonly performed in patients with critical limb ischemia and DFUs but is also performed in patients with less severe arteriopathy. The goal is to restore a palpable pulse on the affected foot.⁶⁵ The postrevascularization ulcer-healing rate ranges from 46% to 91% at 1 year and seems to be improved in those patients with distal arterial reconstruction and restoration of pulsatile flow.⁶⁶

Endovascular approaches are becoming increasingly common in patients whose arterial disease is more limited or morbidity is a significant concern.^67,68 Studies report that the exact role of isolated endovascular procedures is still to be determined, although such interventions are frequently performed in concert with angiography preceding vascular reconstructive procedures.^69,70 However, in many such studies, healing was often a secondary criterion, and there was no description of the initial wound or its management.⁷¹

Challenges

Within the VA setting there is a wide range of patient comorbidities that frequently present clinicians with unique challenges. Often these patients are older with many social and mental health conditions, including self-abuse, drug-abuse, nonadherence, psychological issues and lack of financial and/or educational resources or support. Many of these patients have comorbidities associated with diabetes that can delay healing of their ulcerations.

Systemwide VA mandates have implemented multidisciplinary foot care teams. The teams identify veterans at risk for lower limb complications; provide preventive care; track high-risk foot care across the continuum of outpatient, inpatient, and rehabilitative care; and provide education, orthoses, and social support.^72,73 In the late 1990s, the VHA implemented a national program of foot risk screening and referral, conducted largely in primary care.²⁹ By 1998 as determined from medical record reviews, 95% of veterans had a visual examination, 84% had palpation of pulses, and 78% had undergone a sensory examination. In addition, about 83% of patients had a monofilament examination, and 85% of individuals with risk factors were referred to foot specialists in 2004.^72,74 Veterans at higher risk for lower extremity complications routinely receive subsequent preventive foot care, such as education or prescription of therapeutic shoes in the VHA.

Tseng and colleagues evaluated risk-adjusted trends in amputations among veterans with diabetes during a 5-year period and reported a decrease in amputation rates observed for all types of lower extremity amputations (LEA) and among all racial groups.⁷⁴ Implementation of such universal programs for foot screening, tracked through performance measures, may have contributed to a decrease in LEAs and improved outcomes in the VA patient population.

Prevention

A healthy, intact diabetic foot is best maintained by a consistent and recurrent preventive treatment strategy. Prevention of ulcer recurrence remains to be a major clinical challenge. Andrews and colleagues demonstrated that recurrence rates range from 28% at 12 months to 100% at 40 months.⁷⁵ They report that the highest incidence of reulceration is in the site of a previous ulceration, noting that a newly healed ulcer is covered with fragile skin and after complete healing, there is an area of higher density tissue (scar). Shearing between the different tissue densities often contributes to new ulcers.

After the ulcer heals, the patient and their caregivers must incorporate preventative measures in care plans to reduce the risk of wound reoccurrence. A study reported by Barshes and colleagues demonstrated that a majority of people with diabetes do not receive guideline-recommended foot care, including regular foot examinations.⁷⁶ Identifying the patients with diabetes at risk for ulceration requires foot examination,including the vascular and neurologic systems, skin conditions, and foot structure.⁷⁷ Among the complications of diabetes, lower limb amputation is considered to be preventable.^78,79 Because there is a great beneficial effect of patient education on reducing LEAs, a flexible schedule for diabetes education, that offers education at any time for the maximum convenience of patients rather than focusing on health care provider’s convenience is critical.^79,80 Conservative management of foot problems also has reduced the risk of amputation by simple procedures, such as appropriate foot wear, cleanliness, aggressive surgical debridement, and evidence-based ulcer management.³⁴ This is best accomplished through a multidisciplinary approach involving a team of specialists and personnel who provide a coordinated process of care, including a patient motivated to ensure its success.⁶

 

Conclusions

The authors have described the components of assessment and treatment that can help ensure successful healing of foot ulcers in diabetic patients. These approaches should be used whenever feasible to reduce the high morbidity and risk of serious complications resulting from foot ulcers. Advances in treating chronic diabetic wounds are promising; however, the intrinsic pathophysiologic abnormalities that lead to ulcers in the first place cannot be ignored. No known therapy will be effective without concomitant management of ischemia, infection, and adequate off-loading.^6,75

Not all diabetic foot complications can be prevented, but it is possible to dramatically reduce their incidence through appropriate management and prevention programs. The multidisciplinary team approach that combines the expertise of many types of health care providers for diabetic foot disorders has been demonstrated as the optimal method to achieve favorable rates of limb salvage in the high-risk diabetic patient.

Heat injuries are a major problem worldwide. In a study chronicling heat deaths in the U.S. from 1979 to 1999, a total of 8,015 deaths were associated with excessive heat exposure.¹ Weather conditions caused 3,829 (48%) deaths, and manmade conditions (kitchens, vehicles, boiler rooms, etc) caused 377 (5%) deaths, particularly for those wearing protective clothing.¹

Military members who wear combat gear are especially vulnerable to heat injuries, but none more so than members who wear personal protective equipment (PPE). In this review, PPE is defined as self-contained breathing apparatus protective equipment (SCBA) levels B or C. The challenge of PPE is the inability of the individual to dispel heat through radiation, convection, and evaporation. The only close approximation of the PPE environment is combat and football protective equipment. In 2011, CDC reported that football players in uniforms, which resemble PPE for the purpose of this discussion, experienced heat injury at a rate 10 times higher than the average rate for other sports.² These heat injuries in football players occurred most often during August.² The injuries could be due to the application of protective clothing and the lack of the participants’ acclimatization. Protective clothing impedes the wearer’s ability to balance heat production with heat dissipation.

In 2010, Armstrong and colleagues suggested that the weight of a football uniform increases heat production.³ And the insulation provided by a football uniform reduces heat dissipation to the surrounding air, decreasing heat loss.³ Additionally, this same study indicated that the more protective gear the subject used, the greater the heat stress.³ The most challenging environment for heat injury is PPE due to the inability to facilitate any heat loss. In 2011, Caldwell and colleagues observed that wearing torso armor increased body temperature 10.8% faster than that of the control group, and those wearing full armor increased body temperature 38% faster than that of the control group.⁴ And it was proposed that 60% of this heat effect was from wearing the combat helmet.⁴

The inability to dissipate heat, particularly in protective gear, results in degradation of the effectiveness of the individual and, if left unchecked, may lead to death. Methods exist for health care providers to assess, intervene, and treat populations with heat injuries. These methods include but are not limited to vital signs (blood pressure [BP], body temperature, respiration rate), history of previous heat injury, medications (over-the-counter and prescription), and mental status.

Heat Injuries

Heat injuries are generally divided into 3 categories defined by their severity: heat stress, heat exhaustion, and heat stroke. Heat injuries are due to the individual’s inability to dissipate heat. As the severity of the heat exposure continues, the individual will experience heat stress, and if decompensation continues, the individual will progress to heat exhaustion and finally heat stroke.

If the individual’s physiology is limited or if compensatory mechanisms are compromised, heat stress may occur. Heat compensation can be retarded by any number of the following (including but not limited to): humidity, previous heat injury, lack of sleep, medications, sedentary lifestyle, obesity, caffeinated energy drinks, and dehydration.

In the early phases of heat stress, an individual’s vital signs will increase to compensate for the increase in body heat. Heat exchange is dependent on gradients of temperature and humidity, and as temperature and humidity increase, the ability to transfer heat decreases and becomes less efficient. Failure to accommodate for the increased heat generated and transferred will inevitably result in heat injury.

Working in a hazmat environment in PPE is the worst possible heat transfer scenario due to the inability to use evaporation, the primary means by which heat is released from the body. In this scenario, heat injuries can become dangerous and even fatal if monitoring of vital signs and uncompensated heat production is allowed to continue. As the heat insult progresses from heat stress to heat exhaustion and heat stroke, the core temperature, heart rate, and BP continue to increase. Also, during the progression of heat injury, mental status changes often begin to occur. In 2012, Morley and colleagues found that firefighters wearing protective clothing demonstrated a neurocognitive decline after 50 minutes of treadmill exercise, but these performance declines were not noted until 1 hour or more following the exercise.⁵

Mental status change is a key diagnostic factor that indicates the progression of the patient from heat stress to heat exhaustion and from heat exhaustion to heat stroke. As the hyperthermia progresses, vital signs increase, and the patient’s mental status will begin to deteriorate. If the hyperthermia advances from heat exhaustion to heat stroke, hospitalization is required to reverse the condition. If homeostasis is not restored, the patient may die.

 

Mental status changes are usually described as fatigue, lethargy, disorientation, headache, seizure and coma. Indeed, mental status changes may be one of the most important factors that can assist the clinician in the identification, mitigation, and treatment of heat injury before it reaches a critical stage. Clinical familiarity with and diagnosis of delirium resulting from heat injury could prove beneficial in protecting an individual exposed to severe heat environments.

In 2011, Becker and Stewart suggested that in the absence of hyperthermia, the presence of central nervous system (CNS) symptoms should prompt the clinician to pursue another diagnosis.⁶ However, a core temperature of 104°F with associated CNS changes and anhydrosis should be defined as heat stroke and is a medical emergency.⁶

Death rates from excessive heat are documented as high as 31%.⁷ Signs of CNS dysfunction such as irritability, ataxia, headache, nausea, vomiting, anhydrosis, confusion, and decreased cognitive function are essential to the diagnosis of heat stroke. Classic heat stroke will present as a triad of hyperpyrexia, anhydrosis, and mental status changes.⁸ However, making the diagnosis of heat stroke based on anhydrosis could be dangerous, because in exertional heat stroke, many patients continue to sweat. Overlooking the diagnosis of heat stroke based on anhydrosis could lead to a delay in treatment and severe complications.⁸ These complications may include hyperkalemia, hyperphosphatemia, hypocalcemia, and myoglobinuria.

Once heat stroke has occurred, coagulopathies may manifest as epistaxis, and endothelial damage may present as peripheral or pulmonary edema. Additionally, a core temperature of above 104°F may trigger a cascade of events that may include systemic inflammatory response resulting in increased cell wall permeability and release of endotoxins. These events can lead to tissue hypoxia, metabolic acidosis, and organ failure. Sequalae from heat stroke can result in multisystem failure. A 1998 study of Chicago heat wave victims reported that the degree of functional disability predicted survival at 1 year.⁹ Although hospital mortality was 21%, severe functional impairment at discharge was 33%, with an additional 28% mortality at 1 year.⁹ And the 1-year mortality from heat stroke is similar to that of cerebral vascular accidents.¹⁰ Within 24 hours, heat stroke victims often will display evidence of muscle, kidney, and cardiac dysfunction. Delay in intervention raises the risk of fatalities associated with hyperthermia.^11,12 Tissue destruction due to uncompensated heat may lead to rhabdomyolysis and subsequent myoglobinuria and renal injury. Damaged hepatocytes may lead to coagulopathies and hepatitis. Injured heart muscle may lead to arrhythmias and cardiac arrest.

The CNS symptoms may be difficult to ascertain in an intense working environment. The CNS system dysfunction is indicative of progression from heat injury to heat stroke and thus a medical emergency. It is imperative that the clinician be able to assess the individual quickly and accurately.

Delirium

Along with physical problems associated with it, heat injury can also lead to relatively abrupt mental status changes. In 2005, Glazer reported that even with minimally elevated core temperatures, CNS system changes can present with altered mental status, convulsions, and coma.¹³ This qualifies as a medical emergency known as delirium. Patients with delirium may present with a history of abrupt and fluctuating levels of consciousness. This fluctuation in symptoms that resemble sepsis could confuse medical providers.¹³ Thus, it is imperative that there be continuity of care of the patient with the ability to compare states of consciousness longitudinally over time.

In 1984, Pérez reported that nurses, perhaps because of their familiarity with and proximity to the patient, recorded delirium in 93% of patients, whereas psychiatric consultants recorded delirium only 34% of the time.¹⁴ Delirium manifests with several neurologic signs and symptoms; these include but are not limited to tremor, myoclonus, difficulty reading and writing, and visuoconstructive deficits, such as copying designs and problem solving.¹⁵ No matter the method to discover the delirium, the definitive treatment is to identify and treat the underlying medical condition.¹⁵ The CNS system dysfunction consistent with delirium such as irritability, ataxia, and confusion are essential to the diagnosis of heat stroke.¹³ Coma and seizures may occur, and retarded recovery of functional ability is an indication of a poor prognosis.⁹

Objective

The authors propose that in addition to vital signs, an assessment of a patient’s mental status through the use of a mental status exam could be a tool that identifies the problem early and avoids the progression of symptoms from heat stress to heat exhaustion and heat stroke. Early intervention in the progression of symptoms of hyperthermia can save lives, decrease suffering, and maintain a more robust mission-ready posture for the individual and the unit.

 

Study

During the fall of 2014, the Chemical, Biological, Radiological, Nuclear, and Explosive (CBRNE) unit of the Utah Air and Army National Guard participated in exercises using 2,159 patient encounters that were in PPE (full hazmat and SCBA) also known as level C protective clothing. Temperatures ranged from a minimum of 29°F to a high of 56°F. A mock disaster was practiced for 5 days, and of those 2,159 iterations, 43 were disqualified (2%) for any reason. Two individuals presented with altered mental status and disrupted vital signs and were disqualified for heat injuries with cognitive symptoms (0.00092%). These members were excused from duty, monitored in the medical work/rest tent until mental status and vital signs returned to baseline.

The tool used in the study was the Micro-Mental Test. This is a mental status exam that is more than a simple gestalt of how the patient is performing cognitively but less than a full Mini-Mental State Examination (MMSE). This abbreviated mental status exam provides a field expedient measurement of the individual’s ability to function cognitively. It is important to realize that this exam is most effective when repeated over time to assess the patients’ mental status longitudinally. It would be cavalier to propose that an abbreviated mental status exam would be sufficient to diagnose heat stroke, but a mental status exam—however brief—along with symptoms of hyperpyrexia, abnormal vital signs, and anhydrosis can be a useful tool to make the diagnostic transition from heat exhaustion to heat stroke.

Micro-Mental Status Exam

The traditional mental status measures are appearance, behavior, speech, mood, affect, thought process, thought content, cognition, insight, and judgment. Rapidly assessing mental status is crucial for the assessment of heat injuries, because increased vital signs coupled with neurologic changes indicate a medical emergency. The MMSE is painstaking and a somewhat cumbersome tool to use in the field. Therefore, the authors suggest a micro-mental status exam (Table). This abbreviated mental status exam is performed before the individual is placed in the PPE and enters the working environment.

The individual is then assessed after every rotation exiting the PPE and allowed to rest under supervision. Assessing the individual with vital signs and mental status longitudinally allows the provider to rapidly assess and intervene if the patient begins to exhibit mental status changes along with increased vital signs. The patient is assessed for ataxia, confusion, irritability, and lack of coordination. Patients are asked to find from a file drawer their individual prescreen checklist. This test assesses fine motor skills and cognition. Following this, self-identifying personal information from a precheck sheet is verified, and finally, simple questions regarding orientation to person, place, date, and time are posed.

Assessing Executive Function

Examples of measures of thought processes include assessing executive function by having participants find their paperwork, identifying their platoon leader, and correctly responding to questions, such as, “Where exactly were you working in the emergency area and what exactly were you doing?” This assesses executive function and thought process. Thought content could be assessed with inquiries such as, “Anything troubling about your work?” or “Would you tell me honestly if there were anything troubling or unsafe about the work you have performed?” Cognition could be assessed by questions regarding chain of command (both officer and enlisted), 3 suggestions to improve, 3 suggestions to maintain, and knowledge of the rotation schedule for the rest of the day.

The abbreviated mental status exam should in no way replace the robust and accurate mental status exam. However, in a rapidly changing, austere, or asymmetrical environment, a simple gestalt of the patient is ineffective, and the full mental status evaluation may be too time consuming. The authors propose the Micro-Mental Exam as an alternative. It is imperative that the exam be compared with the baseline assessment of the individual during the prescreening of vital signs before the individual enters the exercise.

This Micro-Mental Exam provides a quick, easy, nonintrusive, and stress-free assessment of the patient. The clarity of cognition and ability to perform simple mental tasks could serve to reassure the provider that the patient has not progressed into the dangerous area of delirium secondary to heat exposure.

Use of this simple tool during the CBRNE exercise resulted in the disqualification of 2 individuals for probable heat injury; additionally, it gave the providers a rapid assessment tool to quickly identify and treat individuals with progressive heat stress to heat stroke.

Discussion

Compared with studies of heat injuries in military and football equipment, the expected heat injury in PPE gear is very low.^2-4 The low number of disqualifications during the CBRNE exercise could be due to the extensive measures in place to assist individuals under heat stress. These measures include strict adherence to the work/rest cycles mandated by the DoD, competent leadership in evaluating and treating individuals participating in the exercise, and paying close attention not only to the vital signs, but also participants’ mental status.

 

A study in 2002 suggested that spending time in an air-conditioned area is the strongest factor in preventing heat-related deaths.¹⁶ The study also recommended prevention measures if heat exposure cannot be avoided: working in the cooler part of the day, plenty of water or nonalcoholic drinks, cool showers, lightweight light-colored clothing, and avoiding direct sunshine.¹⁶

A study in 2013 suggested that heat injuries are a significant threat to the effectiveness of military operations in general and to the youngest (the most inexperienced soldiers) specifically.¹⁷ The study further suggested that it is imperative that leaders be aware of adequate hydration on the one hand and excessive water intake on the other and enforce effective countermeasures against all types of heat injuries.¹⁷

Hyponatremia

Hyponatremia is a possible complication of heat exposure and can be divided into categories according to volume: hypovolemia, euvolemia, and hypervolemia.¹⁸ Hyponatremia is associated with excessive water consumption and excessive sodium losses via sweat during prolonged physical exertion. Symptoms of hyponatremia are related to the severity of sodium deficit and the rate of sodium decline.¹⁸ These symptoms include but are not limited to polydipsia, muscle cramps, headache, altered mental status, coma, and status epilepticus.

Hypovolemic hyponatremia usually will have signs of volume depletion, and sodium levels < 20 mEq/L. Treatment typically consists of volume replenishment with isotonic saline (0.9%), treatment of the underlying condition, and correction of the factors causing hypovolemia.

Euvolemic hyponatremia is typically due to the syndrome of inappropriate antidiuretic hormone (SIADH) and spot urinary sodium is > 20 mEq/L. Correction consists of fluid restriction and correction of the underlying cause.¹⁸

Hypervolemic hyponatremia occurs when the kidneys are overwhelmed and cannot excrete water effectively. It is commonly caused by heart failure, cirrhosis, or renal injury. Treatment consists of correction of the underlying cause, sodium and fluid restriction, and diuretic therapy.¹⁸ In severe cases of hyponatremia, sodium levels usually have decreased rapidly—typically in less than 24 hours.

Hyponatremia is defined as plasma sodium levels < 135 mEq/L, and severe symptoms often occur when the sodium level reaches 120 mEq/L. Treatment must be initiated quickly to avoid cerebral edema, respiratory failure, brain stem herniation, and death. Correction includes hypertonic 3% saline infusion at a rate of 0.5 to 2 mL/kg per hour until symptoms resolve. Two separate studies in 2014 and 2013 suggested that the rate of sodium correction should be 6 to 12 mEq/L in the first 24 hours and 18 mEq/L or less in 48 hours.^19,20

In 2009, Sterns and colleagues suggested that for the treatment of hyponatremia the therapeutic goals for serum sodium concentrations should be 6 to 8 mmol/L in 24 hours, 12 to 14 mmol/L in 48 hours, and 14 to 16 mmol/L in 72 hours.²¹ To exceed these parameters in the correction of hyponatremia risks overcorrection and iatrogenic brain damage.²¹

Care must be taken not to overcorrect sodium levels. In 2013, Sood and colleagues reported that in severe hyponatremia, a combination of 3% saline and 1 to 2 µg of desmopressin every 6 to 8 hours achieved a predictable correction of 3 to 7 mEq/L per hour with no overcorrection.²²

In the spring of 1998, U.S. Army guidelines were revised not only to protect service members from heat injury, but also from hyponatremia caused by excessive sodium loss due to exertion combined with excessive water consumption. There were fewer hospitalizations of soldiers for hyponatremia due to excessive water consumption after the guidelines were implemented.²³ Potential hyponatremia in PPE is even greater due to the strenuous environment. The potential injury due to heat injury on the one hand and hyponatremia on the other demands tailored scrutiny by experienced providers and commanders who can make appropriate changes to the work-rest cycle as needed.

