MDedge Dermatology

Dermatomyositis (DM) is an uncommon idiopathic inflammatory myopathy (IIM) characterized by muscle inflammation; proximal muscle weakness; and dermatologic findings, such as the heliotrope eruption and Gottron papules.^1-3 Dermatomyositis is associated with an increased malignancy risk compared to other IIMs, with a 13% to 42% lifetime risk for malignancy development.^4,5 The incidence for malignancy peaks during the first year following diagnosis and falls gradually over 5 years but remains increased compared to the general population.^6-11 Adenocarcinoma represents the majority of cancers associated with DM, particularly of the ovaries, lungs, breasts, gastrointestinal tract, pancreas, bladder, and prostate. The lymphatic system (non-Hodgkin lymphoma) also is overrepresented among cancers in DM.¹²

Because of the increased malignancy risk and cancer-related mortality in patients with DM, cancer screening generally is recommended following diagnosis.^13,14 However, consensus guidelines for screening modalities and frequency currently do not exist, resulting in widely varying practice patterns.¹⁵ Some experts advocate for a conventional cancer screening panel (CSP), as summarized in Table 1.^15-18 These tests may be repeated annually for 3 to 5 years following the diagnosis of DM. Although the use of myositis-specific antibodies (MSAs) recently has helped to risk-stratify DM patients, up to half of patients are MSA negative,¹⁹ and broad malignancy screening remains essential. Individualized discussions with patients about their risk factors, screening options, and risks and benefits of screening also are strongly encouraged.^19-22 Studies of the direct costs and effectiveness of streamlined screening with positron emission tomography/computed tomography (PET/CT) compared with a CSP have shown similar efficacy and lower out-of-pocket costs for patients receiving PET/CT imaging.^16-18

The goal of our study was to further characterize patients’ perspectives and experience of cancer screening in DM as well as indirect costs, both of which must be taken into consideration when developing consensus guidelines for DM malignancy screening. Inclusion of patient voice is essential given the similar efficacy of both screening methods. We assessed the indirect costs (eg, travel, lost work or wages, childcare) of a CSP in patients with DM. We theorized that the large quantity of tests involved in a CSP, which are performed at various locations on multiple days over the course of several years, may have substantial costs to patients beyond the co-pay and deductible. We also sought to measure patients’ perception of the burden associated with an annual CSP, which we defined to participants as the inconvenience or unpleasantness experienced by the patient, compared with an annual whole-body PET/CT. Finally, we examined the relative value of these screening methods to patients using a willingness-to-pay (WTP) analysis.

Materials and Methods

Patient Eligibility—Our study included Penn State Health (Hershey, Pennsylvania) patients 18 years or older with a recent diagnosis of DM—International Classification of Diseases, Ninth Revision code 710.3 or International Classification of Diseases, Tenth Revision codes M33.10 or M33.90—who were undergoing or had recently completed a CSP. Patients were excluded from the study if they had a concurrent or preceding diagnosis of malignancy (excluding nonmelanoma skin cancers) or had another IIM. The institutional review board at Penn State Health College of Medicine approved the study. Data for all patients were prospectively obtained.

Survey Design—A survey was generated to assess the burden and indirect costs associated with a CSP, which was modified from work done by Tchuenche et al²³ and Teni et al.²⁴ Focus groups were held in 2018 and 2019 with patients who met our inclusion criteria with the purpose of refining the survey instrument based on patient input. A summary explanation of research was provided to all participants, and informed consent was obtained. Patients were compensated for their time for focus groups. Audio of each focus group was then transcribed and analyzed for common themes. Following focus group feedback, a finalized survey was generated for assessing burden and indirect costs (survey instrument provided in the Supplementary Information). REDCap (Vanderbilt University), a secure web application, was used to construct the finalized survey and to collect and manage data.²⁵

Patients who fit our inclusion criteria were identified and recruited in multiple ways. Patients with appointments at the Penn State Milton S. Hershey Medical Center Department of Dermatology were presented with the opportunity to participate, Penn State Health records with the appropriate billing codes were collected and patients were contacted, and an advertisement for the study was posted on StudyFinder. Surveys constructed on REDCap were then sent electronically to patients who agreed to participate in the study. A second summary explanation of research was included on the first page of the survey to describe the process.

The survey had 3 main sections. The first section collected demographic information. In the second section, we surveyed patients regarding the various aspects of a CSP that focus groups identified as burdensome. In addition, patients were asked to compare their feelings regarding an annual CSP vs whole-body PET/CT for a 3-year period utilizing a rating scale of strongly disagree, somewhat disagree, somewhat agree, and strongly agree. This section also included a willingness-to-pay (WTP) analysis for each modality. We defined WTP as the maximum out-of-pocket cost that the patient would be willing to pay to receive testing, which was measured in a hypothetical scenario where neither whole-body PET/CT nor CSP was covered by insurance.²⁶ Although WTP may be influenced by external factors such as patient income, it can serve as a numerical measure of how much the patient values each service. Furthermore, these external factors become less relevant when comparing the relative value of 2 separate tests, as such factors apply equally in both scenarios. In the third section of the survey, patients were queried regarding various indirect costs associated with a CSP. Descriptions for a CSP and whole-body PET/CT, including risks and benefits, were provided to allow patients to make informed decisions.

Statistical Analysis—Because of the rarity of DM and the subsequently limited sample size, summary and descriptive statistics were utilized to characterize the sample and identify patterns in the results. Continuous variables are presented with means and standard deviations, and proportions are presented with frequencies and percentages. All analyses were done using SAS Version 9.4 (SAS Institute Inc).

Results

Patient Demographics—Fifty-four patients were identified using StudyFinder, physician referral, and search of the electronic health record. Nine patients agreed to take part in the focus groups, and 27 offered email addresses to be contacted for the survey. Of those 27 patients, 16 (59.3%) fit our inclusion criteria and completed the survey. Patient demographics are detailed in Table 2. The mean age was 55 years, and most patients were White (88% [14/16]), female (81% [13/16]), and had at least a bachelor’s degree (69% [11/16]). Most patients (69% [11/16]) had an annual income of less than $50,000, and half (50% [8/16]) were employed. All patients had been diagnosed with DM in or after 2013. Two patients were diagnosed with basal cell carcinoma during or after cancer screening.

Patient Preference for Screening and WTP—A majority (81% [13/16]) of patients desired some form of screening for occult malignancy following the diagnosis of DM, even in the hypothetical situation in which screening did not provide survival benefit (Figure 1). Twenty-five percent (4/16) of patients expressed that a CSP was burdensome, and 12.5% of patients (2/16) missed a CSP appointment; all of these patients rescheduled or were planning to reschedule. Assuming that both screening methods had similar predictive value in detecting malignancy, all 16 patients felt annual whole-body PET/CT for a 3-year period would be less burdensome than a CSP, and most (73% [11/15]) felt that it would decrease the likelihood of missed appointments. Overall, 93% (13/14) of patients preferred whole-body PET/CT over a CSP when given the choice between the 2 options (Figure 2). This preference was consistent with the patients’ WTP for these tests; patients reliably reported that they would pay more for annual whole-body PET/CT than for a CSP (Figure 3). Specifically, 75% (12/16) and 38% (6/16) of patients were willing to spend $250 or more and $1000 or more for annual whole-body PET/CT, respectively, compared with 56% (9/16) and 19% (3/16), respectively, for an annual CSP. Many patients (38% [6/16]) reported that they would not be willing to pay any out-of-pocket cost for a CSP compared with 13% (2/16) for PET/CT.Indirect Costs of Screening for Patients—Indirect costs incurred by patients undergoing a CSP are summarized in Table 3. Specifically, a large percentage of employed patients missed work (63% [5/8]) or had family miss work (38% [3/8]), necessitating the use of vacation and/or sick days to attend CSP appointments. A subset (25% [2/8]) lost income (average, $1500), and 1 patient reported that a family member lost income due to attending a CSP appointment. Most (75% [12/16]) patients also incurred substantial transportation costs (average, $243), with 1 patient spending $1000. No patients incurred child or elder care costs. One patient paid a small sum for lodging/meals while traveling to attend a CSP appointment.

Comment

Patients with DM have an increased incidence of malignancy, thus cancer screening serves a crucial role in the detection of occult disease.¹³ Up to half of DM patients are MSA negative, and most cancers in these patients are found with blind screening. Whole-body PET/CT has emerged as an alternative to a CSP. Evidence suggests that it has similar efficacy in detecting malignancy and may be particularly useful for identifying malignancies not routinely screened for in a CSP. In a prospective study of patients diagnosed with DM and polymyositis (N=55), whole-body PET/CT had a positive predictive value of 85.7% and negative predictive value for detecting occult malignancy of 93.8% compared with 77.8% and 95.7%, respectively, for a CSP.¹⁷

The results of our study showed that cancer screening is important to patients diagnosed with DM and that most of these patients desire some form of cancer screening. This finding held true even when patients were presented with a hypothetical situation in which screening was proven to have no survival benefit. Based on focus group data, this desire was likely driven by the fear generated by not knowing whether cancer is present, as reported by the following DM patients:

“I mean [cancer screening] is peace of mind. It is ultimately worth it. You know, better than . . . not doing the screenings and finding 3 years down the road that you have, you know, a serious problem . . . you had the cancer, and you didn’t have the screenings.” (DM patient 1)

“I would rather know than not know, even if it is bad news, just tell me. The sooner the better, and give me the whole spiel . . . maybe all the screenings don’t need to be done, done so much, so often afterwards if the initial ones are ok, but I think too, for peace of mind, I would rather know it all up front.” (DM patient 2)

Further, when presented with the hypothetical situation that insurance would not cover screenings, a few patients remarked they would relocate to obtain them:

“I would find a place where the screenings were done. I’d move.” (DM patient 4)

“If it was just sky high and [insurance companies] weren’t willing to negotiate, I would consider moving.” (DM patient 3).

Sentiments such as these emphasize the importance and value that DM patients place on being screened for cancer and also may explain why only 25% of patients felt a CSP was burdensome and only 13% reported missing appointments, all of whom planned on making them up at a later time.

When presented with the choice of a CSP or annual whole-body PET/CT for a 3-year period following the diagnosis of DM, all patients expressed that whole-body PET/CT would be less burdensome. Most preferred annual whole-body PET/CT despite the slightly increased radiation exposure associated and thought that it would limit missed appointments. Accordingly, more patients responded that they would pay more money out-of-pocket for annual whole-body PET/CT. Given that WTP can function as a numerical measure of value, our results showed that patients placed a higher value on whole-body PET/CT compared with a CSP. The indirect costs associated with a CSP also were substantial, particularly regarding missed work, use of vacation and/or sick days, and travel expenses, which is particularly important because most patients reported an annual income less than $50,000.

The direct costs of a CSP and whole-body PET/CT have been studied. Specifically, Kundrick et al¹⁸ found that whole-body PET/CT was less expensive for patients (by approximately $111) out-of-pocket compared with a CSP, though cost to insurance companies was slightly greater. The present study adds to these findings by better illustrating the burden and indirect costs that patients experience while undergoing a CSP and by characterizing the patient’s perception and preference of these 2 screening methods.

Limitations of our study include a small sample size willing to complete the survey. There also was a predominance of White and female participants, partially attributed to the greater number of female patients who develop DM compared to male patients. However, this still may limit applicability of this study to males and patients of other races. Another limitation includes recall bias on survey responses, particularly regarding indirect costs incurred with a CSP. A final limitation was that only patients with a recent diagnosis of DM who were actively undergoing screening or had recently completed malignancy screening were included in the study. Given that these patients were receiving (or had completed) exclusively a CSP, patients were comparing their personal experience with a described experience. In addition, only 2 patients were diagnosed with cancer—both with basal cell carcinoma diagnosed on physical examination—which may have influenced their perception of a CSP, given that nothing was found on an extensive number of tests. However, these patients still greatly valued their screening, as evidenced in the survey.

Conclusion

Our study contributes to a better understanding of the costs patients face while undergoing malignancy screening for DM and highlights the great value patients assign to undergoing screening regardless of impact on outcome. Our study also shows a preference for streamlined testing, which whole-body PET/CT may represent. Patients incurred substantial indirect costs with a CSP and perceived that a single test, such as whole-body PET/CT, would be less burdensome and result in better compliance with screening. As groups work to establish consensus guidelines for cancer screening in DM, it is important to include the patient’s perspective. Ultimately, prospective trials comparing these modalities are needed, at which time the efficacy, direct and indirect costs, and burden of each modality can be compared.

Dermatomyositis (DM) is an uncommon idiopathic inflammatory myopathy (IIM) characterized by muscle inflammation; proximal muscle weakness; and dermatologic findings, such as the heliotrope eruption and Gottron papules.^1-3 Dermatomyositis is associated with an increased malignancy risk compared to other IIMs, with a 13% to 42% lifetime risk for malignancy development.^4,5 The incidence for malignancy peaks during the first year following diagnosis and falls gradually over 5 years but remains increased compared to the general population.^6-11 Adenocarcinoma represents the majority of cancers associated with DM, particularly of the ovaries, lungs, breasts, gastrointestinal tract, pancreas, bladder, and prostate. The lymphatic system (non-Hodgkin lymphoma) also is overrepresented among cancers in DM.¹²

Because of the increased malignancy risk and cancer-related mortality in patients with DM, cancer screening generally is recommended following diagnosis.^13,14 However, consensus guidelines for screening modalities and frequency currently do not exist, resulting in widely varying practice patterns.¹⁵ Some experts advocate for a conventional cancer screening panel (CSP), as summarized in Table 1.^15-18 These tests may be repeated annually for 3 to 5 years following the diagnosis of DM. Although the use of myositis-specific antibodies (MSAs) recently has helped to risk-stratify DM patients, up to half of patients are MSA negative,¹⁹ and broad malignancy screening remains essential. Individualized discussions with patients about their risk factors, screening options, and risks and benefits of screening also are strongly encouraged.^19-22 Studies of the direct costs and effectiveness of streamlined screening with positron emission tomography/computed tomography (PET/CT) compared with a CSP have shown similar efficacy and lower out-of-pocket costs for patients receiving PET/CT imaging.^16-18

The goal of our study was to further characterize patients’ perspectives and experience of cancer screening in DM as well as indirect costs, both of which must be taken into consideration when developing consensus guidelines for DM malignancy screening. Inclusion of patient voice is essential given the similar efficacy of both screening methods. We assessed the indirect costs (eg, travel, lost work or wages, childcare) of a CSP in patients with DM. We theorized that the large quantity of tests involved in a CSP, which are performed at various locations on multiple days over the course of several years, may have substantial costs to patients beyond the co-pay and deductible. We also sought to measure patients’ perception of the burden associated with an annual CSP, which we defined to participants as the inconvenience or unpleasantness experienced by the patient, compared with an annual whole-body PET/CT. Finally, we examined the relative value of these screening methods to patients using a willingness-to-pay (WTP) analysis.

Materials and Methods

Patient Eligibility—Our study included Penn State Health (Hershey, Pennsylvania) patients 18 years or older with a recent diagnosis of DM—International Classification of Diseases, Ninth Revision code 710.3 or International Classification of Diseases, Tenth Revision codes M33.10 or M33.90—who were undergoing or had recently completed a CSP. Patients were excluded from the study if they had a concurrent or preceding diagnosis of malignancy (excluding nonmelanoma skin cancers) or had another IIM. The institutional review board at Penn State Health College of Medicine approved the study. Data for all patients were prospectively obtained.

Survey Design—A survey was generated to assess the burden and indirect costs associated with a CSP, which was modified from work done by Tchuenche et al²³ and Teni et al.²⁴ Focus groups were held in 2018 and 2019 with patients who met our inclusion criteria with the purpose of refining the survey instrument based on patient input. A summary explanation of research was provided to all participants, and informed consent was obtained. Patients were compensated for their time for focus groups. Audio of each focus group was then transcribed and analyzed for common themes. Following focus group feedback, a finalized survey was generated for assessing burden and indirect costs (survey instrument provided in the Supplementary Information). REDCap (Vanderbilt University), a secure web application, was used to construct the finalized survey and to collect and manage data.²⁵

Patients who fit our inclusion criteria were identified and recruited in multiple ways. Patients with appointments at the Penn State Milton S. Hershey Medical Center Department of Dermatology were presented with the opportunity to participate, Penn State Health records with the appropriate billing codes were collected and patients were contacted, and an advertisement for the study was posted on StudyFinder. Surveys constructed on REDCap were then sent electronically to patients who agreed to participate in the study. A second summary explanation of research was included on the first page of the survey to describe the process.

The survey had 3 main sections. The first section collected demographic information. In the second section, we surveyed patients regarding the various aspects of a CSP that focus groups identified as burdensome. In addition, patients were asked to compare their feelings regarding an annual CSP vs whole-body PET/CT for a 3-year period utilizing a rating scale of strongly disagree, somewhat disagree, somewhat agree, and strongly agree. This section also included a willingness-to-pay (WTP) analysis for each modality. We defined WTP as the maximum out-of-pocket cost that the patient would be willing to pay to receive testing, which was measured in a hypothetical scenario where neither whole-body PET/CT nor CSP was covered by insurance.²⁶ Although WTP may be influenced by external factors such as patient income, it can serve as a numerical measure of how much the patient values each service. Furthermore, these external factors become less relevant when comparing the relative value of 2 separate tests, as such factors apply equally in both scenarios. In the third section of the survey, patients were queried regarding various indirect costs associated with a CSP. Descriptions for a CSP and whole-body PET/CT, including risks and benefits, were provided to allow patients to make informed decisions.

Statistical Analysis—Because of the rarity of DM and the subsequently limited sample size, summary and descriptive statistics were utilized to characterize the sample and identify patterns in the results. Continuous variables are presented with means and standard deviations, and proportions are presented with frequencies and percentages. All analyses were done using SAS Version 9.4 (SAS Institute Inc).

Results

Patient Demographics—Fifty-four patients were identified using StudyFinder, physician referral, and search of the electronic health record. Nine patients agreed to take part in the focus groups, and 27 offered email addresses to be contacted for the survey. Of those 27 patients, 16 (59.3%) fit our inclusion criteria and completed the survey. Patient demographics are detailed in Table 2. The mean age was 55 years, and most patients were White (88% [14/16]), female (81% [13/16]), and had at least a bachelor’s degree (69% [11/16]). Most patients (69% [11/16]) had an annual income of less than $50,000, and half (50% [8/16]) were employed. All patients had been diagnosed with DM in or after 2013. Two patients were diagnosed with basal cell carcinoma during or after cancer screening.

Patient Preference for Screening and WTP—A majority (81% [13/16]) of patients desired some form of screening for occult malignancy following the diagnosis of DM, even in the hypothetical situation in which screening did not provide survival benefit (Figure 1). Twenty-five percent (4/16) of patients expressed that a CSP was burdensome, and 12.5% of patients (2/16) missed a CSP appointment; all of these patients rescheduled or were planning to reschedule. Assuming that both screening methods had similar predictive value in detecting malignancy, all 16 patients felt annual whole-body PET/CT for a 3-year period would be less burdensome than a CSP, and most (73% [11/15]) felt that it would decrease the likelihood of missed appointments. Overall, 93% (13/14) of patients preferred whole-body PET/CT over a CSP when given the choice between the 2 options (Figure 2). This preference was consistent with the patients’ WTP for these tests; patients reliably reported that they would pay more for annual whole-body PET/CT than for a CSP (Figure 3). Specifically, 75% (12/16) and 38% (6/16) of patients were willing to spend $250 or more and $1000 or more for annual whole-body PET/CT, respectively, compared with 56% (9/16) and 19% (3/16), respectively, for an annual CSP. Many patients (38% [6/16]) reported that they would not be willing to pay any out-of-pocket cost for a CSP compared with 13% (2/16) for PET/CT.Indirect Costs of Screening for Patients—Indirect costs incurred by patients undergoing a CSP are summarized in Table 3. Specifically, a large percentage of employed patients missed work (63% [5/8]) or had family miss work (38% [3/8]), necessitating the use of vacation and/or sick days to attend CSP appointments. A subset (25% [2/8]) lost income (average, $1500), and 1 patient reported that a family member lost income due to attending a CSP appointment. Most (75% [12/16]) patients also incurred substantial transportation costs (average, $243), with 1 patient spending $1000. No patients incurred child or elder care costs. One patient paid a small sum for lodging/meals while traveling to attend a CSP appointment.

Comment

Patients with DM have an increased incidence of malignancy, thus cancer screening serves a crucial role in the detection of occult disease.¹³ Up to half of DM patients are MSA negative, and most cancers in these patients are found with blind screening. Whole-body PET/CT has emerged as an alternative to a CSP. Evidence suggests that it has similar efficacy in detecting malignancy and may be particularly useful for identifying malignancies not routinely screened for in a CSP. In a prospective study of patients diagnosed with DM and polymyositis (N=55), whole-body PET/CT had a positive predictive value of 85.7% and negative predictive value for detecting occult malignancy of 93.8% compared with 77.8% and 95.7%, respectively, for a CSP.¹⁷

The results of our study showed that cancer screening is important to patients diagnosed with DM and that most of these patients desire some form of cancer screening. This finding held true even when patients were presented with a hypothetical situation in which screening was proven to have no survival benefit. Based on focus group data, this desire was likely driven by the fear generated by not knowing whether cancer is present, as reported by the following DM patients:

“I mean [cancer screening] is peace of mind. It is ultimately worth it. You know, better than . . . not doing the screenings and finding 3 years down the road that you have, you know, a serious problem . . . you had the cancer, and you didn’t have the screenings.” (DM patient 1)

“I would rather know than not know, even if it is bad news, just tell me. The sooner the better, and give me the whole spiel . . . maybe all the screenings don’t need to be done, done so much, so often afterwards if the initial ones are ok, but I think too, for peace of mind, I would rather know it all up front.” (DM patient 2)

Further, when presented with the hypothetical situation that insurance would not cover screenings, a few patients remarked they would relocate to obtain them:

“I would find a place where the screenings were done. I’d move.” (DM patient 4)

“If it was just sky high and [insurance companies] weren’t willing to negotiate, I would consider moving.” (DM patient 3).

Sentiments such as these emphasize the importance and value that DM patients place on being screened for cancer and also may explain why only 25% of patients felt a CSP was burdensome and only 13% reported missing appointments, all of whom planned on making them up at a later time.

When presented with the choice of a CSP or annual whole-body PET/CT for a 3-year period following the diagnosis of DM, all patients expressed that whole-body PET/CT would be less burdensome. Most preferred annual whole-body PET/CT despite the slightly increased radiation exposure associated and thought that it would limit missed appointments. Accordingly, more patients responded that they would pay more money out-of-pocket for annual whole-body PET/CT. Given that WTP can function as a numerical measure of value, our results showed that patients placed a higher value on whole-body PET/CT compared with a CSP. The indirect costs associated with a CSP also were substantial, particularly regarding missed work, use of vacation and/or sick days, and travel expenses, which is particularly important because most patients reported an annual income less than $50,000.

