User login
Collagen powder deemed noninferior to primary closure for punch-biopsy healing
Collagen powder may be noninferior to primary closure for healing punch biopsy–induced wounds and possibly leads to improved early cosmetic outcomes and accelerated wound maturation, according to Azam Qureshi of the University of Maryland, Baltimore, and associates.
In a small pilot study published in Journal of Drugs in Dermatology, eight volunteers (mean age, 37 years) received a 4-mm punch biopsy on each thigh. One wound was managed with primary closure, the other with daily application of collagen powder. The wounds were biopsied at 4 weeks for histopathologic analysis, and the study subjects rated pain, itch, and treatment preferences at 1, 2, 4, 6, and 12 weeks.
The size of wounds treated with collagen was reduced by 28.95% at 1 week, 55.76% at 2 weeks, and 95.94% at 4 weeks; six of the eight collagen-treated wounds were completely healed at 4 weeks. Wound size was reduced by 75.71% 1 week after the second biopsy, much faster than the initial healing. In addition to collagen, one patient required hyfrecation for hemostasis, which did not affect results; three of the eight subjects rated the collagen treatment as “annoying,” but no one rated it as “difficult,” and patients generally regarded collagen treatment as more time consuming.
The histopathologic analysis showed epidermal reepithelialization in collagen-treated wounds and wounds managed with primary closure, with more organized granulation tissue in the collagen-treated wounds. Similar pain and itch ratings were reported between wound types, and both patients and blinded dermatologists observing the study preferred the appearance of collagen-treated wounds.
“Future research elucidating the optimal duration of collagen therapy is needed, as less than 4 weeks may be sufficient. Shortened treatment courses would decrease the cost and effort required by patients. Future studies should also investigate the efficacy of collagen powder in healing larger wounds and in comparison to healing by secondary intention,” the investigators wrote.
CPN Biosciences funded the study. No authors had relevant financial disclosures.
SOURCE: Qureshi A et al. J Drug Dermatol. 2019;18(7):667-73
Collagen powder may be noninferior to primary closure for healing punch biopsy–induced wounds and possibly leads to improved early cosmetic outcomes and accelerated wound maturation, according to Azam Qureshi of the University of Maryland, Baltimore, and associates.
In a small pilot study published in Journal of Drugs in Dermatology, eight volunteers (mean age, 37 years) received a 4-mm punch biopsy on each thigh. One wound was managed with primary closure, the other with daily application of collagen powder. The wounds were biopsied at 4 weeks for histopathologic analysis, and the study subjects rated pain, itch, and treatment preferences at 1, 2, 4, 6, and 12 weeks.
The size of wounds treated with collagen was reduced by 28.95% at 1 week, 55.76% at 2 weeks, and 95.94% at 4 weeks; six of the eight collagen-treated wounds were completely healed at 4 weeks. Wound size was reduced by 75.71% 1 week after the second biopsy, much faster than the initial healing. In addition to collagen, one patient required hyfrecation for hemostasis, which did not affect results; three of the eight subjects rated the collagen treatment as “annoying,” but no one rated it as “difficult,” and patients generally regarded collagen treatment as more time consuming.
The histopathologic analysis showed epidermal reepithelialization in collagen-treated wounds and wounds managed with primary closure, with more organized granulation tissue in the collagen-treated wounds. Similar pain and itch ratings were reported between wound types, and both patients and blinded dermatologists observing the study preferred the appearance of collagen-treated wounds.
“Future research elucidating the optimal duration of collagen therapy is needed, as less than 4 weeks may be sufficient. Shortened treatment courses would decrease the cost and effort required by patients. Future studies should also investigate the efficacy of collagen powder in healing larger wounds and in comparison to healing by secondary intention,” the investigators wrote.
CPN Biosciences funded the study. No authors had relevant financial disclosures.
SOURCE: Qureshi A et al. J Drug Dermatol. 2019;18(7):667-73
Collagen powder may be noninferior to primary closure for healing punch biopsy–induced wounds and possibly leads to improved early cosmetic outcomes and accelerated wound maturation, according to Azam Qureshi of the University of Maryland, Baltimore, and associates.
In a small pilot study published in Journal of Drugs in Dermatology, eight volunteers (mean age, 37 years) received a 4-mm punch biopsy on each thigh. One wound was managed with primary closure, the other with daily application of collagen powder. The wounds were biopsied at 4 weeks for histopathologic analysis, and the study subjects rated pain, itch, and treatment preferences at 1, 2, 4, 6, and 12 weeks.