Quick recognition and treatment of exercise-induced hyponatremia is essential to avoid altered mental status, seizures, coma, and death. Current guidelines for the correction of exercise-induced hyponatremia suggest rapid correction of hyponatremia with up to three 100 mL boluses of 3% NaCl in 10-minute intervals. A 2012 case study by Elsaesser and colleagues reported that a severely dehydrated marathon runner with exercise-induced hyponatremic encephalopathy achieved a resolution of symptoms with rapid correction with 100 mL boluses of 3% NaCl spaced in 10-minute intervals. An additional volume of 650 mL of 3% NaCl given over 2 hours for a total volume of 950 mL was needed to resolve the exercise-induced hyponatremia.²⁴ It seems that a 4- to 6-mmol/L increase in serum (Na+) is adequate to reverse most serious clinical manifestations of acute hyponatremia.²¹

When hyponatremia is corrected too rapidly, the brain’s ability to absorb the metabolites is overwhelmed, resulting in osmotic demyelination.²¹ Demyelination was produced in animal models by the rapid induction of hypernatremia and can occur in patients who are overcorrected to a hypernatremic state.²⁰ When individuals with chronic hyponatremia are corrected to normal sodium levels, an initial improvement may occur followed by new and often progressive neurologic deficits.²⁰

 

In 2012, Elsaesser and colleagues suggested that concern regarding overcorrection of hyponatremia might be exaggerated in the setting of exercise-induced hyponatremia. Indeed, the only cases of death associated with exercise-induced hyponatremia have been in the setting of no treatment or slow correction of hyponatremia with normal saline.²⁴

Conclusions

The issue of heat injury in athletic and military environments plagues participants and leaders alike. This article has sought to shed light on mechanisms that are helpful in mitigating heat injury. Football equipment and military protective gear that diminishes that ability to dissipate heat through the retardation of evaporation, convection, and radiation is a key factor in the development of heat injury.

Personal protective equipment is the most hazardous environment for the development of heat injury. This protective gear along with increased environmental humidity, elevated temperature, and increased workload create a dangerous environment for the individuals involved. Careful monitoring of vital signs is an important factor in avoiding heat injuries.

This article proposes that vital signs along with strict monitoring of mental status through (1) orientation; (2) simple task completion; (3) thought processes; and (4) cognitive ability over time combine to be a powerful deterrent to heat injury in an austere and dangerous working environment. It would be cavalier to propose that all heat injuries in any environment could be avoided by following these guidelines, and more tools to avoid heat injury will be developed. But medical providers trained not only to use vital signs, but also monitor and respond to mental status changes in the patient can mitigate heat injuries more effectively. Finally, careful attention should be placed on correcting hypo- and hypernatremia when rehydrating individuals in this challenging environment.

Acknowledgements
The authors wish to thank the following for their contribution to this manuscript: Sarah M. Paulsen, REB Smith, and the entire CERF-P leadership of the Utah National Guard.

Heat injuries are a major problem worldwide. In a study chronicling heat deaths in the U.S. from 1979 to 1999, a total of 8,015 deaths were associated with excessive heat exposure.¹ Weather conditions caused 3,829 (48%) deaths, and manmade conditions (kitchens, vehicles, boiler rooms, etc) caused 377 (5%) deaths, particularly for those wearing protective clothing.¹

Military members who wear combat gear are especially vulnerable to heat injuries, but none more so than members who wear personal protective equipment (PPE). In this review, PPE is defined as self-contained breathing apparatus protective equipment (SCBA) levels B or C. The challenge of PPE is the inability of the individual to dispel heat through radiation, convection, and evaporation. The only close approximation of the PPE environment is combat and football protective equipment. In 2011, CDC reported that football players in uniforms, which resemble PPE for the purpose of this discussion, experienced heat injury at a rate 10 times higher than the average rate for other sports.² These heat injuries in football players occurred most often during August.² The injuries could be due to the application of protective clothing and the lack of the participants’ acclimatization. Protective clothing impedes the wearer’s ability to balance heat production with heat dissipation.

In 2010, Armstrong and colleagues suggested that the weight of a football uniform increases heat production.³ And the insulation provided by a football uniform reduces heat dissipation to the surrounding air, decreasing heat loss.³ Additionally, this same study indicated that the more protective gear the subject used, the greater the heat stress.³ The most challenging environment for heat injury is PPE due to the inability to facilitate any heat loss. In 2011, Caldwell and colleagues observed that wearing torso armor increased body temperature 10.8% faster than that of the control group, and those wearing full armor increased body temperature 38% faster than that of the control group.⁴ And it was proposed that 60% of this heat effect was from wearing the combat helmet.⁴

The inability to dissipate heat, particularly in protective gear, results in degradation of the effectiveness of the individual and, if left unchecked, may lead to death. Methods exist for health care providers to assess, intervene, and treat populations with heat injuries. These methods include but are not limited to vital signs (blood pressure [BP], body temperature, respiration rate), history of previous heat injury, medications (over-the-counter and prescription), and mental status.

Heat Injuries

Heat injuries are generally divided into 3 categories defined by their severity: heat stress, heat exhaustion, and heat stroke. Heat injuries are due to the individual’s inability to dissipate heat. As the severity of the heat exposure continues, the individual will experience heat stress, and if decompensation continues, the individual will progress to heat exhaustion and finally heat stroke.

If the individual’s physiology is limited or if compensatory mechanisms are compromised, heat stress may occur. Heat compensation can be retarded by any number of the following (including but not limited to): humidity, previous heat injury, lack of sleep, medications, sedentary lifestyle, obesity, caffeinated energy drinks, and dehydration.

In the early phases of heat stress, an individual’s vital signs will increase to compensate for the increase in body heat. Heat exchange is dependent on gradients of temperature and humidity, and as temperature and humidity increase, the ability to transfer heat decreases and becomes less efficient. Failure to accommodate for the increased heat generated and transferred will inevitably result in heat injury.

Working in a hazmat environment in PPE is the worst possible heat transfer scenario due to the inability to use evaporation, the primary means by which heat is released from the body. In this scenario, heat injuries can become dangerous and even fatal if monitoring of vital signs and uncompensated heat production is allowed to continue. As the heat insult progresses from heat stress to heat exhaustion and heat stroke, the core temperature, heart rate, and BP continue to increase. Also, during the progression of heat injury, mental status changes often begin to occur. In 2012, Morley and colleagues found that firefighters wearing protective clothing demonstrated a neurocognitive decline after 50 minutes of treadmill exercise, but these performance declines were not noted until 1 hour or more following the exercise.⁵

Mental status change is a key diagnostic factor that indicates the progression of the patient from heat stress to heat exhaustion and from heat exhaustion to heat stroke. As the hyperthermia progresses, vital signs increase, and the patient’s mental status will begin to deteriorate. If the hyperthermia advances from heat exhaustion to heat stroke, hospitalization is required to reverse the condition. If homeostasis is not restored, the patient may die.

 

Mental status changes are usually described as fatigue, lethargy, disorientation, headache, seizure and coma. Indeed, mental status changes may be one of the most important factors that can assist the clinician in the identification, mitigation, and treatment of heat injury before it reaches a critical stage. Clinical familiarity with and diagnosis of delirium resulting from heat injury could prove beneficial in protecting an individual exposed to severe heat environments.

In 2011, Becker and Stewart suggested that in the absence of hyperthermia, the presence of central nervous system (CNS) symptoms should prompt the clinician to pursue another diagnosis.⁶ However, a core temperature of 104°F with associated CNS changes and anhydrosis should be defined as heat stroke and is a medical emergency.⁶

Death rates from excessive heat are documented as high as 31%.⁷ Signs of CNS dysfunction such as irritability, ataxia, headache, nausea, vomiting, anhydrosis, confusion, and decreased cognitive function are essential to the diagnosis of heat stroke. Classic heat stroke will present as a triad of hyperpyrexia, anhydrosis, and mental status changes.⁸ However, making the diagnosis of heat stroke based on anhydrosis could be dangerous, because in exertional heat stroke, many patients continue to sweat. Overlooking the diagnosis of heat stroke based on anhydrosis could lead to a delay in treatment and severe complications.⁸ These complications may include hyperkalemia, hyperphosphatemia, hypocalcemia, and myoglobinuria.

Once heat stroke has occurred, coagulopathies may manifest as epistaxis, and endothelial damage may present as peripheral or pulmonary edema. Additionally, a core temperature of above 104°F may trigger a cascade of events that may include systemic inflammatory response resulting in increased cell wall permeability and release of endotoxins. These events can lead to tissue hypoxia, metabolic acidosis, and organ failure. Sequalae from heat stroke can result in multisystem failure. A 1998 study of Chicago heat wave victims reported that the degree of functional disability predicted survival at 1 year.⁹ Although hospital mortality was 21%, severe functional impairment at discharge was 33%, with an additional 28% mortality at 1 year.⁹ And the 1-year mortality from heat stroke is similar to that of cerebral vascular accidents.¹⁰ Within 24 hours, heat stroke victims often will display evidence of muscle, kidney, and cardiac dysfunction. Delay in intervention raises the risk of fatalities associated with hyperthermia.^11,12 Tissue destruction due to uncompensated heat may lead to rhabdomyolysis and subsequent myoglobinuria and renal injury. Damaged hepatocytes may lead to coagulopathies and hepatitis. Injured heart muscle may lead to arrhythmias and cardiac arrest.

The CNS symptoms may be difficult to ascertain in an intense working environment. The CNS system dysfunction is indicative of progression from heat injury to heat stroke and thus a medical emergency. It is imperative that the clinician be able to assess the individual quickly and accurately.

Delirium

Along with physical problems associated with it, heat injury can also lead to relatively abrupt mental status changes. In 2005, Glazer reported that even with minimally elevated core temperatures, CNS system changes can present with altered mental status, convulsions, and coma.¹³ This qualifies as a medical emergency known as delirium. Patients with delirium may present with a history of abrupt and fluctuating levels of consciousness. This fluctuation in symptoms that resemble sepsis could confuse medical providers.¹³ Thus, it is imperative that there be continuity of care of the patient with the ability to compare states of consciousness longitudinally over time.

In 1984, Pérez reported that nurses, perhaps because of their familiarity with and proximity to the patient, recorded delirium in 93% of patients, whereas psychiatric consultants recorded delirium only 34% of the time.¹⁴ Delirium manifests with several neurologic signs and symptoms; these include but are not limited to tremor, myoclonus, difficulty reading and writing, and visuoconstructive deficits, such as copying designs and problem solving.¹⁵ No matter the method to discover the delirium, the definitive treatment is to identify and treat the underlying medical condition.¹⁵ The CNS system dysfunction consistent with delirium such as irritability, ataxia, and confusion are essential to the diagnosis of heat stroke.¹³ Coma and seizures may occur, and retarded recovery of functional ability is an indication of a poor prognosis.⁹

Objective

The authors propose that in addition to vital signs, an assessment of a patient’s mental status through the use of a mental status exam could be a tool that identifies the problem early and avoids the progression of symptoms from heat stress to heat exhaustion and heat stroke. Early intervention in the progression of symptoms of hyperthermia can save lives, decrease suffering, and maintain a more robust mission-ready posture for the individual and the unit.

 

Study

During the fall of 2014, the Chemical, Biological, Radiological, Nuclear, and Explosive (CBRNE) unit of the Utah Air and Army National Guard participated in exercises using 2,159 patient encounters that were in PPE (full hazmat and SCBA) also known as level C protective clothing. Temperatures ranged from a minimum of 29°F to a high of 56°F. A mock disaster was practiced for 5 days, and of those 2,159 iterations, 43 were disqualified (2%) for any reason. Two individuals presented with altered mental status and disrupted vital signs and were disqualified for heat injuries with cognitive symptoms (0.00092%). These members were excused from duty, monitored in the medical work/rest tent until mental status and vital signs returned to baseline.

The tool used in the study was the Micro-Mental Test. This is a mental status exam that is more than a simple gestalt of how the patient is performing cognitively but less than a full Mini-Mental State Examination (MMSE). This abbreviated mental status exam provides a field expedient measurement of the individual’s ability to function cognitively. It is important to realize that this exam is most effective when repeated over time to assess the patients’ mental status longitudinally. It would be cavalier to propose that an abbreviated mental status exam would be sufficient to diagnose heat stroke, but a mental status exam—however brief—along with symptoms of hyperpyrexia, abnormal vital signs, and anhydrosis can be a useful tool to make the diagnostic transition from heat exhaustion to heat stroke.

Micro-Mental Status Exam

The traditional mental status measures are appearance, behavior, speech, mood, affect, thought process, thought content, cognition, insight, and judgment. Rapidly assessing mental status is crucial for the assessment of heat injuries, because increased vital signs coupled with neurologic changes indicate a medical emergency. The MMSE is painstaking and a somewhat cumbersome tool to use in the field. Therefore, the authors suggest a micro-mental status exam (Table). This abbreviated mental status exam is performed before the individual is placed in the PPE and enters the working environment.

The individual is then assessed after every rotation exiting the PPE and allowed to rest under supervision. Assessing the individual with vital signs and mental status longitudinally allows the provider to rapidly assess and intervene if the patient begins to exhibit mental status changes along with increased vital signs. The patient is assessed for ataxia, confusion, irritability, and lack of coordination. Patients are asked to find from a file drawer their individual prescreen checklist. This test assesses fine motor skills and cognition. Following this, self-identifying personal information from a precheck sheet is verified, and finally, simple questions regarding orientation to person, place, date, and time are posed.

Assessing Executive Function

Examples of measures of thought processes include assessing executive function by having participants find their paperwork, identifying their platoon leader, and correctly responding to questions, such as, “Where exactly were you working in the emergency area and what exactly were you doing?” This assesses executive function and thought process. Thought content could be assessed with inquiries such as, “Anything troubling about your work?” or “Would you tell me honestly if there were anything troubling or unsafe about the work you have performed?” Cognition could be assessed by questions regarding chain of command (both officer and enlisted), 3 suggestions to improve, 3 suggestions to maintain, and knowledge of the rotation schedule for the rest of the day.

The abbreviated mental status exam should in no way replace the robust and accurate mental status exam. However, in a rapidly changing, austere, or asymmetrical environment, a simple gestalt of the patient is ineffective, and the full mental status evaluation may be too time consuming. The authors propose the Micro-Mental Exam as an alternative. It is imperative that the exam be compared with the baseline assessment of the individual during the prescreening of vital signs before the individual enters the exercise.

This Micro-Mental Exam provides a quick, easy, nonintrusive, and stress-free assessment of the patient. The clarity of cognition and ability to perform simple mental tasks could serve to reassure the provider that the patient has not progressed into the dangerous area of delirium secondary to heat exposure.

Use of this simple tool during the CBRNE exercise resulted in the disqualification of 2 individuals for probable heat injury; additionally, it gave the providers a rapid assessment tool to quickly identify and treat individuals with progressive heat stress to heat stroke.

Discussion

Compared with studies of heat injuries in military and football equipment, the expected heat injury in PPE gear is very low.^2-4 The low number of disqualifications during the CBRNE exercise could be due to the extensive measures in place to assist individuals under heat stress. These measures include strict adherence to the work/rest cycles mandated by the DoD, competent leadership in evaluating and treating individuals participating in the exercise, and paying close attention not only to the vital signs, but also participants’ mental status.

 

A study in 2002 suggested that spending time in an air-conditioned area is the strongest factor in preventing heat-related deaths.¹⁶ The study also recommended prevention measures if heat exposure cannot be avoided: working in the cooler part of the day, plenty of water or nonalcoholic drinks, cool showers, lightweight light-colored clothing, and avoiding direct sunshine.¹⁶

A study in 2013 suggested that heat injuries are a significant threat to the effectiveness of military operations in general and to the youngest (the most inexperienced soldiers) specifically.¹⁷ The study further suggested that it is imperative that leaders be aware of adequate hydration on the one hand and excessive water intake on the other and enforce effective countermeasures against all types of heat injuries.¹⁷

Hyponatremia

Hyponatremia is a possible complication of heat exposure and can be divided into categories according to volume: hypovolemia, euvolemia, and hypervolemia.¹⁸ Hyponatremia is associated with excessive water consumption and excessive sodium losses via sweat during prolonged physical exertion. Symptoms of hyponatremia are related to the severity of sodium deficit and the rate of sodium decline.¹⁸ These symptoms include but are not limited to polydipsia, muscle cramps, headache, altered mental status, coma, and status epilepticus.

Hypovolemic hyponatremia usually will have signs of volume depletion, and sodium levels < 20 mEq/L. Treatment typically consists of volume replenishment with isotonic saline (0.9%), treatment of the underlying condition, and correction of the factors causing hypovolemia.

Euvolemic hyponatremia is typically due to the syndrome of inappropriate antidiuretic hormone (SIADH) and spot urinary sodium is > 20 mEq/L. Correction consists of fluid restriction and correction of the underlying cause.¹⁸

Hypervolemic hyponatremia occurs when the kidneys are overwhelmed and cannot excrete water effectively. It is commonly caused by heart failure, cirrhosis, or renal injury. Treatment consists of correction of the underlying cause, sodium and fluid restriction, and diuretic therapy.¹⁸ In severe cases of hyponatremia, sodium levels usually have decreased rapidly—typically in less than 24 hours.

Hyponatremia is defined as plasma sodium levels < 135 mEq/L, and severe symptoms often occur when the sodium level reaches 120 mEq/L. Treatment must be initiated quickly to avoid cerebral edema, respiratory failure, brain stem herniation, and death. Correction includes hypertonic 3% saline infusion at a rate of 0.5 to 2 mL/kg per hour until symptoms resolve. Two separate studies in 2014 and 2013 suggested that the rate of sodium correction should be 6 to 12 mEq/L in the first 24 hours and 18 mEq/L or less in 48 hours.^19,20

In 2009, Sterns and colleagues suggested that for the treatment of hyponatremia the therapeutic goals for serum sodium concentrations should be 6 to 8 mmol/L in 24 hours, 12 to 14 mmol/L in 48 hours, and 14 to 16 mmol/L in 72 hours.²¹ To exceed these parameters in the correction of hyponatremia risks overcorrection and iatrogenic brain damage.²¹

Care must be taken not to overcorrect sodium levels. In 2013, Sood and colleagues reported that in severe hyponatremia, a combination of 3% saline and 1 to 2 µg of desmopressin every 6 to 8 hours achieved a predictable correction of 3 to 7 mEq/L per hour with no overcorrection.²²

In the spring of 1998, U.S. Army guidelines were revised not only to protect service members from heat injury, but also from hyponatremia caused by excessive sodium loss due to exertion combined with excessive water consumption. There were fewer hospitalizations of soldiers for hyponatremia due to excessive water consumption after the guidelines were implemented.²³ Potential hyponatremia in PPE is even greater due to the strenuous environment. The potential injury due to heat injury on the one hand and hyponatremia on the other demands tailored scrutiny by experienced providers and commanders who can make appropriate changes to the work-rest cycle as needed.

Quick recognition and treatment of exercise-induced hyponatremia is essential to avoid altered mental status, seizures, coma, and death. Current guidelines for the correction of exercise-induced hyponatremia suggest rapid correction of hyponatremia with up to three 100 mL boluses of 3% NaCl in 10-minute intervals. A 2012 case study by Elsaesser and colleagues reported that a severely dehydrated marathon runner with exercise-induced hyponatremic encephalopathy achieved a resolution of symptoms with rapid correction with 100 mL boluses of 3% NaCl spaced in 10-minute intervals. An additional volume of 650 mL of 3% NaCl given over 2 hours for a total volume of 950 mL was needed to resolve the exercise-induced hyponatremia.²⁴ It seems that a 4- to 6-mmol/L increase in serum (Na+) is adequate to reverse most serious clinical manifestations of acute hyponatremia.²¹

When hyponatremia is corrected too rapidly, the brain’s ability to absorb the metabolites is overwhelmed, resulting in osmotic demyelination.²¹ Demyelination was produced in animal models by the rapid induction of hypernatremia and can occur in patients who are overcorrected to a hypernatremic state.²⁰ When individuals with chronic hyponatremia are corrected to normal sodium levels, an initial improvement may occur followed by new and often progressive neurologic deficits.²⁰

 

In 2012, Elsaesser and colleagues suggested that concern regarding overcorrection of hyponatremia might be exaggerated in the setting of exercise-induced hyponatremia. Indeed, the only cases of death associated with exercise-induced hyponatremia have been in the setting of no treatment or slow correction of hyponatremia with normal saline.²⁴

Conclusions

The issue of heat injury in athletic and military environments plagues participants and leaders alike. This article has sought to shed light on mechanisms that are helpful in mitigating heat injury. Football equipment and military protective gear that diminishes that ability to dissipate heat through the retardation of evaporation, convection, and radiation is a key factor in the development of heat injury.