The direct costs of a CSP and whole-body PET/CT have been studied. Specifically, Kundrick et al¹⁸ found that whole-body PET/CT was less expensive for patients (by approximately $111) out-of-pocket compared with a CSP, though cost to insurance companies was slightly greater. The present study adds to these findings by better illustrating the burden and indirect costs that patients experience while undergoing a CSP and by characterizing the patient’s perception and preference of these 2 screening methods.

Limitations of our study include a small sample size willing to complete the survey. There also was a predominance of White and female participants, partially attributed to the greater number of female patients who develop DM compared to male patients. However, this still may limit applicability of this study to males and patients of other races. Another limitation includes recall bias on survey responses, particularly regarding indirect costs incurred with a CSP. A final limitation was that only patients with a recent diagnosis of DM who were actively undergoing screening or had recently completed malignancy screening were included in the study. Given that these patients were receiving (or had completed) exclusively a CSP, patients were comparing their personal experience with a described experience. In addition, only 2 patients were diagnosed with cancer—both with basal cell carcinoma diagnosed on physical examination—which may have influenced their perception of a CSP, given that nothing was found on an extensive number of tests. However, these patients still greatly valued their screening, as evidenced in the survey.

Conclusion

Our study contributes to a better understanding of the costs patients face while undergoing malignancy screening for DM and highlights the great value patients assign to undergoing screening regardless of impact on outcome. Our study also shows a preference for streamlined testing, which whole-body PET/CT may represent. Patients incurred substantial indirect costs with a CSP and perceived that a single test, such as whole-body PET/CT, would be less burdensome and result in better compliance with screening. As groups work to establish consensus guidelines for cancer screening in DM, it is important to include the patient’s perspective. Ultimately, prospective trials comparing these modalities are needed, at which time the efficacy, direct and indirect costs, and burden of each modality can be compared.

Dermatomyositis (DM) is an uncommon idiopathic inflammatory myopathy (IIM) characterized by muscle inflammation; proximal muscle weakness; and dermatologic findings, such as the heliotrope eruption and Gottron papules.^1-3 Dermatomyositis is associated with an increased malignancy risk compared to other IIMs, with a 13% to 42% lifetime risk for malignancy development.^4,5 The incidence for malignancy peaks during the first year following diagnosis and falls gradually over 5 years but remains increased compared to the general population.^6-11 Adenocarcinoma represents the majority of cancers associated with DM, particularly of the ovaries, lungs, breasts, gastrointestinal tract, pancreas, bladder, and prostate. The lymphatic system (non-Hodgkin lymphoma) also is overrepresented among cancers in DM.¹²

Because of the increased malignancy risk and cancer-related mortality in patients with DM, cancer screening generally is recommended following diagnosis.^13,14 However, consensus guidelines for screening modalities and frequency currently do not exist, resulting in widely varying practice patterns.¹⁵ Some experts advocate for a conventional cancer screening panel (CSP), as summarized in Table 1.^15-18 These tests may be repeated annually for 3 to 5 years following the diagnosis of DM. Although the use of myositis-specific antibodies (MSAs) recently has helped to risk-stratify DM patients, up to half of patients are MSA negative,¹⁹ and broad malignancy screening remains essential. Individualized discussions with patients about their risk factors, screening options, and risks and benefits of screening also are strongly encouraged.^19-22 Studies of the direct costs and effectiveness of streamlined screening with positron emission tomography/computed tomography (PET/CT) compared with a CSP have shown similar efficacy and lower out-of-pocket costs for patients receiving PET/CT imaging.^16-18

The goal of our study was to further characterize patients’ perspectives and experience of cancer screening in DM as well as indirect costs, both of which must be taken into consideration when developing consensus guidelines for DM malignancy screening. Inclusion of patient voice is essential given the similar efficacy of both screening methods. We assessed the indirect costs (eg, travel, lost work or wages, childcare) of a CSP in patients with DM. We theorized that the large quantity of tests involved in a CSP, which are performed at various locations on multiple days over the course of several years, may have substantial costs to patients beyond the co-pay and deductible. We also sought to measure patients’ perception of the burden associated with an annual CSP, which we defined to participants as the inconvenience or unpleasantness experienced by the patient, compared with an annual whole-body PET/CT. Finally, we examined the relative value of these screening methods to patients using a willingness-to-pay (WTP) analysis.

Materials and Methods

Patient Eligibility—Our study included Penn State Health (Hershey, Pennsylvania) patients 18 years or older with a recent diagnosis of DM—International Classification of Diseases, Ninth Revision code 710.3 or International Classification of Diseases, Tenth Revision codes M33.10 or M33.90—who were undergoing or had recently completed a CSP. Patients were excluded from the study if they had a concurrent or preceding diagnosis of malignancy (excluding nonmelanoma skin cancers) or had another IIM. The institutional review board at Penn State Health College of Medicine approved the study. Data for all patients were prospectively obtained.

Survey Design—A survey was generated to assess the burden and indirect costs associated with a CSP, which was modified from work done by Tchuenche et al²³ and Teni et al.²⁴ Focus groups were held in 2018 and 2019 with patients who met our inclusion criteria with the purpose of refining the survey instrument based on patient input. A summary explanation of research was provided to all participants, and informed consent was obtained. Patients were compensated for their time for focus groups. Audio of each focus group was then transcribed and analyzed for common themes. Following focus group feedback, a finalized survey was generated for assessing burden and indirect costs (survey instrument provided in the Supplementary Information). REDCap (Vanderbilt University), a secure web application, was used to construct the finalized survey and to collect and manage data.²⁵

Patients who fit our inclusion criteria were identified and recruited in multiple ways. Patients with appointments at the Penn State Milton S. Hershey Medical Center Department of Dermatology were presented with the opportunity to participate, Penn State Health records with the appropriate billing codes were collected and patients were contacted, and an advertisement for the study was posted on StudyFinder. Surveys constructed on REDCap were then sent electronically to patients who agreed to participate in the study. A second summary explanation of research was included on the first page of the survey to describe the process.

The survey had 3 main sections. The first section collected demographic information. In the second section, we surveyed patients regarding the various aspects of a CSP that focus groups identified as burdensome. In addition, patients were asked to compare their feelings regarding an annual CSP vs whole-body PET/CT for a 3-year period utilizing a rating scale of strongly disagree, somewhat disagree, somewhat agree, and strongly agree. This section also included a willingness-to-pay (WTP) analysis for each modality. We defined WTP as the maximum out-of-pocket cost that the patient would be willing to pay to receive testing, which was measured in a hypothetical scenario where neither whole-body PET/CT nor CSP was covered by insurance.²⁶ Although WTP may be influenced by external factors such as patient income, it can serve as a numerical measure of how much the patient values each service. Furthermore, these external factors become less relevant when comparing the relative value of 2 separate tests, as such factors apply equally in both scenarios. In the third section of the survey, patients were queried regarding various indirect costs associated with a CSP. Descriptions for a CSP and whole-body PET/CT, including risks and benefits, were provided to allow patients to make informed decisions.

Statistical Analysis—Because of the rarity of DM and the subsequently limited sample size, summary and descriptive statistics were utilized to characterize the sample and identify patterns in the results. Continuous variables are presented with means and standard deviations, and proportions are presented with frequencies and percentages. All analyses were done using SAS Version 9.4 (SAS Institute Inc).

Results

Patient Demographics—Fifty-four patients were identified using StudyFinder, physician referral, and search of the electronic health record. Nine patients agreed to take part in the focus groups, and 27 offered email addresses to be contacted for the survey. Of those 27 patients, 16 (59.3%) fit our inclusion criteria and completed the survey. Patient demographics are detailed in Table 2. The mean age was 55 years, and most patients were White (88% [14/16]), female (81% [13/16]), and had at least a bachelor’s degree (69% [11/16]). Most patients (69% [11/16]) had an annual income of less than $50,000, and half (50% [8/16]) were employed. All patients had been diagnosed with DM in or after 2013. Two patients were diagnosed with basal cell carcinoma during or after cancer screening.

Patient Preference for Screening and WTP—A majority (81% [13/16]) of patients desired some form of screening for occult malignancy following the diagnosis of DM, even in the hypothetical situation in which screening did not provide survival benefit (Figure 1). Twenty-five percent (4/16) of patients expressed that a CSP was burdensome, and 12.5% of patients (2/16) missed a CSP appointment; all of these patients rescheduled or were planning to reschedule. Assuming that both screening methods had similar predictive value in detecting malignancy, all 16 patients felt annual whole-body PET/CT for a 3-year period would be less burdensome than a CSP, and most (73% [11/15]) felt that it would decrease the likelihood of missed appointments. Overall, 93% (13/14) of patients preferred whole-body PET/CT over a CSP when given the choice between the 2 options (Figure 2). This preference was consistent with the patients’ WTP for these tests; patients reliably reported that they would pay more for annual whole-body PET/CT than for a CSP (Figure 3). Specifically, 75% (12/16) and 38% (6/16) of patients were willing to spend $250 or more and $1000 or more for annual whole-body PET/CT, respectively, compared with 56% (9/16) and 19% (3/16), respectively, for an annual CSP. Many patients (38% [6/16]) reported that they would not be willing to pay any out-of-pocket cost for a CSP compared with 13% (2/16) for PET/CT.Indirect Costs of Screening for Patients—Indirect costs incurred by patients undergoing a CSP are summarized in Table 3. Specifically, a large percentage of employed patients missed work (63% [5/8]) or had family miss work (38% [3/8]), necessitating the use of vacation and/or sick days to attend CSP appointments. A subset (25% [2/8]) lost income (average, $1500), and 1 patient reported that a family member lost income due to attending a CSP appointment. Most (75% [12/16]) patients also incurred substantial transportation costs (average, $243), with 1 patient spending $1000. No patients incurred child or elder care costs. One patient paid a small sum for lodging/meals while traveling to attend a CSP appointment.

Comment

Patients with DM have an increased incidence of malignancy, thus cancer screening serves a crucial role in the detection of occult disease.¹³ Up to half of DM patients are MSA negative, and most cancers in these patients are found with blind screening. Whole-body PET/CT has emerged as an alternative to a CSP. Evidence suggests that it has similar efficacy in detecting malignancy and may be particularly useful for identifying malignancies not routinely screened for in a CSP. In a prospective study of patients diagnosed with DM and polymyositis (N=55), whole-body PET/CT had a positive predictive value of 85.7% and negative predictive value for detecting occult malignancy of 93.8% compared with 77.8% and 95.7%, respectively, for a CSP.¹⁷

The results of our study showed that cancer screening is important to patients diagnosed with DM and that most of these patients desire some form of cancer screening. This finding held true even when patients were presented with a hypothetical situation in which screening was proven to have no survival benefit. Based on focus group data, this desire was likely driven by the fear generated by not knowing whether cancer is present, as reported by the following DM patients:

“I mean [cancer screening] is peace of mind. It is ultimately worth it. You know, better than . . . not doing the screenings and finding 3 years down the road that you have, you know, a serious problem . . . you had the cancer, and you didn’t have the screenings.” (DM patient 1)

“I would rather know than not know, even if it is bad news, just tell me. The sooner the better, and give me the whole spiel . . . maybe all the screenings don’t need to be done, done so much, so often afterwards if the initial ones are ok, but I think too, for peace of mind, I would rather know it all up front.” (DM patient 2)

Further, when presented with the hypothetical situation that insurance would not cover screenings, a few patients remarked they would relocate to obtain them:

“I would find a place where the screenings were done. I’d move.” (DM patient 4)

“If it was just sky high and [insurance companies] weren’t willing to negotiate, I would consider moving.” (DM patient 3).

Sentiments such as these emphasize the importance and value that DM patients place on being screened for cancer and also may explain why only 25% of patients felt a CSP was burdensome and only 13% reported missing appointments, all of whom planned on making them up at a later time.

When presented with the choice of a CSP or annual whole-body PET/CT for a 3-year period following the diagnosis of DM, all patients expressed that whole-body PET/CT would be less burdensome. Most preferred annual whole-body PET/CT despite the slightly increased radiation exposure associated and thought that it would limit missed appointments. Accordingly, more patients responded that they would pay more money out-of-pocket for annual whole-body PET/CT. Given that WTP can function as a numerical measure of value, our results showed that patients placed a higher value on whole-body PET/CT compared with a CSP. The indirect costs associated with a CSP also were substantial, particularly regarding missed work, use of vacation and/or sick days, and travel expenses, which is particularly important because most patients reported an annual income less than $50,000.

The direct costs of a CSP and whole-body PET/CT have been studied. Specifically, Kundrick et al¹⁸ found that whole-body PET/CT was less expensive for patients (by approximately $111) out-of-pocket compared with a CSP, though cost to insurance companies was slightly greater. The present study adds to these findings by better illustrating the burden and indirect costs that patients experience while undergoing a CSP and by characterizing the patient’s perception and preference of these 2 screening methods.

Limitations of our study include a small sample size willing to complete the survey. There also was a predominance of White and female participants, partially attributed to the greater number of female patients who develop DM compared to male patients. However, this still may limit applicability of this study to males and patients of other races. Another limitation includes recall bias on survey responses, particularly regarding indirect costs incurred with a CSP. A final limitation was that only patients with a recent diagnosis of DM who were actively undergoing screening or had recently completed malignancy screening were included in the study. Given that these patients were receiving (or had completed) exclusively a CSP, patients were comparing their personal experience with a described experience. In addition, only 2 patients were diagnosed with cancer—both with basal cell carcinoma diagnosed on physical examination—which may have influenced their perception of a CSP, given that nothing was found on an extensive number of tests. However, these patients still greatly valued their screening, as evidenced in the survey.

Conclusion

Our study contributes to a better understanding of the costs patients face while undergoing malignancy screening for DM and highlights the great value patients assign to undergoing screening regardless of impact on outcome. Our study also shows a preference for streamlined testing, which whole-body PET/CT may represent. Patients incurred substantial indirect costs with a CSP and perceived that a single test, such as whole-body PET/CT, would be less burdensome and result in better compliance with screening. As groups work to establish consensus guidelines for cancer screening in DM, it is important to include the patient’s perspective. Ultimately, prospective trials comparing these modalities are needed, at which time the efficacy, direct and indirect costs, and burden of each modality can be compared.

Brachioradial pruritus (BRP) is a neuropathic condition typically characterized by localized dysesthesia of the dorsolateral arms.¹ This dysesthesia has been described as a persistent painful itching, burning, tingling, or stinging sensation^2-4 and has a median duration of expression of 24 months.^5,6 The condition may be unilateral or bilateral in nature but tends to have a predilection for a bilateral distribution along the C5 to C6 dermatomes.^1,7,8 There are no primary skin lesions associated with BRP; however, excoriations, prurigo nodules, and lichenification may arise secondary to scratching of the irritated skin.^1,4,5,9 Brachioradial pruritus tends to have a predilection for adult females (3:1 ratio) with lighter skin. The mean age at diagnosis is 59 years, but cases have been reported in patients aged 12 to 84 years.^1,5 The diagnosis of BRP is based on clinical signs and symptoms, though the ice-pack sign tends to be pathognomonic for the diagnosis.^10,11 Although there is no clear evidence on the exact cause of BRP, there are 2 prevalent theories: cervical radiculopathy secondary to cervical spine pathology and/or excessive exposure to UV radiation (UVR) in the summer months.^3-5,12 Brachioradial pruritus remains poorly described in the literature, and even its origin is under debate. As such, the clinician may have difficulty deciding on the best course of management. The goal of this article is to identify and discuss known treatment options for BRP (Table).

Etiology 

Cervical Spine Pathology—A correlation appears to exist between BRP and cervical spine changes seen on plain film radiographs at the levels of C3 to C7, with increased incidence at the C5 to C6 levels. These plain film radiographs typically show degenerative joint disease and neural foraminal stenosis at levels that correlate to the dermatomal distribution of BRP.^1,7,10,12-14 In addition to plain film radiography, some studies have utilized magnetic resonance imaging to view the cervical spine and have documented evidence of intervertebral disc protrusion/bulging, central canal stenosis, neuroforaminal stenosis, and spondylosis at the affected regions.^5,15-17 Moreover, supporting the theory that the cervical spine is responsible for the emergence of BRP, Marziniak et al¹⁷ investigated 41 patients with BRP utilizing magnetic resonance tomography to find that 33 patients (80.5%) had changes in nerve compression, and 8 patients (19.5%) had degenerative changes. In addition to these findings, they found that there was a significant correlation (P<.01) between the dermatomal expression of BRP and the location of cervical anatomical changes.¹⁷ Further validating the relationship between cervical spine pathology and BRP is a case study of a patient who saw rapid and complete resolution of the pruritus following spinal decompression surgery.¹⁰ Another case study described an intramedullary tumor found in a patient with BRP that was diagnosed as an ependymoma after magnetic resonance imaging revealed an intramedullary lesion within the spinal cord between C4 and C7. The location of the tumor and dermatomal pattern of the neuropathic itch pointed to a possible association between nerve compression and BRP.¹⁴ Electromyography studies performed on individuals with BRP have shown an increase in polyphasic units, decreased motor units, and/or denervation changes along the C5/C6 or C6 nerve roots, which provides additional support for the theory of cervical spine pathology as a causative factor for BRP.¹⁶

UVR Exposure—Another etiologic theory for BRP is that UVR exposure may be responsible for the genesis of pruritus. Previously known as solar pruritus, BRP was deemed a clinical condition, as there was increased prevalence in patients living in warmer climates, such as Florida.⁹ Wallengren and Dahlbäck¹⁸ reported that sun exposure is a notable factor in the onset of BRP, as they saw an increase in symptoms during the late summer and a decrease in symptoms over the winter months.To further support the theory that UVR is linked to BRP, several studies have shown that the utilization of sun protection is linked to a reduction of symptoms, specifically in patients who showed seasonal variations of their symptoms.^9,12,19 Additionally, a study by Mirzoyev and Davis⁵ retrospectively reviewed 111 patients diagnosed with BRP. Of these patients, 84 (75.7%) presented with bilateral symptoms, and 54 (48.6%) reported prolonged sun exposure. Both of these findings demonstrate correlation between UVR and BRP.⁵ Interestingly, UV light exposure is known to release β-endorphin in the skin and may theoretically provide an area of exploration between UVR and cervical spine theories.

Conservative Treatment 

Chiropractic Manipulation—Because one etiologic theory includes disease of the cervical spine, there is evidence that targeting this region with treatment is beneficial.⁷ Two case reports found in the literature noted that cervical spine manipulation and cervical traction yielded positive results.^20,21 It has been established that pain generated by disc lesions can be the result of local nociceptive fiber activation, direct mechanical compression of the nerve roots, or inflammatory mediators.²² There are several postulated models describing the hypoalgesic effects of spinal manipulation, which contains both biomechanical and neurophysiological mechanisms. Biomechanical changes theorized to elicit analgesia include restoration of faulty biomechanical movement patterns, breaking up of periarticular adhesions, and reflexogenic muscle inhibition of hypertonic musculature. Hypothesized neurophysiological effects of joint manipulation include an increase in afferent information overwhelming the nociceptive input, reduction of temporal summation, and autonomic activation leading to non–opioid-induced hypoalgesia.²³ Cervical traction is another plausible treatment for BRP, wherein the physiological effects of traction allow for a separation of vertebral bodies and expansion of the intervertebral foramen circumference, thus decreasing compression of the nerve roots.²⁴

Acupuncture—Neurogenic pruritus, including BRP, is a group of conditions that have been treated using acupuncture. Acupuncture treatment consists of intramuscular needle stimulation and has been found to alleviate itching in patients with neurogenic pruritus. In 1 retrospective case series, acupuncture was used to treat 16 patients who were identified as having segmental pruritus. Acupuncture targeted the spasmed paravertebral muscles of the affected dermatomal levels as well as other regions of the body, and it was found that 12 patients (75%) experienced full resolution of symptoms. However, relapse did occur in 6 patients (37%) within 1 to 12 months following treatment.²⁵ Multiple theories exist as to why acupuncture may help. One is that it relieves muscle spasms, which in turn relieves neural irritation of the spinal nerves as they traverse the respective paraspinal musculature. Another is that acupuncture decreases nociception by stimulating release of opioid peptides in the dorsal horn.²⁶ A third proposed theory is that acupuncture acts on the afferent nerve fibers responsible for transmitting pain—Aδ and C fibers—activating these afferent nerves to produce an analgesic effect.²⁷

Physiotherapy—The literature suggests that possible first-line therapies for neurogenic pruritus, including BRP and notalgia paresthetica, consist of noninvasive nondermatologic treatments that target cervical spine disease. Notalgia paresthetica and BRP have similar proposed mechanisms of nerve impingement; therefore, they often are grouped together when discussing proposed manual treatment options. Physiotherapy treatment includes cervical muscle strengthening, increased range of motion, application of cervical soft collars, massage, transcutaneous electronic nerve stimulation, and cervical traction.⁷ A study of 12 patients by Raison-Peyron et al²⁸ in 1999 discussed the use of spinal and paraspinal ultrasound or radiation physiotherapy. Six patients underwent this treatment, and the symptoms subsided in 4 cases.²⁸ Another study by Fleischer et al²⁹ in 2011 discussed improvement in 2 patients with notalgia paresthetica by exercise involving active range of motion and strengthening.

Photoprotection—Avoidance of UVR exposure has been beneficial to some patients to reduce symptoms. Use of sunscreen and long-sleeved UV-protective clothing during outdoor activities or the warmer summer months may be beneficial.¹

Medication—Because of the nonspecific clinical presentation of BRP, initial treatment often involves prescription of first-line antipruritic agents, including steroid creams and systemic antihistamines, both of which generally fail to provide symptom relief.^1,30 Medications with neurologic mechanisms of action appear to provide potentially superior outcomes. Neuroleptics, including gabapentin and pregabalin, are typical therapeutic agents for neurogenic pruritus and inhibit nociceptive pain propagation.³¹ Intervention with pregabalin in 3 patients with BRP achieved complete symptom relief in all patients, with initial improvement occurring in as little as 1 week.⁸Mirogabalin, operating under a similar mechanism, has shown preliminary success in treating BRP, causing anecdotal patient improvement within 4 months of initial dosage.³² Prolonged 1-month intravenous naloxone treatment also appars to be promising, offering symptom improvement of at least 80% six months posttreatment.¹⁵ 

Topical interventions for BRP and related neurogenic pruritus have shown limited success. A case series evaluating capsaicin for pruritus offered only transient relief, likely because of its temporary hyperstimulatory and desensitizing effect on neuropeptides.^7,33 In small populations, the use of topical antidepressants has yielded cutaneous and pathological relief for BRP. A case study of a 70-year-old woman evaluated the efficacy of a combination cream of ketamine and amitriptyline (a tricyclic antidepressant) yielding moderate pruritus improvement and notable improvement of secondary brachial skin lesions.³⁴ Oral steroids also have shown success in the treatment of chronic pruritus; however, limited research is available on the efficacy of such medications for BRP, and the long-term use of oral steroids is limited by many side effects.³⁰ 

Interventional Pain Procedure—A 2018 case series investigated 3 patients with a clinical diagnosis of BRP who were treated between 2010 and 2016 with epidural steroid injection using computed tomography guidance of the cervical spine.³⁵ The authors reported that 2 patients had near-complete resolution after 1 interventional procedure. The third patient had a total of 3 injections, with mild to moderate relief that continued to improve on mexiletine.³⁵ Another case in 2010 of a 56-year-old man with BRP documented use of a series of 2 epidural steroid injections that resulted in clinical resolution of symptoms.³⁶

Surgery—There are multiple case studies in the literature that discuss anterior cervical discectomy and fusion (ACDF) as a last resort in patients with refractory BRP of discogenic cause. In 2022, Morosanu et al³⁷ described a case of a 63-year-old woman with BRP in the C5–C6 distribution who had an associated disc protrusion at this level following magnetic resonance imaging. The patient underwent a C5/C6 ACDF after conservative and medical treatment failed, and at 3-month follow up her symptoms had resolved entirely.³⁷ Another case report described a 56-year-old man who ultimately underwent ACDF after failed multimodal treatment attempts, with instant improvement in symptoms. Four months after surgery, the patient reported a 95% improvement of symptoms.¹⁹ An older case in 2008 discussed the use of ACDF in a 64-year-old woman with severe distress and an identifiable surgical target. The patient’s symptoms resolved completely within 1 week after surgery.¹⁰

Conclusion 

The pathogenesis of BRP continues to be an area of debate—it may be secondary to cervical spine disease or UVR. This review found there is more research pointing to cervical spine disease. There is an abundance of literature discussing both conservative and invasive treatment strategies, both of which carry benefits. Further research is needed to better establish the etiology of BRP so that formal treatment guidelines may be established. 