The size of wounds treated with collagen was reduced by 28.95% at 1 week, 55.76% at 2 weeks, and 95.94% at 4 weeks; six of the eight collagen-treated wounds were completely healed at 4 weeks. Wound size was reduced by 75.71% 1 week after the second biopsy, much faster than the initial healing. In addition to collagen, one patient required hyfrecation for hemostasis, which did not affect results; three of the eight subjects rated the collagen treatment as “annoying,” but no one rated it as “difficult,” and patients generally regarded collagen treatment as more time consuming.
The histopathologic analysis showed epidermal reepithelialization in collagen-treated wounds and wounds managed with primary closure, with more organized granulation tissue in the collagen-treated wounds. Similar pain and itch ratings were reported between wound types, and both patients and blinded dermatologists observing the study preferred the appearance of collagen-treated wounds.
“Future research elucidating the optimal duration of collagen therapy is needed, as less than 4 weeks may be sufficient. Shortened treatment courses would decrease the cost and effort required by patients. Future studies should also investigate the efficacy of collagen powder in healing larger wounds and in comparison to healing by secondary intention,” the investigators wrote.
CPN Biosciences funded the study. No authors had relevant financial disclosures.
SOURCE: Qureshi A et al. J Drug Dermatol. 2019;18(7):667-73
FROM JOURNAL OF DRUGS IN DERMATOLOGY
Cellulitis ranks as top reason for skin-related pediatric inpatient admissions
AUSTIN, TEX. – showed.
“Skin conditions significantly affect pediatric inpatients, and dermatologists ought be accessible for consultation to enhance care and costs,” the study’s first author, Marcus L. Elias, said in an interview prior to the annual meeting of the Society for Pediatric Dermatology.
According to Mr. Elias, who is a 4th-year medical student at Rutgers New Jersey Medical School–Newark, few national studies on skin diseases for pediatric inpatients have been published in the medical literature. Earlier this year, researchers examined inpatient dermatologic conditions in patients aged 18 years and older (J Am Acad Dermatol 2019;80[2]:425-32), but Mr. Elias and associates set out to analyze the burden of inpatient pediatric dermatologic conditions on a national basis. “We wanted to see if the same conditions that were hospitalizing adults were also hospitalizing kids,” he said. “We found that this was indeed the case.”
The researchers queried the National Inpatient Sample database for all cases involving patients aged 18 years and younger during 2001-2013. The search yielded a sample of 16,837,857 patients. From this, the researchers analyzed diagnosis-related groups for dermatologic conditions denoting the principal diagnosis at discharge, which left a final sample of 84,090 patients. Frequency and chi-squared tests were used to analyze categorical variables.
More than half of patients (54%) were male, 36% were white, 48% had Medicaid insurance, and 43% had private insurance. Mr. Elias reported that the median length of stay for patients was 2 days and the median cost of care was $6,289.50 for each case. More than three-quarters of pediatric inpatients with dermatologic diagnoses were treated for “cellulitis” (66,147 cases, or 79%), with most cases involving the legs (16,875 cases, or 20%). Other pediatric inpatients were admitted for “minor skin disorder without complications” (5,458 cases, or 7%), and “minor skin disorder with complications” (2,822 cases, or 3%). A total of 64 patients died during the study period. Of these, 31 cases (50%) involved “skin graft and/or debridement of skin ulcer or cellulitis without complications,” the study found.
“We were surprised that the major cause of mortality for our patients was classified as ‘skin graft and/or debridement of skin ulcer or cellulitis without complications,’ as a similar diagnosis-related groupings exist denoting that complications did arise,” Mr. Elias said. “Still, it is not possible for us to determine if the mortality was from the skin graft/debridement or another cause entirely. It is possible that the procedure was without complications, only to have the patient succumb to an ancillary process.”
He acknowledged certain limitations of the study, including the fact that the function of dermatologic consults for hospitalized patients was not examined. “We also cannot draw conclusions as to whether improved outpatient therapy reduces the need for hospitalization,” he said. Mr. Elias reported having no financial disclosures.
AUSTIN, TEX. – showed.
“Skin conditions significantly affect pediatric inpatients, and dermatologists ought be accessible for consultation to enhance care and costs,” the study’s first author, Marcus L. Elias, said in an interview prior to the annual meeting of the Society for Pediatric Dermatology.
According to Mr. Elias, who is a 4th-year medical student at Rutgers New Jersey Medical School–Newark, few national studies on skin diseases for pediatric inpatients have been published in the medical literature. Earlier this year, researchers examined inpatient dermatologic conditions in patients aged 18 years and older (J Am Acad Dermatol 2019;80[2]:425-32), but Mr. Elias and associates set out to analyze the burden of inpatient pediatric dermatologic conditions on a national basis. “We wanted to see if the same conditions that were hospitalizing adults were also hospitalizing kids,” he said. “We found that this was indeed the case.”