Personal protective equipment is the most hazardous environment for the development of heat injury. This protective gear along with increased environmental humidity, elevated temperature, and increased workload create a dangerous environment for the individuals involved. Careful monitoring of vital signs is an important factor in avoiding heat injuries.

This article proposes that vital signs along with strict monitoring of mental status through (1) orientation; (2) simple task completion; (3) thought processes; and (4) cognitive ability over time combine to be a powerful deterrent to heat injury in an austere and dangerous working environment. It would be cavalier to propose that all heat injuries in any environment could be avoided by following these guidelines, and more tools to avoid heat injury will be developed. But medical providers trained not only to use vital signs, but also monitor and respond to mental status changes in the patient can mitigate heat injuries more effectively. Finally, careful attention should be placed on correcting hypo- and hypernatremia when rehydrating individuals in this challenging environment.

Acknowledgements
The authors wish to thank the following for their contribution to this manuscript: Sarah M. Paulsen, REB Smith, and the entire CERF-P leadership of the Utah National Guard.

Heat injuries are a major problem worldwide. In a study chronicling heat deaths in the U.S. from 1979 to 1999, a total of 8,015 deaths were associated with excessive heat exposure.¹ Weather conditions caused 3,829 (48%) deaths, and manmade conditions (kitchens, vehicles, boiler rooms, etc) caused 377 (5%) deaths, particularly for those wearing protective clothing.¹

Military members who wear combat gear are especially vulnerable to heat injuries, but none more so than members who wear personal protective equipment (PPE). In this review, PPE is defined as self-contained breathing apparatus protective equipment (SCBA) levels B or C. The challenge of PPE is the inability of the individual to dispel heat through radiation, convection, and evaporation. The only close approximation of the PPE environment is combat and football protective equipment. In 2011, CDC reported that football players in uniforms, which resemble PPE for the purpose of this discussion, experienced heat injury at a rate 10 times higher than the average rate for other sports.² These heat injuries in football players occurred most often during August.² The injuries could be due to the application of protective clothing and the lack of the participants’ acclimatization. Protective clothing impedes the wearer’s ability to balance heat production with heat dissipation.

In 2010, Armstrong and colleagues suggested that the weight of a football uniform increases heat production.³ And the insulation provided by a football uniform reduces heat dissipation to the surrounding air, decreasing heat loss.³ Additionally, this same study indicated that the more protective gear the subject used, the greater the heat stress.³ The most challenging environment for heat injury is PPE due to the inability to facilitate any heat loss. In 2011, Caldwell and colleagues observed that wearing torso armor increased body temperature 10.8% faster than that of the control group, and those wearing full armor increased body temperature 38% faster than that of the control group.⁴ And it was proposed that 60% of this heat effect was from wearing the combat helmet.⁴

The inability to dissipate heat, particularly in protective gear, results in degradation of the effectiveness of the individual and, if left unchecked, may lead to death. Methods exist for health care providers to assess, intervene, and treat populations with heat injuries. These methods include but are not limited to vital signs (blood pressure [BP], body temperature, respiration rate), history of previous heat injury, medications (over-the-counter and prescription), and mental status.

Heat Injuries

Heat injuries are generally divided into 3 categories defined by their severity: heat stress, heat exhaustion, and heat stroke. Heat injuries are due to the individual’s inability to dissipate heat. As the severity of the heat exposure continues, the individual will experience heat stress, and if decompensation continues, the individual will progress to heat exhaustion and finally heat stroke.

If the individual’s physiology is limited or if compensatory mechanisms are compromised, heat stress may occur. Heat compensation can be retarded by any number of the following (including but not limited to): humidity, previous heat injury, lack of sleep, medications, sedentary lifestyle, obesity, caffeinated energy drinks, and dehydration.

In the early phases of heat stress, an individual’s vital signs will increase to compensate for the increase in body heat. Heat exchange is dependent on gradients of temperature and humidity, and as temperature and humidity increase, the ability to transfer heat decreases and becomes less efficient. Failure to accommodate for the increased heat generated and transferred will inevitably result in heat injury.

Working in a hazmat environment in PPE is the worst possible heat transfer scenario due to the inability to use evaporation, the primary means by which heat is released from the body. In this scenario, heat injuries can become dangerous and even fatal if monitoring of vital signs and uncompensated heat production is allowed to continue. As the heat insult progresses from heat stress to heat exhaustion and heat stroke, the core temperature, heart rate, and BP continue to increase. Also, during the progression of heat injury, mental status changes often begin to occur. In 2012, Morley and colleagues found that firefighters wearing protective clothing demonstrated a neurocognitive decline after 50 minutes of treadmill exercise, but these performance declines were not noted until 1 hour or more following the exercise.⁵

Mental status change is a key diagnostic factor that indicates the progression of the patient from heat stress to heat exhaustion and from heat exhaustion to heat stroke. As the hyperthermia progresses, vital signs increase, and the patient’s mental status will begin to deteriorate. If the hyperthermia advances from heat exhaustion to heat stroke, hospitalization is required to reverse the condition. If homeostasis is not restored, the patient may die.

 

Mental status changes are usually described as fatigue, lethargy, disorientation, headache, seizure and coma. Indeed, mental status changes may be one of the most important factors that can assist the clinician in the identification, mitigation, and treatment of heat injury before it reaches a critical stage. Clinical familiarity with and diagnosis of delirium resulting from heat injury could prove beneficial in protecting an individual exposed to severe heat environments.

In 2011, Becker and Stewart suggested that in the absence of hyperthermia, the presence of central nervous system (CNS) symptoms should prompt the clinician to pursue another diagnosis.⁶ However, a core temperature of 104°F with associated CNS changes and anhydrosis should be defined as heat stroke and is a medical emergency.⁶

Death rates from excessive heat are documented as high as 31%.⁷ Signs of CNS dysfunction such as irritability, ataxia, headache, nausea, vomiting, anhydrosis, confusion, and decreased cognitive function are essential to the diagnosis of heat stroke. Classic heat stroke will present as a triad of hyperpyrexia, anhydrosis, and mental status changes.⁸ However, making the diagnosis of heat stroke based on anhydrosis could be dangerous, because in exertional heat stroke, many patients continue to sweat. Overlooking the diagnosis of heat stroke based on anhydrosis could lead to a delay in treatment and severe complications.⁸ These complications may include hyperkalemia, hyperphosphatemia, hypocalcemia, and myoglobinuria.

Once heat stroke has occurred, coagulopathies may manifest as epistaxis, and endothelial damage may present as peripheral or pulmonary edema. Additionally, a core temperature of above 104°F may trigger a cascade of events that may include systemic inflammatory response resulting in increased cell wall permeability and release of endotoxins. These events can lead to tissue hypoxia, metabolic acidosis, and organ failure. Sequalae from heat stroke can result in multisystem failure. A 1998 study of Chicago heat wave victims reported that the degree of functional disability predicted survival at 1 year.⁹ Although hospital mortality was 21%, severe functional impairment at discharge was 33%, with an additional 28% mortality at 1 year.⁹ And the 1-year mortality from heat stroke is similar to that of cerebral vascular accidents.¹⁰ Within 24 hours, heat stroke victims often will display evidence of muscle, kidney, and cardiac dysfunction. Delay in intervention raises the risk of fatalities associated with hyperthermia.^11,12 Tissue destruction due to uncompensated heat may lead to rhabdomyolysis and subsequent myoglobinuria and renal injury. Damaged hepatocytes may lead to coagulopathies and hepatitis. Injured heart muscle may lead to arrhythmias and cardiac arrest.

The CNS symptoms may be difficult to ascertain in an intense working environment. The CNS system dysfunction is indicative of progression from heat injury to heat stroke and thus a medical emergency. It is imperative that the clinician be able to assess the individual quickly and accurately.

Delirium

Along with physical problems associated with it, heat injury can also lead to relatively abrupt mental status changes. In 2005, Glazer reported that even with minimally elevated core temperatures, CNS system changes can present with altered mental status, convulsions, and coma.¹³ This qualifies as a medical emergency known as delirium. Patients with delirium may present with a history of abrupt and fluctuating levels of consciousness. This fluctuation in symptoms that resemble sepsis could confuse medical providers.¹³ Thus, it is imperative that there be continuity of care of the patient with the ability to compare states of consciousness longitudinally over time.

In 1984, Pérez reported that nurses, perhaps because of their familiarity with and proximity to the patient, recorded delirium in 93% of patients, whereas psychiatric consultants recorded delirium only 34% of the time.¹⁴ Delirium manifests with several neurologic signs and symptoms; these include but are not limited to tremor, myoclonus, difficulty reading and writing, and visuoconstructive deficits, such as copying designs and problem solving.¹⁵ No matter the method to discover the delirium, the definitive treatment is to identify and treat the underlying medical condition.¹⁵ The CNS system dysfunction consistent with delirium such as irritability, ataxia, and confusion are essential to the diagnosis of heat stroke.¹³ Coma and seizures may occur, and retarded recovery of functional ability is an indication of a poor prognosis.⁹

Objective

The authors propose that in addition to vital signs, an assessment of a patient’s mental status through the use of a mental status exam could be a tool that identifies the problem early and avoids the progression of symptoms from heat stress to heat exhaustion and heat stroke. Early intervention in the progression of symptoms of hyperthermia can save lives, decrease suffering, and maintain a more robust mission-ready posture for the individual and the unit.

 

Study

During the fall of 2014, the Chemical, Biological, Radiological, Nuclear, and Explosive (CBRNE) unit of the Utah Air and Army National Guard participated in exercises using 2,159 patient encounters that were in PPE (full hazmat and SCBA) also known as level C protective clothing. Temperatures ranged from a minimum of 29°F to a high of 56°F. A mock disaster was practiced for 5 days, and of those 2,159 iterations, 43 were disqualified (2%) for any reason. Two individuals presented with altered mental status and disrupted vital signs and were disqualified for heat injuries with cognitive symptoms (0.00092%). These members were excused from duty, monitored in the medical work/rest tent until mental status and vital signs returned to baseline.

The tool used in the study was the Micro-Mental Test. This is a mental status exam that is more than a simple gestalt of how the patient is performing cognitively but less than a full Mini-Mental State Examination (MMSE). This abbreviated mental status exam provides a field expedient measurement of the individual’s ability to function cognitively. It is important to realize that this exam is most effective when repeated over time to assess the patients’ mental status longitudinally. It would be cavalier to propose that an abbreviated mental status exam would be sufficient to diagnose heat stroke, but a mental status exam—however brief—along with symptoms of hyperpyrexia, abnormal vital signs, and anhydrosis can be a useful tool to make the diagnostic transition from heat exhaustion to heat stroke.

Micro-Mental Status Exam

The traditional mental status measures are appearance, behavior, speech, mood, affect, thought process, thought content, cognition, insight, and judgment. Rapidly assessing mental status is crucial for the assessment of heat injuries, because increased vital signs coupled with neurologic changes indicate a medical emergency. The MMSE is painstaking and a somewhat cumbersome tool to use in the field. Therefore, the authors suggest a micro-mental status exam (Table). This abbreviated mental status exam is performed before the individual is placed in the PPE and enters the working environment.

The individual is then assessed after every rotation exiting the PPE and allowed to rest under supervision. Assessing the individual with vital signs and mental status longitudinally allows the provider to rapidly assess and intervene if the patient begins to exhibit mental status changes along with increased vital signs. The patient is assessed for ataxia, confusion, irritability, and lack of coordination. Patients are asked to find from a file drawer their individual prescreen checklist. This test assesses fine motor skills and cognition. Following this, self-identifying personal information from a precheck sheet is verified, and finally, simple questions regarding orientation to person, place, date, and time are posed.

Assessing Executive Function

Examples of measures of thought processes include assessing executive function by having participants find their paperwork, identifying their platoon leader, and correctly responding to questions, such as, “Where exactly were you working in the emergency area and what exactly were you doing?” This assesses executive function and thought process. Thought content could be assessed with inquiries such as, “Anything troubling about your work?” or “Would you tell me honestly if there were anything troubling or unsafe about the work you have performed?” Cognition could be assessed by questions regarding chain of command (both officer and enlisted), 3 suggestions to improve, 3 suggestions to maintain, and knowledge of the rotation schedule for the rest of the day.

The abbreviated mental status exam should in no way replace the robust and accurate mental status exam. However, in a rapidly changing, austere, or asymmetrical environment, a simple gestalt of the patient is ineffective, and the full mental status evaluation may be too time consuming. The authors propose the Micro-Mental Exam as an alternative. It is imperative that the exam be compared with the baseline assessment of the individual during the prescreening of vital signs before the individual enters the exercise.

This Micro-Mental Exam provides a quick, easy, nonintrusive, and stress-free assessment of the patient. The clarity of cognition and ability to perform simple mental tasks could serve to reassure the provider that the patient has not progressed into the dangerous area of delirium secondary to heat exposure.

Use of this simple tool during the CBRNE exercise resulted in the disqualification of 2 individuals for probable heat injury; additionally, it gave the providers a rapid assessment tool to quickly identify and treat individuals with progressive heat stress to heat stroke.

Discussion

Compared with studies of heat injuries in military and football equipment, the expected heat injury in PPE gear is very low.^2-4 The low number of disqualifications during the CBRNE exercise could be due to the extensive measures in place to assist individuals under heat stress. These measures include strict adherence to the work/rest cycles mandated by the DoD, competent leadership in evaluating and treating individuals participating in the exercise, and paying close attention not only to the vital signs, but also participants’ mental status.

 

A study in 2002 suggested that spending time in an air-conditioned area is the strongest factor in preventing heat-related deaths.¹⁶ The study also recommended prevention measures if heat exposure cannot be avoided: working in the cooler part of the day, plenty of water or nonalcoholic drinks, cool showers, lightweight light-colored clothing, and avoiding direct sunshine.¹⁶

A study in 2013 suggested that heat injuries are a significant threat to the effectiveness of military operations in general and to the youngest (the most inexperienced soldiers) specifically.¹⁷ The study further suggested that it is imperative that leaders be aware of adequate hydration on the one hand and excessive water intake on the other and enforce effective countermeasures against all types of heat injuries.¹⁷

Hyponatremia

Hyponatremia is a possible complication of heat exposure and can be divided into categories according to volume: hypovolemia, euvolemia, and hypervolemia.¹⁸ Hyponatremia is associated with excessive water consumption and excessive sodium losses via sweat during prolonged physical exertion. Symptoms of hyponatremia are related to the severity of sodium deficit and the rate of sodium decline.¹⁸ These symptoms include but are not limited to polydipsia, muscle cramps, headache, altered mental status, coma, and status epilepticus.

Hypovolemic hyponatremia usually will have signs of volume depletion, and sodium levels < 20 mEq/L. Treatment typically consists of volume replenishment with isotonic saline (0.9%), treatment of the underlying condition, and correction of the factors causing hypovolemia.

Euvolemic hyponatremia is typically due to the syndrome of inappropriate antidiuretic hormone (SIADH) and spot urinary sodium is > 20 mEq/L. Correction consists of fluid restriction and correction of the underlying cause.¹⁸

Hypervolemic hyponatremia occurs when the kidneys are overwhelmed and cannot excrete water effectively. It is commonly caused by heart failure, cirrhosis, or renal injury. Treatment consists of correction of the underlying cause, sodium and fluid restriction, and diuretic therapy.¹⁸ In severe cases of hyponatremia, sodium levels usually have decreased rapidly—typically in less than 24 hours.

Hyponatremia is defined as plasma sodium levels < 135 mEq/L, and severe symptoms often occur when the sodium level reaches 120 mEq/L. Treatment must be initiated quickly to avoid cerebral edema, respiratory failure, brain stem herniation, and death. Correction includes hypertonic 3% saline infusion at a rate of 0.5 to 2 mL/kg per hour until symptoms resolve. Two separate studies in 2014 and 2013 suggested that the rate of sodium correction should be 6 to 12 mEq/L in the first 24 hours and 18 mEq/L or less in 48 hours.^19,20

In 2009, Sterns and colleagues suggested that for the treatment of hyponatremia the therapeutic goals for serum sodium concentrations should be 6 to 8 mmol/L in 24 hours, 12 to 14 mmol/L in 48 hours, and 14 to 16 mmol/L in 72 hours.²¹ To exceed these parameters in the correction of hyponatremia risks overcorrection and iatrogenic brain damage.²¹

Care must be taken not to overcorrect sodium levels. In 2013, Sood and colleagues reported that in severe hyponatremia, a combination of 3% saline and 1 to 2 µg of desmopressin every 6 to 8 hours achieved a predictable correction of 3 to 7 mEq/L per hour with no overcorrection.²²

In the spring of 1998, U.S. Army guidelines were revised not only to protect service members from heat injury, but also from hyponatremia caused by excessive sodium loss due to exertion combined with excessive water consumption. There were fewer hospitalizations of soldiers for hyponatremia due to excessive water consumption after the guidelines were implemented.²³ Potential hyponatremia in PPE is even greater due to the strenuous environment. The potential injury due to heat injury on the one hand and hyponatremia on the other demands tailored scrutiny by experienced providers and commanders who can make appropriate changes to the work-rest cycle as needed.

Quick recognition and treatment of exercise-induced hyponatremia is essential to avoid altered mental status, seizures, coma, and death. Current guidelines for the correction of exercise-induced hyponatremia suggest rapid correction of hyponatremia with up to three 100 mL boluses of 3% NaCl in 10-minute intervals. A 2012 case study by Elsaesser and colleagues reported that a severely dehydrated marathon runner with exercise-induced hyponatremic encephalopathy achieved a resolution of symptoms with rapid correction with 100 mL boluses of 3% NaCl spaced in 10-minute intervals. An additional volume of 650 mL of 3% NaCl given over 2 hours for a total volume of 950 mL was needed to resolve the exercise-induced hyponatremia.²⁴ It seems that a 4- to 6-mmol/L increase in serum (Na+) is adequate to reverse most serious clinical manifestations of acute hyponatremia.²¹

When hyponatremia is corrected too rapidly, the brain’s ability to absorb the metabolites is overwhelmed, resulting in osmotic demyelination.²¹ Demyelination was produced in animal models by the rapid induction of hypernatremia and can occur in patients who are overcorrected to a hypernatremic state.²⁰ When individuals with chronic hyponatremia are corrected to normal sodium levels, an initial improvement may occur followed by new and often progressive neurologic deficits.²⁰

 

In 2012, Elsaesser and colleagues suggested that concern regarding overcorrection of hyponatremia might be exaggerated in the setting of exercise-induced hyponatremia. Indeed, the only cases of death associated with exercise-induced hyponatremia have been in the setting of no treatment or slow correction of hyponatremia with normal saline.²⁴

Conclusions

The issue of heat injury in athletic and military environments plagues participants and leaders alike. This article has sought to shed light on mechanisms that are helpful in mitigating heat injury. Football equipment and military protective gear that diminishes that ability to dissipate heat through the retardation of evaporation, convection, and radiation is a key factor in the development of heat injury.

Personal protective equipment is the most hazardous environment for the development of heat injury. This protective gear along with increased environmental humidity, elevated temperature, and increased workload create a dangerous environment for the individuals involved. Careful monitoring of vital signs is an important factor in avoiding heat injuries.

This article proposes that vital signs along with strict monitoring of mental status through (1) orientation; (2) simple task completion; (3) thought processes; and (4) cognitive ability over time combine to be a powerful deterrent to heat injury in an austere and dangerous working environment. It would be cavalier to propose that all heat injuries in any environment could be avoided by following these guidelines, and more tools to avoid heat injury will be developed. But medical providers trained not only to use vital signs, but also monitor and respond to mental status changes in the patient can mitigate heat injuries more effectively. Finally, careful attention should be placed on correcting hypo- and hypernatremia when rehydrating individuals in this challenging environment.

Acknowledgements
The authors wish to thank the following for their contribution to this manuscript: Sarah M. Paulsen, REB Smith, and the entire CERF-P leadership of the Utah National Guard.

Angiotensin-converting enzyme (ACE) inhibitors are commonly used medications in the treatment of hypertension in the ambulatory care setting. Serum sodium concentrations are not usually affected in the majority of patients treated with ACE inhibitors. Nonetheless, hyponatremia, defined as serum sodium level < 135 mEq/L, has been reported in patients taking ACE inhibitors.^1,2 The authors report a case of hyponatremia attributed to the use of lisinopril.