Neuropathic itch can be a frustrating condition for providers and patients, and many treatment modalities often are tried before arriving at a helpful treatment for a particular patient. Clinicians who may encounter BRP in practice benefit from up-to-date literature reviews that provide a summary of management strategies.

Brachioradial pruritus (BRP) is a neuropathic condition typically characterized by localized dysesthesia of the dorsolateral arms.¹ This dysesthesia has been described as a persistent painful itching, burning, tingling, or stinging sensation^2-4 and has a median duration of expression of 24 months.^5,6 The condition may be unilateral or bilateral in nature but tends to have a predilection for a bilateral distribution along the C5 to C6 dermatomes.^1,7,8 There are no primary skin lesions associated with BRP; however, excoriations, prurigo nodules, and lichenification may arise secondary to scratching of the irritated skin.^1,4,5,9 Brachioradial pruritus tends to have a predilection for adult females (3:1 ratio) with lighter skin. The mean age at diagnosis is 59 years, but cases have been reported in patients aged 12 to 84 years.^1,5 The diagnosis of BRP is based on clinical signs and symptoms, though the ice-pack sign tends to be pathognomonic for the diagnosis.^10,11 Although there is no clear evidence on the exact cause of BRP, there are 2 prevalent theories: cervical radiculopathy secondary to cervical spine pathology and/or excessive exposure to UV radiation (UVR) in the summer months.^3-5,12 Brachioradial pruritus remains poorly described in the literature, and even its origin is under debate. As such, the clinician may have difficulty deciding on the best course of management. The goal of this article is to identify and discuss known treatment options for BRP (Table).

Etiology 

Cervical Spine Pathology—A correlation appears to exist between BRP and cervical spine changes seen on plain film radiographs at the levels of C3 to C7, with increased incidence at the C5 to C6 levels. These plain film radiographs typically show degenerative joint disease and neural foraminal stenosis at levels that correlate to the dermatomal distribution of BRP.^1,7,10,12-14 In addition to plain film radiography, some studies have utilized magnetic resonance imaging to view the cervical spine and have documented evidence of intervertebral disc protrusion/bulging, central canal stenosis, neuroforaminal stenosis, and spondylosis at the affected regions.^5,15-17 Moreover, supporting the theory that the cervical spine is responsible for the emergence of BRP, Marziniak et al¹⁷ investigated 41 patients with BRP utilizing magnetic resonance tomography to find that 33 patients (80.5%) had changes in nerve compression, and 8 patients (19.5%) had degenerative changes. In addition to these findings, they found that there was a significant correlation (P<.01) between the dermatomal expression of BRP and the location of cervical anatomical changes.¹⁷ Further validating the relationship between cervical spine pathology and BRP is a case study of a patient who saw rapid and complete resolution of the pruritus following spinal decompression surgery.¹⁰ Another case study described an intramedullary tumor found in a patient with BRP that was diagnosed as an ependymoma after magnetic resonance imaging revealed an intramedullary lesion within the spinal cord between C4 and C7. The location of the tumor and dermatomal pattern of the neuropathic itch pointed to a possible association between nerve compression and BRP.¹⁴ Electromyography studies performed on individuals with BRP have shown an increase in polyphasic units, decreased motor units, and/or denervation changes along the C5/C6 or C6 nerve roots, which provides additional support for the theory of cervical spine pathology as a causative factor for BRP.¹⁶

UVR Exposure—Another etiologic theory for BRP is that UVR exposure may be responsible for the genesis of pruritus. Previously known as solar pruritus, BRP was deemed a clinical condition, as there was increased prevalence in patients living in warmer climates, such as Florida.⁹ Wallengren and Dahlbäck¹⁸ reported that sun exposure is a notable factor in the onset of BRP, as they saw an increase in symptoms during the late summer and a decrease in symptoms over the winter months.To further support the theory that UVR is linked to BRP, several studies have shown that the utilization of sun protection is linked to a reduction of symptoms, specifically in patients who showed seasonal variations of their symptoms.^9,12,19 Additionally, a study by Mirzoyev and Davis⁵ retrospectively reviewed 111 patients diagnosed with BRP. Of these patients, 84 (75.7%) presented with bilateral symptoms, and 54 (48.6%) reported prolonged sun exposure. Both of these findings demonstrate correlation between UVR and BRP.⁵ Interestingly, UV light exposure is known to release β-endorphin in the skin and may theoretically provide an area of exploration between UVR and cervical spine theories.

Conservative Treatment 

Chiropractic Manipulation—Because one etiologic theory includes disease of the cervical spine, there is evidence that targeting this region with treatment is beneficial.⁷ Two case reports found in the literature noted that cervical spine manipulation and cervical traction yielded positive results.^20,21 It has been established that pain generated by disc lesions can be the result of local nociceptive fiber activation, direct mechanical compression of the nerve roots, or inflammatory mediators.²² There are several postulated models describing the hypoalgesic effects of spinal manipulation, which contains both biomechanical and neurophysiological mechanisms. Biomechanical changes theorized to elicit analgesia include restoration of faulty biomechanical movement patterns, breaking up of periarticular adhesions, and reflexogenic muscle inhibition of hypertonic musculature. Hypothesized neurophysiological effects of joint manipulation include an increase in afferent information overwhelming the nociceptive input, reduction of temporal summation, and autonomic activation leading to non–opioid-induced hypoalgesia.²³ Cervical traction is another plausible treatment for BRP, wherein the physiological effects of traction allow for a separation of vertebral bodies and expansion of the intervertebral foramen circumference, thus decreasing compression of the nerve roots.²⁴

Acupuncture—Neurogenic pruritus, including BRP, is a group of conditions that have been treated using acupuncture. Acupuncture treatment consists of intramuscular needle stimulation and has been found to alleviate itching in patients with neurogenic pruritus. In 1 retrospective case series, acupuncture was used to treat 16 patients who were identified as having segmental pruritus. Acupuncture targeted the spasmed paravertebral muscles of the affected dermatomal levels as well as other regions of the body, and it was found that 12 patients (75%) experienced full resolution of symptoms. However, relapse did occur in 6 patients (37%) within 1 to 12 months following treatment.²⁵ Multiple theories exist as to why acupuncture may help. One is that it relieves muscle spasms, which in turn relieves neural irritation of the spinal nerves as they traverse the respective paraspinal musculature. Another is that acupuncture decreases nociception by stimulating release of opioid peptides in the dorsal horn.²⁶ A third proposed theory is that acupuncture acts on the afferent nerve fibers responsible for transmitting pain—Aδ and C fibers—activating these afferent nerves to produce an analgesic effect.²⁷

Physiotherapy—The literature suggests that possible first-line therapies for neurogenic pruritus, including BRP and notalgia paresthetica, consist of noninvasive nondermatologic treatments that target cervical spine disease. Notalgia paresthetica and BRP have similar proposed mechanisms of nerve impingement; therefore, they often are grouped together when discussing proposed manual treatment options. Physiotherapy treatment includes cervical muscle strengthening, increased range of motion, application of cervical soft collars, massage, transcutaneous electronic nerve stimulation, and cervical traction.⁷ A study of 12 patients by Raison-Peyron et al²⁸ in 1999 discussed the use of spinal and paraspinal ultrasound or radiation physiotherapy. Six patients underwent this treatment, and the symptoms subsided in 4 cases.²⁸ Another study by Fleischer et al²⁹ in 2011 discussed improvement in 2 patients with notalgia paresthetica by exercise involving active range of motion and strengthening.

Photoprotection—Avoidance of UVR exposure has been beneficial to some patients to reduce symptoms. Use of sunscreen and long-sleeved UV-protective clothing during outdoor activities or the warmer summer months may be beneficial.¹

Medication—Because of the nonspecific clinical presentation of BRP, initial treatment often involves prescription of first-line antipruritic agents, including steroid creams and systemic antihistamines, both of which generally fail to provide symptom relief.^1,30 Medications with neurologic mechanisms of action appear to provide potentially superior outcomes. Neuroleptics, including gabapentin and pregabalin, are typical therapeutic agents for neurogenic pruritus and inhibit nociceptive pain propagation.³¹ Intervention with pregabalin in 3 patients with BRP achieved complete symptom relief in all patients, with initial improvement occurring in as little as 1 week.⁸Mirogabalin, operating under a similar mechanism, has shown preliminary success in treating BRP, causing anecdotal patient improvement within 4 months of initial dosage.³² Prolonged 1-month intravenous naloxone treatment also appars to be promising, offering symptom improvement of at least 80% six months posttreatment.¹⁵ 

Topical interventions for BRP and related neurogenic pruritus have shown limited success. A case series evaluating capsaicin for pruritus offered only transient relief, likely because of its temporary hyperstimulatory and desensitizing effect on neuropeptides.^7,33 In small populations, the use of topical antidepressants has yielded cutaneous and pathological relief for BRP. A case study of a 70-year-old woman evaluated the efficacy of a combination cream of ketamine and amitriptyline (a tricyclic antidepressant) yielding moderate pruritus improvement and notable improvement of secondary brachial skin lesions.³⁴ Oral steroids also have shown success in the treatment of chronic pruritus; however, limited research is available on the efficacy of such medications for BRP, and the long-term use of oral steroids is limited by many side effects.³⁰ 

Interventional Pain Procedure—A 2018 case series investigated 3 patients with a clinical diagnosis of BRP who were treated between 2010 and 2016 with epidural steroid injection using computed tomography guidance of the cervical spine.³⁵ The authors reported that 2 patients had near-complete resolution after 1 interventional procedure. The third patient had a total of 3 injections, with mild to moderate relief that continued to improve on mexiletine.³⁵ Another case in 2010 of a 56-year-old man with BRP documented use of a series of 2 epidural steroid injections that resulted in clinical resolution of symptoms.³⁶

Surgery—There are multiple case studies in the literature that discuss anterior cervical discectomy and fusion (ACDF) as a last resort in patients with refractory BRP of discogenic cause. In 2022, Morosanu et al³⁷ described a case of a 63-year-old woman with BRP in the C5–C6 distribution who had an associated disc protrusion at this level following magnetic resonance imaging. The patient underwent a C5/C6 ACDF after conservative and medical treatment failed, and at 3-month follow up her symptoms had resolved entirely.³⁷ Another case report described a 56-year-old man who ultimately underwent ACDF after failed multimodal treatment attempts, with instant improvement in symptoms. Four months after surgery, the patient reported a 95% improvement of symptoms.¹⁹ An older case in 2008 discussed the use of ACDF in a 64-year-old woman with severe distress and an identifiable surgical target. The patient’s symptoms resolved completely within 1 week after surgery.¹⁰

Conclusion 

The pathogenesis of BRP continues to be an area of debate—it may be secondary to cervical spine disease or UVR. This review found there is more research pointing to cervical spine disease. There is an abundance of literature discussing both conservative and invasive treatment strategies, both of which carry benefits. Further research is needed to better establish the etiology of BRP so that formal treatment guidelines may be established. 

Neuropathic itch can be a frustrating condition for providers and patients, and many treatment modalities often are tried before arriving at a helpful treatment for a particular patient. Clinicians who may encounter BRP in practice benefit from up-to-date literature reviews that provide a summary of management strategies.

Brachioradial pruritus (BRP) is a neuropathic condition typically characterized by localized dysesthesia of the dorsolateral arms.¹ This dysesthesia has been described as a persistent painful itching, burning, tingling, or stinging sensation^2-4 and has a median duration of expression of 24 months.^5,6 The condition may be unilateral or bilateral in nature but tends to have a predilection for a bilateral distribution along the C5 to C6 dermatomes.^1,7,8 There are no primary skin lesions associated with BRP; however, excoriations, prurigo nodules, and lichenification may arise secondary to scratching of the irritated skin.^1,4,5,9 Brachioradial pruritus tends to have a predilection for adult females (3:1 ratio) with lighter skin. The mean age at diagnosis is 59 years, but cases have been reported in patients aged 12 to 84 years.^1,5 The diagnosis of BRP is based on clinical signs and symptoms, though the ice-pack sign tends to be pathognomonic for the diagnosis.^10,11 Although there is no clear evidence on the exact cause of BRP, there are 2 prevalent theories: cervical radiculopathy secondary to cervical spine pathology and/or excessive exposure to UV radiation (UVR) in the summer months.^3-5,12 Brachioradial pruritus remains poorly described in the literature, and even its origin is under debate. As such, the clinician may have difficulty deciding on the best course of management. The goal of this article is to identify and discuss known treatment options for BRP (Table).

Etiology 

Cervical Spine Pathology—A correlation appears to exist between BRP and cervical spine changes seen on plain film radiographs at the levels of C3 to C7, with increased incidence at the C5 to C6 levels. These plain film radiographs typically show degenerative joint disease and neural foraminal stenosis at levels that correlate to the dermatomal distribution of BRP.^1,7,10,12-14 In addition to plain film radiography, some studies have utilized magnetic resonance imaging to view the cervical spine and have documented evidence of intervertebral disc protrusion/bulging, central canal stenosis, neuroforaminal stenosis, and spondylosis at the affected regions.^5,15-17 Moreover, supporting the theory that the cervical spine is responsible for the emergence of BRP, Marziniak et al¹⁷ investigated 41 patients with BRP utilizing magnetic resonance tomography to find that 33 patients (80.5%) had changes in nerve compression, and 8 patients (19.5%) had degenerative changes. In addition to these findings, they found that there was a significant correlation (P<.01) between the dermatomal expression of BRP and the location of cervical anatomical changes.¹⁷ Further validating the relationship between cervical spine pathology and BRP is a case study of a patient who saw rapid and complete resolution of the pruritus following spinal decompression surgery.¹⁰ Another case study described an intramedullary tumor found in a patient with BRP that was diagnosed as an ependymoma after magnetic resonance imaging revealed an intramedullary lesion within the spinal cord between C4 and C7. The location of the tumor and dermatomal pattern of the neuropathic itch pointed to a possible association between nerve compression and BRP.¹⁴ Electromyography studies performed on individuals with BRP have shown an increase in polyphasic units, decreased motor units, and/or denervation changes along the C5/C6 or C6 nerve roots, which provides additional support for the theory of cervical spine pathology as a causative factor for BRP.¹⁶

UVR Exposure—Another etiologic theory for BRP is that UVR exposure may be responsible for the genesis of pruritus. Previously known as solar pruritus, BRP was deemed a clinical condition, as there was increased prevalence in patients living in warmer climates, such as Florida.⁹ Wallengren and Dahlbäck¹⁸ reported that sun exposure is a notable factor in the onset of BRP, as they saw an increase in symptoms during the late summer and a decrease in symptoms over the winter months.To further support the theory that UVR is linked to BRP, several studies have shown that the utilization of sun protection is linked to a reduction of symptoms, specifically in patients who showed seasonal variations of their symptoms.^9,12,19 Additionally, a study by Mirzoyev and Davis⁵ retrospectively reviewed 111 patients diagnosed with BRP. Of these patients, 84 (75.7%) presented with bilateral symptoms, and 54 (48.6%) reported prolonged sun exposure. Both of these findings demonstrate correlation between UVR and BRP.⁵ Interestingly, UV light exposure is known to release β-endorphin in the skin and may theoretically provide an area of exploration between UVR and cervical spine theories.

Conservative Treatment 

Chiropractic Manipulation—Because one etiologic theory includes disease of the cervical spine, there is evidence that targeting this region with treatment is beneficial.⁷ Two case reports found in the literature noted that cervical spine manipulation and cervical traction yielded positive results.^20,21 It has been established that pain generated by disc lesions can be the result of local nociceptive fiber activation, direct mechanical compression of the nerve roots, or inflammatory mediators.²² There are several postulated models describing the hypoalgesic effects of spinal manipulation, which contains both biomechanical and neurophysiological mechanisms. Biomechanical changes theorized to elicit analgesia include restoration of faulty biomechanical movement patterns, breaking up of periarticular adhesions, and reflexogenic muscle inhibition of hypertonic musculature. Hypothesized neurophysiological effects of joint manipulation include an increase in afferent information overwhelming the nociceptive input, reduction of temporal summation, and autonomic activation leading to non–opioid-induced hypoalgesia.²³ Cervical traction is another plausible treatment for BRP, wherein the physiological effects of traction allow for a separation of vertebral bodies and expansion of the intervertebral foramen circumference, thus decreasing compression of the nerve roots.²⁴

Acupuncture—Neurogenic pruritus, including BRP, is a group of conditions that have been treated using acupuncture. Acupuncture treatment consists of intramuscular needle stimulation and has been found to alleviate itching in patients with neurogenic pruritus. In 1 retrospective case series, acupuncture was used to treat 16 patients who were identified as having segmental pruritus. Acupuncture targeted the spasmed paravertebral muscles of the affected dermatomal levels as well as other regions of the body, and it was found that 12 patients (75%) experienced full resolution of symptoms. However, relapse did occur in 6 patients (37%) within 1 to 12 months following treatment.²⁵ Multiple theories exist as to why acupuncture may help. One is that it relieves muscle spasms, which in turn relieves neural irritation of the spinal nerves as they traverse the respective paraspinal musculature. Another is that acupuncture decreases nociception by stimulating release of opioid peptides in the dorsal horn.²⁶ A third proposed theory is that acupuncture acts on the afferent nerve fibers responsible for transmitting pain—Aδ and C fibers—activating these afferent nerves to produce an analgesic effect.²⁷

Physiotherapy—The literature suggests that possible first-line therapies for neurogenic pruritus, including BRP and notalgia paresthetica, consist of noninvasive nondermatologic treatments that target cervical spine disease. Notalgia paresthetica and BRP have similar proposed mechanisms of nerve impingement; therefore, they often are grouped together when discussing proposed manual treatment options. Physiotherapy treatment includes cervical muscle strengthening, increased range of motion, application of cervical soft collars, massage, transcutaneous electronic nerve stimulation, and cervical traction.⁷ A study of 12 patients by Raison-Peyron et al²⁸ in 1999 discussed the use of spinal and paraspinal ultrasound or radiation physiotherapy. Six patients underwent this treatment, and the symptoms subsided in 4 cases.²⁸ Another study by Fleischer et al²⁹ in 2011 discussed improvement in 2 patients with notalgia paresthetica by exercise involving active range of motion and strengthening.

Photoprotection—Avoidance of UVR exposure has been beneficial to some patients to reduce symptoms. Use of sunscreen and long-sleeved UV-protective clothing during outdoor activities or the warmer summer months may be beneficial.¹

Medication—Because of the nonspecific clinical presentation of BRP, initial treatment often involves prescription of first-line antipruritic agents, including steroid creams and systemic antihistamines, both of which generally fail to provide symptom relief.^1,30 Medications with neurologic mechanisms of action appear to provide potentially superior outcomes. Neuroleptics, including gabapentin and pregabalin, are typical therapeutic agents for neurogenic pruritus and inhibit nociceptive pain propagation.³¹ Intervention with pregabalin in 3 patients with BRP achieved complete symptom relief in all patients, with initial improvement occurring in as little as 1 week.⁸Mirogabalin, operating under a similar mechanism, has shown preliminary success in treating BRP, causing anecdotal patient improvement within 4 months of initial dosage.³² Prolonged 1-month intravenous naloxone treatment also appars to be promising, offering symptom improvement of at least 80% six months posttreatment.¹⁵ 

Topical interventions for BRP and related neurogenic pruritus have shown limited success. A case series evaluating capsaicin for pruritus offered only transient relief, likely because of its temporary hyperstimulatory and desensitizing effect on neuropeptides.^7,33 In small populations, the use of topical antidepressants has yielded cutaneous and pathological relief for BRP. A case study of a 70-year-old woman evaluated the efficacy of a combination cream of ketamine and amitriptyline (a tricyclic antidepressant) yielding moderate pruritus improvement and notable improvement of secondary brachial skin lesions.³⁴ Oral steroids also have shown success in the treatment of chronic pruritus; however, limited research is available on the efficacy of such medications for BRP, and the long-term use of oral steroids is limited by many side effects.³⁰ 

Interventional Pain Procedure—A 2018 case series investigated 3 patients with a clinical diagnosis of BRP who were treated between 2010 and 2016 with epidural steroid injection using computed tomography guidance of the cervical spine.³⁵ The authors reported that 2 patients had near-complete resolution after 1 interventional procedure. The third patient had a total of 3 injections, with mild to moderate relief that continued to improve on mexiletine.³⁵ Another case in 2010 of a 56-year-old man with BRP documented use of a series of 2 epidural steroid injections that resulted in clinical resolution of symptoms.³⁶

Surgery—There are multiple case studies in the literature that discuss anterior cervical discectomy and fusion (ACDF) as a last resort in patients with refractory BRP of discogenic cause. In 2022, Morosanu et al³⁷ described a case of a 63-year-old woman with BRP in the C5–C6 distribution who had an associated disc protrusion at this level following magnetic resonance imaging. The patient underwent a C5/C6 ACDF after conservative and medical treatment failed, and at 3-month follow up her symptoms had resolved entirely.³⁷ Another case report described a 56-year-old man who ultimately underwent ACDF after failed multimodal treatment attempts, with instant improvement in symptoms. Four months after surgery, the patient reported a 95% improvement of symptoms.¹⁹ An older case in 2008 discussed the use of ACDF in a 64-year-old woman with severe distress and an identifiable surgical target. The patient’s symptoms resolved completely within 1 week after surgery.¹⁰

Conclusion 

The pathogenesis of BRP continues to be an area of debate—it may be secondary to cervical spine disease or UVR. This review found there is more research pointing to cervical spine disease. There is an abundance of literature discussing both conservative and invasive treatment strategies, both of which carry benefits. Further research is needed to better establish the etiology of BRP so that formal treatment guidelines may be established. 