The researchers queried the National Inpatient Sample database for all cases involving patients aged 18 years and younger during 2001-2013. The search yielded a sample of 16,837,857 patients. From this, the researchers analyzed diagnosis-related groups for dermatologic conditions denoting the principal diagnosis at discharge, which left a final sample of 84,090 patients. Frequency and chi-squared tests were used to analyze categorical variables.
More than half of patients (54%) were male, 36% were white, 48% had Medicaid insurance, and 43% had private insurance. Mr. Elias reported that the median length of stay for patients was 2 days and the median cost of care was $6,289.50 for each case. More than three-quarters of pediatric inpatients with dermatologic diagnoses were treated for “cellulitis” (66,147 cases, or 79%), with most cases involving the legs (16,875 cases, or 20%). Other pediatric inpatients were admitted for “minor skin disorder without complications” (5,458 cases, or 7%), and “minor skin disorder with complications” (2,822 cases, or 3%). A total of 64 patients died during the study period. Of these, 31 cases (50%) involved “skin graft and/or debridement of skin ulcer or cellulitis without complications,” the study found.
“We were surprised that the major cause of mortality for our patients was classified as ‘skin graft and/or debridement of skin ulcer or cellulitis without complications,’ as a similar diagnosis-related groupings exist denoting that complications did arise,” Mr. Elias said. “Still, it is not possible for us to determine if the mortality was from the skin graft/debridement or another cause entirely. It is possible that the procedure was without complications, only to have the patient succumb to an ancillary process.”
He acknowledged certain limitations of the study, including the fact that the function of dermatologic consults for hospitalized patients was not examined. “We also cannot draw conclusions as to whether improved outpatient therapy reduces the need for hospitalization,” he said. Mr. Elias reported having no financial disclosures.
AUSTIN, TEX. – showed.
“Skin conditions significantly affect pediatric inpatients, and dermatologists ought be accessible for consultation to enhance care and costs,” the study’s first author, Marcus L. Elias, said in an interview prior to the annual meeting of the Society for Pediatric Dermatology.
According to Mr. Elias, who is a 4th-year medical student at Rutgers New Jersey Medical School–Newark, few national studies on skin diseases for pediatric inpatients have been published in the medical literature. Earlier this year, researchers examined inpatient dermatologic conditions in patients aged 18 years and older (J Am Acad Dermatol 2019;80[2]:425-32), but Mr. Elias and associates set out to analyze the burden of inpatient pediatric dermatologic conditions on a national basis. “We wanted to see if the same conditions that were hospitalizing adults were also hospitalizing kids,” he said. “We found that this was indeed the case.”
The researchers queried the National Inpatient Sample database for all cases involving patients aged 18 years and younger during 2001-2013. The search yielded a sample of 16,837,857 patients. From this, the researchers analyzed diagnosis-related groups for dermatologic conditions denoting the principal diagnosis at discharge, which left a final sample of 84,090 patients. Frequency and chi-squared tests were used to analyze categorical variables.
More than half of patients (54%) were male, 36% were white, 48% had Medicaid insurance, and 43% had private insurance. Mr. Elias reported that the median length of stay for patients was 2 days and the median cost of care was $6,289.50 for each case. More than three-quarters of pediatric inpatients with dermatologic diagnoses were treated for “cellulitis” (66,147 cases, or 79%), with most cases involving the legs (16,875 cases, or 20%). Other pediatric inpatients were admitted for “minor skin disorder without complications” (5,458 cases, or 7%), and “minor skin disorder with complications” (2,822 cases, or 3%). A total of 64 patients died during the study period. Of these, 31 cases (50%) involved “skin graft and/or debridement of skin ulcer or cellulitis without complications,” the study found.
“We were surprised that the major cause of mortality for our patients was classified as ‘skin graft and/or debridement of skin ulcer or cellulitis without complications,’ as a similar diagnosis-related groupings exist denoting that complications did arise,” Mr. Elias said. “Still, it is not possible for us to determine if the mortality was from the skin graft/debridement or another cause entirely. It is possible that the procedure was without complications, only to have the patient succumb to an ancillary process.”
He acknowledged certain limitations of the study, including the fact that the function of dermatologic consults for hospitalized patients was not examined. “We also cannot draw conclusions as to whether improved outpatient therapy reduces the need for hospitalization,” he said. Mr. Elias reported having no financial disclosures.
REPORTING FROM SPD 2019
Key clinical point: Cellulitis is the cause of the majority of skin-related pediatric inpatient admissions in the United States.