Case Presentation

In 2012, a 49-year-old man with a past medical history significant for polysubstance abuse, alcohol use, and hypertension was referred to the pharmacy clinic by his primary care physician (PCP) for management of hypertension. At the PCP visit, the patient’s blood pressure (BP) was above the goal of < 140/90 mm Hg and hydrochlorothiazide (HCTZ) 12.5 mg by mouth daily monotherapy was initiated. At the follow-up pharmacy appointment 6 weeks later, his BP remained uncontrolled, and HCTZ was increased to 25 mg daily. Of note, at that time the patient reported drinking about 6 beers per week. His electrolytes—serum sodium, potassium, chloride, carbon dioxide (CO₂), blood urea nitrogen (BUN), and serum creatinine (SCr)—were all within normal limits and stable to previous baseline results after taking HCTZ for about 2 weeks.

The patient returned to the pharmacy clinic at week 11, and his BP was controlled (136/83 mm Hg) on HCTZ 25 mg daily. His electrolytes, BUN, and SCr continued to be stable. The patient requested another appointment 8 weeks later to continue to monitor his BP.

The patient did not return to the pharmacy clinic until week 31, when he reported that he was told his BP was very high when attempting to donate plasma. The patient reported drinking a “6 pack of beer per day” at that visit. Two BP readings were taken in the clinic. The first of systolic blood pressure (SBP) was 144 mm Hg and the second was below the patient’s goal (< 140 mm Hg). His pulse (94 bpm) was also noted to be higher than baseline range (66-84 bpm). Atenolol 25 mg daily by mouth was added to the patient’s regimen of HCTZ 25 mg daily.

The patient returned at week 38, and his BP of 149/101 mm Hg was elevated above goal range. Lisinopril was added to HCTZ 25 mg in a combination formulation of lisinopril/HCTZ 20 mg/25 mg by mouth daily. The patient reported drinking 4 beers on days he worked (5 days per week) and 6 beers on days he was off (2 days per week). A repeated electrolyte, BUN, and SCr panel 1 month later (week 42) revealed a drop in the patient’s sodium level from 136 mEq/L (baseline) to 130 mEq/L (Table 1). Other measured electrolytes remained within normal limits with the exception of a slight decrease in serum chloride to 93 mEq/L (Table 2). No symptoms of hyponatremia were noted.

The patient was instructed to cut the lisinopril/HCTZ tablet in half and take it daily, then repeat blood work in 5 days. The patient’s repeated laboratory work noted an increase in sodium level to 134 mEq/L. All other measured electrolytes, including serum chloride, were within normal limits. During his follow-up visit, the patient reported stopping lisinopril/HCTZ altogether and resuming HCTZ 25 mg daily for the 5 days prior, in lieu of taking the reduced lisinopril/HCTZ dose as instructed. The patient continued to report drinking 6 beers daily.

Medication was changed to HCTZ 25 mg daily, with lisinopril discontinued, and atenolol increased to 50 mg daily. At week 46, the patient repeated electrolytes, BUN, and SCr laboratory work while on HCTZ 25 mg and atenolol 50 mg daily, and the serum sodium level increased to 139 mEq/L. After the laboratory work at week 49, he noted a reduction in alcohol to 4 beers daily at the pharmacy appointment. The patient’s BP was controlled to below the < 140/90 mm Hg goal. Medications were not changed. He was instructed to follow up with his PCP and return to the pharmacy clinic as needed for BP control.

Of note, serum magnesium levels are not included in the standard electrolyte panel and must be ordered separately. Additionally, serum magnesium levels are not monitored routinely with thiazide and ACE inhibitor therapy. In this case, serum magnesium levels were not drawn at baseline or in subsequent laboratory monitoring.

Discussion

This case demonstrates a potential link between administration of lisinopril and the development of hyponatremia. Adverse effects (AEs) of ACE inhibitors frequently include elevation in SCr, hyperkalemia, and/or a dry cough. Hyponatremia, although not commonly associated with ACE inhibitors, has been reported in the literature.^1,2

 

Although the mechanism is not completely understood, previous case reports hypothesized that ACE inhibitor therapy can lead to Syndrome of Inappropriate Antidiuretic Hormone (SIADH).^1,3 Angiotensin I is not converted to angiotensin II peripherally with ACE inhibitor therapy. This elevated circulating level of angiotensin I is available to cross the blood-brain barrier where it is converted to angiotensin II. Angiotensin can then stimulate vasopressin release, which, in turn, increases thirst and leads to decreased amounts of concentrated urine.⁴ The combination of increased thirst and concentrated urine can lead to hyponatremia.

The clinical manifestations of hyponatremia can vary. In patients with ACE inhibitor-induced hyponatremia, an early sign may be polydipsia. Once hyponatremia develops, patients may experience nausea, muscle spasms or weakness, and general malaise. Additionally, lethargy, a decreased level of consciousness, and headaches may occur. In the most severe cases, hyponatremia may lead to seizures, coma, and eventually death.

Several case reports involving various ACE inhibitors, such as captopril, enalapril, and lisinopril, have been reported over the past 30 years, citing the connection linking these medications to SIADH and symptomatic hyponatremia. A large number of cases involved patients with established congestive heart failure for whom ACE inhibitors were added because of their beneficial impact on improved survival and reduced left ventricular dysfunction.⁵ Angiotensin converting enzyme inhibitor-induced hyponatremia may be confounded by heart failure, due to the complex disease pathophysiology.¹ Therefore, case reports of ACE inhibitors use in patients treated for indications other than heart failure, such as hypertension, provide a clearer picture of ACE inhibitor-induced hyponatremia.

One such striking case report involved a 63-year-old woman taking lisinopril 10 mg daily as monotherapy (no other medications) for mild hypertension with a baseline serum sodium level within normal limits.⁶ One month later, the patient was admitted a with serum sodium level of 101 mEq/L and symptomatic with altered mental status and generalized tonic-clonic seizures. Once the serum sodium was corrected, the patient’s mental status improved, and her 1-year follow-up examination was unremarkable. This case report is significant for its findings that there may be a cause-and-effect relationship between lisinopril monotherapy and symptomatic hyponatremia that occurred within a month. There are cases of hyponatremia in patients receiving ACE inhibitor therapy in addition to established diuretic therapy. For example, a woman aged 71 years was admitted for elevated BP with an initial medication regimen that included HCTZ and other antihypertensive medications.⁷ She was given captopril at increasing doses up to 150 mg daily. The patient’s serum sodium levels dropped correspondingly with titrated doses of captopril. The patient reported feeling confusion, and her serum sodium levels dropped to 114 mEq/L. Once captopril was discontinued and serum sodium corrected with IV fluids, the patient’s confusion subsided. The patient was discharged on a medication regimen that continued HCTZ but not the ACE inhibitor, with no clinical consequences and normal serum sodium levels over the following year. Similarly, the patient in this case study had established HCTZ therapy with normal serum sodium that declined upon addition of an ACE inhibitor.

Other factors that could contribute to hyponatremia, such as beer potomania, confound the current case of hyponatremia. This patient reported chronic beer ingestion, which can lead to hyponatremia and may have aggravated the hyponatremia upon initiation of lisinopril. Additionally, the patient was taking HCTZ, an agent known to cause hyponatremia, prior to initiation of the ACE inhibitor. Another limiting factor noted was that serum magnesium levels were not measured to assess for potential hypomagnesemia, which may affect other electrolytes.

Using the Naranjo Assessment scale, a score of 3 was calculated, indicating a possible link to lisinopril as the cause of hyponatremia.⁸ Although the patient had the aforementioned risk factors, the notable drop of serum sodium level correlated with the lisinopril administration, which was previously stable despite HCTZ treatment and alcohol consumption. The time line of events led the authors to believe that hyponatremia was strongly related to lisinopril. This patient was fortunate that he experienced no neurologic complications, which have been reported in other cases of ACE inhibitor-induced hyponatremia, manifested from the drop in serum sodium.

Conclusion

Though rarely occurring, hyponatremia should be considered a potentially serious AE associated with ACE inhibitor therapy. Timely monitoring of electrolytes, BUN, and SCr should continue to assess for more common AEs of elevated SCr and hyperkalemia, but clinicians should be aware of the potential for ACE inhibitor-induced hyponatremia.

Angiotensin-converting enzyme (ACE) inhibitors are commonly used medications in the treatment of hypertension in the ambulatory care setting. Serum sodium concentrations are not usually affected in the majority of patients treated with ACE inhibitors. Nonetheless, hyponatremia, defined as serum sodium level < 135 mEq/L, has been reported in patients taking ACE inhibitors.^1,2 The authors report a case of hyponatremia attributed to the use of lisinopril.

Case Presentation

In 2012, a 49-year-old man with a past medical history significant for polysubstance abuse, alcohol use, and hypertension was referred to the pharmacy clinic by his primary care physician (PCP) for management of hypertension. At the PCP visit, the patient’s blood pressure (BP) was above the goal of < 140/90 mm Hg and hydrochlorothiazide (HCTZ) 12.5 mg by mouth daily monotherapy was initiated. At the follow-up pharmacy appointment 6 weeks later, his BP remained uncontrolled, and HCTZ was increased to 25 mg daily. Of note, at that time the patient reported drinking about 6 beers per week. His electrolytes—serum sodium, potassium, chloride, carbon dioxide (CO₂), blood urea nitrogen (BUN), and serum creatinine (SCr)—were all within normal limits and stable to previous baseline results after taking HCTZ for about 2 weeks.

The patient returned to the pharmacy clinic at week 11, and his BP was controlled (136/83 mm Hg) on HCTZ 25 mg daily. His electrolytes, BUN, and SCr continued to be stable. The patient requested another appointment 8 weeks later to continue to monitor his BP.

The patient did not return to the pharmacy clinic until week 31, when he reported that he was told his BP was very high when attempting to donate plasma. The patient reported drinking a “6 pack of beer per day” at that visit. Two BP readings were taken in the clinic. The first of systolic blood pressure (SBP) was 144 mm Hg and the second was below the patient’s goal (< 140 mm Hg). His pulse (94 bpm) was also noted to be higher than baseline range (66-84 bpm). Atenolol 25 mg daily by mouth was added to the patient’s regimen of HCTZ 25 mg daily.

The patient returned at week 38, and his BP of 149/101 mm Hg was elevated above goal range. Lisinopril was added to HCTZ 25 mg in a combination formulation of lisinopril/HCTZ 20 mg/25 mg by mouth daily. The patient reported drinking 4 beers on days he worked (5 days per week) and 6 beers on days he was off (2 days per week). A repeated electrolyte, BUN, and SCr panel 1 month later (week 42) revealed a drop in the patient’s sodium level from 136 mEq/L (baseline) to 130 mEq/L (Table 1). Other measured electrolytes remained within normal limits with the exception of a slight decrease in serum chloride to 93 mEq/L (Table 2). No symptoms of hyponatremia were noted.

The patient was instructed to cut the lisinopril/HCTZ tablet in half and take it daily, then repeat blood work in 5 days. The patient’s repeated laboratory work noted an increase in sodium level to 134 mEq/L. All other measured electrolytes, including serum chloride, were within normal limits. During his follow-up visit, the patient reported stopping lisinopril/HCTZ altogether and resuming HCTZ 25 mg daily for the 5 days prior, in lieu of taking the reduced lisinopril/HCTZ dose as instructed. The patient continued to report drinking 6 beers daily.

Medication was changed to HCTZ 25 mg daily, with lisinopril discontinued, and atenolol increased to 50 mg daily. At week 46, the patient repeated electrolytes, BUN, and SCr laboratory work while on HCTZ 25 mg and atenolol 50 mg daily, and the serum sodium level increased to 139 mEq/L. After the laboratory work at week 49, he noted a reduction in alcohol to 4 beers daily at the pharmacy appointment. The patient’s BP was controlled to below the < 140/90 mm Hg goal. Medications were not changed. He was instructed to follow up with his PCP and return to the pharmacy clinic as needed for BP control.

Of note, serum magnesium levels are not included in the standard electrolyte panel and must be ordered separately. Additionally, serum magnesium levels are not monitored routinely with thiazide and ACE inhibitor therapy. In this case, serum magnesium levels were not drawn at baseline or in subsequent laboratory monitoring.

Discussion

This case demonstrates a potential link between administration of lisinopril and the development of hyponatremia. Adverse effects (AEs) of ACE inhibitors frequently include elevation in SCr, hyperkalemia, and/or a dry cough. Hyponatremia, although not commonly associated with ACE inhibitors, has been reported in the literature.^1,2

 

Although the mechanism is not completely understood, previous case reports hypothesized that ACE inhibitor therapy can lead to Syndrome of Inappropriate Antidiuretic Hormone (SIADH).^1,3 Angiotensin I is not converted to angiotensin II peripherally with ACE inhibitor therapy. This elevated circulating level of angiotensin I is available to cross the blood-brain barrier where it is converted to angiotensin II. Angiotensin can then stimulate vasopressin release, which, in turn, increases thirst and leads to decreased amounts of concentrated urine.⁴ The combination of increased thirst and concentrated urine can lead to hyponatremia.

The clinical manifestations of hyponatremia can vary. In patients with ACE inhibitor-induced hyponatremia, an early sign may be polydipsia. Once hyponatremia develops, patients may experience nausea, muscle spasms or weakness, and general malaise. Additionally, lethargy, a decreased level of consciousness, and headaches may occur. In the most severe cases, hyponatremia may lead to seizures, coma, and eventually death.

Several case reports involving various ACE inhibitors, such as captopril, enalapril, and lisinopril, have been reported over the past 30 years, citing the connection linking these medications to SIADH and symptomatic hyponatremia. A large number of cases involved patients with established congestive heart failure for whom ACE inhibitors were added because of their beneficial impact on improved survival and reduced left ventricular dysfunction.⁵ Angiotensin converting enzyme inhibitor-induced hyponatremia may be confounded by heart failure, due to the complex disease pathophysiology.¹ Therefore, case reports of ACE inhibitors use in patients treated for indications other than heart failure, such as hypertension, provide a clearer picture of ACE inhibitor-induced hyponatremia.

One such striking case report involved a 63-year-old woman taking lisinopril 10 mg daily as monotherapy (no other medications) for mild hypertension with a baseline serum sodium level within normal limits.⁶ One month later, the patient was admitted a with serum sodium level of 101 mEq/L and symptomatic with altered mental status and generalized tonic-clonic seizures. Once the serum sodium was corrected, the patient’s mental status improved, and her 1-year follow-up examination was unremarkable. This case report is significant for its findings that there may be a cause-and-effect relationship between lisinopril monotherapy and symptomatic hyponatremia that occurred within a month. There are cases of hyponatremia in patients receiving ACE inhibitor therapy in addition to established diuretic therapy. For example, a woman aged 71 years was admitted for elevated BP with an initial medication regimen that included HCTZ and other antihypertensive medications.⁷ She was given captopril at increasing doses up to 150 mg daily. The patient’s serum sodium levels dropped correspondingly with titrated doses of captopril. The patient reported feeling confusion, and her serum sodium levels dropped to 114 mEq/L. Once captopril was discontinued and serum sodium corrected with IV fluids, the patient’s confusion subsided. The patient was discharged on a medication regimen that continued HCTZ but not the ACE inhibitor, with no clinical consequences and normal serum sodium levels over the following year. Similarly, the patient in this case study had established HCTZ therapy with normal serum sodium that declined upon addition of an ACE inhibitor.

Other factors that could contribute to hyponatremia, such as beer potomania, confound the current case of hyponatremia. This patient reported chronic beer ingestion, which can lead to hyponatremia and may have aggravated the hyponatremia upon initiation of lisinopril. Additionally, the patient was taking HCTZ, an agent known to cause hyponatremia, prior to initiation of the ACE inhibitor. Another limiting factor noted was that serum magnesium levels were not measured to assess for potential hypomagnesemia, which may affect other electrolytes.

Using the Naranjo Assessment scale, a score of 3 was calculated, indicating a possible link to lisinopril as the cause of hyponatremia.⁸ Although the patient had the aforementioned risk factors, the notable drop of serum sodium level correlated with the lisinopril administration, which was previously stable despite HCTZ treatment and alcohol consumption. The time line of events led the authors to believe that hyponatremia was strongly related to lisinopril. This patient was fortunate that he experienced no neurologic complications, which have been reported in other cases of ACE inhibitor-induced hyponatremia, manifested from the drop in serum sodium.

Conclusion

Though rarely occurring, hyponatremia should be considered a potentially serious AE associated with ACE inhibitor therapy. Timely monitoring of electrolytes, BUN, and SCr should continue to assess for more common AEs of elevated SCr and hyperkalemia, but clinicians should be aware of the potential for ACE inhibitor-induced hyponatremia.

Angiotensin-converting enzyme (ACE) inhibitors are commonly used medications in the treatment of hypertension in the ambulatory care setting. Serum sodium concentrations are not usually affected in the majority of patients treated with ACE inhibitors. Nonetheless, hyponatremia, defined as serum sodium level < 135 mEq/L, has been reported in patients taking ACE inhibitors.^1,2 The authors report a case of hyponatremia attributed to the use of lisinopril.

Case Presentation

In 2012, a 49-year-old man with a past medical history significant for polysubstance abuse, alcohol use, and hypertension was referred to the pharmacy clinic by his primary care physician (PCP) for management of hypertension. At the PCP visit, the patient’s blood pressure (BP) was above the goal of < 140/90 mm Hg and hydrochlorothiazide (HCTZ) 12.5 mg by mouth daily monotherapy was initiated. At the follow-up pharmacy appointment 6 weeks later, his BP remained uncontrolled, and HCTZ was increased to 25 mg daily. Of note, at that time the patient reported drinking about 6 beers per week. His electrolytes—serum sodium, potassium, chloride, carbon dioxide (CO₂), blood urea nitrogen (BUN), and serum creatinine (SCr)—were all within normal limits and stable to previous baseline results after taking HCTZ for about 2 weeks.

The patient returned to the pharmacy clinic at week 11, and his BP was controlled (136/83 mm Hg) on HCTZ 25 mg daily. His electrolytes, BUN, and SCr continued to be stable. The patient requested another appointment 8 weeks later to continue to monitor his BP.

The patient did not return to the pharmacy clinic until week 31, when he reported that he was told his BP was very high when attempting to donate plasma. The patient reported drinking a “6 pack of beer per day” at that visit. Two BP readings were taken in the clinic. The first of systolic blood pressure (SBP) was 144 mm Hg and the second was below the patient’s goal (< 140 mm Hg). His pulse (94 bpm) was also noted to be higher than baseline range (66-84 bpm). Atenolol 25 mg daily by mouth was added to the patient’s regimen of HCTZ 25 mg daily.

The patient returned at week 38, and his BP of 149/101 mm Hg was elevated above goal range. Lisinopril was added to HCTZ 25 mg in a combination formulation of lisinopril/HCTZ 20 mg/25 mg by mouth daily. The patient reported drinking 4 beers on days he worked (5 days per week) and 6 beers on days he was off (2 days per week). A repeated electrolyte, BUN, and SCr panel 1 month later (week 42) revealed a drop in the patient’s sodium level from 136 mEq/L (baseline) to 130 mEq/L (Table 1). Other measured electrolytes remained within normal limits with the exception of a slight decrease in serum chloride to 93 mEq/L (Table 2). No symptoms of hyponatremia were noted.

The patient was instructed to cut the lisinopril/HCTZ tablet in half and take it daily, then repeat blood work in 5 days. The patient’s repeated laboratory work noted an increase in sodium level to 134 mEq/L. All other measured electrolytes, including serum chloride, were within normal limits. During his follow-up visit, the patient reported stopping lisinopril/HCTZ altogether and resuming HCTZ 25 mg daily for the 5 days prior, in lieu of taking the reduced lisinopril/HCTZ dose as instructed. The patient continued to report drinking 6 beers daily.

Medication was changed to HCTZ 25 mg daily, with lisinopril discontinued, and atenolol increased to 50 mg daily. At week 46, the patient repeated electrolytes, BUN, and SCr laboratory work while on HCTZ 25 mg and atenolol 50 mg daily, and the serum sodium level increased to 139 mEq/L. After the laboratory work at week 49, he noted a reduction in alcohol to 4 beers daily at the pharmacy appointment. The patient’s BP was controlled to below the < 140/90 mm Hg goal. Medications were not changed. He was instructed to follow up with his PCP and return to the pharmacy clinic as needed for BP control.