Neuropathic itch can be a frustrating condition for providers and patients, and many treatment modalities often are tried before arriving at a helpful treatment for a particular patient. Clinicians who may encounter BRP in practice benefit from up-to-date literature reviews that provide a summary of management strategies.

The Diagnosis: Mycobacterial Infection

Mycobacterium marinum is a waterborne nontuberculous mycobacterium prevailing in salt water, brackish water, and still or streaming fresh water that infects fish and amphibians worldwide.^1,2 Although first described in 1926 as the organism responsible for the demise of fish in an aquarium in Philadelphia, Pennsylvania, it was not until 1954 that the organism was linked to the cause of infection in humans after it was identified in 80 individuals who had utilized the same swimming pool.¹ Due to its ability to secondarily contaminate aquariums, swimming pools, and rivers, this species can give rise to infection in humans, likely though an impaired skin barrier or points of trauma. It commonly is known as swimming pool or fish tank granuloma.^3,4

Infection by M marinum commonly presents with lesions on the upper extremities, particularly the hands, that appear approximately 2 to 3 weeks following exposure to the organism.² Lesions are categorized as superficial (type 1), granulomatous (type 2), or deep (type 3).¹ Superficial lesions usually are solitary and painless; may exhibit purulent secretions; and consist of papulonodular, verrucose, or ulcerated granulomatous inflammation.¹ These lesions may spread in a sporotrichoidlike pattern or in a linear fashion along lymphatic channels, similar to sporotrichosis. Granulomatous lesions present as solitary or numerous granulomas that typically are swollen, tender, and purulent. Deep lesions are the rarest form and primarily are seen in immunocompromised patients, particularly transplant recipients. Infection can lead to arthritis, tenosynovitis, or osteomyelitis.¹

Mycobacterium marinum infection is diagnosed via tissue biopsy for concomitant histopathologic examination and culture from a nonulcerated area close to the lesion.^1,2 If cultures do not grow, polymerase chain reaction (PCR) or PCR restriction fragment length polymorphism analysis can be conducted. These techniques can exclude other potential diagnoses; however, PCR is unable to provide information on antibiotic susceptibility.1 Biopsy of lesions reveals a nonspecific inflammatory type of reaction within the dermis consisting of lymphocytes, polymorphonuclear cells, and histiocytes.^1,4 Additionally, a granulomatous inflammatory infiltrate resembling tuberculoid granuloma, sarcoidlike granuloma, or rheumatoidlike nodules also may be observed.1 With staining, the acid-fast organisms can be viewed within histiocytes, sometimes demonstrating transverse bands.⁴

The preferred treatment of M marinum infection is antibiotic therapy.² It generally is not recommended to obtain in vitro drug sensitivity testing, as mutational resistance to the commonly utilized drugs is minimal. Microbiologic investigation may be warranted in cases of treatment failure or persistently positive cultures over a period of several months.^1,2 Due to its rarity, no clinical trials exist to guide optimal management of M marinum infection, according to a search of ClinicalTrials.gov. Nonetheless, anecdotal evidence of prior cases can direct the selection of antibiotics. Mycobacterium marinum appears to respond to certain tetracyclines, including minocycline followed by doxycycline. Other options include clarithromycin, clarithromycin in combination with rifampin, rifampin in combination with ethambutol, trimethoprimsulfamethoxazole, and ciprofloxacin.^1,2 Surgical debridement or excision may be indicated, especially in an infection involving deep structures, though recurrences have been reported in some individuals following surgery.^2,4 Nonspecific treatment such as hyperthermic or liquid nitrogen local treatment have been used experimentally with positive outcomes; however, experience with this treatment modality is limited.²

Sarcoidosis is an immune-mediated systemic disorder that most commonly affects the lungs and skin. Histopathology shows sarcoidal granulomas with features similar to M marinum infection. The clinical presentation often is described as red-brown macules or papules affecting the face, rarely with overlying scale or ulceration.⁵ Majocchi granuloma is a dermatophyte fungal infection involving the hair follicles. Although application of topical steroids can worsen the involvement, it commonly displays perifollicular pustules,⁶ which were not seen in our patient. Granuloma annulare is a benign granulomatous disorder that will spontaneously resolve, typically within 2 years of onset. It presents as an annular or arcuate red-brown papule or plaque without overlying scale or ulceration,⁷ unlike the lesion seen in our patient. Cutaneous lymphoma is a malignant lymphoproliferative disease most commonly affecting middle-aged White men. The presentation is variable and may include an ulcerated plaque⁸; the lack of systemic symptoms and notable progression over several years in our patient made this a less likely diagnosis.

The Diagnosis: Mycobacterial Infection

Mycobacterium marinum is a waterborne nontuberculous mycobacterium prevailing in salt water, brackish water, and still or streaming fresh water that infects fish and amphibians worldwide.^1,2 Although first described in 1926 as the organism responsible for the demise of fish in an aquarium in Philadelphia, Pennsylvania, it was not until 1954 that the organism was linked to the cause of infection in humans after it was identified in 80 individuals who had utilized the same swimming pool.¹ Due to its ability to secondarily contaminate aquariums, swimming pools, and rivers, this species can give rise to infection in humans, likely though an impaired skin barrier or points of trauma. It commonly is known as swimming pool or fish tank granuloma.^3,4

Infection by M marinum commonly presents with lesions on the upper extremities, particularly the hands, that appear approximately 2 to 3 weeks following exposure to the organism.² Lesions are categorized as superficial (type 1), granulomatous (type 2), or deep (type 3).¹ Superficial lesions usually are solitary and painless; may exhibit purulent secretions; and consist of papulonodular, verrucose, or ulcerated granulomatous inflammation.¹ These lesions may spread in a sporotrichoidlike pattern or in a linear fashion along lymphatic channels, similar to sporotrichosis. Granulomatous lesions present as solitary or numerous granulomas that typically are swollen, tender, and purulent. Deep lesions are the rarest form and primarily are seen in immunocompromised patients, particularly transplant recipients. Infection can lead to arthritis, tenosynovitis, or osteomyelitis.¹

Mycobacterium marinum infection is diagnosed via tissue biopsy for concomitant histopathologic examination and culture from a nonulcerated area close to the lesion.^1,2 If cultures do not grow, polymerase chain reaction (PCR) or PCR restriction fragment length polymorphism analysis can be conducted. These techniques can exclude other potential diagnoses; however, PCR is unable to provide information on antibiotic susceptibility.1 Biopsy of lesions reveals a nonspecific inflammatory type of reaction within the dermis consisting of lymphocytes, polymorphonuclear cells, and histiocytes.^1,4 Additionally, a granulomatous inflammatory infiltrate resembling tuberculoid granuloma, sarcoidlike granuloma, or rheumatoidlike nodules also may be observed.1 With staining, the acid-fast organisms can be viewed within histiocytes, sometimes demonstrating transverse bands.⁴

The preferred treatment of M marinum infection is antibiotic therapy.² It generally is not recommended to obtain in vitro drug sensitivity testing, as mutational resistance to the commonly utilized drugs is minimal. Microbiologic investigation may be warranted in cases of treatment failure or persistently positive cultures over a period of several months.^1,2 Due to its rarity, no clinical trials exist to guide optimal management of M marinum infection, according to a search of ClinicalTrials.gov. Nonetheless, anecdotal evidence of prior cases can direct the selection of antibiotics. Mycobacterium marinum appears to respond to certain tetracyclines, including minocycline followed by doxycycline. Other options include clarithromycin, clarithromycin in combination with rifampin, rifampin in combination with ethambutol, trimethoprimsulfamethoxazole, and ciprofloxacin.^1,2 Surgical debridement or excision may be indicated, especially in an infection involving deep structures, though recurrences have been reported in some individuals following surgery.^2,4 Nonspecific treatment such as hyperthermic or liquid nitrogen local treatment have been used experimentally with positive outcomes; however, experience with this treatment modality is limited.²

Sarcoidosis is an immune-mediated systemic disorder that most commonly affects the lungs and skin. Histopathology shows sarcoidal granulomas with features similar to M marinum infection. The clinical presentation often is described as red-brown macules or papules affecting the face, rarely with overlying scale or ulceration.⁵ Majocchi granuloma is a dermatophyte fungal infection involving the hair follicles. Although application of topical steroids can worsen the involvement, it commonly displays perifollicular pustules,⁶ which were not seen in our patient. Granuloma annulare is a benign granulomatous disorder that will spontaneously resolve, typically within 2 years of onset. It presents as an annular or arcuate red-brown papule or plaque without overlying scale or ulceration,⁷ unlike the lesion seen in our patient. Cutaneous lymphoma is a malignant lymphoproliferative disease most commonly affecting middle-aged White men. The presentation is variable and may include an ulcerated plaque⁸; the lack of systemic symptoms and notable progression over several years in our patient made this a less likely diagnosis.

The Diagnosis: Mycobacterial Infection

Mycobacterium marinum is a waterborne nontuberculous mycobacterium prevailing in salt water, brackish water, and still or streaming fresh water that infects fish and amphibians worldwide.^1,2 Although first described in 1926 as the organism responsible for the demise of fish in an aquarium in Philadelphia, Pennsylvania, it was not until 1954 that the organism was linked to the cause of infection in humans after it was identified in 80 individuals who had utilized the same swimming pool.¹ Due to its ability to secondarily contaminate aquariums, swimming pools, and rivers, this species can give rise to infection in humans, likely though an impaired skin barrier or points of trauma. It commonly is known as swimming pool or fish tank granuloma.^3,4

Infection by M marinum commonly presents with lesions on the upper extremities, particularly the hands, that appear approximately 2 to 3 weeks following exposure to the organism.² Lesions are categorized as superficial (type 1), granulomatous (type 2), or deep (type 3).¹ Superficial lesions usually are solitary and painless; may exhibit purulent secretions; and consist of papulonodular, verrucose, or ulcerated granulomatous inflammation.¹ These lesions may spread in a sporotrichoidlike pattern or in a linear fashion along lymphatic channels, similar to sporotrichosis. Granulomatous lesions present as solitary or numerous granulomas that typically are swollen, tender, and purulent. Deep lesions are the rarest form and primarily are seen in immunocompromised patients, particularly transplant recipients. Infection can lead to arthritis, tenosynovitis, or osteomyelitis.¹

Mycobacterium marinum infection is diagnosed via tissue biopsy for concomitant histopathologic examination and culture from a nonulcerated area close to the lesion.^1,2 If cultures do not grow, polymerase chain reaction (PCR) or PCR restriction fragment length polymorphism analysis can be conducted. These techniques can exclude other potential diagnoses; however, PCR is unable to provide information on antibiotic susceptibility.1 Biopsy of lesions reveals a nonspecific inflammatory type of reaction within the dermis consisting of lymphocytes, polymorphonuclear cells, and histiocytes.^1,4 Additionally, a granulomatous inflammatory infiltrate resembling tuberculoid granuloma, sarcoidlike granuloma, or rheumatoidlike nodules also may be observed.1 With staining, the acid-fast organisms can be viewed within histiocytes, sometimes demonstrating transverse bands.⁴

The preferred treatment of M marinum infection is antibiotic therapy.² It generally is not recommended to obtain in vitro drug sensitivity testing, as mutational resistance to the commonly utilized drugs is minimal. Microbiologic investigation may be warranted in cases of treatment failure or persistently positive cultures over a period of several months.^1,2 Due to its rarity, no clinical trials exist to guide optimal management of M marinum infection, according to a search of ClinicalTrials.gov. Nonetheless, anecdotal evidence of prior cases can direct the selection of antibiotics. Mycobacterium marinum appears to respond to certain tetracyclines, including minocycline followed by doxycycline. Other options include clarithromycin, clarithromycin in combination with rifampin, rifampin in combination with ethambutol, trimethoprimsulfamethoxazole, and ciprofloxacin.^1,2 Surgical debridement or excision may be indicated, especially in an infection involving deep structures, though recurrences have been reported in some individuals following surgery.^2,4 Nonspecific treatment such as hyperthermic or liquid nitrogen local treatment have been used experimentally with positive outcomes; however, experience with this treatment modality is limited.²

Sarcoidosis is an immune-mediated systemic disorder that most commonly affects the lungs and skin. Histopathology shows sarcoidal granulomas with features similar to M marinum infection. The clinical presentation often is described as red-brown macules or papules affecting the face, rarely with overlying scale or ulceration.⁵ Majocchi granuloma is a dermatophyte fungal infection involving the hair follicles. Although application of topical steroids can worsen the involvement, it commonly displays perifollicular pustules,⁶ which were not seen in our patient. Granuloma annulare is a benign granulomatous disorder that will spontaneously resolve, typically within 2 years of onset. It presents as an annular or arcuate red-brown papule or plaque without overlying scale or ulceration,⁷ unlike the lesion seen in our patient. Cutaneous lymphoma is a malignant lymphoproliferative disease most commonly affecting middle-aged White men. The presentation is variable and may include an ulcerated plaque⁸; the lack of systemic symptoms and notable progression over several years in our patient made this a less likely diagnosis.

To the Editor:

Palifermin is a recombinant keratinocyte growth factor (KGF) approved by the US Food and Drug Administration to prevent oral mucositis following radiation therapy or chemotherapy. Cutaneous reactions associated with palifermin have been reported.^1-5 One case described a distinctive polymorphous eruption in a patient treated with palifermin.⁶ On histologic analysis, papules demonstrated findings similar to verrucae, with evidence of papillomatosis, hypergranulosis, and hyperorthokeratosis. Given its mechanism of action as a KGF, it was concluded that these findings were likely the direct result of palifermin.⁶ We report a similar case of a patient who was given palifermin prior to an autologous stem cell transplant. Histopathologic analysis confirmed epidermal dysmaturation and marked hypergranulosis. We present this case to expand the paucity of data on palifermin-associated cutaneous reactions.

A 63-year-old man with a history of psoriasis, eczema, and relapsed diffuse large B-cell lymphoma was admitted to the hospital for routine management of an autologous stem cell transplant with a conditioning regimen involving thiotepa, busulfan, and cyclophosphamide. The patient had completed a 3-day course of palifermin 1 day prior to the current presentation. On admission, he developed a pruritic erythematous rash over the face and axillae. Within 24 hours, the facial rash progressed with appreciable edema, and he reported difficulty opening his eyes. He denied any fever, nausea, vomiting, diarrhea, or increased fatigue. He also denied use of any other medications other than starting a course of prophylactic trimethoprim-sulfamethoxazole 3 times weekly 2 months prior to admission.

Diffuse blanching erythema with a well-demarcated linear border was noted along the lower anterior neck extending to the posterior hairline. There was notable edema but no evidence of pustules or overlying scale. Similar areas of blanchable erythema were present along the axillae and inguinal folds. There also were flesh-colored to pink papules within the axillary vaults and on the back that occasionally coalesced into plaques. There was no involvement of the mucous membranes or acral sites.

A complete blood cell count with differential and a comprehensive metabolic profile largely were unremarkable. A potassium hydroxide preparation of the face and groin was negative for hyphae and Demodex mites. Histopathologic analysis from a punch biopsy of a representative papule from the posterior neck demonstrated epidermal dysmaturation with marked thickening of the granular cell layer with notably large keratohyalin granules (Figure 1).

In the setting of treatment with thiotepa, we recommended supportive care with cool compresses rather than topical medication because he was neutropenic, and we wanted to avoid further immunosuppression or toxicity. By 24 hours after completing the course of palifermin, the patient experienced complete resolution of the rash. At his request, the trial of palifermin was restarted 10 days into conditioning therapy. A similar rash with less facial edema but more prominent involvement of the chest appeared 3 days into the retrial (Figure 2). The medication was discontinued, which resulted in resolution of the rash. Again, the patient remained afebrile without involvement of the mucous membranes. Liver enzyme and creatinine levels remained within reference range.Eosinophilia and the level of atypical lymphocytes could not be assessed because of leukopenia in the setting of recent chemotherapy. The rash self-resolved in 4 days.

Palifermin is a recombinant form of human KGF that is more stable than the endogenous form but retains all vital properties of the protein.^5-7 Similar to other growth factors, KGF induces differentiation, proliferation, and migration of cells in vivo.⁸ However, it uniquely produces a targeted effect on epithelial cells in the skin, oral mucosa, lungs, gastrointestinal tract, and genitourinary system.^7-9

Palifermin was approved by the US Food and Drug Administration in 2004 for the prevention and treatment of severe oral mucositis in patients receiving myelotoxic therapy prior to stem cell transplantation.^7,9 Severe mucositis occurs in approximately 70% to 80% of patients receiving radiation or chemotherapy-based conditioning treatments.^4,7 Compared to placebo, palifermin has been shown to greatly reduce the incidence of Grade 4 oral mucositis, defined as severe enough to prevent alimentation.¹⁰

The proliferative effect of palifermin on the oral mucosa is beneficial to patients but likely is the driving force behind its cutaneous adverse effects. A nonspecific rash is the most commonly cited treatment-related adverse event associated with palifermin, occurring in approximately 62% of patients.^5,7,9

Our case is a rare report of a palifermin-associated cutaneous reaction. Previous cases have cited the occurrence of palmoplantar erythrodysesthesias, papulopustular eruptions involving the face and chest, and a papular rash involving the dorsal hands and intertriginous areas.^1-4 Another report documented a “mild rash” but failed to further characterize the morphology or the body site involved.⁵

In 2009, King et al⁶ reported the occurrence of a lichen planus–like eruption involving the intertriginous regions and of white oral plaques in a patient treated with palifermin. Hematoxylin and eosin staining of a representative lesion in that patient demonstrated an appearance similar to that of verrucae, including papillomatosis, hypergranulosis, and hyperorthokeratosis.

King et al⁶ expanded analysis of the reaction to include immunohistochemical study, using targeted antibody stains for cytokeratin 5/6 and Ki-67 protein.Staining with Ki-67 showed dramatically increased activity within basilar and suprabasilar keratinocytes in a biopsy taken at the height of the reaction. Biopsy specimens obtained when the eruption was clinically resolving—2 days after the first biopsy—showed decreased Ki-67 staining.These findings taken together suggest a direct causal effect of palifermin inducing hyperkeratotic changes appreciated on examination of treated patients.⁶

We present this case to add to current data regarding palifermin-induced cutaneous changes. Unique to our patient was a strikingly well-demarcated rash confined to the head and neck. Although a photosensitive eruption due to trimethoprim-sulfamethoxazole is conceivable, the fixed time course of the eruption—corresponding to (1) initiation and discontinuation of palifermin and (2) histologic findings—led us to conclude that this self-limited eruption likely was due to palifermin.

To the Editor:

Palifermin is a recombinant keratinocyte growth factor (KGF) approved by the US Food and Drug Administration to prevent oral mucositis following radiation therapy or chemotherapy. Cutaneous reactions associated with palifermin have been reported.^1-5 One case described a distinctive polymorphous eruption in a patient treated with palifermin.⁶ On histologic analysis, papules demonstrated findings similar to verrucae, with evidence of papillomatosis, hypergranulosis, and hyperorthokeratosis. Given its mechanism of action as a KGF, it was concluded that these findings were likely the direct result of palifermin.⁶ We report a similar case of a patient who was given palifermin prior to an autologous stem cell transplant. Histopathologic analysis confirmed epidermal dysmaturation and marked hypergranulosis. We present this case to expand the paucity of data on palifermin-associated cutaneous reactions.

A 63-year-old man with a history of psoriasis, eczema, and relapsed diffuse large B-cell lymphoma was admitted to the hospital for routine management of an autologous stem cell transplant with a conditioning regimen involving thiotepa, busulfan, and cyclophosphamide. The patient had completed a 3-day course of palifermin 1 day prior to the current presentation. On admission, he developed a pruritic erythematous rash over the face and axillae. Within 24 hours, the facial rash progressed with appreciable edema, and he reported difficulty opening his eyes. He denied any fever, nausea, vomiting, diarrhea, or increased fatigue. He also denied use of any other medications other than starting a course of prophylactic trimethoprim-sulfamethoxazole 3 times weekly 2 months prior to admission.

Diffuse blanching erythema with a well-demarcated linear border was noted along the lower anterior neck extending to the posterior hairline. There was notable edema but no evidence of pustules or overlying scale. Similar areas of blanchable erythema were present along the axillae and inguinal folds. There also were flesh-colored to pink papules within the axillary vaults and on the back that occasionally coalesced into plaques. There was no involvement of the mucous membranes or acral sites.

A complete blood cell count with differential and a comprehensive metabolic profile largely were unremarkable. A potassium hydroxide preparation of the face and groin was negative for hyphae and Demodex mites. Histopathologic analysis from a punch biopsy of a representative papule from the posterior neck demonstrated epidermal dysmaturation with marked thickening of the granular cell layer with notably large keratohyalin granules (Figure 1).

In the setting of treatment with thiotepa, we recommended supportive care with cool compresses rather than topical medication because he was neutropenic, and we wanted to avoid further immunosuppression or toxicity. By 24 hours after completing the course of palifermin, the patient experienced complete resolution of the rash. At his request, the trial of palifermin was restarted 10 days into conditioning therapy. A similar rash with less facial edema but more prominent involvement of the chest appeared 3 days into the retrial (Figure 2). The medication was discontinued, which resulted in resolution of the rash. Again, the patient remained afebrile without involvement of the mucous membranes. Liver enzyme and creatinine levels remained within reference range.Eosinophilia and the level of atypical lymphocytes could not be assessed because of leukopenia in the setting of recent chemotherapy. The rash self-resolved in 4 days.

Palifermin is a recombinant form of human KGF that is more stable than the endogenous form but retains all vital properties of the protein.^5-7 Similar to other growth factors, KGF induces differentiation, proliferation, and migration of cells in vivo.⁸ However, it uniquely produces a targeted effect on epithelial cells in the skin, oral mucosa, lungs, gastrointestinal tract, and genitourinary system.^7-9

Palifermin was approved by the US Food and Drug Administration in 2004 for the prevention and treatment of severe oral mucositis in patients receiving myelotoxic therapy prior to stem cell transplantation.^7,9 Severe mucositis occurs in approximately 70% to 80% of patients receiving radiation or chemotherapy-based conditioning treatments.^4,7 Compared to placebo, palifermin has been shown to greatly reduce the incidence of Grade 4 oral mucositis, defined as severe enough to prevent alimentation.¹⁰

The proliferative effect of palifermin on the oral mucosa is beneficial to patients but likely is the driving force behind its cutaneous adverse effects. A nonspecific rash is the most commonly cited treatment-related adverse event associated with palifermin, occurring in approximately 62% of patients.^5,7,9

Our case is a rare report of a palifermin-associated cutaneous reaction. Previous cases have cited the occurrence of palmoplantar erythrodysesthesias, papulopustular eruptions involving the face and chest, and a papular rash involving the dorsal hands and intertriginous areas.^1-4 Another report documented a “mild rash” but failed to further characterize the morphology or the body site involved.⁵

In 2009, King et al⁶ reported the occurrence of a lichen planus–like eruption involving the intertriginous regions and of white oral plaques in a patient treated with palifermin. Hematoxylin and eosin staining of a representative lesion in that patient demonstrated an appearance similar to that of verrucae, including papillomatosis, hypergranulosis, and hyperorthokeratosis.