Of note, serum magnesium levels are not included in the standard electrolyte panel and must be ordered separately. Additionally, serum magnesium levels are not monitored routinely with thiazide and ACE inhibitor therapy. In this case, serum magnesium levels were not drawn at baseline or in subsequent laboratory monitoring.

Discussion

This case demonstrates a potential link between administration of lisinopril and the development of hyponatremia. Adverse effects (AEs) of ACE inhibitors frequently include elevation in SCr, hyperkalemia, and/or a dry cough. Hyponatremia, although not commonly associated with ACE inhibitors, has been reported in the literature.^1,2

 

Although the mechanism is not completely understood, previous case reports hypothesized that ACE inhibitor therapy can lead to Syndrome of Inappropriate Antidiuretic Hormone (SIADH).^1,3 Angiotensin I is not converted to angiotensin II peripherally with ACE inhibitor therapy. This elevated circulating level of angiotensin I is available to cross the blood-brain barrier where it is converted to angiotensin II. Angiotensin can then stimulate vasopressin release, which, in turn, increases thirst and leads to decreased amounts of concentrated urine.⁴ The combination of increased thirst and concentrated urine can lead to hyponatremia.

The clinical manifestations of hyponatremia can vary. In patients with ACE inhibitor-induced hyponatremia, an early sign may be polydipsia. Once hyponatremia develops, patients may experience nausea, muscle spasms or weakness, and general malaise. Additionally, lethargy, a decreased level of consciousness, and headaches may occur. In the most severe cases, hyponatremia may lead to seizures, coma, and eventually death.

Several case reports involving various ACE inhibitors, such as captopril, enalapril, and lisinopril, have been reported over the past 30 years, citing the connection linking these medications to SIADH and symptomatic hyponatremia. A large number of cases involved patients with established congestive heart failure for whom ACE inhibitors were added because of their beneficial impact on improved survival and reduced left ventricular dysfunction.⁵ Angiotensin converting enzyme inhibitor-induced hyponatremia may be confounded by heart failure, due to the complex disease pathophysiology.¹ Therefore, case reports of ACE inhibitors use in patients treated for indications other than heart failure, such as hypertension, provide a clearer picture of ACE inhibitor-induced hyponatremia.

One such striking case report involved a 63-year-old woman taking lisinopril 10 mg daily as monotherapy (no other medications) for mild hypertension with a baseline serum sodium level within normal limits.⁶ One month later, the patient was admitted a with serum sodium level of 101 mEq/L and symptomatic with altered mental status and generalized tonic-clonic seizures. Once the serum sodium was corrected, the patient’s mental status improved, and her 1-year follow-up examination was unremarkable. This case report is significant for its findings that there may be a cause-and-effect relationship between lisinopril monotherapy and symptomatic hyponatremia that occurred within a month. There are cases of hyponatremia in patients receiving ACE inhibitor therapy in addition to established diuretic therapy. For example, a woman aged 71 years was admitted for elevated BP with an initial medication regimen that included HCTZ and other antihypertensive medications.⁷ She was given captopril at increasing doses up to 150 mg daily. The patient’s serum sodium levels dropped correspondingly with titrated doses of captopril. The patient reported feeling confusion, and her serum sodium levels dropped to 114 mEq/L. Once captopril was discontinued and serum sodium corrected with IV fluids, the patient’s confusion subsided. The patient was discharged on a medication regimen that continued HCTZ but not the ACE inhibitor, with no clinical consequences and normal serum sodium levels over the following year. Similarly, the patient in this case study had established HCTZ therapy with normal serum sodium that declined upon addition of an ACE inhibitor.

Other factors that could contribute to hyponatremia, such as beer potomania, confound the current case of hyponatremia. This patient reported chronic beer ingestion, which can lead to hyponatremia and may have aggravated the hyponatremia upon initiation of lisinopril. Additionally, the patient was taking HCTZ, an agent known to cause hyponatremia, prior to initiation of the ACE inhibitor. Another limiting factor noted was that serum magnesium levels were not measured to assess for potential hypomagnesemia, which may affect other electrolytes.

Using the Naranjo Assessment scale, a score of 3 was calculated, indicating a possible link to lisinopril as the cause of hyponatremia.⁸ Although the patient had the aforementioned risk factors, the notable drop of serum sodium level correlated with the lisinopril administration, which was previously stable despite HCTZ treatment and alcohol consumption. The time line of events led the authors to believe that hyponatremia was strongly related to lisinopril. This patient was fortunate that he experienced no neurologic complications, which have been reported in other cases of ACE inhibitor-induced hyponatremia, manifested from the drop in serum sodium.

Conclusion

Though rarely occurring, hyponatremia should be considered a potentially serious AE associated with ACE inhibitor therapy. Timely monitoring of electrolytes, BUN, and SCr should continue to assess for more common AEs of elevated SCr and hyperkalemia, but clinicians should be aware of the potential for ACE inhibitor-induced hyponatremia.

Total hip arthroplasty (THA) is considered to be one of the most successful orthopedic interventions of its generation.¹ In 2010, 332,000 THAs were performed in the U.S.² Although used to correct advanced joint diseases in the elderly, the THA procedure has become increasingly common in a younger population for posttraumatic fractures and conditions that lead to early onset secondary arthritis such as avascular necrosis, juvenile rheumatoid arthritis, hip dysplasia, Perthes disease, and femoro-acetabular impingement.

Current hip replacements are expected to function at least 10 to 20 years in 90% of patients.³ As increasing numbers of young patients have these procedures and as seniors continue to live longer, patients will outlast their implants. Younger and more active patients have a higher rate of revision, because the longevity of the prosthesis is usually a function of usage.³ The number of revision THAs is projected to increase 137% by 2030.⁴

Hip resurfacing has been developed as a bone preserving surgical alternative to THA. The first system for use in the U.S. received FDA approval in 2006, but concerns about the metal on metal bearing surfaces, high failure and revision rates, and early catastrophic modes of failure compared with THAs has resulted in the recall of many of these devices. Hip resurfacing may offer some advantages compared with those of a THA in a carefully selected population, but its use will not be further discussed in this case study.⁵ Periprosthetic osteolysis and aseptic loosening are 2 of the long-term consequences of THA.⁶ Bone loss is felt to be secondary to a biologic reaction to particulate debris from implants.⁶ Some patients, especially those with loosening, complete wear, or fracture, will be symptomatic with pain. However, wear and osteolysis is a silent disease unless there is mechanical failure. Other patients may not experience discomfort. Radiographic studies may reveal significant changes, which warrant the recommendation for a hip revision.

Hip revision surgery has 3 major purposes: relieving pain in the affected joint, restoring the patient’s mobility, and removing a loose or damaged prosthesis before irreversible harm is done to the joint. It’s anticipated that most primary care providers (PCPs) will encounter patients who seek advice on the need for a revision hip arthroplasty.

This case will present an asymptomatic patient who underwent a THA in 1997 at age 37, to address developmental dysplasia of the hip (DDH) and was advised to undergo a revision hip arthroplasty due to abnormal radiographic findings at age 55 years. A discussion will follow that includes a brief review of the history of THA, the materials and bearings commonly used, the presenting symptoms or radiographic changes that signal the need for a revision, and the current options available for a patient such as this.

Case Report

A man aged 55 years presented to a new orthopedic surgeon for his first orthopedic appointment in 10 years. The patient had a left metal-on-polyethylene (M-on-PE) THA 18 years prior due to early onset secondary degenerative joint disease from DDH. The patient’s M-on-PE THA was a titanium acetabular socket and femoral stem with a cobalt-chromium alloy femoral head and a polyethylene liner. The patient remained physically active with an exercise routine consisting of walking, swimming, and weight training.

The patient’s orthopedic history was notable for a right knee arthroscopy for intervention due to a torn medial and lateral meniscus, and birth history was noteworthy for a breech presentation. The physical exam was unremarkable except for a slight leg length discrepancy, but the patient did not exhibit a Trendelenburg gait.

Plain X-rays and a computed tomography (CT) scan showed eccentric PE wear and superior migration of the femoral head, which was indicative of significant PE liner wear. No significant osteolysis or periprosthetic loosening was observed on the X-rays or CT scan. He was advised that a hip revision procedure would need to be done, optimally, within the next 6 months to a year.

Discussion

Hip dysplasia represents a broad group of disorders and generally means abnormal development of the hip joint. The term is most commonly used to refer to DDH with inadequate coverage of the femoral head. In one study, 25% of hip replacements performed in patients aged ≤ 40 years were due to underlying hip dysplasia.⁷

Developmental dysplasia of the hip occurs more often in children who present in the breech position.⁸ One theory argues that packaging issues in utero may account for the increased incidence of DDH.⁹ The earliest recorded attempts at hip replacement occurred in Germany, in 1891, when ivory was used to replace the femoral heads of patients whose hip joints had been destroyed by tuberculosis.¹

 

The orthopedic surgeon Sir John Charnley, who worked at the Manchester Royal Infirmary, is considered the father of the modern THA.¹ His low friction arthroplasty, designed in the early 1960s is identical, in principle, to the M-on-PE prosthesis used today.¹ The PE liner used was ultrahigh molecular weight polyethylene (UHMWPE).¹

Due to the early success of the Charnley prosthesis, the M-on-PE prosthesis became the most widely used. Although PE is the most studied and understood of all acetabular liner materials, it will eventually wear and shed debris. Acetabular cup wear is the most frequent reason for mid-to-long-term revisions, especially in young and active patients.¹⁰ More active patients shed more debris.³ The PE debris instigates the release of inflammatory mediators, which results in chronic inflammation and tissue damage that erodes the supporting bone and can lead to implant loosening or fracture.⁶ Ongoing studies seek to optimize and improve properties of the UHMWPE and to develop alternative bearings. After FDA approval in 1999, highly cross-linked polyethylene liners (HXLPE) rapidly became the standard of care for THAs, at least in the U.S.¹¹ Highly cross-linked polyethylene liners are created from UHMWPE through a process of cross-linking by exposure to gamma radiation, and subsequent heat treatment to neutralize free radicals and limit oxidative degradation.¹²

In one study, the 5-year annual linear wear rate for a HXLPE liner was only 45% of that seen with the UHMWPE liner, although the qualitative wear pattern was the same.¹³ In a study that followed patients for 7 years postoperatively, the mean steady-state wear rate of the HXLPE was 0.005 mm/y compared with 0.037 mm/y for UHMWPE.¹⁴ In a long-term study (a minimum follow-up of 10 years) of 50 patients who were aged < 50 years and underwent THA using HXLPE liners, there was no radiographic evidence of osteolysis or component loosening, and liner wear was 0.020 ± 0.0047 mm/y.¹² In 2005, second-generation HXLPE liners were introduced clinically and have been shown to further reduce wear in vitro compared with both UHMWPE and first-generation HXLPE liners. Callary and colleagues calculated that the wear rates between 1 year and 5 years were all < 0.001 mm/y.¹⁵

The use of ceramic for THAs began in 1970, and ceramic heads on polyethylene (C-on-PE) liners and ceramic-on-ceramic (C-on-C) bearings have been in continual use for > 30 years in Europe. Premarket FDA approval based on European data was granted in 1983; however, the manufacturer voluntarily removed it from the market because of a high incidence of stem loosening (> 30% within 3 years in some series).¹⁶ FDA approvals came much later for C-on-PE (1989) and C-on-C (2003) bearings.

Ceramic is the hardest implant material used, and it can be concluded from many clinical and laboratory reports that C-on-PE and C-on-C combinations confer a potentially significant reduction in wear on THA bearings.¹⁶ Ceramic hips initially had 2 concerns: catastrophic shattering and squeaking. Current ceramic hips have been substantially improved, and some experts feel shattering has been essentially eliminated.¹⁶ Other experts note that ceramic brittleness remains a major concern.¹⁷ Squeaking remains a problem for some, but it usually abates over time. No study has correlated squeaking with impending failure or increased pain or disability.

While C-on-C bearings are now felt to be a good implant for young active patients, these bearings have generally not resulted in significantly lower wear rates and fewer revisions.¹⁸ High rates of wear and osteolysis have been sporadically documented over the 35-year history of ceramic implants.¹⁶ The FDA approved the first ceramic-on-metal total hip replacement system on June 13, 2011.

Metal-on-metal (M-on-M) implants have been used by some for decades, although they were not approved by the FDA until the late 1990s. However, some device recalls have brought negative attention to M-on-M implants.¹⁹ It was felt that they would generate less wear debris than PE, but reports of pseudotumors (from inflammatory mediators) and metallosis have significantly tempered enthusiasm for these products.^20,21 The wear rates are very low, estimated to be only 0.01 mm/y, but concerns about the carcinogenetic potential of systemically increased metal ions remains a possible and much debated concern.^19,22,23 In January 2013, FDA issued a safety communication on M-on-M implants.

Many experts feel that modern ceramic or metal on second-generation HXLPE represents the gold standard and the most predictable bearing choice for young, active patients.¹⁸ Others feel that the optimal choice of bearing surfaces in THA, particularly in the younger and more active patient, remains controversial.²⁴

Follow-Up

Intermittent orthopedic monitoring is recommended for all patients who have undergone a THA. The frequency of hip X-rays on follow-up appointments is left to the orthopedic surgeon. After the initial recovery, serial images every 2 to 5 years can identify progressive failure, and annual X-rays may be used for closer follow-up in high-risk patients.

 

Patients who experience dislocations, fractures, infections, or pain usually maintain close orthopedic follow-up. Significant wear of the prosthesis damages the socket; osteolysis can cause irreversible bone loss, fracture, and loosening. Massive acetabular bone loss is very difficult to reverse and creates major reconstruction challenges.

Figure 1A is a 2009 X-ray of a woman aged 44 years who underwent a THA after a motor vehicle accident in 1997 and who was advised to have a revision THA when seen in 2009.

The X-ray revealed significant wear of the acetabular liner. Unfortunately, the patient was lost to follow-up, and when she returned 5 years later, she had severe pain and was unable to walk. Figure 1B shows that the patient’s femoral head had broken through the acetabular component. She had massive bone loss that required a complex revision and bone grafting. (Figure 1C). Operative findings included severe metal debris from socket damage (Figure 2).

Asymptomatic patients can generate significant wear and debris and may experience osteolysis. A revision hip arthroplasty may be needed to prevent long-term damage. Routine surveillance can detect these issues and allow intervention at a time when the simplest revision could be performed. Eccentric alignment of the femoral head in the acetabular cup suggests wear or breakdown of the liner and increases the likelihood of instability or dislocation. In advanced cases, plain radiographs may show osteolysis in the surrounding bone.

Figure 3A is an X-ray of a man aged 71 years who had undergone THA 21 years earlier and had complied with routine follow-up. When his X-rays showed significant wear of the liner and some osteolysis, he was able to undergo a simple revision (Figure 3B).

Three-dimensional CT is useful for quantifying the presence and severity of osteolytic lesions, because plain radiographs may underestimate the amount of bone loss that is present.²⁵ The CT in Figure 3C shows the magnitude of osteolysis that was underestimated by the preoperative plain X-rays (Figure 3A). Computed tomography scans are crucial for surgical planning in the setting of severe acetabular bone loss.

There is a wide spectrum of signs and symptoms that can occur in the setting of acetabular component failure. Pain is a common presenting symptom. Groin pain can represent acetabular failure; thigh pain may be correlated to femoral component failure.²⁵ The clinical patient presentation ultimately depends on the underlying cause: an infection, polyethylene wear, instability, or aseptic loosening.²⁵ Leg-length discrepancy, joint deformity, location of prior incisions, functional status, and baseline neurologic status should be evaluated and documented during the preoperative evaluation as well.²⁵

Case Study Revision Options

The X-rays and CT scans for this case study patient showed that he was a possible candidate for the simplest revision surgery; an isolated liner exchange and replacement of the femoral head. When the original surgery was performed (1997), the only FDA approved PE liner was UHMWPE. To justify isolated liner exchange, the modular acetabular metallic shell also should be well-fixed and appropriately oriented.²⁶ This is evaluated both preoperatively and intraoperatively.

If found to be well fixed with an appropriate orientation and locking mechanism, the UHMWPE liner could be replaced with a HXLPE liner and a larger metal femoral head for improved wear and stability. Acetabular revision is indicted for an asymptomatic patient who has progressive osteolysis, severe wear, or bone loss that would compromise future reconstruction.

Conclusions

Over the past several decades, THA has become recognized as an effective treatment option for the reduction of pain and disability associated with hip joint disease and is associated with successful clinical outcomes. The most frequently noted recommendations for trying to increase the life expectancy of an artificial hip replacement include maintaining a normal weight, keeping leg muscles strong, and avoiding repetitive squatting and kneeling.

As the number of primary THAs has increased and the average age of those undergoing a primary THA has decreased, the need for revisions has risen. Reviews have demonstrated that the most common causes for early total hip revision, regardless of component, included infection, instability/dislocation, and fracture, whereas wear is the most common reason for mid to late revisions.

The wear of all materials used has been shown to be greatest in the most active patients.

Studies continue to identify ways to potentially prevent or reverse osteolysis from wear debris. Alendronate therapy has been shown to prevent and treat PE debris-induced periprosthetic bone loss in rats.²⁷ It also was successfully used in a case report of an asymptomatic woman aged 39 years who had rapid PE wear and aggressive periprosthetic osteolysis within just 2 years of a bilateral THA.²⁸ Other areas of research on decreasing osteolysis in THA recipients include trials with mesenchymal stem cells, bone morphogenic proteins, and gene therapy.⁶

In the U.S., 46,000 revisions were performed in 2004 and this number is expected to more than double by 2030.⁴ Primary care providers are sure to encounter patients who will be in need of a hip revision procedure. It’s important for them to make sure that their patients who have undergone a THA are periodically seen for orthopedic follow-up. Despite the long history of primary THAs, there is still not a single technique and material to suit all patient characteristics.¹ Unfortunately, the same currently applies to hip revision procedures.

Total hip arthroplasty (THA) is considered to be one of the most successful orthopedic interventions of its generation.¹ In 2010, 332,000 THAs were performed in the U.S.² Although used to correct advanced joint diseases in the elderly, the THA procedure has become increasingly common in a younger population for posttraumatic fractures and conditions that lead to early onset secondary arthritis such as avascular necrosis, juvenile rheumatoid arthritis, hip dysplasia, Perthes disease, and femoro-acetabular impingement.

Current hip replacements are expected to function at least 10 to 20 years in 90% of patients.³ As increasing numbers of young patients have these procedures and as seniors continue to live longer, patients will outlast their implants. Younger and more active patients have a higher rate of revision, because the longevity of the prosthesis is usually a function of usage.³ The number of revision THAs is projected to increase 137% by 2030.⁴

Hip resurfacing has been developed as a bone preserving surgical alternative to THA. The first system for use in the U.S. received FDA approval in 2006, but concerns about the metal on metal bearing surfaces, high failure and revision rates, and early catastrophic modes of failure compared with THAs has resulted in the recall of many of these devices. Hip resurfacing may offer some advantages compared with those of a THA in a carefully selected population, but its use will not be further discussed in this case study.⁵ Periprosthetic osteolysis and aseptic loosening are 2 of the long-term consequences of THA.⁶ Bone loss is felt to be secondary to a biologic reaction to particulate debris from implants.⁶ Some patients, especially those with loosening, complete wear, or fracture, will be symptomatic with pain. However, wear and osteolysis is a silent disease unless there is mechanical failure. Other patients may not experience discomfort. Radiographic studies may reveal significant changes, which warrant the recommendation for a hip revision.

Hip revision surgery has 3 major purposes: relieving pain in the affected joint, restoring the patient’s mobility, and removing a loose or damaged prosthesis before irreversible harm is done to the joint. It’s anticipated that most primary care providers (PCPs) will encounter patients who seek advice on the need for a revision hip arthroplasty.

This case will present an asymptomatic patient who underwent a THA in 1997 at age 37, to address developmental dysplasia of the hip (DDH) and was advised to undergo a revision hip arthroplasty due to abnormal radiographic findings at age 55 years. A discussion will follow that includes a brief review of the history of THA, the materials and bearings commonly used, the presenting symptoms or radiographic changes that signal the need for a revision, and the current options available for a patient such as this.

Case Report

A man aged 55 years presented to a new orthopedic surgeon for his first orthopedic appointment in 10 years. The patient had a left metal-on-polyethylene (M-on-PE) THA 18 years prior due to early onset secondary degenerative joint disease from DDH. The patient’s M-on-PE THA was a titanium acetabular socket and femoral stem with a cobalt-chromium alloy femoral head and a polyethylene liner. The patient remained physically active with an exercise routine consisting of walking, swimming, and weight training.

The patient’s orthopedic history was notable for a right knee arthroscopy for intervention due to a torn medial and lateral meniscus, and birth history was noteworthy for a breech presentation. The physical exam was unremarkable except for a slight leg length discrepancy, but the patient did not exhibit a Trendelenburg gait.

Plain X-rays and a computed tomography (CT) scan showed eccentric PE wear and superior migration of the femoral head, which was indicative of significant PE liner wear. No significant osteolysis or periprosthetic loosening was observed on the X-rays or CT scan. He was advised that a hip revision procedure would need to be done, optimally, within the next 6 months to a year.

Discussion

Hip dysplasia represents a broad group of disorders and generally means abnormal development of the hip joint. The term is most commonly used to refer to DDH with inadequate coverage of the femoral head. In one study, 25% of hip replacements performed in patients aged ≤ 40 years were due to underlying hip dysplasia.⁷

Developmental dysplasia of the hip occurs more often in children who present in the breech position.⁸ One theory argues that packaging issues in utero may account for the increased incidence of DDH.⁹ The earliest recorded attempts at hip replacement occurred in Germany, in 1891, when ivory was used to replace the femoral heads of patients whose hip joints had been destroyed by tuberculosis.¹

 

The orthopedic surgeon Sir John Charnley, who worked at the Manchester Royal Infirmary, is considered the father of the modern THA.¹ His low friction arthroplasty, designed in the early 1960s is identical, in principle, to the M-on-PE prosthesis used today.¹ The PE liner used was ultrahigh molecular weight polyethylene (UHMWPE).¹

Due to the early success of the Charnley prosthesis, the M-on-PE prosthesis became the most widely used. Although PE is the most studied and understood of all acetabular liner materials, it will eventually wear and shed debris. Acetabular cup wear is the most frequent reason for mid-to-long-term revisions, especially in young and active patients.¹⁰ More active patients shed more debris.³ The PE debris instigates the release of inflammatory mediators, which results in chronic inflammation and tissue damage that erodes the supporting bone and can lead to implant loosening or fracture.⁶ Ongoing studies seek to optimize and improve properties of the UHMWPE and to develop alternative bearings. After FDA approval in 1999, highly cross-linked polyethylene liners (HXLPE) rapidly became the standard of care for THAs, at least in the U.S.¹¹ Highly cross-linked polyethylene liners are created from UHMWPE through a process of cross-linking by exposure to gamma radiation, and subsequent heat treatment to neutralize free radicals and limit oxidative degradation.¹²

In one study, the 5-year annual linear wear rate for a HXLPE liner was only 45% of that seen with the UHMWPE liner, although the qualitative wear pattern was the same.¹³ In a study that followed patients for 7 years postoperatively, the mean steady-state wear rate of the HXLPE was 0.005 mm/y compared with 0.037 mm/y for UHMWPE.¹⁴ In a long-term study (a minimum follow-up of 10 years) of 50 patients who were aged < 50 years and underwent THA using HXLPE liners, there was no radiographic evidence of osteolysis or component loosening, and liner wear was 0.020 ± 0.0047 mm/y.¹² In 2005, second-generation HXLPE liners were introduced clinically and have been shown to further reduce wear in vitro compared with both UHMWPE and first-generation HXLPE liners. Callary and colleagues calculated that the wear rates between 1 year and 5 years were all < 0.001 mm/y.¹⁵

The use of ceramic for THAs began in 1970, and ceramic heads on polyethylene (C-on-PE) liners and ceramic-on-ceramic (C-on-C) bearings have been in continual use for > 30 years in Europe. Premarket FDA approval based on European data was granted in 1983; however, the manufacturer voluntarily removed it from the market because of a high incidence of stem loosening (> 30% within 3 years in some series).¹⁶ FDA approvals came much later for C-on-PE (1989) and C-on-C (2003) bearings.

Ceramic is the hardest implant material used, and it can be concluded from many clinical and laboratory reports that C-on-PE and C-on-C combinations confer a potentially significant reduction in wear on THA bearings.¹⁶ Ceramic hips initially had 2 concerns: catastrophic shattering and squeaking. Current ceramic hips have been substantially improved, and some experts feel shattering has been essentially eliminated.¹⁶ Other experts note that ceramic brittleness remains a major concern.¹⁷ Squeaking remains a problem for some, but it usually abates over time. No study has correlated squeaking with impending failure or increased pain or disability.

While C-on-C bearings are now felt to be a good implant for young active patients, these bearings have generally not resulted in significantly lower wear rates and fewer revisions.¹⁸ High rates of wear and osteolysis have been sporadically documented over the 35-year history of ceramic implants.¹⁶ The FDA approved the first ceramic-on-metal total hip replacement system on June 13, 2011.

Metal-on-metal (M-on-M) implants have been used by some for decades, although they were not approved by the FDA until the late 1990s. However, some device recalls have brought negative attention to M-on-M implants.¹⁹ It was felt that they would generate less wear debris than PE, but reports of pseudotumors (from inflammatory mediators) and metallosis have significantly tempered enthusiasm for these products.^20,21 The wear rates are very low, estimated to be only 0.01 mm/y, but concerns about the carcinogenetic potential of systemically increased metal ions remains a possible and much debated concern.^19,22,23 In January 2013, FDA issued a safety communication on M-on-M implants.

Many experts feel that modern ceramic or metal on second-generation HXLPE represents the gold standard and the most predictable bearing choice for young, active patients.¹⁸ Others feel that the optimal choice of bearing surfaces in THA, particularly in the younger and more active patient, remains controversial.²⁴

Follow-Up

Intermittent orthopedic monitoring is recommended for all patients who have undergone a THA. The frequency of hip X-rays on follow-up appointments is left to the orthopedic surgeon. After the initial recovery, serial images every 2 to 5 years can identify progressive failure, and annual X-rays may be used for closer follow-up in high-risk patients.

 

Patients who experience dislocations, fractures, infections, or pain usually maintain close orthopedic follow-up. Significant wear of the prosthesis damages the socket; osteolysis can cause irreversible bone loss, fracture, and loosening. Massive acetabular bone loss is very difficult to reverse and creates major reconstruction challenges.

Figure 1A is a 2009 X-ray of a woman aged 44 years who underwent a THA after a motor vehicle accident in 1997 and who was advised to have a revision THA when seen in 2009.

The X-ray revealed significant wear of the acetabular liner. Unfortunately, the patient was lost to follow-up, and when she returned 5 years later, she had severe pain and was unable to walk. Figure 1B shows that the patient’s femoral head had broken through the acetabular component. She had massive bone loss that required a complex revision and bone grafting. (Figure 1C). Operative findings included severe metal debris from socket damage (Figure 2).

Asymptomatic patients can generate significant wear and debris and may experience osteolysis. A revision hip arthroplasty may be needed to prevent long-term damage. Routine surveillance can detect these issues and allow intervention at a time when the simplest revision could be performed. Eccentric alignment of the femoral head in the acetabular cup suggests wear or breakdown of the liner and increases the likelihood of instability or dislocation. In advanced cases, plain radiographs may show osteolysis in the surrounding bone.

Figure 3A is an X-ray of a man aged 71 years who had undergone THA 21 years earlier and had complied with routine follow-up. When his X-rays showed significant wear of the liner and some osteolysis, he was able to undergo a simple revision (Figure 3B).

Three-dimensional CT is useful for quantifying the presence and severity of osteolytic lesions, because plain radiographs may underestimate the amount of bone loss that is present.²⁵ The CT in Figure 3C shows the magnitude of osteolysis that was underestimated by the preoperative plain X-rays (Figure 3A). Computed tomography scans are crucial for surgical planning in the setting of severe acetabular bone loss.

There is a wide spectrum of signs and symptoms that can occur in the setting of acetabular component failure. Pain is a common presenting symptom. Groin pain can represent acetabular failure; thigh pain may be correlated to femoral component failure.²⁵ The clinical patient presentation ultimately depends on the underlying cause: an infection, polyethylene wear, instability, or aseptic loosening.²⁵ Leg-length discrepancy, joint deformity, location of prior incisions, functional status, and baseline neurologic status should be evaluated and documented during the preoperative evaluation as well.²⁵

Case Study Revision Options

The X-rays and CT scans for this case study patient showed that he was a possible candidate for the simplest revision surgery; an isolated liner exchange and replacement of the femoral head. When the original surgery was performed (1997), the only FDA approved PE liner was UHMWPE. To justify isolated liner exchange, the modular acetabular metallic shell also should be well-fixed and appropriately oriented.²⁶ This is evaluated both preoperatively and intraoperatively.

If found to be well fixed with an appropriate orientation and locking mechanism, the UHMWPE liner could be replaced with a HXLPE liner and a larger metal femoral head for improved wear and stability. Acetabular revision is indicted for an asymptomatic patient who has progressive osteolysis, severe wear, or bone loss that would compromise future reconstruction.

Conclusions

Over the past several decades, THA has become recognized as an effective treatment option for the reduction of pain and disability associated with hip joint disease and is associated with successful clinical outcomes. The most frequently noted recommendations for trying to increase the life expectancy of an artificial hip replacement include maintaining a normal weight, keeping leg muscles strong, and avoiding repetitive squatting and kneeling.

As the number of primary THAs has increased and the average age of those undergoing a primary THA has decreased, the need for revisions has risen. Reviews have demonstrated that the most common causes for early total hip revision, regardless of component, included infection, instability/dislocation, and fracture, whereas wear is the most common reason for mid to late revisions.

The wear of all materials used has been shown to be greatest in the most active patients.

Studies continue to identify ways to potentially prevent or reverse osteolysis from wear debris. Alendronate therapy has been shown to prevent and treat PE debris-induced periprosthetic bone loss in rats.²⁷ It also was successfully used in a case report of an asymptomatic woman aged 39 years who had rapid PE wear and aggressive periprosthetic osteolysis within just 2 years of a bilateral THA.²⁸ Other areas of research on decreasing osteolysis in THA recipients include trials with mesenchymal stem cells, bone morphogenic proteins, and gene therapy.⁶

In the U.S., 46,000 revisions were performed in 2004 and this number is expected to more than double by 2030.⁴ Primary care providers are sure to encounter patients who will be in need of a hip revision procedure. It’s important for them to make sure that their patients who have undergone a THA are periodically seen for orthopedic follow-up. Despite the long history of primary THAs, there is still not a single technique and material to suit all patient characteristics.¹ Unfortunately, the same currently applies to hip revision procedures.

Total hip arthroplasty (THA) is considered to be one of the most successful orthopedic interventions of its generation.¹ In 2010, 332,000 THAs were performed in the U.S.² Although used to correct advanced joint diseases in the elderly, the THA procedure has become increasingly common in a younger population for posttraumatic fractures and conditions that lead to early onset secondary arthritis such as avascular necrosis, juvenile rheumatoid arthritis, hip dysplasia, Perthes disease, and femoro-acetabular impingement.

Current hip replacements are expected to function at least 10 to 20 years in 90% of patients.³ As increasing numbers of young patients have these procedures and as seniors continue to live longer, patients will outlast their implants. Younger and more active patients have a higher rate of revision, because the longevity of the prosthesis is usually a function of usage.³ The number of revision THAs is projected to increase 137% by 2030.⁴

Hip resurfacing has been developed as a bone preserving surgical alternative to THA. The first system for use in the U.S. received FDA approval in 2006, but concerns about the metal on metal bearing surfaces, high failure and revision rates, and early catastrophic modes of failure compared with THAs has resulted in the recall of many of these devices. Hip resurfacing may offer some advantages compared with those of a THA in a carefully selected population, but its use will not be further discussed in this case study.⁵ Periprosthetic osteolysis and aseptic loosening are 2 of the long-term consequences of THA.⁶ Bone loss is felt to be secondary to a biologic reaction to particulate debris from implants.⁶ Some patients, especially those with loosening, complete wear, or fracture, will be symptomatic with pain. However, wear and osteolysis is a silent disease unless there is mechanical failure. Other patients may not experience discomfort. Radiographic studies may reveal significant changes, which warrant the recommendation for a hip revision.

Hip revision surgery has 3 major purposes: relieving pain in the affected joint, restoring the patient’s mobility, and removing a loose or damaged prosthesis before irreversible harm is done to the joint. It’s anticipated that most primary care providers (PCPs) will encounter patients who seek advice on the need for a revision hip arthroplasty.

This case will present an asymptomatic patient who underwent a THA in 1997 at age 37, to address developmental dysplasia of the hip (DDH) and was advised to undergo a revision hip arthroplasty due to abnormal radiographic findings at age 55 years. A discussion will follow that includes a brief review of the history of THA, the materials and bearings commonly used, the presenting symptoms or radiographic changes that signal the need for a revision, and the current options available for a patient such as this.

Case Report

A man aged 55 years presented to a new orthopedic surgeon for his first orthopedic appointment in 10 years. The patient had a left metal-on-polyethylene (M-on-PE) THA 18 years prior due to early onset secondary degenerative joint disease from DDH. The patient’s M-on-PE THA was a titanium acetabular socket and femoral stem with a cobalt-chromium alloy femoral head and a polyethylene liner. The patient remained physically active with an exercise routine consisting of walking, swimming, and weight training.

The patient’s orthopedic history was notable for a right knee arthroscopy for intervention due to a torn medial and lateral meniscus, and birth history was noteworthy for a breech presentation. The physical exam was unremarkable except for a slight leg length discrepancy, but the patient did not exhibit a Trendelenburg gait.

Plain X-rays and a computed tomography (CT) scan showed eccentric PE wear and superior migration of the femoral head, which was indicative of significant PE liner wear. No significant osteolysis or periprosthetic loosening was observed on the X-rays or CT scan. He was advised that a hip revision procedure would need to be done, optimally, within the next 6 months to a year.

Discussion

Hip dysplasia represents a broad group of disorders and generally means abnormal development of the hip joint. The term is most commonly used to refer to DDH with inadequate coverage of the femoral head. In one study, 25% of hip replacements performed in patients aged ≤ 40 years were due to underlying hip dysplasia.⁷

Developmental dysplasia of the hip occurs more often in children who present in the breech position.⁸ One theory argues that packaging issues in utero may account for the increased incidence of DDH.⁹ The earliest recorded attempts at hip replacement occurred in Germany, in 1891, when ivory was used to replace the femoral heads of patients whose hip joints had been destroyed by tuberculosis.¹

 

The orthopedic surgeon Sir John Charnley, who worked at the Manchester Royal Infirmary, is considered the father of the modern THA.¹ His low friction arthroplasty, designed in the early 1960s is identical, in principle, to the M-on-PE prosthesis used today.¹ The PE liner used was ultrahigh molecular weight polyethylene (UHMWPE).¹

Due to the early success of the Charnley prosthesis, the M-on-PE prosthesis became the most widely used. Although PE is the most studied and understood of all acetabular liner materials, it will eventually wear and shed debris. Acetabular cup wear is the most frequent reason for mid-to-long-term revisions, especially in young and active patients.¹⁰ More active patients shed more debris.³ The PE debris instigates the release of inflammatory mediators, which results in chronic inflammation and tissue damage that erodes the supporting bone and can lead to implant loosening or fracture.⁶ Ongoing studies seek to optimize and improve properties of the UHMWPE and to develop alternative bearings. After FDA approval in 1999, highly cross-linked polyethylene liners (HXLPE) rapidly became the standard of care for THAs, at least in the U.S.¹¹ Highly cross-linked polyethylene liners are created from UHMWPE through a process of cross-linking by exposure to gamma radiation, and subsequent heat treatment to neutralize free radicals and limit oxidative degradation.¹²

In one study, the 5-year annual linear wear rate for a HXLPE liner was only 45% of that seen with the UHMWPE liner, although the qualitative wear pattern was the same.¹³ In a study that followed patients for 7 years postoperatively, the mean steady-state wear rate of the HXLPE was 0.005 mm/y compared with 0.037 mm/y for UHMWPE.¹⁴ In a long-term study (a minimum follow-up of 10 years) of 50 patients who were aged < 50 years and underwent THA using HXLPE liners, there was no radiographic evidence of osteolysis or component loosening, and liner wear was 0.020 ± 0.0047 mm/y.¹² In 2005, second-generation HXLPE liners were introduced clinically and have been shown to further reduce wear in vitro compared with both UHMWPE and first-generation HXLPE liners. Callary and colleagues calculated that the wear rates between 1 year and 5 years were all < 0.001 mm/y.¹⁵

The use of ceramic for THAs began in 1970, and ceramic heads on polyethylene (C-on-PE) liners and ceramic-on-ceramic (C-on-C) bearings have been in continual use for > 30 years in Europe. Premarket FDA approval based on European data was granted in 1983; however, the manufacturer voluntarily removed it from the market because of a high incidence of stem loosening (> 30% within 3 years in some series).¹⁶ FDA approvals came much later for C-on-PE (1989) and C-on-C (2003) bearings.

Ceramic is the hardest implant material used, and it can be concluded from many clinical and laboratory reports that C-on-PE and C-on-C combinations confer a potentially significant reduction in wear on THA bearings.¹⁶ Ceramic hips initially had 2 concerns: catastrophic shattering and squeaking. Current ceramic hips have been substantially improved, and some experts feel shattering has been essentially eliminated.¹⁶ Other experts note that ceramic brittleness remains a major concern.¹⁷ Squeaking remains a problem for some, but it usually abates over time. No study has correlated squeaking with impending failure or increased pain or disability.

While C-on-C bearings are now felt to be a good implant for young active patients, these bearings have generally not resulted in significantly lower wear rates and fewer revisions.¹⁸ High rates of wear and osteolysis have been sporadically documented over the 35-year history of ceramic implants.¹⁶ The FDA approved the first ceramic-on-metal total hip replacement system on June 13, 2011.

Metal-on-metal (M-on-M) implants have been used by some for decades, although they were not approved by the FDA until the late 1990s. However, some device recalls have brought negative attention to M-on-M implants.¹⁹ It was felt that they would generate less wear debris than PE, but reports of pseudotumors (from inflammatory mediators) and metallosis have significantly tempered enthusiasm for these products.^20,21 The wear rates are very low, estimated to be only 0.01 mm/y, but concerns about the carcinogenetic potential of systemically increased metal ions remains a possible and much debated concern.^19,22,23 In January 2013, FDA issued a safety communication on M-on-M implants.

Many experts feel that modern ceramic or metal on second-generation HXLPE represents the gold standard and the most predictable bearing choice for young, active patients.¹⁸ Others feel that the optimal choice of bearing surfaces in THA, particularly in the younger and more active patient, remains controversial.²⁴

Follow-Up

Intermittent orthopedic monitoring is recommended for all patients who have undergone a THA. The frequency of hip X-rays on follow-up appointments is left to the orthopedic surgeon. After the initial recovery, serial images every 2 to 5 years can identify progressive failure, and annual X-rays may be used for closer follow-up in high-risk patients.

 

Patients who experience dislocations, fractures, infections, or pain usually maintain close orthopedic follow-up. Significant wear of the prosthesis damages the socket; osteolysis can cause irreversible bone loss, fracture, and loosening. Massive acetabular bone loss is very difficult to reverse and creates major reconstruction challenges.

Figure 1A is a 2009 X-ray of a woman aged 44 years who underwent a THA after a motor vehicle accident in 1997 and who was advised to have a revision THA when seen in 2009.

The X-ray revealed significant wear of the acetabular liner. Unfortunately, the patient was lost to follow-up, and when she returned 5 years later, she had severe pain and was unable to walk. Figure 1B shows that the patient’s femoral head had broken through the acetabular component. She had massive bone loss that required a complex revision and bone grafting. (Figure 1C). Operative findings included severe metal debris from socket damage (Figure 2).

Asymptomatic patients can generate significant wear and debris and may experience osteolysis. A revision hip arthroplasty may be needed to prevent long-term damage. Routine surveillance can detect these issues and allow intervention at a time when the simplest revision could be performed. Eccentric alignment of the femoral head in the acetabular cup suggests wear or breakdown of the liner and increases the likelihood of instability or dislocation. In advanced cases, plain radiographs may show osteolysis in the surrounding bone.

Figure 3A is an X-ray of a man aged 71 years who had undergone THA 21 years earlier and had complied with routine follow-up. When his X-rays showed significant wear of the liner and some osteolysis, he was able to undergo a simple revision (Figure 3B).