King et al⁶ expanded analysis of the reaction to include immunohistochemical study, using targeted antibody stains for cytokeratin 5/6 and Ki-67 protein.Staining with Ki-67 showed dramatically increased activity within basilar and suprabasilar keratinocytes in a biopsy taken at the height of the reaction. Biopsy specimens obtained when the eruption was clinically resolving—2 days after the first biopsy—showed decreased Ki-67 staining.These findings taken together suggest a direct causal effect of palifermin inducing hyperkeratotic changes appreciated on examination of treated patients.⁶

We present this case to add to current data regarding palifermin-induced cutaneous changes. Unique to our patient was a strikingly well-demarcated rash confined to the head and neck. Although a photosensitive eruption due to trimethoprim-sulfamethoxazole is conceivable, the fixed time course of the eruption—corresponding to (1) initiation and discontinuation of palifermin and (2) histologic findings—led us to conclude that this self-limited eruption likely was due to palifermin.

To the Editor:

Palifermin is a recombinant keratinocyte growth factor (KGF) approved by the US Food and Drug Administration to prevent oral mucositis following radiation therapy or chemotherapy. Cutaneous reactions associated with palifermin have been reported.^1-5 One case described a distinctive polymorphous eruption in a patient treated with palifermin.⁶ On histologic analysis, papules demonstrated findings similar to verrucae, with evidence of papillomatosis, hypergranulosis, and hyperorthokeratosis. Given its mechanism of action as a KGF, it was concluded that these findings were likely the direct result of palifermin.⁶ We report a similar case of a patient who was given palifermin prior to an autologous stem cell transplant. Histopathologic analysis confirmed epidermal dysmaturation and marked hypergranulosis. We present this case to expand the paucity of data on palifermin-associated cutaneous reactions.

A 63-year-old man with a history of psoriasis, eczema, and relapsed diffuse large B-cell lymphoma was admitted to the hospital for routine management of an autologous stem cell transplant with a conditioning regimen involving thiotepa, busulfan, and cyclophosphamide. The patient had completed a 3-day course of palifermin 1 day prior to the current presentation. On admission, he developed a pruritic erythematous rash over the face and axillae. Within 24 hours, the facial rash progressed with appreciable edema, and he reported difficulty opening his eyes. He denied any fever, nausea, vomiting, diarrhea, or increased fatigue. He also denied use of any other medications other than starting a course of prophylactic trimethoprim-sulfamethoxazole 3 times weekly 2 months prior to admission.

Diffuse blanching erythema with a well-demarcated linear border was noted along the lower anterior neck extending to the posterior hairline. There was notable edema but no evidence of pustules or overlying scale. Similar areas of blanchable erythema were present along the axillae and inguinal folds. There also were flesh-colored to pink papules within the axillary vaults and on the back that occasionally coalesced into plaques. There was no involvement of the mucous membranes or acral sites.

A complete blood cell count with differential and a comprehensive metabolic profile largely were unremarkable. A potassium hydroxide preparation of the face and groin was negative for hyphae and Demodex mites. Histopathologic analysis from a punch biopsy of a representative papule from the posterior neck demonstrated epidermal dysmaturation with marked thickening of the granular cell layer with notably large keratohyalin granules (Figure 1).

In the setting of treatment with thiotepa, we recommended supportive care with cool compresses rather than topical medication because he was neutropenic, and we wanted to avoid further immunosuppression or toxicity. By 24 hours after completing the course of palifermin, the patient experienced complete resolution of the rash. At his request, the trial of palifermin was restarted 10 days into conditioning therapy. A similar rash with less facial edema but more prominent involvement of the chest appeared 3 days into the retrial (Figure 2). The medication was discontinued, which resulted in resolution of the rash. Again, the patient remained afebrile without involvement of the mucous membranes. Liver enzyme and creatinine levels remained within reference range.Eosinophilia and the level of atypical lymphocytes could not be assessed because of leukopenia in the setting of recent chemotherapy. The rash self-resolved in 4 days.

Palifermin is a recombinant form of human KGF that is more stable than the endogenous form but retains all vital properties of the protein.^5-7 Similar to other growth factors, KGF induces differentiation, proliferation, and migration of cells in vivo.⁸ However, it uniquely produces a targeted effect on epithelial cells in the skin, oral mucosa, lungs, gastrointestinal tract, and genitourinary system.^7-9

Palifermin was approved by the US Food and Drug Administration in 2004 for the prevention and treatment of severe oral mucositis in patients receiving myelotoxic therapy prior to stem cell transplantation.^7,9 Severe mucositis occurs in approximately 70% to 80% of patients receiving radiation or chemotherapy-based conditioning treatments.^4,7 Compared to placebo, palifermin has been shown to greatly reduce the incidence of Grade 4 oral mucositis, defined as severe enough to prevent alimentation.¹⁰

The proliferative effect of palifermin on the oral mucosa is beneficial to patients but likely is the driving force behind its cutaneous adverse effects. A nonspecific rash is the most commonly cited treatment-related adverse event associated with palifermin, occurring in approximately 62% of patients.^5,7,9

Our case is a rare report of a palifermin-associated cutaneous reaction. Previous cases have cited the occurrence of palmoplantar erythrodysesthesias, papulopustular eruptions involving the face and chest, and a papular rash involving the dorsal hands and intertriginous areas.^1-4 Another report documented a “mild rash” but failed to further characterize the morphology or the body site involved.⁵

In 2009, King et al⁶ reported the occurrence of a lichen planus–like eruption involving the intertriginous regions and of white oral plaques in a patient treated with palifermin. Hematoxylin and eosin staining of a representative lesion in that patient demonstrated an appearance similar to that of verrucae, including papillomatosis, hypergranulosis, and hyperorthokeratosis.

King et al⁶ expanded analysis of the reaction to include immunohistochemical study, using targeted antibody stains for cytokeratin 5/6 and Ki-67 protein.Staining with Ki-67 showed dramatically increased activity within basilar and suprabasilar keratinocytes in a biopsy taken at the height of the reaction. Biopsy specimens obtained when the eruption was clinically resolving—2 days after the first biopsy—showed decreased Ki-67 staining.These findings taken together suggest a direct causal effect of palifermin inducing hyperkeratotic changes appreciated on examination of treated patients.⁶

We present this case to add to current data regarding palifermin-induced cutaneous changes. Unique to our patient was a strikingly well-demarcated rash confined to the head and neck. Although a photosensitive eruption due to trimethoprim-sulfamethoxazole is conceivable, the fixed time course of the eruption—corresponding to (1) initiation and discontinuation of palifermin and (2) histologic findings—led us to conclude that this self-limited eruption likely was due to palifermin.

Skin reactions at insulin pump infusion sites are common among people with type 1 diabetes who use the devices and can lead to delivery failure, new research suggests.
 

Insulin pump use is increasingly common, but many patients experience infusion-site failure that in some cases leads to discontinuation. In a novel investigation, researchers at the University of Washington, Seattle, used biopsies and noninvasive imaging to compare insulin pump sites with control sites in 30 patients. Several differences were found at pump sites in comparison with control sites, including fibrosis, inflammation, eosinophils, and increased vessel density.

“These findings support allergic sensitization as a potentially common reaction at [insulin pump] sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing,” wrote Andrea Kalus, MD, of the university’s dermatology division, and colleagues. The findings were published recently in Diabetes Care.

The inflammatory response, they wrote, “may result in tissue changes responsible for the infusion-site failures seen frequently in clinical practice.”

Such infusion site problems represent an “Achilles heel” of these otherwise highly beneficial devices, lead author Irl Hirsch, MD, professor of medicine in the division of metabolism, endocrinology, and nutrition, said in a statement. “It doesn’t really matter how good the technology is. We still don’t understand what is happening with the infusion sites, much less to [be able to] fix it.”
 

Significant differences between pump and nonpump sites

In the cross-sectional study, Dr. Kalus and colleagues used noninvasive optical coherence tomography (OCT) immediately prior to performing punch biopsies at three sites: the site currently in active use, the “recovery site” used 3-5 days prior to the procedures, and control sites never used for pump infusion. Punch biopsies were also performed at those sites.

The mean age of the patients was 48.3 years, the mean diabetes duration was 30.4 years, and the mean duration of pump use was 15.8 years. Nearly all patients (93.3%) reported itchiness at the site, and 76.7% reported skin redness.

Of the 25 patients for whom OCT imaging was successful, statistical analysis showed significant differences in vascular area density and the optical attenuation coefficient, a surrogate for skin inflammation, between the pump and control sites and between recovery sites and current pump sites. The greater vessel density is likely a result of injury and repair related to catheter insertion, the authors said.

In the biopsy samples, both current and recovery sites showed increased fibrosis, fibrin, inflammation, fat necrosis, vascularity, and eosinophils, compared with the control sites, but no significant differences were found between current and recovery sites.

Eosinophils: ‘The most surprising histologic finding’

Eosinophils were found in 73% of skin biopsy specimens from current sites and in 75% of specimens from recovery sites, compared with none from the control sites (for both, P < .01). In all study participants, eosinophils were found in at least one current and/or recovery infusion site deep in the dermis near the interface with fat. The number of eosinophils ranged from 0 to 31 per high-power field, with a median of 4.

The number of eosinophils didn’t vary by type of insulin or brand of pump, but higher counts were seen in those who had used pumps for less than 10 years, compared with more than 20 years (P = .02).

The prevalence and degree of eosinophils were “the most surprising histologic finding,” the authors wrote, adding that “eosinophils are not typically present as a component of resident inflammatory cells in the skin.”

While eosinophils may be present in normal wound healing, “the absolute number and density of eosinophil in these samples support a delayed-type hypersensitivity response, which is typically observed between 2 and 7 days after exposure to an allergen. ... Eosinophils are often correlated with symptoms of itchiness and likely explain the high percentage of participants who reported itchiness in this study,” Dr. Kalus and colleagues wrote.
 

Correlation found between inflammation and glycemic control

All participants used the Dexcom G6 continuous glucose monitor as part of their usual care. Inflammation scores were positively correlated with insulin dose (P = .009) and were negatively correlated with time in range (P = .01).

No other OCT or biopsy findings differed by duration of pump use, previous use of animal insulin, or type of insulin.

The reason for these findings is unclear, Dr. Hirsch said. “How much was the catheter or the insulin causing the irritation around the sites? How much was it from the preservatives, or is this because of the insulin pump itself? All these questions need to be answered in future studies. ... The real goal of all of this is to minimize skin damage and improve the experience for our patients.”

The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Hirsch reported grants and contracts from Insulet, Medtronic, and Dexcom outside the submitted work; consulting fees from Abbott Diabetes Care, Lifescan, and Hagar outside the submitted work; and honoraria for lectures, presentations, participation on speaker’s bureaus, manuscript writing, or educational events as section editor for UpToDate outside the submitted work. Dr. Kalus has no disclosures.

A version of this article first appeared on Medscape.com.

Skin reactions at insulin pump infusion sites are common among people with type 1 diabetes who use the devices and can lead to delivery failure, new research suggests.
 

Insulin pump use is increasingly common, but many patients experience infusion-site failure that in some cases leads to discontinuation. In a novel investigation, researchers at the University of Washington, Seattle, used biopsies and noninvasive imaging to compare insulin pump sites with control sites in 30 patients. Several differences were found at pump sites in comparison with control sites, including fibrosis, inflammation, eosinophils, and increased vessel density.

“These findings support allergic sensitization as a potentially common reaction at [insulin pump] sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing,” wrote Andrea Kalus, MD, of the university’s dermatology division, and colleagues. The findings were published recently in Diabetes Care.

The inflammatory response, they wrote, “may result in tissue changes responsible for the infusion-site failures seen frequently in clinical practice.”

Such infusion site problems represent an “Achilles heel” of these otherwise highly beneficial devices, lead author Irl Hirsch, MD, professor of medicine in the division of metabolism, endocrinology, and nutrition, said in a statement. “It doesn’t really matter how good the technology is. We still don’t understand what is happening with the infusion sites, much less to [be able to] fix it.”
 

Significant differences between pump and nonpump sites

In the cross-sectional study, Dr. Kalus and colleagues used noninvasive optical coherence tomography (OCT) immediately prior to performing punch biopsies at three sites: the site currently in active use, the “recovery site” used 3-5 days prior to the procedures, and control sites never used for pump infusion. Punch biopsies were also performed at those sites.

The mean age of the patients was 48.3 years, the mean diabetes duration was 30.4 years, and the mean duration of pump use was 15.8 years. Nearly all patients (93.3%) reported itchiness at the site, and 76.7% reported skin redness.

Of the 25 patients for whom OCT imaging was successful, statistical analysis showed significant differences in vascular area density and the optical attenuation coefficient, a surrogate for skin inflammation, between the pump and control sites and between recovery sites and current pump sites. The greater vessel density is likely a result of injury and repair related to catheter insertion, the authors said.

In the biopsy samples, both current and recovery sites showed increased fibrosis, fibrin, inflammation, fat necrosis, vascularity, and eosinophils, compared with the control sites, but no significant differences were found between current and recovery sites.

Eosinophils: ‘The most surprising histologic finding’

Eosinophils were found in 73% of skin biopsy specimens from current sites and in 75% of specimens from recovery sites, compared with none from the control sites (for both, P < .01). In all study participants, eosinophils were found in at least one current and/or recovery infusion site deep in the dermis near the interface with fat. The number of eosinophils ranged from 0 to 31 per high-power field, with a median of 4.

The number of eosinophils didn’t vary by type of insulin or brand of pump, but higher counts were seen in those who had used pumps for less than 10 years, compared with more than 20 years (P = .02).

The prevalence and degree of eosinophils were “the most surprising histologic finding,” the authors wrote, adding that “eosinophils are not typically present as a component of resident inflammatory cells in the skin.”

While eosinophils may be present in normal wound healing, “the absolute number and density of eosinophil in these samples support a delayed-type hypersensitivity response, which is typically observed between 2 and 7 days after exposure to an allergen. ... Eosinophils are often correlated with symptoms of itchiness and likely explain the high percentage of participants who reported itchiness in this study,” Dr. Kalus and colleagues wrote.
 

Correlation found between inflammation and glycemic control

All participants used the Dexcom G6 continuous glucose monitor as part of their usual care. Inflammation scores were positively correlated with insulin dose (P = .009) and were negatively correlated with time in range (P = .01).

No other OCT or biopsy findings differed by duration of pump use, previous use of animal insulin, or type of insulin.

The reason for these findings is unclear, Dr. Hirsch said. “How much was the catheter or the insulin causing the irritation around the sites? How much was it from the preservatives, or is this because of the insulin pump itself? All these questions need to be answered in future studies. ... The real goal of all of this is to minimize skin damage and improve the experience for our patients.”

The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Hirsch reported grants and contracts from Insulet, Medtronic, and Dexcom outside the submitted work; consulting fees from Abbott Diabetes Care, Lifescan, and Hagar outside the submitted work; and honoraria for lectures, presentations, participation on speaker’s bureaus, manuscript writing, or educational events as section editor for UpToDate outside the submitted work. Dr. Kalus has no disclosures.

A version of this article first appeared on Medscape.com.

Skin reactions at insulin pump infusion sites are common among people with type 1 diabetes who use the devices and can lead to delivery failure, new research suggests.
 

Insulin pump use is increasingly common, but many patients experience infusion-site failure that in some cases leads to discontinuation. In a novel investigation, researchers at the University of Washington, Seattle, used biopsies and noninvasive imaging to compare insulin pump sites with control sites in 30 patients. Several differences were found at pump sites in comparison with control sites, including fibrosis, inflammation, eosinophils, and increased vessel density.

“These findings support allergic sensitization as a potentially common reaction at [insulin pump] sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing,” wrote Andrea Kalus, MD, of the university’s dermatology division, and colleagues. The findings were published recently in Diabetes Care.

The inflammatory response, they wrote, “may result in tissue changes responsible for the infusion-site failures seen frequently in clinical practice.”

Such infusion site problems represent an “Achilles heel” of these otherwise highly beneficial devices, lead author Irl Hirsch, MD, professor of medicine in the division of metabolism, endocrinology, and nutrition, said in a statement. “It doesn’t really matter how good the technology is. We still don’t understand what is happening with the infusion sites, much less to [be able to] fix it.”
 

Significant differences between pump and nonpump sites

In the cross-sectional study, Dr. Kalus and colleagues used noninvasive optical coherence tomography (OCT) immediately prior to performing punch biopsies at three sites: the site currently in active use, the “recovery site” used 3-5 days prior to the procedures, and control sites never used for pump infusion. Punch biopsies were also performed at those sites.

The mean age of the patients was 48.3 years, the mean diabetes duration was 30.4 years, and the mean duration of pump use was 15.8 years. Nearly all patients (93.3%) reported itchiness at the site, and 76.7% reported skin redness.

Of the 25 patients for whom OCT imaging was successful, statistical analysis showed significant differences in vascular area density and the optical attenuation coefficient, a surrogate for skin inflammation, between the pump and control sites and between recovery sites and current pump sites. The greater vessel density is likely a result of injury and repair related to catheter insertion, the authors said.

In the biopsy samples, both current and recovery sites showed increased fibrosis, fibrin, inflammation, fat necrosis, vascularity, and eosinophils, compared with the control sites, but no significant differences were found between current and recovery sites.

Eosinophils: ‘The most surprising histologic finding’

Eosinophils were found in 73% of skin biopsy specimens from current sites and in 75% of specimens from recovery sites, compared with none from the control sites (for both, P < .01). In all study participants, eosinophils were found in at least one current and/or recovery infusion site deep in the dermis near the interface with fat. The number of eosinophils ranged from 0 to 31 per high-power field, with a median of 4.

The number of eosinophils didn’t vary by type of insulin or brand of pump, but higher counts were seen in those who had used pumps for less than 10 years, compared with more than 20 years (P = .02).

The prevalence and degree of eosinophils were “the most surprising histologic finding,” the authors wrote, adding that “eosinophils are not typically present as a component of resident inflammatory cells in the skin.”

While eosinophils may be present in normal wound healing, “the absolute number and density of eosinophil in these samples support a delayed-type hypersensitivity response, which is typically observed between 2 and 7 days after exposure to an allergen. ... Eosinophils are often correlated with symptoms of itchiness and likely explain the high percentage of participants who reported itchiness in this study,” Dr. Kalus and colleagues wrote.
 

Correlation found between inflammation and glycemic control

All participants used the Dexcom G6 continuous glucose monitor as part of their usual care. Inflammation scores were positively correlated with insulin dose (P = .009) and were negatively correlated with time in range (P = .01).

No other OCT or biopsy findings differed by duration of pump use, previous use of animal insulin, or type of insulin.

The reason for these findings is unclear, Dr. Hirsch said. “How much was the catheter or the insulin causing the irritation around the sites? How much was it from the preservatives, or is this because of the insulin pump itself? All these questions need to be answered in future studies. ... The real goal of all of this is to minimize skin damage and improve the experience for our patients.”

The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Hirsch reported grants and contracts from Insulet, Medtronic, and Dexcom outside the submitted work; consulting fees from Abbott Diabetes Care, Lifescan, and Hagar outside the submitted work; and honoraria for lectures, presentations, participation on speaker’s bureaus, manuscript writing, or educational events as section editor for UpToDate outside the submitted work. Dr. Kalus has no disclosures.

A version of this article first appeared on Medscape.com.

In patients aged 2-11 years, roflumilast cream was well tolerated and improved signs and symptoms of psoriasis over 4 weeks, according to results from a pair of phase two studies.

“Limited topical treatments are approved for children younger than 12 years old with psoriasis,” researchers led by Adelaide A. Hebert, MD, wrote in their abstract. The results were presented during a poster session at the annual meeting of the Society for Pediatric Dermatology.

Roflumilast cream 0.3% (Zoryve) is a once-daily, topical nonsteroidal treatment from Arcutis Biotherapeutics. A phosphodiesterase-4 inhibitor, it was approved by the Food and Drug Administration in 2022 for mild, moderate and severe psoriasis in individuals aged 12 and older, including intertriginous psoriasis.

For the analysis, Dr. Hebert, chief of pediatric dermatology at the University of Texas, Houston, and colleagues conducted two 4-week, phase 2, open-label safety studies of roflumilast cream 0.3%.

One, study 216, enrolled 10 children aged 2-5, and all but one were Black. The other, study 215, enrolled 20 children aged 6-11, and half were Black and nearly half were White. At baseline, patients had 2% or greater body surface area (BSA) involvement and an Investigator Global Assessment (IGA) score of at least mild.

Caregivers applied roflumilast cream to all affected areas once daily for 28 days. The researchers collected pharmacokinetic samples at week 2 and week 4. The primary endpoints were pharmacokinetic, safety, and tolerability.

Efficacy was evaluated as exploratory endpoints: An IGA of clear or almost clear plus a 2-grade or more improvement from baseline, a 50% or greater improvement and a 75% or greater improvement on the Psoriasis Area and Severity Index (PASI-50 and PASI-75), a 4-point or greater reduction in the Worst Itch–Numeric Rating Scale (WI-NRS) in patients with a baseline score of 4 or greater, a mean change from baseline in BSA, and improvement in the Children’s Dermatology Life Quality Index (CDLQI).

At baseline, the mean BSA was similar for patients enrolled in studies 216 and 215 (9.6% and 8.8%, respectively), and 80% of all patients had baseline IGA of moderate. By week 2, the mean roflumilast and N-oxide predose plasma concentrations among patients in the younger group were 2.15 and 22.4 ng/mL, compared with 3.15 and 28.9 ng/mL among those in the older group. At week 4, the mean roflumilast and N-oxide predose concentrations were 2.04 and 15.8 ng/mL in the younger group (study 216), compared with 1.68 and 15.7 ng/mL in the older group (study 215).

As for efficacy, 90% and 40% of patients in studies 216 and 215 achieved IGA success at week 4, respectively, while 90% and 50% achieved PASI-75, 90% and 40% achieved WI-NRS success, and the mean BSA reductions at week 4 were 79.1% and 44.4%. Meanwhile, one younger patient in study 216 reported a treatment-emergent adverse event (TEAE) of headache, which was considered mild, while four older patients in study 215 reported 8 TEAEs, which were considered mild and ranged from back pain to nasal congestion.

“The rapid onset of action was surprising but exceedingly rewarding for the subjects enrolled in the study,” Dr. Hebert told this news organization after the meeting. “The PASI scores and itch scores were markedly improved at the end of the 4-week clinical trial. Patient and parents alike were pleased to use a steroid-free option with once-daily application and rapid onset of action to help control plaque psoriasis.”

In the poster abstract, she and her coauthors concluded that “under maximal use conditions in children aged 2-11 years, roflumilast cream 0.3% was well tolerated and improved signs and symptoms of psoriasis with measured improvements in IGA score, PASI score, BSA involvement, CDLQI, and WI-NRS. Overall, pharmacokinetics, safety, tolerability, and efficacy in patients aged 2-11 years were consistent with prior results in adults and adolescents.”