Three-dimensional CT is useful for quantifying the presence and severity of osteolytic lesions, because plain radiographs may underestimate the amount of bone loss that is present.²⁵ The CT in Figure 3C shows the magnitude of osteolysis that was underestimated by the preoperative plain X-rays (Figure 3A). Computed tomography scans are crucial for surgical planning in the setting of severe acetabular bone loss.

There is a wide spectrum of signs and symptoms that can occur in the setting of acetabular component failure. Pain is a common presenting symptom. Groin pain can represent acetabular failure; thigh pain may be correlated to femoral component failure.²⁵ The clinical patient presentation ultimately depends on the underlying cause: an infection, polyethylene wear, instability, or aseptic loosening.²⁵ Leg-length discrepancy, joint deformity, location of prior incisions, functional status, and baseline neurologic status should be evaluated and documented during the preoperative evaluation as well.²⁵

Case Study Revision Options

The X-rays and CT scans for this case study patient showed that he was a possible candidate for the simplest revision surgery; an isolated liner exchange and replacement of the femoral head. When the original surgery was performed (1997), the only FDA approved PE liner was UHMWPE. To justify isolated liner exchange, the modular acetabular metallic shell also should be well-fixed and appropriately oriented.²⁶ This is evaluated both preoperatively and intraoperatively.

If found to be well fixed with an appropriate orientation and locking mechanism, the UHMWPE liner could be replaced with a HXLPE liner and a larger metal femoral head for improved wear and stability. Acetabular revision is indicted for an asymptomatic patient who has progressive osteolysis, severe wear, or bone loss that would compromise future reconstruction.

Conclusions

Over the past several decades, THA has become recognized as an effective treatment option for the reduction of pain and disability associated with hip joint disease and is associated with successful clinical outcomes. The most frequently noted recommendations for trying to increase the life expectancy of an artificial hip replacement include maintaining a normal weight, keeping leg muscles strong, and avoiding repetitive squatting and kneeling.

As the number of primary THAs has increased and the average age of those undergoing a primary THA has decreased, the need for revisions has risen. Reviews have demonstrated that the most common causes for early total hip revision, regardless of component, included infection, instability/dislocation, and fracture, whereas wear is the most common reason for mid to late revisions.

The wear of all materials used has been shown to be greatest in the most active patients.

Studies continue to identify ways to potentially prevent or reverse osteolysis from wear debris. Alendronate therapy has been shown to prevent and treat PE debris-induced periprosthetic bone loss in rats.²⁷ It also was successfully used in a case report of an asymptomatic woman aged 39 years who had rapid PE wear and aggressive periprosthetic osteolysis within just 2 years of a bilateral THA.²⁸ Other areas of research on decreasing osteolysis in THA recipients include trials with mesenchymal stem cells, bone morphogenic proteins, and gene therapy.⁶

In the U.S., 46,000 revisions were performed in 2004 and this number is expected to more than double by 2030.⁴ Primary care providers are sure to encounter patients who will be in need of a hip revision procedure. It’s important for them to make sure that their patients who have undergone a THA are periodically seen for orthopedic follow-up. Despite the long history of primary THAs, there is still not a single technique and material to suit all patient characteristics.¹ Unfortunately, the same currently applies to hip revision procedures.

Chronic conditions contribute to increasing health care expenditures, and a small number of patients with chronic medical conditions consume a disproportionately larger amount of health care resources.^1,2 Naessens and colleagues showed that 2.6% of adult patients accounted for 20.7% of all primary care clinic visits during a calendar year.² These high-risk patients may be using much of the health care resources but have unmet needs even with the increased amount of health care services they receive.

The impact of interprofessional forms of chronic disease management on patient outcomes is unclear.^3-5 Definitions for high-risk patients and interprofessional care are broad, making comparison of studies difficult. In a team setting, it is difficult to discern the exact contributions of a single member of the team. Katon and colleagues concluded in a randomized, controlled trial that a nurse care manager collaborative treatment program added additional depression-free days and quality-adjusted life-years in adults with depression and poorly controlled diabetes mellitus (DM), coronary artery disease, or both.³ The intervention also resulted in improvements in a composite outcome of hemoglobin A_1c (A_1c), low-densitylipoprotein cholesterol, systolic blood pressure (BP) levels, and depression symptoms at 12 months, but these improvements were not sustained at 24 months.^3,4

A study looked at interprofessional team care provided by primary care internal medicine residents, nurse practitioner students, and pharmacy students, compared with usual care by only internal medicine residents. The study showed improvements in patient assessments and a trend toward the decreased use of urgent care in patients with type 2 DM over 18 months but no significant improvements in A_1c or BP values.⁵ The impact of pharmacists participating in team-based care and patient-centered medical home models has also been shown to be positive regarding metabolic parameters.^6,7Patient aligned care teams (PACT), the VA patient-centered medical home model initiative, seek to optimize patient care through provision of interprofessional, team-based care. At the Boise VAMC in Idaho, PACT training occurs at a primary care academic training clinic that includes 40 primary care providers, supervisors, and trainees in internal medicine, nurse practitioner programs, pharmacy, and behavioral health.

The Boise VAMC is also 1 of 5 VA Centers of Excellence in Primary Care Education (CoEPCE), institutions that prepare health care trainees from many disciplines to participate in interprofessional PACTs, provide patient-centered, team-based care, and learn and understand the roles of other team members.⁸ This VAMC CoEPCE, implemented in 2010, is an academic partnership with area professional schools of medicine, nursing, and pharmacy.

Team-Based Care

At the Boise VAMC CoEPCE, primary care trainees are taught a team-based approach to providing more effective care for high-risk patients through a complex curriculum that includes interprofessional case conferences called PACT interprofessional care updates (ICU). During these case conferences, high-risk patients on a primary care trainee’s panel are presented to an interprofessional group of health care professionals (HCPs) for recommendations to improve care. Trainees from the various disciplines participate in these PACT ICU presentations during time spent rotating through the institution’s academic clinic.

The CoEPCE activities include PACT ICU, interprofessional didactic sessions, and provision of primary care to patients in an interprofessional clinic. Physician trainees participate in one-half day per week of ambulatory didactics and conferences during a 2-week clinic block, which occurs every 2 months. Other health care disciplines participate in PACT ICU during longitudinal experiences (ranging from 4 to 12 months) in the primary care training clinic throughout the academic year.

The PACT ICU case conferences occur weekly at the academic clinic with 2 patient cases presented and discussed at each meeting. Prior to each conference, a primary care trainee, generally an internal medicine resident, is given a list of the top 5 high-risk patients from their panel, determined by a care assessment needs score that is based on high health care use and risk of hospitalization or death within 90 days. To determine care assessment needs scores, patient electronic health records (EHRs) are scanned weekly to review more than 150 data elements, including vital signs; recent clinic, urgent care, and emergency department (ED) visits; medications; laboratory values; and the number and types of illnesses. Statistical analyses are run on the EHR data to provide up-to-date estimates of likelihood of hospital admission or death.

Trainees may also select any patient on their panel whose health care they feel would benefit from a case conference discussion. The trainee presents all medical and social problems related to the selected patient to a team of HCPs, including other trainees and their supervisors, from multiple different disciplines, such as medicine, nursing, pharmacy, behavioral health, and social work. The interprofessional team then provides recommendations.

 

A care plan is developed by the group to implement as appropriate. The care plan may consist of various recommendations from the different disciplines, such as consults to a pharmacist for medication review or medication management, referrals to social work to coordinate care with home health services, or asking the nurse care manager to follow up with a patient by phone on a more regular basis. Trainees are encouraged to use alternate forms of care, including team-based care from other health care disciplines as well as other methods of communication, such as secure electronic messaging to increase access.

Interprofessional patient case conferences could offer another tool for HCPs to improve the care of high-risk patients through team-based efforts if the effect on patient outcomes or health care use is beneficial. The objective of this study was to evaluate the relationship of interprofessional case conferences and A_1c levels in high-risk patients with DM and BP measurements in patients with hypertension whose case was discussed at PACT ICU case conferences at the Boise VAMC. The authors hypothesized that the PACT ICU presentation intervention would lead to improved metabolic parameters as care plans were implemented. This evaluation is a subset of a larger study assessing the impact of PACT ICU presentation on various patient, trainee, and team level outcomes.

Methods

This study was a retrospective, observational analysis of patients seen at the Boise VAMC academic clinic whose cases were discussed at PACT ICU case conferences from January 2013 to April 2014. For the analysis of A_1c values, patients must have been discussed at a PACT ICU presentation during the study time period and had a diagnosis of DM in the EHR. Those included must have A_1c results in the EHR before and after the patient case presentation. The most recent A_1c measured prior to presentation was chosen as the prepresentation value. The next measured value 2 to 6 months after the case presentation date was chosen as the postpresentation value. This was chosen as the postpresentation value because it may be more indicative of the impact of the PACT ICU care plan. An A_1c measured at least 2 months following the case conference intervention was chosen to allow all possible measurements to be included in the analysis, according to usual care for measuring A_1c at the clinic. The primary outcome was the mean change in A_1c values pre- and post-PACT ICU presentation.

Blood pressure analyses were included if patients had a diagnosis of hypertension in the EHR as well as recorded BP values measured during the 6 months prior to PACT ICU presentation and 1 to 6 months after presentation. Blood pressure values were limited to 1 to 6 months after presentation to be more suggestive of the case conference care plan impact. Blood pressure measured during hospitalizations, urgent care, or ED visits were excluded from the analysis. The primary outcome in the BP analysis was the mean change in systolic and diastolic BP pre- and post-PACT ICU presentation. The mean of all in-clinic BP measurements was calculated as the prepresentation value and compared with the mean of all postpresentation BP measurements in the designated time period.

Assessment of DM or hypertension control was not a factor for inclusion in the study. The types of interventions and recommendations resulting from the case conferences were not evaluated.

Statistical analysis included paired t tests comparing mean values before and after PACT ICU presentation, with an a priori level for finding a significant difference at 0.05. This study was approved as expedited research by the institutional review board associated with the Boise VAMC.

Results

During the study period, 65 patients were discussed at a PACT ICU case conferences (Figure). The average age was 67 years, and 89% of patients were male. Of these patients, 32 had a DM diagnosis. A total of 12 patients had A_1c values within the parameters specified for this study and were included in the final analysis for the A_1c group.

The mean A_1c value for patients before PACT ICU presentation was 8.5% (SD 2.11). After presentation, the mean A_1c decreased to 7.9% (-0.6%, SD 1.32, P = .10; Table 1).

Of all patients discussed at a PACT ICU case conference, 52 had a diagnosis of hypertension (Table 2).

A total of 45 patients were included in the final BP analysis. The mean systolic BP prior to PACT ICU presentation was 134 mm Hg (SD 20.3), which decreased to 132.2 mm Hg (SD 21.6) following PACT ICU presentation (P = .23). Mean diastolic BP prepresentation was 81 mm Hg (SD 17.1) and 80.6 mm Hg (SD 16.8) postpresentation (P = .40).

 

Discussion

High-risk patients with DM enrolled in this primary care academic clinic and discussed at interprofessional case conferences did not have a statistically significant change in A_1c values following the case conferences. There was also no statistically significant change in systolic and diastolic BP measurements following PACT ICU case conferences in high-risk patients with hypertension. The relationship between PACT ICU presentations and patient outcomes may not be direct, but the potential to decrease A_1c values by 0.6% may be of clinical benefit to patients enrolled at the Boise VAMC academic clinic.

The results of this study are comparable with other studies where the impact of interprofessional forms of care on patient outcomes such as A_1c and BP is not as apparent.^3-5 The patients included in this study were high-risk compared with other patients, and patient outcome goals for DM and hypertension management according to clinical practice guidelines may be less stringent for these patients.^9-11

Interprofessional case conferences are being used at the Boise VAMC academic clinic to teach primary care trainees how to improve care for patients by working on teams, with a goal of promoting alternate forms of health care. Referrals of patients to pharmacy services for chronic disease management may result from these case conferences, and patients could benefit from pharmacy review and management of medications for the treatment of DM and hypertension. There may be other advantages to patients and to the health system in the form of more appropriate health care use, increased contact with providers, and use of other health care resources to decrease costs and medication burden, although these are speculative at this time.

Limitations

This study had several limitations. The patients included in this study were high-risk patients seen by primary care trainees at the Boise VAMC academic clinic, and a small number of patients were included in the final analysis, limiting the generalizability of the results to other patient populations. Finding a difference in A_1c and BP values before and after PACT ICU case conferences was also limited by the small number of patients who met inclusion criteria. Many patients included in the study also had reasonably controlled A_1c and BP levels prior to PACT ICU case conferences; therefore, a difference would be more difficult to determine.

The PACT ICU case conferences occur at one point in time, but the impact of the intervention and recommendations may take longer to appreciate. A longer study duration may be needed to determine differences in A_1c and BP values over time. Regression to the mean is also a possibility given the type of data collected. As each primary care trainee selects the patient to be discussed at a PACT ICU case conference, bias could also be present, because the provider may focus on patients with recent clinic visits or on patients who are the most difficult for the provider to manage or contact.

The Boise VAMC PACTs include many different health care disciplines; therefore, the institution may foster interprofessional, team-based care more easily compared with that of other health care systems. Trainees in the CoEPCE also are aware of other team members’ roles, and clinical pharmacists are currently part of PACTs at the institution. The idea of interprofessional case conferences may be simple, but the process at this institution requires time and effort from a nurse care manager who coordinates patient selection and information distribution and an attending physician supervisor who facilitates each case conference. The Boise VAMC also supports pharmacy chronic disease management services, and several of these patients with uncontrolled DM or resistant hypertension may have been seen by the pharmacy-managed insulin titration or hypertension clinics. Finally, there is also limited documentation of whether DM or hypertension management was discussed at the case conferences.

Despite the medical complexities seen in these patients, discussions during PACT ICU presentations may involve many social and behavioral interventions, and DM and hypertension issues may not be significant enough for review at a case conference. However, the intervention of PACT ICU case conferences encompassed a variety of care plans, and this study evaluated the impact of the entire discussion and recommendations and not any individual component. Other recommendations were not evaluated due to the wide variety of interventions that were potentially discussed, and a process for tracking these was not in place.

The results of this study did not show that the care plans that develop at PACT ICU case conferences impacted high-risk patients with DM or hypertension, likely due to small sample sizes (2 patient cases were discussed per week). The impact could be better determined through a larger sample size, longer duration, or assessment of patients whose disease was not controlled. The impact may also be more significant for individuals who benefit from the increased review and assessment of their chronic medical conditions and increased access to care.

 

Seeing a possible trend toward benefit in A_1c values in this short time frame helps support continuing and expanding case conferences at the Boise VAMC. The goals of these interprofessional case conferences include developing a proactive approach to identify high-risk patients to improve the care of these patients and increase use of more appropriate health care resources. Other outcomes currently being studied include the impact of PACT ICU presentations on health care use, the impact on alternate health care consult patterns, and trainee participant opinions. Future directions for the interprofessional case conferences include expansion to other nonacademic primary care teams. The benefit of PACT ICU case conferences also extends to the primary care trainees as they continue to learn how to best work with other HCPs as part of a team and how to use the resources available through these other health care disciplines.

Conclusions

Presentation at an interprofessional case conference was not associated with a statistically significant change in mean A_1c or BP values in a small group of high-risk patients at the Boise VAMC PACT academic clinic. Although there was a trend toward a decrease in A_1c values, it is difficult to determine whether there is a relation to the interprofessional case conferences. Interprofessional case conferences are still occurring at the Boise VAMC with efforts in place to incorporate concurrent PACT ICU outcomes data collection and further the educational goals of primary care trainees.

Acknowledgments
The authors would like to express their appreciation to Rick Tivis, MPH, and Tim Gordon, MA, MPH, MS, for their assistance in the analysis and collection of data for this study.

Chronic conditions contribute to increasing health care expenditures, and a small number of patients with chronic medical conditions consume a disproportionately larger amount of health care resources.^1,2 Naessens and colleagues showed that 2.6% of adult patients accounted for 20.7% of all primary care clinic visits during a calendar year.² These high-risk patients may be using much of the health care resources but have unmet needs even with the increased amount of health care services they receive.

The impact of interprofessional forms of chronic disease management on patient outcomes is unclear.^3-5 Definitions for high-risk patients and interprofessional care are broad, making comparison of studies difficult. In a team setting, it is difficult to discern the exact contributions of a single member of the team. Katon and colleagues concluded in a randomized, controlled trial that a nurse care manager collaborative treatment program added additional depression-free days and quality-adjusted life-years in adults with depression and poorly controlled diabetes mellitus (DM), coronary artery disease, or both.³ The intervention also resulted in improvements in a composite outcome of hemoglobin A_1c (A_1c), low-densitylipoprotein cholesterol, systolic blood pressure (BP) levels, and depression symptoms at 12 months, but these improvements were not sustained at 24 months.^3,4

A study looked at interprofessional team care provided by primary care internal medicine residents, nurse practitioner students, and pharmacy students, compared with usual care by only internal medicine residents. The study showed improvements in patient assessments and a trend toward the decreased use of urgent care in patients with type 2 DM over 18 months but no significant improvements in A_1c or BP values.⁵ The impact of pharmacists participating in team-based care and patient-centered medical home models has also been shown to be positive regarding metabolic parameters.^6,7Patient aligned care teams (PACT), the VA patient-centered medical home model initiative, seek to optimize patient care through provision of interprofessional, team-based care. At the Boise VAMC in Idaho, PACT training occurs at a primary care academic training clinic that includes 40 primary care providers, supervisors, and trainees in internal medicine, nurse practitioner programs, pharmacy, and behavioral health.

The Boise VAMC is also 1 of 5 VA Centers of Excellence in Primary Care Education (CoEPCE), institutions that prepare health care trainees from many disciplines to participate in interprofessional PACTs, provide patient-centered, team-based care, and learn and understand the roles of other team members.⁸ This VAMC CoEPCE, implemented in 2010, is an academic partnership with area professional schools of medicine, nursing, and pharmacy.

Team-Based Care

At the Boise VAMC CoEPCE, primary care trainees are taught a team-based approach to providing more effective care for high-risk patients through a complex curriculum that includes interprofessional case conferences called PACT interprofessional care updates (ICU). During these case conferences, high-risk patients on a primary care trainee’s panel are presented to an interprofessional group of health care professionals (HCPs) for recommendations to improve care. Trainees from the various disciplines participate in these PACT ICU presentations during time spent rotating through the institution’s academic clinic.

The CoEPCE activities include PACT ICU, interprofessional didactic sessions, and provision of primary care to patients in an interprofessional clinic. Physician trainees participate in one-half day per week of ambulatory didactics and conferences during a 2-week clinic block, which occurs every 2 months. Other health care disciplines participate in PACT ICU during longitudinal experiences (ranging from 4 to 12 months) in the primary care training clinic throughout the academic year.

The PACT ICU case conferences occur weekly at the academic clinic with 2 patient cases presented and discussed at each meeting. Prior to each conference, a primary care trainee, generally an internal medicine resident, is given a list of the top 5 high-risk patients from their panel, determined by a care assessment needs score that is based on high health care use and risk of hospitalization or death within 90 days. To determine care assessment needs scores, patient electronic health records (EHRs) are scanned weekly to review more than 150 data elements, including vital signs; recent clinic, urgent care, and emergency department (ED) visits; medications; laboratory values; and the number and types of illnesses. Statistical analyses are run on the EHR data to provide up-to-date estimates of likelihood of hospital admission or death.

Trainees may also select any patient on their panel whose health care they feel would benefit from a case conference discussion. The trainee presents all medical and social problems related to the selected patient to a team of HCPs, including other trainees and their supervisors, from multiple different disciplines, such as medicine, nursing, pharmacy, behavioral health, and social work. The interprofessional team then provides recommendations.

 

A care plan is developed by the group to implement as appropriate. The care plan may consist of various recommendations from the different disciplines, such as consults to a pharmacist for medication review or medication management, referrals to social work to coordinate care with home health services, or asking the nurse care manager to follow up with a patient by phone on a more regular basis. Trainees are encouraged to use alternate forms of care, including team-based care from other health care disciplines as well as other methods of communication, such as secure electronic messaging to increase access.

Interprofessional patient case conferences could offer another tool for HCPs to improve the care of high-risk patients through team-based efforts if the effect on patient outcomes or health care use is beneficial. The objective of this study was to evaluate the relationship of interprofessional case conferences and A_1c levels in high-risk patients with DM and BP measurements in patients with hypertension whose case was discussed at PACT ICU case conferences at the Boise VAMC. The authors hypothesized that the PACT ICU presentation intervention would lead to improved metabolic parameters as care plans were implemented. This evaluation is a subset of a larger study assessing the impact of PACT ICU presentation on various patient, trainee, and team level outcomes.

Methods

This study was a retrospective, observational analysis of patients seen at the Boise VAMC academic clinic whose cases were discussed at PACT ICU case conferences from January 2013 to April 2014. For the analysis of A_1c values, patients must have been discussed at a PACT ICU presentation during the study time period and had a diagnosis of DM in the EHR. Those included must have A_1c results in the EHR before and after the patient case presentation. The most recent A_1c measured prior to presentation was chosen as the prepresentation value. The next measured value 2 to 6 months after the case presentation date was chosen as the postpresentation value. This was chosen as the postpresentation value because it may be more indicative of the impact of the PACT ICU care plan. An A_1c measured at least 2 months following the case conference intervention was chosen to allow all possible measurements to be included in the analysis, according to usual care for measuring A_1c at the clinic. The primary outcome was the mean change in A_1c values pre- and post-PACT ICU presentation.

Blood pressure analyses were included if patients had a diagnosis of hypertension in the EHR as well as recorded BP values measured during the 6 months prior to PACT ICU presentation and 1 to 6 months after presentation. Blood pressure values were limited to 1 to 6 months after presentation to be more suggestive of the case conference care plan impact. Blood pressure measured during hospitalizations, urgent care, or ED visits were excluded from the analysis. The primary outcome in the BP analysis was the mean change in systolic and diastolic BP pre- and post-PACT ICU presentation. The mean of all in-clinic BP measurements was calculated as the prepresentation value and compared with the mean of all postpresentation BP measurements in the designated time period.

Assessment of DM or hypertension control was not a factor for inclusion in the study. The types of interventions and recommendations resulting from the case conferences were not evaluated.

Statistical analysis included paired t tests comparing mean values before and after PACT ICU presentation, with an a priori level for finding a significant difference at 0.05. This study was approved as expedited research by the institutional review board associated with the Boise VAMC.

Results

During the study period, 65 patients were discussed at a PACT ICU case conferences (Figure). The average age was 67 years, and 89% of patients were male. Of these patients, 32 had a DM diagnosis. A total of 12 patients had A_1c values within the parameters specified for this study and were included in the final analysis for the A_1c group.

The mean A_1c value for patients before PACT ICU presentation was 8.5% (SD 2.11). After presentation, the mean A_1c decreased to 7.9% (-0.6%, SD 1.32, P = .10; Table 1).

Of all patients discussed at a PACT ICU case conference, 52 had a diagnosis of hypertension (Table 2).

A total of 45 patients were included in the final BP analysis. The mean systolic BP prior to PACT ICU presentation was 134 mm Hg (SD 20.3), which decreased to 132.2 mm Hg (SD 21.6) following PACT ICU presentation (P = .23). Mean diastolic BP prepresentation was 81 mm Hg (SD 17.1) and 80.6 mm Hg (SD 16.8) postpresentation (P = .40).

 

Discussion

High-risk patients with DM enrolled in this primary care academic clinic and discussed at interprofessional case conferences did not have a statistically significant change in A_1c values following the case conferences. There was also no statistically significant change in systolic and diastolic BP measurements following PACT ICU case conferences in high-risk patients with hypertension. The relationship between PACT ICU presentations and patient outcomes may not be direct, but the potential to decrease A_1c values by 0.6% may be of clinical benefit to patients enrolled at the Boise VAMC academic clinic.

The results of this study are comparable with other studies where the impact of interprofessional forms of care on patient outcomes such as A_1c and BP is not as apparent.^3-5 The patients included in this study were high-risk compared with other patients, and patient outcome goals for DM and hypertension management according to clinical practice guidelines may be less stringent for these patients.^9-11

Interprofessional case conferences are being used at the Boise VAMC academic clinic to teach primary care trainees how to improve care for patients by working on teams, with a goal of promoting alternate forms of health care. Referrals of patients to pharmacy services for chronic disease management may result from these case conferences, and patients could benefit from pharmacy review and management of medications for the treatment of DM and hypertension. There may be other advantages to patients and to the health system in the form of more appropriate health care use, increased contact with providers, and use of other health care resources to decrease costs and medication burden, although these are speculative at this time.

Limitations

This study had several limitations. The patients included in this study were high-risk patients seen by primary care trainees at the Boise VAMC academic clinic, and a small number of patients were included in the final analysis, limiting the generalizability of the results to other patient populations. Finding a difference in A_1c and BP values before and after PACT ICU case conferences was also limited by the small number of patients who met inclusion criteria. Many patients included in the study also had reasonably controlled A_1c and BP levels prior to PACT ICU case conferences; therefore, a difference would be more difficult to determine.

The PACT ICU case conferences occur at one point in time, but the impact of the intervention and recommendations may take longer to appreciate. A longer study duration may be needed to determine differences in A_1c and BP values over time. Regression to the mean is also a possibility given the type of data collected. As each primary care trainee selects the patient to be discussed at a PACT ICU case conference, bias could also be present, because the provider may focus on patients with recent clinic visits or on patients who are the most difficult for the provider to manage or contact.

The Boise VAMC PACTs include many different health care disciplines; therefore, the institution may foster interprofessional, team-based care more easily compared with that of other health care systems. Trainees in the CoEPCE also are aware of other team members’ roles, and clinical pharmacists are currently part of PACTs at the institution. The idea of interprofessional case conferences may be simple, but the process at this institution requires time and effort from a nurse care manager who coordinates patient selection and information distribution and an attending physician supervisor who facilitates each case conference. The Boise VAMC also supports pharmacy chronic disease management services, and several of these patients with uncontrolled DM or resistant hypertension may have been seen by the pharmacy-managed insulin titration or hypertension clinics. Finally, there is also limited documentation of whether DM or hypertension management was discussed at the case conferences.

Despite the medical complexities seen in these patients, discussions during PACT ICU presentations may involve many social and behavioral interventions, and DM and hypertension issues may not be significant enough for review at a case conference. However, the intervention of PACT ICU case conferences encompassed a variety of care plans, and this study evaluated the impact of the entire discussion and recommendations and not any individual component. Other recommendations were not evaluated due to the wide variety of interventions that were potentially discussed, and a process for tracking these was not in place.

The results of this study did not show that the care plans that develop at PACT ICU case conferences impacted high-risk patients with DM or hypertension, likely due to small sample sizes (2 patient cases were discussed per week). The impact could be better determined through a larger sample size, longer duration, or assessment of patients whose disease was not controlled. The impact may also be more significant for individuals who benefit from the increased review and assessment of their chronic medical conditions and increased access to care.

 

Seeing a possible trend toward benefit in A_1c values in this short time frame helps support continuing and expanding case conferences at the Boise VAMC. The goals of these interprofessional case conferences include developing a proactive approach to identify high-risk patients to improve the care of these patients and increase use of more appropriate health care resources. Other outcomes currently being studied include the impact of PACT ICU presentations on health care use, the impact on alternate health care consult patterns, and trainee participant opinions. Future directions for the interprofessional case conferences include expansion to other nonacademic primary care teams. The benefit of PACT ICU case conferences also extends to the primary care trainees as they continue to learn how to best work with other HCPs as part of a team and how to use the resources available through these other health care disciplines.

Conclusions

Presentation at an interprofessional case conference was not associated with a statistically significant change in mean A_1c or BP values in a small group of high-risk patients at the Boise VAMC PACT academic clinic. Although there was a trend toward a decrease in A_1c values, it is difficult to determine whether there is a relation to the interprofessional case conferences. Interprofessional case conferences are still occurring at the Boise VAMC with efforts in place to incorporate concurrent PACT ICU outcomes data collection and further the educational goals of primary care trainees.

Acknowledgments
The authors would like to express their appreciation to Rick Tivis, MPH, and Tim Gordon, MA, MPH, MS, for their assistance in the analysis and collection of data for this study.

Chronic conditions contribute to increasing health care expenditures, and a small number of patients with chronic medical conditions consume a disproportionately larger amount of health care resources.^1,2 Naessens and colleagues showed that 2.6% of adult patients accounted for 20.7% of all primary care clinic visits during a calendar year.² These high-risk patients may be using much of the health care resources but have unmet needs even with the increased amount of health care services they receive.

The impact of interprofessional forms of chronic disease management on patient outcomes is unclear.^3-5 Definitions for high-risk patients and interprofessional care are broad, making comparison of studies difficult. In a team setting, it is difficult to discern the exact contributions of a single member of the team. Katon and colleagues concluded in a randomized, controlled trial that a nurse care manager collaborative treatment program added additional depression-free days and quality-adjusted life-years in adults with depression and poorly controlled diabetes mellitus (DM), coronary artery disease, or both.³ The intervention also resulted in improvements in a composite outcome of hemoglobin A_1c (A_1c), low-densitylipoprotein cholesterol, systolic blood pressure (BP) levels, and depression symptoms at 12 months, but these improvements were not sustained at 24 months.^3,4

A study looked at interprofessional team care provided by primary care internal medicine residents, nurse practitioner students, and pharmacy students, compared with usual care by only internal medicine residents. The study showed improvements in patient assessments and a trend toward the decreased use of urgent care in patients with type 2 DM over 18 months but no significant improvements in A_1c or BP values.⁵ The impact of pharmacists participating in team-based care and patient-centered medical home models has also been shown to be positive regarding metabolic parameters.^6,7Patient aligned care teams (PACT), the VA patient-centered medical home model initiative, seek to optimize patient care through provision of interprofessional, team-based care. At the Boise VAMC in Idaho, PACT training occurs at a primary care academic training clinic that includes 40 primary care providers, supervisors, and trainees in internal medicine, nurse practitioner programs, pharmacy, and behavioral health.

The Boise VAMC is also 1 of 5 VA Centers of Excellence in Primary Care Education (CoEPCE), institutions that prepare health care trainees from many disciplines to participate in interprofessional PACTs, provide patient-centered, team-based care, and learn and understand the roles of other team members.⁸ This VAMC CoEPCE, implemented in 2010, is an academic partnership with area professional schools of medicine, nursing, and pharmacy.

Team-Based Care

At the Boise VAMC CoEPCE, primary care trainees are taught a team-based approach to providing more effective care for high-risk patients through a complex curriculum that includes interprofessional case conferences called PACT interprofessional care updates (ICU). During these case conferences, high-risk patients on a primary care trainee’s panel are presented to an interprofessional group of health care professionals (HCPs) for recommendations to improve care. Trainees from the various disciplines participate in these PACT ICU presentations during time spent rotating through the institution’s academic clinic.

The CoEPCE activities include PACT ICU, interprofessional didactic sessions, and provision of primary care to patients in an interprofessional clinic. Physician trainees participate in one-half day per week of ambulatory didactics and conferences during a 2-week clinic block, which occurs every 2 months. Other health care disciplines participate in PACT ICU during longitudinal experiences (ranging from 4 to 12 months) in the primary care training clinic throughout the academic year.

The PACT ICU case conferences occur weekly at the academic clinic with 2 patient cases presented and discussed at each meeting. Prior to each conference, a primary care trainee, generally an internal medicine resident, is given a list of the top 5 high-risk patients from their panel, determined by a care assessment needs score that is based on high health care use and risk of hospitalization or death within 90 days. To determine care assessment needs scores, patient electronic health records (EHRs) are scanned weekly to review more than 150 data elements, including vital signs; recent clinic, urgent care, and emergency department (ED) visits; medications; laboratory values; and the number and types of illnesses. Statistical analyses are run on the EHR data to provide up-to-date estimates of likelihood of hospital admission or death.

Trainees may also select any patient on their panel whose health care they feel would benefit from a case conference discussion. The trainee presents all medical and social problems related to the selected patient to a team of HCPs, including other trainees and their supervisors, from multiple different disciplines, such as medicine, nursing, pharmacy, behavioral health, and social work. The interprofessional team then provides recommendations.

 

A care plan is developed by the group to implement as appropriate. The care plan may consist of various recommendations from the different disciplines, such as consults to a pharmacist for medication review or medication management, referrals to social work to coordinate care with home health services, or asking the nurse care manager to follow up with a patient by phone on a more regular basis. Trainees are encouraged to use alternate forms of care, including team-based care from other health care disciplines as well as other methods of communication, such as secure electronic messaging to increase access.

Interprofessional patient case conferences could offer another tool for HCPs to improve the care of high-risk patients through team-based efforts if the effect on patient outcomes or health care use is beneficial. The objective of this study was to evaluate the relationship of interprofessional case conferences and A_1c levels in high-risk patients with DM and BP measurements in patients with hypertension whose case was discussed at PACT ICU case conferences at the Boise VAMC. The authors hypothesized that the PACT ICU presentation intervention would lead to improved metabolic parameters as care plans were implemented. This evaluation is a subset of a larger study assessing the impact of PACT ICU presentation on various patient, trainee, and team level outcomes.

Methods

This study was a retrospective, observational analysis of patients seen at the Boise VAMC academic clinic whose cases were discussed at PACT ICU case conferences from January 2013 to April 2014. For the analysis of A_1c values, patients must have been discussed at a PACT ICU presentation during the study time period and had a diagnosis of DM in the EHR. Those included must have A_1c results in the EHR before and after the patient case presentation. The most recent A_1c measured prior to presentation was chosen as the prepresentation value. The next measured value 2 to 6 months after the case presentation date was chosen as the postpresentation value. This was chosen as the postpresentation value because it may be more indicative of the impact of the PACT ICU care plan. An A_1c measured at least 2 months following the case conference intervention was chosen to allow all possible measurements to be included in the analysis, according to usual care for measuring A_1c at the clinic. The primary outcome was the mean change in A_1c values pre- and post-PACT ICU presentation.

Blood pressure analyses were included if patients had a diagnosis of hypertension in the EHR as well as recorded BP values measured during the 6 months prior to PACT ICU presentation and 1 to 6 months after presentation. Blood pressure values were limited to 1 to 6 months after presentation to be more suggestive of the case conference care plan impact. Blood pressure measured during hospitalizations, urgent care, or ED visits were excluded from the analysis. The primary outcome in the BP analysis was the mean change in systolic and diastolic BP pre- and post-PACT ICU presentation. The mean of all in-clinic BP measurements was calculated as the prepresentation value and compared with the mean of all postpresentation BP measurements in the designated time period.

Assessment of DM or hypertension control was not a factor for inclusion in the study. The types of interventions and recommendations resulting from the case conferences were not evaluated.

Statistical analysis included paired t tests comparing mean values before and after PACT ICU presentation, with an a priori level for finding a significant difference at 0.05. This study was approved as expedited research by the institutional review board associated with the Boise VAMC.

Results

During the study period, 65 patients were discussed at a PACT ICU case conferences (Figure). The average age was 67 years, and 89% of patients were male. Of these patients, 32 had a DM diagnosis. A total of 12 patients had A_1c values within the parameters specified for this study and were included in the final analysis for the A_1c group.

The mean A_1c value for patients before PACT ICU presentation was 8.5% (SD 2.11). After presentation, the mean A_1c decreased to 7.9% (-0.6%, SD 1.32, P = .10; Table 1).

Of all patients discussed at a PACT ICU case conference, 52 had a diagnosis of hypertension (Table 2).

A total of 45 patients were included in the final BP analysis. The mean systolic BP prior to PACT ICU presentation was 134 mm Hg (SD 20.3), which decreased to 132.2 mm Hg (SD 21.6) following PACT ICU presentation (P = .23). Mean diastolic BP prepresentation was 81 mm Hg (SD 17.1) and 80.6 mm Hg (SD 16.8) postpresentation (P = .40).

 

Discussion

High-risk patients with DM enrolled in this primary care academic clinic and discussed at interprofessional case conferences did not have a statistically significant change in A_1c values following the case conferences. There was also no statistically significant change in systolic and diastolic BP measurements following PACT ICU case conferences in high-risk patients with hypertension. The relationship between PACT ICU presentations and patient outcomes may not be direct, but the potential to decrease A_1c values by 0.6% may be of clinical benefit to patients enrolled at the Boise VAMC academic clinic.

The results of this study are comparable with other studies where the impact of interprofessional forms of care on patient outcomes such as A_1c and BP is not as apparent.^3-5 The patients included in this study were high-risk compared with other patients, and patient outcome goals for DM and hypertension management according to clinical practice guidelines may be less stringent for these patients.^9-11

Interprofessional case conferences are being used at the Boise VAMC academic clinic to teach primary care trainees how to improve care for patients by working on teams, with a goal of promoting alternate forms of health care. Referrals of patients to pharmacy services for chronic disease management may result from these case conferences, and patients could benefit from pharmacy review and management of medications for the treatment of DM and hypertension. There may be other advantages to patients and to the health system in the form of more appropriate health care use, increased contact with providers, and use of other health care resources to decrease costs and medication burden, although these are speculative at this time.

Limitations

This study had several limitations. The patients included in this study were high-risk patients seen by primary care trainees at the Boise VAMC academic clinic, and a small number of patients were included in the final analysis, limiting the generalizability of the results to other patient populations. Finding a difference in A_1c and BP values before and after PACT ICU case conferences was also limited by the small number of patients who met inclusion criteria. Many patients included in the study also had reasonably controlled A_1c and BP levels prior to PACT ICU case conferences; therefore, a difference would be more difficult to determine.

The PACT ICU case conferences occur at one point in time, but the impact of the intervention and recommendations may take longer to appreciate. A longer study duration may be needed to determine differences in A_1c and BP values over time. Regression to the mean is also a possibility given the type of data collected. As each primary care trainee selects the patient to be discussed at a PACT ICU case conference, bias could also be present, because the provider may focus on patients with recent clinic visits or on patients who are the most difficult for the provider to manage or contact.

The Boise VAMC PACTs include many different health care disciplines; therefore, the institution may foster interprofessional, team-based care more easily compared with that of other health care systems. Trainees in the CoEPCE also are aware of other team members’ roles, and clinical pharmacists are currently part of PACTs at the institution. The idea of interprofessional case conferences may be simple, but the process at this institution requires time and effort from a nurse care manager who coordinates patient selection and information distribution and an attending physician supervisor who facilitates each case conference. The Boise VAMC also supports pharmacy chronic disease management services, and several of these patients with uncontrolled DM or resistant hypertension may have been seen by the pharmacy-managed insulin titration or hypertension clinics. Finally, there is also limited documentation of whether DM or hypertension management was discussed at the case conferences.

Despite the medical complexities seen in these patients, discussions during PACT ICU presentations may involve many social and behavioral interventions, and DM and hypertension issues may not be significant enough for review at a case conference. However, the intervention of PACT ICU case conferences encompassed a variety of care plans, and this study evaluated the impact of the entire discussion and recommendations and not any individual component. Other recommendations were not evaluated due to the wide variety of interventions that were potentially discussed, and a process for tracking these was not in place.

The results of this study did not show that the care plans that develop at PACT ICU case conferences impacted high-risk patients with DM or hypertension, likely due to small sample sizes (2 patient cases were discussed per week). The impact could be better determined through a larger sample size, longer duration, or assessment of patients whose disease was not controlled. The impact may also be more significant for individuals who benefit from the increased review and assessment of their chronic medical conditions and increased access to care.

 

Seeing a possible trend toward benefit in A_1c values in this short time frame helps support continuing and expanding case conferences at the Boise VAMC. The goals of these interprofessional case conferences include developing a proactive approach to identify high-risk patients to improve the care of these patients and increase use of more appropriate health care resources. Other outcomes currently being studied include the impact of PACT ICU presentations on health care use, the impact on alternate health care consult patterns, and trainee participant opinions. Future directions for the interprofessional case conferences include expansion to other nonacademic primary care teams. The benefit of PACT ICU case conferences also extends to the primary care trainees as they continue to learn how to best work with other HCPs as part of a team and how to use the resources available through these other health care disciplines.

Conclusions

Presentation at an interprofessional case conference was not associated with a statistically significant change in mean A_1c or BP values in a small group of high-risk patients at the Boise VAMC PACT academic clinic. Although there was a trend toward a decrease in A_1c values, it is difficult to determine whether there is a relation to the interprofessional case conferences. Interprofessional case conferences are still occurring at the Boise VAMC with efforts in place to incorporate concurrent PACT ICU outcomes data collection and further the educational goals of primary care trainees.

Acknowledgments
The authors would like to express their appreciation to Rick Tivis, MPH, and Tim Gordon, MA, MPH, MS, for their assistance in the analysis and collection of data for this study.