The study was funded by Arcutis Biotherapeutics. Dr. Hebert reported that she is an investigator for Arcutis. About half the coauthors are employees of Arcutis, and the other half disclosed grants, research funding and/or honoraria from the company. Research grants from the company for this study were paid to the McGovern Medical School at the University of Texas.

In patients aged 2-11 years, roflumilast cream was well tolerated and improved signs and symptoms of psoriasis over 4 weeks, according to results from a pair of phase two studies.

“Limited topical treatments are approved for children younger than 12 years old with psoriasis,” researchers led by Adelaide A. Hebert, MD, wrote in their abstract. The results were presented during a poster session at the annual meeting of the Society for Pediatric Dermatology.

Roflumilast cream 0.3% (Zoryve) is a once-daily, topical nonsteroidal treatment from Arcutis Biotherapeutics. A phosphodiesterase-4 inhibitor, it was approved by the Food and Drug Administration in 2022 for mild, moderate and severe psoriasis in individuals aged 12 and older, including intertriginous psoriasis.

For the analysis, Dr. Hebert, chief of pediatric dermatology at the University of Texas, Houston, and colleagues conducted two 4-week, phase 2, open-label safety studies of roflumilast cream 0.3%.

One, study 216, enrolled 10 children aged 2-5, and all but one were Black. The other, study 215, enrolled 20 children aged 6-11, and half were Black and nearly half were White. At baseline, patients had 2% or greater body surface area (BSA) involvement and an Investigator Global Assessment (IGA) score of at least mild.

Caregivers applied roflumilast cream to all affected areas once daily for 28 days. The researchers collected pharmacokinetic samples at week 2 and week 4. The primary endpoints were pharmacokinetic, safety, and tolerability.

Efficacy was evaluated as exploratory endpoints: An IGA of clear or almost clear plus a 2-grade or more improvement from baseline, a 50% or greater improvement and a 75% or greater improvement on the Psoriasis Area and Severity Index (PASI-50 and PASI-75), a 4-point or greater reduction in the Worst Itch–Numeric Rating Scale (WI-NRS) in patients with a baseline score of 4 or greater, a mean change from baseline in BSA, and improvement in the Children’s Dermatology Life Quality Index (CDLQI).

At baseline, the mean BSA was similar for patients enrolled in studies 216 and 215 (9.6% and 8.8%, respectively), and 80% of all patients had baseline IGA of moderate. By week 2, the mean roflumilast and N-oxide predose plasma concentrations among patients in the younger group were 2.15 and 22.4 ng/mL, compared with 3.15 and 28.9 ng/mL among those in the older group. At week 4, the mean roflumilast and N-oxide predose concentrations were 2.04 and 15.8 ng/mL in the younger group (study 216), compared with 1.68 and 15.7 ng/mL in the older group (study 215).

As for efficacy, 90% and 40% of patients in studies 216 and 215 achieved IGA success at week 4, respectively, while 90% and 50% achieved PASI-75, 90% and 40% achieved WI-NRS success, and the mean BSA reductions at week 4 were 79.1% and 44.4%. Meanwhile, one younger patient in study 216 reported a treatment-emergent adverse event (TEAE) of headache, which was considered mild, while four older patients in study 215 reported 8 TEAEs, which were considered mild and ranged from back pain to nasal congestion.

“The rapid onset of action was surprising but exceedingly rewarding for the subjects enrolled in the study,” Dr. Hebert told this news organization after the meeting. “The PASI scores and itch scores were markedly improved at the end of the 4-week clinical trial. Patient and parents alike were pleased to use a steroid-free option with once-daily application and rapid onset of action to help control plaque psoriasis.”

In the poster abstract, she and her coauthors concluded that “under maximal use conditions in children aged 2-11 years, roflumilast cream 0.3% was well tolerated and improved signs and symptoms of psoriasis with measured improvements in IGA score, PASI score, BSA involvement, CDLQI, and WI-NRS. Overall, pharmacokinetics, safety, tolerability, and efficacy in patients aged 2-11 years were consistent with prior results in adults and adolescents.”

The study was funded by Arcutis Biotherapeutics. Dr. Hebert reported that she is an investigator for Arcutis. About half the coauthors are employees of Arcutis, and the other half disclosed grants, research funding and/or honoraria from the company. Research grants from the company for this study were paid to the McGovern Medical School at the University of Texas.

In patients aged 2-11 years, roflumilast cream was well tolerated and improved signs and symptoms of psoriasis over 4 weeks, according to results from a pair of phase two studies.

“Limited topical treatments are approved for children younger than 12 years old with psoriasis,” researchers led by Adelaide A. Hebert, MD, wrote in their abstract. The results were presented during a poster session at the annual meeting of the Society for Pediatric Dermatology.

Roflumilast cream 0.3% (Zoryve) is a once-daily, topical nonsteroidal treatment from Arcutis Biotherapeutics. A phosphodiesterase-4 inhibitor, it was approved by the Food and Drug Administration in 2022 for mild, moderate and severe psoriasis in individuals aged 12 and older, including intertriginous psoriasis.

For the analysis, Dr. Hebert, chief of pediatric dermatology at the University of Texas, Houston, and colleagues conducted two 4-week, phase 2, open-label safety studies of roflumilast cream 0.3%.

One, study 216, enrolled 10 children aged 2-5, and all but one were Black. The other, study 215, enrolled 20 children aged 6-11, and half were Black and nearly half were White. At baseline, patients had 2% or greater body surface area (BSA) involvement and an Investigator Global Assessment (IGA) score of at least mild.

Caregivers applied roflumilast cream to all affected areas once daily for 28 days. The researchers collected pharmacokinetic samples at week 2 and week 4. The primary endpoints were pharmacokinetic, safety, and tolerability.

Efficacy was evaluated as exploratory endpoints: An IGA of clear or almost clear plus a 2-grade or more improvement from baseline, a 50% or greater improvement and a 75% or greater improvement on the Psoriasis Area and Severity Index (PASI-50 and PASI-75), a 4-point or greater reduction in the Worst Itch–Numeric Rating Scale (WI-NRS) in patients with a baseline score of 4 or greater, a mean change from baseline in BSA, and improvement in the Children’s Dermatology Life Quality Index (CDLQI).

At baseline, the mean BSA was similar for patients enrolled in studies 216 and 215 (9.6% and 8.8%, respectively), and 80% of all patients had baseline IGA of moderate. By week 2, the mean roflumilast and N-oxide predose plasma concentrations among patients in the younger group were 2.15 and 22.4 ng/mL, compared with 3.15 and 28.9 ng/mL among those in the older group. At week 4, the mean roflumilast and N-oxide predose concentrations were 2.04 and 15.8 ng/mL in the younger group (study 216), compared with 1.68 and 15.7 ng/mL in the older group (study 215).

As for efficacy, 90% and 40% of patients in studies 216 and 215 achieved IGA success at week 4, respectively, while 90% and 50% achieved PASI-75, 90% and 40% achieved WI-NRS success, and the mean BSA reductions at week 4 were 79.1% and 44.4%. Meanwhile, one younger patient in study 216 reported a treatment-emergent adverse event (TEAE) of headache, which was considered mild, while four older patients in study 215 reported 8 TEAEs, which were considered mild and ranged from back pain to nasal congestion.

“The rapid onset of action was surprising but exceedingly rewarding for the subjects enrolled in the study,” Dr. Hebert told this news organization after the meeting. “The PASI scores and itch scores were markedly improved at the end of the 4-week clinical trial. Patient and parents alike were pleased to use a steroid-free option with once-daily application and rapid onset of action to help control plaque psoriasis.”

In the poster abstract, she and her coauthors concluded that “under maximal use conditions in children aged 2-11 years, roflumilast cream 0.3% was well tolerated and improved signs and symptoms of psoriasis with measured improvements in IGA score, PASI score, BSA involvement, CDLQI, and WI-NRS. Overall, pharmacokinetics, safety, tolerability, and efficacy in patients aged 2-11 years were consistent with prior results in adults and adolescents.”

The study was funded by Arcutis Biotherapeutics. Dr. Hebert reported that she is an investigator for Arcutis. About half the coauthors are employees of Arcutis, and the other half disclosed grants, research funding and/or honoraria from the company. Research grants from the company for this study were paid to the McGovern Medical School at the University of Texas.

An influential Nature paper predicted in 2017 that advances in artificial intelligence (AI) could unleash remarkable changes in dermatology, such as using phones to help detect skin cancer earlier.

Given that about 6.3 billion smartphones would soon be in use, this AI approach could provide a gateway for “low-cost universal access to vital diagnostic care,” wrote Justin M. Ko, MD, MBA, a dermatologist, and colleagues from Stanford (Calif.) University that included other dermatologists and engineers.

Dr. Ko and his coauthors described how they trained a computer system to identify both benign and cancerous skin lesions. They used an approach known as a convolutional neural network, often deployed for projects seeking to train computers to “see” through image analysis. They said that their test of this system found it to be on par with the performance of 21 board-certified dermatologists.

“This fast, scalable method is deployable on mobile devices and holds the potential for substantial clinical impact, including broadening the scope of primary care practice and augmenting clinical decision-making for dermatology specialists,” they wrote in their paper.

More than 6 years later, there are signs that companies are making progress toward moving skin checks using this technology into U.S. primary care settings – but only with devices that employ special tools.

It may prove tougher for companies to eventually secure the sign-off of the U.S. Food and Drug Administration for mobile apps intended to let consumers handle this task with smartphones.

Such tools would need to be proven highly accurate before release, because too many false positives mean that people would be needlessly exposed to biopsies, said Sancy A. Leachman, MD, PhD, director of the melanoma research program and chair of the department of dermatology at Oregon Health & Science University, Portland.

And false-negative readings would allow melanoma to advance and even be fatal, Dr. Leachman told this news organization.

Roxana Daneshjou, MD, PhD, a dermatologist at Stanford who has studied the promise and the pitfalls of AI in medicine, said that developers of a consumer skin-check app would need to know how people would react to their readings. That includes a good sense of how often they would appropriately seek medical care for a concerning reading. (She was not an author of the previously cited Nature paper but has published widely on AI.)

Christopher Smith

“The direct-to-consumer diagnostic space makes me nervous,” Dr. Daneshjou said in an interview. “In order to do it, you really need to have good studies in consumer populations prior to release. You need to show how effective it is with follow up.”
 

FDA shows interest – and reservations

As of July, the FDA had not yet given its okay for marketing of any consumer apps intended to help people detect signs of skin cancer, an agency spokesperson told this news organization.

To date, the agency has only cleared two AI-based products for this task, both meant to be used by dermatologists. And only one of these two products, Scibase’s Nevisense, remains in use in the United States. The other, MelaFind, has been discontinued. In 2017, Strata Skin Sciences said that the product did not win “a significant enough level of acceptance by dermatologists to justify the continued investment” in it. And the company said it notified the 90 owners of MelaFind devices in the United States that it would no longer support the device.

But another company, DermaSensor, said in a 2021 press release that it expects its AI-powered tool, also named DermaSensor, to be the “first ever FDA cleared or approved skin cancer detection device for primary care providers.”

The Miami-based firm said that the FDA had granted its product a “breakthrough” device designation. A breakthrough designation means that agency staff will offer extra help and guidance to companies in developing a product, because of its expected benefit for patients.

In a 2020 press release, 3Derm Systems, now owned by Digital Diagnostics, made a similar announcement about winning FDA breakthrough designation for an AI-powered tool intended to allow skin checks in primary care settings.

(The FDA generally does not comment on its reviews of experimental drugs and devices, but companies can do so. Several other companies have announced FDA breakthrough designations for AI-driven products intended to check for skin lesions, but these might be used in settings other than primary care.)

Both DermaSensor and Digital Diagnostics have chairs with notable track records for winning FDA approvals of other devices. DermaSensor’s Maurice Ferre, MD, also is the chairman of Insightec, which in 2016 won the first FDA approval for a device with a breakthrough designation device that uses ultrasound to treat tremors.

In 2018, the FDA allowed Digital Diagnostics, then called IDx, to introduce in the United States the first medical device using AI in primary care offices to check for signs of diabetic retinopathy. This product also had an FDA breakthrough designation. The executive chairman and founder of Digital Diagnostics is Michael Abramoff, MD, PhD, professor of engineering and ophthalmology at the University of Iowa, Iowa City. Dr. Abramoff and the team behind the AI tool for retinopathy, now called the LumineticsCore system, also scored a notable win with Medicare, which agreed to cover use of the product through a dedicated CPT code.
 

FDA draft guidance

The FDA has acknowledged the interest in broadening access to skin checks via AI.

This was a topic of discussion at a 2-day advisory committee meeting the FDA held last year. In April 2023, the FDA outlined some of its expectations for future regulation of skin-analyzing tools as part of a wide-ranging draft guidance document intended to aid companies in their efforts to develop products using a form of AI known as machine learning.

In the document, the FDA described how it might approach applications for “hypothetical” devices using this kind of AI, such as a special tool to help primary care clinicians identify lesions in need of further investigation. Such a product would use a specific camera for gathering data for its initial clearance, in the FDA’s hypothetical scenario.

The FDA staff offered technical suggestions about what the developer of this hypothetical device would have to do to extend its use to smartphones and tablets while keeping clinicians as the intended users.

Some of these expanded uses could fall within the bounds of the FDA’s initial clearance and thus not trigger a need for a new marketing submission, the agency said. But seeking to shift this hypothetical product to “patient-facing” use would require a new marketing submission to the FDA, the agency said.

In this scenario, a company would expect people to follow up with a dermatologist after receiving a report suggesting cancer. Thus, this kind of a change could expose patients to “many new, unconsidered risks,” the FDA said.
 

Reality check?

The state of current efforts to develop consumer apps for checking for skin cancer seems to be summarized well on the website for the MoleMapper. The app was developed by researchers at OHSU to help people track how their moles change over time.

“Mole Mapper is NOT designed to provide medical advice, professional diagnosis, opinion, or treatment. Currently, there is not enough data to develop an app that can diagnose melanoma, but if enough data is collected through Mole Mapper and shared with researchers, it may be possible in the future,” the app’s website says.

OHSU released MoleMapper as an iPhone app in 2015. The aim of this project was to help people track the moles on their skin while also fostering an experiment in “citizen science,” OHSU’s Dr. Leachman told this news organization.

OHSU researchers hoped that the digital images taken by members of the public on cell phones could one day be used to develop diagnostic algorithms for melanoma.

But around 2017, the MoleMapper team realized that they would not be able to create a diagnostic app at this time, Dr. Leachman explained. They could not collect enough data of adequate quality.

And by 2021, it was clear that they could not even develop a successful app to triage patients to assess who needs to be seen quickly. The amount of data required was, at this point, beyond what the team could collect, Dr. Leachman said in an interview.

That was a disappointment because the team had successfully completed the difficult task of creating a confidential pathway for collecting these images via both iPhones and smartphones run on Android.

“We thought if we built it, people would come, but that’s not what happened,” Dr. Leachman said. Many patients didn’t want their images used for research or would fail to follow up with details of biopsy reports. Sometimes images were not captured well enough to be of use.

“You need at least hundreds of thousands, if not millions, of data points that have been verified with pathologies, and nobody was giving us back that data. That was the reality,” Dr. Leachman said.

There were valuable lessons in that setback. The OHSU team now has a better grasp of the challenges of trying to build a data-collection system that could prove helpful in assessing skin lesions.

“If you don’t build it, you don’t know” what can go wrong, she said.

Dr. Leachman said other scientists who have worked on similar projects to build skin-analyzing apps have probably encountered the same difficulties, although they may not reveal these issues. “I think that a lot of people build these things and then they try to make it into something that it’s not,” she said.

In addition to the challenges with gathering images, dermatologists frequently need to rely on touch and other clues from in-person visits when diagnosing a suspicious lesion. “There’s something about seeing and feeling the skin in person that can’t be captured completely with an image,” Dr. Leachman said.
 

Public demand

Still, regulators must face the strong and immediate interest consumers have in using AI to check on moles and skin conditions, despite continuing questions about how well this approach might work.

In June, Google announced in a blog post that its Google Lens tool can help people research skin conditions.

“Just take a picture or upload a photo through Lens, and you’ll find visual matches to inform your search,” Google said in a blog post. “This feature also works if you’re not sure how to describe something else on your body, like a bump on your lip, a line on your nails or hair loss on your head. This feature is currently available in the U.S.”

Google also continues work on DermAssist, an app that’s intended to help people get personalized information about skin concerns using three photos. It is not currently publicly available, a Google spokesperson told this news organization.

Several skin-analyzing apps are already available in the Apple and Google Play stores. The British Association of Dermatologists last year issued a press release warning consumers that these apps may not be safe or effective and thus may put patients at risk for misdiagnosis.

“Unfortunately, AI-based apps which do not appear to meet regulatory requirements crop up more often than we would like,” the association said. “Additionally, the evidence to support the use of AI to diagnose skin conditions is weak which means that when it is used, it may not be safe or effective and it is possible that AI is putting patients at risk of misdiagnosis.”

Delicate and difficult balancing act

At this time, regulators, entrepreneurs, and the medical community face a delicate balancing act in considering how best to deploy AI in skin care, Dr. Ko said in an interview. (In addition to being one of the authors on the widely cited 2017 Nature paper mentioned above, Dr. Ko served until March as the initial chair of the American Academy of Dermatology’s Augmented Intelligence Committee.)

There are many solid reasons why there hasn’t been speedy progress to deploy AI in dermatology, as many envisioned a few years ago, Dr. Ko said.

Some of those reasons are specific to dermatology; this field doesn’t have a ready set of robust data from which to build AI-driven tools. In this aspect, dermatology is decades behind specialties like radiology, pathology, and ophthalmology, where clinicians have long been accumulating and storing images and other data in more standardized ways, Dr. Ko said.

“If you went to most dermatology practices and said, ‘Hey, let me learn from the data accumulated over the course of your 30-year practice to help us develop new tools,’” there may not be a whole lot there,” Dr. Ko said.

Beyond the start-up hurdles is the larger concern Dr. Ko shares with other dermatologists who work in this field, such as Dr. Daneshjou and Dr. Leachman. What would clinicians without much dermatology training and patients do with the readings from AI-driven tools and apps?

There would need to be significant research to show that such products actually help get people treated for skin diseases, including skin cancer.

Dr. Ko praised Google for being open about the stumbles with its efforts to use its AI tool for identifying diabetic retinopathy in a test in Thailand. Real-world hitches included poor Internet connections and poor image quality.

Developing reliable systems, processes, and workflows will be paramount for eventual widespread use of AI-driven tools, Dr. Ko said.

“It’s all those hidden things that are not sexy,” as are announcements about algorithms working about as well as clinicians in diagnosis, Dr. Ko said. “They don’t get the media attention, but they’re going to be make or break for AI, not just in our field but [for] AI in general.”

But he added that there also needs to be a recognition that AI-driven tools and products, even if somewhat imperfect, can help people get access to care.

In many cases, shortages of specialists prevent people from getting screened for treatable conditions such as skin cancer and retinopathy. The challenge is setting an appropriate standard to make sure that AI-driven products would help most patients in practice, without raising it so high that no such products emerge.

“There’s a risk of holding too high of a bar,” Dr. Ko said. “There is harm in not moving forward as well.”

A version of this article first appeared on Medscape.com.

An influential Nature paper predicted in 2017 that advances in artificial intelligence (AI) could unleash remarkable changes in dermatology, such as using phones to help detect skin cancer earlier.

Given that about 6.3 billion smartphones would soon be in use, this AI approach could provide a gateway for “low-cost universal access to vital diagnostic care,” wrote Justin M. Ko, MD, MBA, a dermatologist, and colleagues from Stanford (Calif.) University that included other dermatologists and engineers.

Dr. Ko and his coauthors described how they trained a computer system to identify both benign and cancerous skin lesions. They used an approach known as a convolutional neural network, often deployed for projects seeking to train computers to “see” through image analysis. They said that their test of this system found it to be on par with the performance of 21 board-certified dermatologists.

“This fast, scalable method is deployable on mobile devices and holds the potential for substantial clinical impact, including broadening the scope of primary care practice and augmenting clinical decision-making for dermatology specialists,” they wrote in their paper.

More than 6 years later, there are signs that companies are making progress toward moving skin checks using this technology into U.S. primary care settings – but only with devices that employ special tools.

It may prove tougher for companies to eventually secure the sign-off of the U.S. Food and Drug Administration for mobile apps intended to let consumers handle this task with smartphones.

Such tools would need to be proven highly accurate before release, because too many false positives mean that people would be needlessly exposed to biopsies, said Sancy A. Leachman, MD, PhD, director of the melanoma research program and chair of the department of dermatology at Oregon Health & Science University, Portland.

And false-negative readings would allow melanoma to advance and even be fatal, Dr. Leachman told this news organization.

Roxana Daneshjou, MD, PhD, a dermatologist at Stanford who has studied the promise and the pitfalls of AI in medicine, said that developers of a consumer skin-check app would need to know how people would react to their readings. That includes a good sense of how often they would appropriately seek medical care for a concerning reading. (She was not an author of the previously cited Nature paper but has published widely on AI.)

Christopher Smith

“The direct-to-consumer diagnostic space makes me nervous,” Dr. Daneshjou said in an interview. “In order to do it, you really need to have good studies in consumer populations prior to release. You need to show how effective it is with follow up.”
 

FDA shows interest – and reservations

As of July, the FDA had not yet given its okay for marketing of any consumer apps intended to help people detect signs of skin cancer, an agency spokesperson told this news organization.

To date, the agency has only cleared two AI-based products for this task, both meant to be used by dermatologists. And only one of these two products, Scibase’s Nevisense, remains in use in the United States. The other, MelaFind, has been discontinued. In 2017, Strata Skin Sciences said that the product did not win “a significant enough level of acceptance by dermatologists to justify the continued investment” in it. And the company said it notified the 90 owners of MelaFind devices in the United States that it would no longer support the device.

But another company, DermaSensor, said in a 2021 press release that it expects its AI-powered tool, also named DermaSensor, to be the “first ever FDA cleared or approved skin cancer detection device for primary care providers.”

The Miami-based firm said that the FDA had granted its product a “breakthrough” device designation. A breakthrough designation means that agency staff will offer extra help and guidance to companies in developing a product, because of its expected benefit for patients.

In a 2020 press release, 3Derm Systems, now owned by Digital Diagnostics, made a similar announcement about winning FDA breakthrough designation for an AI-powered tool intended to allow skin checks in primary care settings.

(The FDA generally does not comment on its reviews of experimental drugs and devices, but companies can do so. Several other companies have announced FDA breakthrough designations for AI-driven products intended to check for skin lesions, but these might be used in settings other than primary care.)

Both DermaSensor and Digital Diagnostics have chairs with notable track records for winning FDA approvals of other devices. DermaSensor’s Maurice Ferre, MD, also is the chairman of Insightec, which in 2016 won the first FDA approval for a device with a breakthrough designation device that uses ultrasound to treat tremors.

In 2018, the FDA allowed Digital Diagnostics, then called IDx, to introduce in the United States the first medical device using AI in primary care offices to check for signs of diabetic retinopathy. This product also had an FDA breakthrough designation. The executive chairman and founder of Digital Diagnostics is Michael Abramoff, MD, PhD, professor of engineering and ophthalmology at the University of Iowa, Iowa City. Dr. Abramoff and the team behind the AI tool for retinopathy, now called the LumineticsCore system, also scored a notable win with Medicare, which agreed to cover use of the product through a dedicated CPT code.
 

FDA draft guidance

The FDA has acknowledged the interest in broadening access to skin checks via AI.

This was a topic of discussion at a 2-day advisory committee meeting the FDA held last year. In April 2023, the FDA outlined some of its expectations for future regulation of skin-analyzing tools as part of a wide-ranging draft guidance document intended to aid companies in their efforts to develop products using a form of AI known as machine learning.

In the document, the FDA described how it might approach applications for “hypothetical” devices using this kind of AI, such as a special tool to help primary care clinicians identify lesions in need of further investigation. Such a product would use a specific camera for gathering data for its initial clearance, in the FDA’s hypothetical scenario.

The FDA staff offered technical suggestions about what the developer of this hypothetical device would have to do to extend its use to smartphones and tablets while keeping clinicians as the intended users.

Some of these expanded uses could fall within the bounds of the FDA’s initial clearance and thus not trigger a need for a new marketing submission, the agency said. But seeking to shift this hypothetical product to “patient-facing” use would require a new marketing submission to the FDA, the agency said.

In this scenario, a company would expect people to follow up with a dermatologist after receiving a report suggesting cancer. Thus, this kind of a change could expose patients to “many new, unconsidered risks,” the FDA said.
 

Reality check?

The state of current efforts to develop consumer apps for checking for skin cancer seems to be summarized well on the website for the MoleMapper. The app was developed by researchers at OHSU to help people track how their moles change over time.

“Mole Mapper is NOT designed to provide medical advice, professional diagnosis, opinion, or treatment. Currently, there is not enough data to develop an app that can diagnose melanoma, but if enough data is collected through Mole Mapper and shared with researchers, it may be possible in the future,” the app’s website says.

OHSU released MoleMapper as an iPhone app in 2015. The aim of this project was to help people track the moles on their skin while also fostering an experiment in “citizen science,” OHSU’s Dr. Leachman told this news organization.

OHSU researchers hoped that the digital images taken by members of the public on cell phones could one day be used to develop diagnostic algorithms for melanoma.

But around 2017, the MoleMapper team realized that they would not be able to create a diagnostic app at this time, Dr. Leachman explained. They could not collect enough data of adequate quality.

And by 2021, it was clear that they could not even develop a successful app to triage patients to assess who needs to be seen quickly. The amount of data required was, at this point, beyond what the team could collect, Dr. Leachman said in an interview.

That was a disappointment because the team had successfully completed the difficult task of creating a confidential pathway for collecting these images via both iPhones and smartphones run on Android.

“We thought if we built it, people would come, but that’s not what happened,” Dr. Leachman said. Many patients didn’t want their images used for research or would fail to follow up with details of biopsy reports. Sometimes images were not captured well enough to be of use.

“You need at least hundreds of thousands, if not millions, of data points that have been verified with pathologies, and nobody was giving us back that data. That was the reality,” Dr. Leachman said.

There were valuable lessons in that setback. The OHSU team now has a better grasp of the challenges of trying to build a data-collection system that could prove helpful in assessing skin lesions.

“If you don’t build it, you don’t know” what can go wrong, she said.

Dr. Leachman said other scientists who have worked on similar projects to build skin-analyzing apps have probably encountered the same difficulties, although they may not reveal these issues. “I think that a lot of people build these things and then they try to make it into something that it’s not,” she said.

In addition to the challenges with gathering images, dermatologists frequently need to rely on touch and other clues from in-person visits when diagnosing a suspicious lesion. “There’s something about seeing and feeling the skin in person that can’t be captured completely with an image,” Dr. Leachman said.
 

Public demand

Still, regulators must face the strong and immediate interest consumers have in using AI to check on moles and skin conditions, despite continuing questions about how well this approach might work.

In June, Google announced in a blog post that its Google Lens tool can help people research skin conditions.

“Just take a picture or upload a photo through Lens, and you’ll find visual matches to inform your search,” Google said in a blog post. “This feature also works if you’re not sure how to describe something else on your body, like a bump on your lip, a line on your nails or hair loss on your head. This feature is currently available in the U.S.”

Google also continues work on DermAssist, an app that’s intended to help people get personalized information about skin concerns using three photos. It is not currently publicly available, a Google spokesperson told this news organization.

Several skin-analyzing apps are already available in the Apple and Google Play stores. The British Association of Dermatologists last year issued a press release warning consumers that these apps may not be safe or effective and thus may put patients at risk for misdiagnosis.

“Unfortunately, AI-based apps which do not appear to meet regulatory requirements crop up more often than we would like,” the association said. “Additionally, the evidence to support the use of AI to diagnose skin conditions is weak which means that when it is used, it may not be safe or effective and it is possible that AI is putting patients at risk of misdiagnosis.”

Delicate and difficult balancing act

At this time, regulators, entrepreneurs, and the medical community face a delicate balancing act in considering how best to deploy AI in skin care, Dr. Ko said in an interview. (In addition to being one of the authors on the widely cited 2017 Nature paper mentioned above, Dr. Ko served until March as the initial chair of the American Academy of Dermatology’s Augmented Intelligence Committee.)

There are many solid reasons why there hasn’t been speedy progress to deploy AI in dermatology, as many envisioned a few years ago, Dr. Ko said.

Some of those reasons are specific to dermatology; this field doesn’t have a ready set of robust data from which to build AI-driven tools. In this aspect, dermatology is decades behind specialties like radiology, pathology, and ophthalmology, where clinicians have long been accumulating and storing images and other data in more standardized ways, Dr. Ko said.

“If you went to most dermatology practices and said, ‘Hey, let me learn from the data accumulated over the course of your 30-year practice to help us develop new tools,’” there may not be a whole lot there,” Dr. Ko said.

Beyond the start-up hurdles is the larger concern Dr. Ko shares with other dermatologists who work in this field, such as Dr. Daneshjou and Dr. Leachman. What would clinicians without much dermatology training and patients do with the readings from AI-driven tools and apps?

There would need to be significant research to show that such products actually help get people treated for skin diseases, including skin cancer.

Dr. Ko praised Google for being open about the stumbles with its efforts to use its AI tool for identifying diabetic retinopathy in a test in Thailand. Real-world hitches included poor Internet connections and poor image quality.

Developing reliable systems, processes, and workflows will be paramount for eventual widespread use of AI-driven tools, Dr. Ko said.

“It’s all those hidden things that are not sexy,” as are announcements about algorithms working about as well as clinicians in diagnosis, Dr. Ko said. “They don’t get the media attention, but they’re going to be make or break for AI, not just in our field but [for] AI in general.”

But he added that there also needs to be a recognition that AI-driven tools and products, even if somewhat imperfect, can help people get access to care.

In many cases, shortages of specialists prevent people from getting screened for treatable conditions such as skin cancer and retinopathy. The challenge is setting an appropriate standard to make sure that AI-driven products would help most patients in practice, without raising it so high that no such products emerge.

“There’s a risk of holding too high of a bar,” Dr. Ko said. “There is harm in not moving forward as well.”

A version of this article first appeared on Medscape.com.

An influential Nature paper predicted in 2017 that advances in artificial intelligence (AI) could unleash remarkable changes in dermatology, such as using phones to help detect skin cancer earlier.

Given that about 6.3 billion smartphones would soon be in use, this AI approach could provide a gateway for “low-cost universal access to vital diagnostic care,” wrote Justin M. Ko, MD, MBA, a dermatologist, and colleagues from Stanford (Calif.) University that included other dermatologists and engineers.

Dr. Ko and his coauthors described how they trained a computer system to identify both benign and cancerous skin lesions. They used an approach known as a convolutional neural network, often deployed for projects seeking to train computers to “see” through image analysis. They said that their test of this system found it to be on par with the performance of 21 board-certified dermatologists.

“This fast, scalable method is deployable on mobile devices and holds the potential for substantial clinical impact, including broadening the scope of primary care practice and augmenting clinical decision-making for dermatology specialists,” they wrote in their paper.

More than 6 years later, there are signs that companies are making progress toward moving skin checks using this technology into U.S. primary care settings – but only with devices that employ special tools.

It may prove tougher for companies to eventually secure the sign-off of the U.S. Food and Drug Administration for mobile apps intended to let consumers handle this task with smartphones.

Such tools would need to be proven highly accurate before release, because too many false positives mean that people would be needlessly exposed to biopsies, said Sancy A. Leachman, MD, PhD, director of the melanoma research program and chair of the department of dermatology at Oregon Health & Science University, Portland.

And false-negative readings would allow melanoma to advance and even be fatal, Dr. Leachman told this news organization.

Roxana Daneshjou, MD, PhD, a dermatologist at Stanford who has studied the promise and the pitfalls of AI in medicine, said that developers of a consumer skin-check app would need to know how people would react to their readings. That includes a good sense of how often they would appropriately seek medical care for a concerning reading. (She was not an author of the previously cited Nature paper but has published widely on AI.)

Christopher Smith

“The direct-to-consumer diagnostic space makes me nervous,” Dr. Daneshjou said in an interview. “In order to do it, you really need to have good studies in consumer populations prior to release. You need to show how effective it is with follow up.”
 

FDA shows interest – and reservations

As of July, the FDA had not yet given its okay for marketing of any consumer apps intended to help people detect signs of skin cancer, an agency spokesperson told this news organization.

To date, the agency has only cleared two AI-based products for this task, both meant to be used by dermatologists. And only one of these two products, Scibase’s Nevisense, remains in use in the United States. The other, MelaFind, has been discontinued. In 2017, Strata Skin Sciences said that the product did not win “a significant enough level of acceptance by dermatologists to justify the continued investment” in it. And the company said it notified the 90 owners of MelaFind devices in the United States that it would no longer support the device.

But another company, DermaSensor, said in a 2021 press release that it expects its AI-powered tool, also named DermaSensor, to be the “first ever FDA cleared or approved skin cancer detection device for primary care providers.”

The Miami-based firm said that the FDA had granted its product a “breakthrough” device designation. A breakthrough designation means that agency staff will offer extra help and guidance to companies in developing a product, because of its expected benefit for patients.

In a 2020 press release, 3Derm Systems, now owned by Digital Diagnostics, made a similar announcement about winning FDA breakthrough designation for an AI-powered tool intended to allow skin checks in primary care settings.

(The FDA generally does not comment on its reviews of experimental drugs and devices, but companies can do so. Several other companies have announced FDA breakthrough designations for AI-driven products intended to check for skin lesions, but these might be used in settings other than primary care.)

Both DermaSensor and Digital Diagnostics have chairs with notable track records for winning FDA approvals of other devices. DermaSensor’s Maurice Ferre, MD, also is the chairman of Insightec, which in 2016 won the first FDA approval for a device with a breakthrough designation device that uses ultrasound to treat tremors.

In 2018, the FDA allowed Digital Diagnostics, then called IDx, to introduce in the United States the first medical device using AI in primary care offices to check for signs of diabetic retinopathy. This product also had an FDA breakthrough designation. The executive chairman and founder of Digital Diagnostics is Michael Abramoff, MD, PhD, professor of engineering and ophthalmology at the University of Iowa, Iowa City. Dr. Abramoff and the team behind the AI tool for retinopathy, now called the LumineticsCore system, also scored a notable win with Medicare, which agreed to cover use of the product through a dedicated CPT code.
 

FDA draft guidance

The FDA has acknowledged the interest in broadening access to skin checks via AI.

This was a topic of discussion at a 2-day advisory committee meeting the FDA held last year. In April 2023, the FDA outlined some of its expectations for future regulation of skin-analyzing tools as part of a wide-ranging draft guidance document intended to aid companies in their efforts to develop products using a form of AI known as machine learning.

In the document, the FDA described how it might approach applications for “hypothetical” devices using this kind of AI, such as a special tool to help primary care clinicians identify lesions in need of further investigation. Such a product would use a specific camera for gathering data for its initial clearance, in the FDA’s hypothetical scenario.

The FDA staff offered technical suggestions about what the developer of this hypothetical device would have to do to extend its use to smartphones and tablets while keeping clinicians as the intended users.

Some of these expanded uses could fall within the bounds of the FDA’s initial clearance and thus not trigger a need for a new marketing submission, the agency said. But seeking to shift this hypothetical product to “patient-facing” use would require a new marketing submission to the FDA, the agency said.

In this scenario, a company would expect people to follow up with a dermatologist after receiving a report suggesting cancer. Thus, this kind of a change could expose patients to “many new, unconsidered risks,” the FDA said.
 

Reality check?

The state of current efforts to develop consumer apps for checking for skin cancer seems to be summarized well on the website for the MoleMapper. The app was developed by researchers at OHSU to help people track how their moles change over time.

“Mole Mapper is NOT designed to provide medical advice, professional diagnosis, opinion, or treatment. Currently, there is not enough data to develop an app that can diagnose melanoma, but if enough data is collected through Mole Mapper and shared with researchers, it may be possible in the future,” the app’s website says.

OHSU released MoleMapper as an iPhone app in 2015. The aim of this project was to help people track the moles on their skin while also fostering an experiment in “citizen science,” OHSU’s Dr. Leachman told this news organization.

OHSU researchers hoped that the digital images taken by members of the public on cell phones could one day be used to develop diagnostic algorithms for melanoma.

But around 2017, the MoleMapper team realized that they would not be able to create a diagnostic app at this time, Dr. Leachman explained. They could not collect enough data of adequate quality.

And by 2021, it was clear that they could not even develop a successful app to triage patients to assess who needs to be seen quickly. The amount of data required was, at this point, beyond what the team could collect, Dr. Leachman said in an interview.

That was a disappointment because the team had successfully completed the difficult task of creating a confidential pathway for collecting these images via both iPhones and smartphones run on Android.

“We thought if we built it, people would come, but that’s not what happened,” Dr. Leachman said. Many patients didn’t want their images used for research or would fail to follow up with details of biopsy reports. Sometimes images were not captured well enough to be of use.

“You need at least hundreds of thousands, if not millions, of data points that have been verified with pathologies, and nobody was giving us back that data. That was the reality,” Dr. Leachman said.

There were valuable lessons in that setback. The OHSU team now has a better grasp of the challenges of trying to build a data-collection system that could prove helpful in assessing skin lesions.

“If you don’t build it, you don’t know” what can go wrong, she said.

Dr. Leachman said other scientists who have worked on similar projects to build skin-analyzing apps have probably encountered the same difficulties, although they may not reveal these issues. “I think that a lot of people build these things and then they try to make it into something that it’s not,” she said.

In addition to the challenges with gathering images, dermatologists frequently need to rely on touch and other clues from in-person visits when diagnosing a suspicious lesion. “There’s something about seeing and feeling the skin in person that can’t be captured completely with an image,” Dr. Leachman said.
 

Public demand

Still, regulators must face the strong and immediate interest consumers have in using AI to check on moles and skin conditions, despite continuing questions about how well this approach might work.

In June, Google announced in a blog post that its Google Lens tool can help people research skin conditions.

“Just take a picture or upload a photo through Lens, and you’ll find visual matches to inform your search,” Google said in a blog post. “This feature also works if you’re not sure how to describe something else on your body, like a bump on your lip, a line on your nails or hair loss on your head. This feature is currently available in the U.S.”

Google also continues work on DermAssist, an app that’s intended to help people get personalized information about skin concerns using three photos. It is not currently publicly available, a Google spokesperson told this news organization.

Several skin-analyzing apps are already available in the Apple and Google Play stores. The British Association of Dermatologists last year issued a press release warning consumers that these apps may not be safe or effective and thus may put patients at risk for misdiagnosis.

“Unfortunately, AI-based apps which do not appear to meet regulatory requirements crop up more often than we would like,” the association said. “Additionally, the evidence to support the use of AI to diagnose skin conditions is weak which means that when it is used, it may not be safe or effective and it is possible that AI is putting patients at risk of misdiagnosis.”

Delicate and difficult balancing act

At this time, regulators, entrepreneurs, and the medical community face a delicate balancing act in considering how best to deploy AI in skin care, Dr. Ko said in an interview. (In addition to being one of the authors on the widely cited 2017 Nature paper mentioned above, Dr. Ko served until March as the initial chair of the American Academy of Dermatology’s Augmented Intelligence Committee.)

There are many solid reasons why there hasn’t been speedy progress to deploy AI in dermatology, as many envisioned a few years ago, Dr. Ko said.

Some of those reasons are specific to dermatology; this field doesn’t have a ready set of robust data from which to build AI-driven tools. In this aspect, dermatology is decades behind specialties like radiology, pathology, and ophthalmology, where clinicians have long been accumulating and storing images and other data in more standardized ways, Dr. Ko said.

“If you went to most dermatology practices and said, ‘Hey, let me learn from the data accumulated over the course of your 30-year practice to help us develop new tools,’” there may not be a whole lot there,” Dr. Ko said.

Beyond the start-up hurdles is the larger concern Dr. Ko shares with other dermatologists who work in this field, such as Dr. Daneshjou and Dr. Leachman. What would clinicians without much dermatology training and patients do with the readings from AI-driven tools and apps?

There would need to be significant research to show that such products actually help get people treated for skin diseases, including skin cancer.

Dr. Ko praised Google for being open about the stumbles with its efforts to use its AI tool for identifying diabetic retinopathy in a test in Thailand. Real-world hitches included poor Internet connections and poor image quality.

Developing reliable systems, processes, and workflows will be paramount for eventual widespread use of AI-driven tools, Dr. Ko said.

“It’s all those hidden things that are not sexy,” as are announcements about algorithms working about as well as clinicians in diagnosis, Dr. Ko said. “They don’t get the media attention, but they’re going to be make or break for AI, not just in our field but [for] AI in general.”

But he added that there also needs to be a recognition that AI-driven tools and products, even if somewhat imperfect, can help people get access to care.

In many cases, shortages of specialists prevent people from getting screened for treatable conditions such as skin cancer and retinopathy. The challenge is setting an appropriate standard to make sure that AI-driven products would help most patients in practice, without raising it so high that no such products emerge.

“There’s a risk of holding too high of a bar,” Dr. Ko said. “There is harm in not moving forward as well.”

A version of this article first appeared on Medscape.com.

Who owns your genes? The assumption of any sane person would be that he or she owns his or her own genes. I mean, how dumb a question is that?
 

Yet, in 2007, Dov Michaeli, MD, PhD, described how an American company had claimed ownership of genetic materials and believed that it had the right to commercialize those naturally occurring bits of DNA. Myriad Genetics began by patenting mutations of BRCA. Dr. Michaeli issued a call for action to support early efforts to pass legislation to restore and preserve individual ownership of one’s own genes. This is a historically important quick read/watch/listen. Give it a click.

In related legislation, the Genetic Information Nondiscrimination Act (GINA), originally introduced by New York Rep. Louise Slaughter in 1995, was ultimately spearheaded by California Rep. Xavier Becerra (now Secretary of Health & Human Services) to passage by the House of Representatives on April 25, 2007, by a vote of 420-9-3. Led by Sen. Edward Kennedy of Massachusetts, it was passed by the Senate on April 24, 2008, by a vote of 95-0. President George W. Bush signed the bill into law on May 21, 2008.

GINA is a landmark piece of legislation that protects Americans. It prohibits employers and health insurers from discriminating against people on the basis of their genetic information, and it also prohibits the use of genetic information in life insurance and long-term care insurance.

Its impact has been immense. GINA has been indispensable in promoting progress in the field of human genetics. By safeguarding individuals against discrimination based on genetic information, it has encouraged broader participation in research, built public trust, and stimulated advancements in genetic testing and personalized medicine. GINA’s impact extends beyond borders and has influenced much of the rest of the world.

As important as GINA was to the field, more was needed. National legislation to protect ownership of genetic materials has, despite many attempts, still not become law in the United States. However, in our system of divided government and balance of power, we also have independent courts.

June 13, 2023, was the 10th anniversary of another landmark event. The legal case is that of the Association for Molecular Pathology v. Myriad Genetics, a Salt Lake City–based biotech company that held patents on isolated DNA sequences associated with breast and ovarian cancer. The AMP, joined by several other organizations and researchers, challenged Myriad’s gene patents, arguing that human genes are naturally occurring and, therefore, should not be subject to patenting. In a unanimous decision, the Supreme Court held that naturally occurring DNA segments are products of nature and therefore are not eligible for patent protection.

This was a pivotal decision in the field of human genetics and had a broad impact on genetic research. The decision clarified that naturally occurring DNA sequences cannot be patented, which means that researchers are free to use these sequences in their research without fear of patent infringement. This has led to a vast increase in the amount of genetic research being conducted, and it has also led to the development of new genetic tests and treatments.

The numbers of genetic research papers published in scientific journals and of genetic tests available to consumers have increased significantly, while the cost of genetic testing has decreased significantly. The AMP v. Myriad decision is likely to continue to have an impact for many years to come.

In 2023, Americans do own their own genes and can feel secure in them not being used against us. Thank you, common sense, activist American molecular pathologists, Congress, the President, and the Supreme Court for siding with the people.Dr. Lundbert is editor in chief of Cancer Commons. He has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Who owns your genes? The assumption of any sane person would be that he or she owns his or her own genes. I mean, how dumb a question is that?
 

Yet, in 2007, Dov Michaeli, MD, PhD, described how an American company had claimed ownership of genetic materials and believed that it had the right to commercialize those naturally occurring bits of DNA. Myriad Genetics began by patenting mutations of BRCA. Dr. Michaeli issued a call for action to support early efforts to pass legislation to restore and preserve individual ownership of one’s own genes. This is a historically important quick read/watch/listen. Give it a click.

In related legislation, the Genetic Information Nondiscrimination Act (GINA), originally introduced by New York Rep. Louise Slaughter in 1995, was ultimately spearheaded by California Rep. Xavier Becerra (now Secretary of Health & Human Services) to passage by the House of Representatives on April 25, 2007, by a vote of 420-9-3. Led by Sen. Edward Kennedy of Massachusetts, it was passed by the Senate on April 24, 2008, by a vote of 95-0. President George W. Bush signed the bill into law on May 21, 2008.

GINA is a landmark piece of legislation that protects Americans. It prohibits employers and health insurers from discriminating against people on the basis of their genetic information, and it also prohibits the use of genetic information in life insurance and long-term care insurance.

Its impact has been immense. GINA has been indispensable in promoting progress in the field of human genetics. By safeguarding individuals against discrimination based on genetic information, it has encouraged broader participation in research, built public trust, and stimulated advancements in genetic testing and personalized medicine. GINA’s impact extends beyond borders and has influenced much of the rest of the world.

As important as GINA was to the field, more was needed. National legislation to protect ownership of genetic materials has, despite many attempts, still not become law in the United States. However, in our system of divided government and balance of power, we also have independent courts.

June 13, 2023, was the 10th anniversary of another landmark event. The legal case is that of the Association for Molecular Pathology v. Myriad Genetics, a Salt Lake City–based biotech company that held patents on isolated DNA sequences associated with breast and ovarian cancer. The AMP, joined by several other organizations and researchers, challenged Myriad’s gene patents, arguing that human genes are naturally occurring and, therefore, should not be subject to patenting. In a unanimous decision, the Supreme Court held that naturally occurring DNA segments are products of nature and therefore are not eligible for patent protection.

This was a pivotal decision in the field of human genetics and had a broad impact on genetic research. The decision clarified that naturally occurring DNA sequences cannot be patented, which means that researchers are free to use these sequences in their research without fear of patent infringement. This has led to a vast increase in the amount of genetic research being conducted, and it has also led to the development of new genetic tests and treatments.

The numbers of genetic research papers published in scientific journals and of genetic tests available to consumers have increased significantly, while the cost of genetic testing has decreased significantly. The AMP v. Myriad decision is likely to continue to have an impact for many years to come.

In 2023, Americans do own their own genes and can feel secure in them not being used against us. Thank you, common sense, activist American molecular pathologists, Congress, the President, and the Supreme Court for siding with the people.Dr. Lundbert is editor in chief of Cancer Commons. He has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Who owns your genes? The assumption of any sane person would be that he or she owns his or her own genes. I mean, how dumb a question is that?
 

Yet, in 2007, Dov Michaeli, MD, PhD, described how an American company had claimed ownership of genetic materials and believed that it had the right to commercialize those naturally occurring bits of DNA. Myriad Genetics began by patenting mutations of BRCA. Dr. Michaeli issued a call for action to support early efforts to pass legislation to restore and preserve individual ownership of one’s own genes. This is a historically important quick read/watch/listen. Give it a click.

In related legislation, the Genetic Information Nondiscrimination Act (GINA), originally introduced by New York Rep. Louise Slaughter in 1995, was ultimately spearheaded by California Rep. Xavier Becerra (now Secretary of Health & Human Services) to passage by the House of Representatives on April 25, 2007, by a vote of 420-9-3. Led by Sen. Edward Kennedy of Massachusetts, it was passed by the Senate on April 24, 2008, by a vote of 95-0. President George W. Bush signed the bill into law on May 21, 2008.

GINA is a landmark piece of legislation that protects Americans. It prohibits employers and health insurers from discriminating against people on the basis of their genetic information, and it also prohibits the use of genetic information in life insurance and long-term care insurance.

Its impact has been immense. GINA has been indispensable in promoting progress in the field of human genetics. By safeguarding individuals against discrimination based on genetic information, it has encouraged broader participation in research, built public trust, and stimulated advancements in genetic testing and personalized medicine. GINA’s impact extends beyond borders and has influenced much of the rest of the world.

As important as GINA was to the field, more was needed. National legislation to protect ownership of genetic materials has, despite many attempts, still not become law in the United States. However, in our system of divided government and balance of power, we also have independent courts.

June 13, 2023, was the 10th anniversary of another landmark event. The legal case is that of the Association for Molecular Pathology v. Myriad Genetics, a Salt Lake City–based biotech company that held patents on isolated DNA sequences associated with breast and ovarian cancer. The AMP, joined by several other organizations and researchers, challenged Myriad’s gene patents, arguing that human genes are naturally occurring and, therefore, should not be subject to patenting. In a unanimous decision, the Supreme Court held that naturally occurring DNA segments are products of nature and therefore are not eligible for patent protection.

This was a pivotal decision in the field of human genetics and had a broad impact on genetic research. The decision clarified that naturally occurring DNA sequences cannot be patented, which means that researchers are free to use these sequences in their research without fear of patent infringement. This has led to a vast increase in the amount of genetic research being conducted, and it has also led to the development of new genetic tests and treatments.

The numbers of genetic research papers published in scientific journals and of genetic tests available to consumers have increased significantly, while the cost of genetic testing has decreased significantly. The AMP v. Myriad decision is likely to continue to have an impact for many years to come.

In 2023, Americans do own their own genes and can feel secure in them not being used against us. Thank you, common sense, activist American molecular pathologists, Congress, the President, and the Supreme Court for siding with the people.Dr. Lundbert is editor in chief of Cancer Commons. He has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Here are 10 ways to improve health communication with patients. These tips will place patients at ease, increase their adherence to recommendations, and make the doctor’s visit a lot more enjoyable for them.
 

No. 1: Be an active listener

The first tip is to be an active listener and help guide the history-taking process by asking for clarification when needed.

Quickly figure out the patient’s chief complaint. Which symptom is the most severe?

Ask them for symptom-modifying factors, such as onset, duration, frequency, and a pain description. Is the abdominal pain sharp or crampy, dull and achy, or pressure-like? What makes the symptoms better or worse?

As many of us were taught in medical school, 80% of the diagnosis is in a patient’s history and description.
 

No. 2: Ask questions that resonate with patients

What can we do to help elicit an accurate history from the patient when they’re not providing the needed information or being helpful enough?

The easiest way is to ask your patient in a completely different way but one that resonates with them. For instance, ask how the abdominal pain is affecting their quality of life. That will help focus the history taking and encourage the patient to share details.

Does the pain keep them awake at night? Are they able to eat a normal-sized meal? Or are they forced to eat tiny snacks? Is the pain interfering with work or school?

By providing a framework, the patient will be more passionate about sharing the details of their history.
 

No. 3: Help patients organize their story

Sometimes, patients provide details in a nonchronological order, jumping all over the place.

A super helpful technique is to explain to the patient that you have a story to write for your computer note, and for them to think back to when they first started noticing their abdominal pain or rectal bleeding symptoms. When were the most-severe episodes? How frequent are the episodes? What’s the volume of their rectal bleeding?

If the patient realizes that you’re trying to write a story synopsis, they will provide information in a much more organized way.
 

No. 4: Determine patient’s language preference

Quickly determine the patient’s language preference. We want patients to feel extremely comfortable.

Whenever possible, use a certified interpreter. Language phone lines, in-person interpreters, and video conferencing are widely available today. It’s worth investing in this technology so that we can provide the best possible care to immigrants and refugees.

Conversely, avoid using family members as interpreters because they may not be adequately trained in medical vocabulary.
 

No. 5: Use simple language

When providing explanations, use simple language that your patient can understand and identify with.

For example, use analogies like “the heart is a pump” or the diverticula are thin areas of the colon that can bleed if the blood vessel is too close to the surface.
 

No. 6: Determine level of medical literacy

Determine your patient’s level of medical literacy. Some of our patients did not graduate from high school. Some patients can’t read very well. Therefore, your discharge instructions and handouts should sometimes be written on a third-grade level.

If patients can’t read, write medication instructions with symbols. Draw a sun for medications that are supposed to be taken in the morning and draw a moon if a medication is supposed to be taken at night.

Always very carefully review the instructions with the patient.
 

No. 7: Check in with the patient

During the visit, frequently check in with the patient to make sure that they understand what you’re asking or what you’re trying to explain to them.

No. 8: Include family member as patient advocate

If the patient is accompanied by a family member, help them serve in the important role as a patient advocate.

If the family member wants to take notes, encourage them because that provides an awesome value.

Sometimes patients can forget clinic and hospital medical conversations, and that family member might be the key to improving your patient’s health.
 

No. 9: Follow-up with the patient

If your clinic has the capability, follow up with a patient the next day to make sure that they understood everything.

Check to make sure the patient was able to pick up all of the medications that you prescribed.

Check that laboratory tests are arranged or completed.

Check that important procedures, such as esophagogastroduodenoscopy and colonoscopy, and imaging, such as ultrasounds and CTs, are scheduled.
 

No. 10: Identify barriers to care

Have fun talking with a patient. Find out what they do for a living. Build a rapport. Listen to their stressors in life.

Try to identify any barriers to care or external stressors, like taking care of a sick parent, which might interfere with their scheduling an important diagnostic colonoscopy for rectal bleeding.

Good luck incorporating these communication strategies into your clinic and hospital work. Together, we can help improve the delivery of health care.
 

Dr. Levy is a gastroenterologist at the University of Chicago. In 2017, Dr. Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Dr. Levy, who recently gave a TEDx Talk about building health education campaigns using music and concerts, organizes Tune It Up: A Concert To Raise Colorectal Cancer Awareness with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee. He has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Here are 10 ways to improve health communication with patients. These tips will place patients at ease, increase their adherence to recommendations, and make the doctor’s visit a lot more enjoyable for them.
 

No. 1: Be an active listener

The first tip is to be an active listener and help guide the history-taking process by asking for clarification when needed.

Quickly figure out the patient’s chief complaint. Which symptom is the most severe?

Ask them for symptom-modifying factors, such as onset, duration, frequency, and a pain description. Is the abdominal pain sharp or crampy, dull and achy, or pressure-like? What makes the symptoms better or worse?

As many of us were taught in medical school, 80% of the diagnosis is in a patient’s history and description.
 

No. 2: Ask questions that resonate with patients

What can we do to help elicit an accurate history from the patient when they’re not providing the needed information or being helpful enough?

The easiest way is to ask your patient in a completely different way but one that resonates with them. For instance, ask how the abdominal pain is affecting their quality of life. That will help focus the history taking and encourage the patient to share details.

Does the pain keep them awake at night? Are they able to eat a normal-sized meal? Or are they forced to eat tiny snacks? Is the pain interfering with work or school?

By providing a framework, the patient will be more passionate about sharing the details of their history.
 

No. 3: Help patients organize their story

Sometimes, patients provide details in a nonchronological order, jumping all over the place.

A super helpful technique is to explain to the patient that you have a story to write for your computer note, and for them to think back to when they first started noticing their abdominal pain or rectal bleeding symptoms. When were the most-severe episodes? How frequent are the episodes? What’s the volume of their rectal bleeding?

If the patient realizes that you’re trying to write a story synopsis, they will provide information in a much more organized way.
 

No. 4: Determine patient’s language preference

Quickly determine the patient’s language preference. We want patients to feel extremely comfortable.

Whenever possible, use a certified interpreter. Language phone lines, in-person interpreters, and video conferencing are widely available today. It’s worth investing in this technology so that we can provide the best possible care to immigrants and refugees.

Conversely, avoid using family members as interpreters because they may not be adequately trained in medical vocabulary.
 

No. 5: Use simple language

When providing explanations, use simple language that your patient can understand and identify with.

For example, use analogies like “the heart is a pump” or the diverticula are thin areas of the colon that can bleed if the blood vessel is too close to the surface.
 

No. 6: Determine level of medical literacy

Determine your patient’s level of medical literacy. Some of our patients did not graduate from high school. Some patients can’t read very well. Therefore, your discharge instructions and handouts should sometimes be written on a third-grade level.

If patients can’t read, write medication instructions with symbols. Draw a sun for medications that are supposed to be taken in the morning and draw a moon if a medication is supposed to be taken at night.

Always very carefully review the instructions with the patient.
 

No. 7: Check in with the patient

During the visit, frequently check in with the patient to make sure that they understand what you’re asking or what you’re trying to explain to them.

No. 8: Include family member as patient advocate

If the patient is accompanied by a family member, help them serve in the important role as a patient advocate.

If the family member wants to take notes, encourage them because that provides an awesome value.

Sometimes patients can forget clinic and hospital medical conversations, and that family member might be the key to improving your patient’s health.
 

No. 9: Follow-up with the patient

If your clinic has the capability, follow up with a patient the next day to make sure that they understood everything.

Check to make sure the patient was able to pick up all of the medications that you prescribed.

Check that laboratory tests are arranged or completed.

Check that important procedures, such as esophagogastroduodenoscopy and colonoscopy, and imaging, such as ultrasounds and CTs, are scheduled.
 

No. 10: Identify barriers to care

Have fun talking with a patient. Find out what they do for a living. Build a rapport. Listen to their stressors in life.

Try to identify any barriers to care or external stressors, like taking care of a sick parent, which might interfere with their scheduling an important diagnostic colonoscopy for rectal bleeding.

Good luck incorporating these communication strategies into your clinic and hospital work. Together, we can help improve the delivery of health care.
 

Dr. Levy is a gastroenterologist at the University of Chicago. In 2017, Dr. Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Dr. Levy, who recently gave a TEDx Talk about building health education campaigns using music and concerts, organizes Tune It Up: A Concert To Raise Colorectal Cancer Awareness with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee. He has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Here are 10 ways to improve health communication with patients. These tips will place patients at ease, increase their adherence to recommendations, and make the doctor’s visit a lot more enjoyable for them.
 

No. 1: Be an active listener

The first tip is to be an active listener and help guide the history-taking process by asking for clarification when needed.

Quickly figure out the patient’s chief complaint. Which symptom is the most severe?

Ask them for symptom-modifying factors, such as onset, duration, frequency, and a pain description. Is the abdominal pain sharp or crampy, dull and achy, or pressure-like? What makes the symptoms better or worse?

As many of us were taught in medical school, 80% of the diagnosis is in a patient’s history and description.
 

No. 2: Ask questions that resonate with patients

What can we do to help elicit an accurate history from the patient when they’re not providing the needed information or being helpful enough?

The easiest way is to ask your patient in a completely different way but one that resonates with them. For instance, ask how the abdominal pain is affecting their quality of life. That will help focus the history taking and encourage the patient to share details.

Does the pain keep them awake at night? Are they able to eat a normal-sized meal? Or are they forced to eat tiny snacks? Is the pain interfering with work or school?

By providing a framework, the patient will be more passionate about sharing the details of their history.
 

No. 3: Help patients organize their story

Sometimes, patients provide details in a nonchronological order, jumping all over the place.

A super helpful technique is to explain to the patient that you have a story to write for your computer note, and for them to think back to when they first started noticing their abdominal pain or rectal bleeding symptoms. When were the most-severe episodes? How frequent are the episodes? What’s the volume of their rectal bleeding?

If the patient realizes that you’re trying to write a story synopsis, they will provide information in a much more organized way.
 

No. 4: Determine patient’s language preference

Quickly determine the patient’s language preference. We want patients to feel extremely comfortable.

Whenever possible, use a certified interpreter. Language phone lines, in-person interpreters, and video conferencing are widely available today. It’s worth investing in this technology so that we can provide the best possible care to immigrants and refugees.

Conversely, avoid using family members as interpreters because they may not be adequately trained in medical vocabulary.
 

No. 5: Use simple language

When providing explanations, use simple language that your patient can understand and identify with.

For example, use analogies like “the heart is a pump” or the diverticula are thin areas of the colon that can bleed if the blood vessel is too close to the surface.
 

No. 6: Determine level of medical literacy

Determine your patient’s level of medical literacy. Some of our patients did not graduate from high school. Some patients can’t read very well. Therefore, your discharge instructions and handouts should sometimes be written on a third-grade level.

If patients can’t read, write medication instructions with symbols. Draw a sun for medications that are supposed to be taken in the morning and draw a moon if a medication is supposed to be taken at night.

Always very carefully review the instructions with the patient.
 

No. 7: Check in with the patient

During the visit, frequently check in with the patient to make sure that they understand what you’re asking or what you’re trying to explain to them.

No. 8: Include family member as patient advocate

If the patient is accompanied by a family member, help them serve in the important role as a patient advocate.

If the family member wants to take notes, encourage them because that provides an awesome value.

Sometimes patients can forget clinic and hospital medical conversations, and that family member might be the key to improving your patient’s health.
 

No. 9: Follow-up with the patient

If your clinic has the capability, follow up with a patient the next day to make sure that they understood everything.

Check to make sure the patient was able to pick up all of the medications that you prescribed.

Check that laboratory tests are arranged or completed.

Check that important procedures, such as esophagogastroduodenoscopy and colonoscopy, and imaging, such as ultrasounds and CTs, are scheduled.
 

No. 10: Identify barriers to care

Have fun talking with a patient. Find out what they do for a living. Build a rapport. Listen to their stressors in life.

Try to identify any barriers to care or external stressors, like taking care of a sick parent, which might interfere with their scheduling an important diagnostic colonoscopy for rectal bleeding.

Good luck incorporating these communication strategies into your clinic and hospital work. Together, we can help improve the delivery of health care.
 

Dr. Levy is a gastroenterologist at the University of Chicago. In 2017, Dr. Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Dr. Levy, who recently gave a TEDx Talk about building health education campaigns using music and concerts, organizes Tune It Up: A Concert To Raise Colorectal Cancer Awareness with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee. He has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A multicenter, international phase 2 trial known as EDELIFE is underway to investigate the safety and efficacy of an in utero treatment for developing males with X-linked hypohidrotic ectodermal dysplasia (XLHED).

This condition is caused by mutations in the gene coding for ectodysplasin A (EDA), a protein that signals the epithelial-mesenchymal transition during embryogenesis. EDA loss or dysfunction precludes binding to its endogenous EDA1 receptor (EDAR), and downstream development of teeth, hair, nails, and skin adnexae, most notably eccrine glands.

shironosov/Getty Images

The treatment, ER004, is a first-in-class signaling protein EDA replacement molecule now under investigation by the EspeRare Foundation, with support from the Pierre Fabre Foundation. The pioneering clinical trial is evaluating the delivery of ER004 protein replacement in utero to affected fetuses, allowing antenatal binding to the EDAR. According to the EDELIFE web site, when ER004 is administered to XLHED-affected males in utero, it “should act as a replacement for the missing EDA and trigger the process that leads to the normal development of a baby’s skin, teeth, hair, and sweat glands, leading to better formation of these structures.”

The protein is delivered into the amniotic fluid via a needle and syringe under ultrasound guidance. In a report on this treatment used in a pair of affected twins and a third XLHED-affected male published in 2018, the authors reported that the three babies were able to sweat normally after birth, “and XLHED-related illness had not developed by 14-22 months of age.”

The goal of the prospective, open-label, genotype match–controlled EDELIFE trial is to confirm the efficacy and safety results for ER004 in a larger group of boys, and to determine if it can lead to robust, and long-lasting improvement in XLHED-associated defects.

In the United States, the first pregnant woman to join the study received the treatment in February 2023 at Washington University in St. Louis. Other clinical sites are located in France, Germany, Italy, Spain, and the United Kingdom. Led by principal investigator Holm Schneider, MD, of the University Erlanger-Nurnberg (Germany), researchers are seeking to enroll mothers aged 18 years and older who are genetically confirmed carriers of the XLHED mutation and pregnant with a boy or considering pregnancy. The control group will include XLHED-affected males, 6 months to 60 years old, who are blood relatives of the pregnant woman participating in the study.

Clinicians treating affected families or potentially eligible subjects are encouraged to contact the trial investigators at this link.

A multicenter, international phase 2 trial known as EDELIFE is underway to investigate the safety and efficacy of an in utero treatment for developing males with X-linked hypohidrotic ectodermal dysplasia (XLHED).

This condition is caused by mutations in the gene coding for ectodysplasin A (EDA), a protein that signals the epithelial-mesenchymal transition during embryogenesis. EDA loss or dysfunction precludes binding to its endogenous EDA1 receptor (EDAR), and downstream development of teeth, hair, nails, and skin adnexae, most notably eccrine glands.

shironosov/Getty Images

The treatment, ER004, is a first-in-class signaling protein EDA replacement molecule now under investigation by the EspeRare Foundation, with support from the Pierre Fabre Foundation. The pioneering clinical trial is evaluating the delivery of ER004 protein replacement in utero to affected fetuses, allowing antenatal binding to the EDAR. According to the EDELIFE web site, when ER004 is administered to XLHED-affected males in utero, it “should act as a replacement for the missing EDA and trigger the process that leads to the normal development of a baby’s skin, teeth, hair, and sweat glands, leading to better formation of these structures.”

The protein is delivered into the amniotic fluid via a needle and syringe under ultrasound guidance. In a report on this treatment used in a pair of affected twins and a third XLHED-affected male published in 2018, the authors reported that the three babies were able to sweat normally after birth, “and XLHED-related illness had not developed by 14-22 months of age.”

The goal of the prospective, open-label, genotype match–controlled EDELIFE trial is to confirm the efficacy and safety results for ER004 in a larger group of boys, and to determine if it can lead to robust, and long-lasting improvement in XLHED-associated defects.

In the United States, the first pregnant woman to join the study received the treatment in February 2023 at Washington University in St. Louis. Other clinical sites are located in France, Germany, Italy, Spain, and the United Kingdom. Led by principal investigator Holm Schneider, MD, of the University Erlanger-Nurnberg (Germany), researchers are seeking to enroll mothers aged 18 years and older who are genetically confirmed carriers of the XLHED mutation and pregnant with a boy or considering pregnancy. The control group will include XLHED-affected males, 6 months to 60 years old, who are blood relatives of the pregnant woman participating in the study.

Clinicians treating affected families or potentially eligible subjects are encouraged to contact the trial investigators at this link.

A multicenter, international phase 2 trial known as EDELIFE is underway to investigate the safety and efficacy of an in utero treatment for developing males with X-linked hypohidrotic ectodermal dysplasia (XLHED).

This condition is caused by mutations in the gene coding for ectodysplasin A (EDA), a protein that signals the epithelial-mesenchymal transition during embryogenesis. EDA loss or dysfunction precludes binding to its endogenous EDA1 receptor (EDAR), and downstream development of teeth, hair, nails, and skin adnexae, most notably eccrine glands.

shironosov/Getty Images

The treatment, ER004, is a first-in-class signaling protein EDA replacement molecule now under investigation by the EspeRare Foundation, with support from the Pierre Fabre Foundation. The pioneering clinical trial is evaluating the delivery of ER004 protein replacement in utero to affected fetuses, allowing antenatal binding to the EDAR. According to the EDELIFE web site, when ER004 is administered to XLHED-affected males in utero, it “should act as a replacement for the missing EDA and trigger the process that leads to the normal development of a baby’s skin, teeth, hair, and sweat glands, leading to better formation of these structures.”

The protein is delivered into the amniotic fluid via a needle and syringe under ultrasound guidance. In a report on this treatment used in a pair of affected twins and a third XLHED-affected male published in 2018, the authors reported that the three babies were able to sweat normally after birth, “and XLHED-related illness had not developed by 14-22 months of age.”

The goal of the prospective, open-label, genotype match–controlled EDELIFE trial is to confirm the efficacy and safety results for ER004 in a larger group of boys, and to determine if it can lead to robust, and long-lasting improvement in XLHED-associated defects.

In the United States, the first pregnant woman to join the study received the treatment in February 2023 at Washington University in St. Louis. Other clinical sites are located in France, Germany, Italy, Spain, and the United Kingdom. Led by principal investigator Holm Schneider, MD, of the University Erlanger-Nurnberg (Germany), researchers are seeking to enroll mothers aged 18 years and older who are genetically confirmed carriers of the XLHED mutation and pregnant with a boy or considering pregnancy. The control group will include XLHED-affected males, 6 months to 60 years old, who are blood relatives of the pregnant woman participating in the study.

Clinicians treating affected families or potentially eligible subjects are encouraged to contact the trial investigators at this link.