Major finding: In all, 79% of pediatric inpatients with dermatologic diagnoses were treated for cellulitis.
Study details: An analysis of data from 84,090 patients younger than age 18 in the National Inpatient Sample.
Disclosures: The researchers reported having no financial disclosures.
An 89-year-old woman presented with an ulceration overlying a cardiac pacemaker
Cardiac implantable electronic devices (CIEDs) – cardiac pacemakers and implantable cardioverter defibrillators –are an established treatment for the management of cardiac dysrhythmias in millions of patients. Complications occur in up to 15%, some of which may present first to the dermatologist.
The differential
Erosion and extrusion is a major complication with significant morbidity and mortality. The two main causes are pressure necrosis and infection. Pressure necrosis is influenced by the size of the device, complexity of the connections, and technical skill with which the pacemaker chest wall pocket is created.
After extrusion, the pacemaker should be considered contaminated and removed, and the necrotic tissue debrided. If infected, a prolonged course of appropriate antibiotic therapy is indicated. A bacterial culture in the patient presented here was negative.
Pocket infection of CIEDs is rare and may manifest as erythema, tenderness, drainage, erosion, or pruritus above the site of the pacemaker, along with systemic symptoms and signs, including fever, chills, or malaise. Some may have just the systemic symptoms. Fewer than half of patients with CIED infection present within 1 year of their last procedure.
Ruptured epidermal cysts usually manifest as acute swelling, inflammation, and tenderness of previously long-standing asymptomatic epidermal cysts. There may be drainage of malodorous keratinous and purulent debris. They are typically not infected. Treatment includes incision and drainage for fluctuant lesions or intralesional corticosteroid injection for early, nonfluctuant cases.
Allergic contact dermatitis to metal may be seen with implantable devices. Patch testing to various metal allergens can be helpful in determining if any allergy is present.
This case and photo were submitted by Michael Stierstorfer, MD, East Penn Dermatology, North Wales, Pa.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
Cardiac implantable electronic devices (CIEDs) – cardiac pacemakers and implantable cardioverter defibrillators –are an established treatment for the management of cardiac dysrhythmias in millions of patients. Complications occur in up to 15%, some of which may present first to the dermatologist.
The differential
Erosion and extrusion is a major complication with significant morbidity and mortality. The two main causes are pressure necrosis and infection. Pressure necrosis is influenced by the size of the device, complexity of the connections, and technical skill with which the pacemaker chest wall pocket is created.
After extrusion, the pacemaker should be considered contaminated and removed, and the necrotic tissue debrided. If infected, a prolonged course of appropriate antibiotic therapy is indicated. A bacterial culture in the patient presented here was negative.
Pocket infection of CIEDs is rare and may manifest as erythema, tenderness, drainage, erosion, or pruritus above the site of the pacemaker, along with systemic symptoms and signs, including fever, chills, or malaise. Some may have just the systemic symptoms. Fewer than half of patients with CIED infection present within 1 year of their last procedure.
Ruptured epidermal cysts usually manifest as acute swelling, inflammation, and tenderness of previously long-standing asymptomatic epidermal cysts. There may be drainage of malodorous keratinous and purulent debris. They are typically not infected. Treatment includes incision and drainage for fluctuant lesions or intralesional corticosteroid injection for early, nonfluctuant cases.
Allergic contact dermatitis to metal may be seen with implantable devices. Patch testing to various metal allergens can be helpful in determining if any allergy is present.
This case and photo were submitted by Michael Stierstorfer, MD, East Penn Dermatology, North Wales, Pa.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
Cardiac implantable electronic devices (CIEDs) – cardiac pacemakers and implantable cardioverter defibrillators –are an established treatment for the management of cardiac dysrhythmias in millions of patients. Complications occur in up to 15%, some of which may present first to the dermatologist.
The differential
Erosion and extrusion is a major complication with significant morbidity and mortality. The two main causes are pressure necrosis and infection. Pressure necrosis is influenced by the size of the device, complexity of the connections, and technical skill with which the pacemaker chest wall pocket is created.
After extrusion, the pacemaker should be considered contaminated and removed, and the necrotic tissue debrided. If infected, a prolonged course of appropriate antibiotic therapy is indicated. A bacterial culture in the patient presented here was negative.
Pocket infection of CIEDs is rare and may manifest as erythema, tenderness, drainage, erosion, or pruritus above the site of the pacemaker, along with systemic symptoms and signs, including fever, chills, or malaise. Some may have just the systemic symptoms. Fewer than half of patients with CIED infection present within 1 year of their last procedure.
Ruptured epidermal cysts usually manifest as acute swelling, inflammation, and tenderness of previously long-standing asymptomatic epidermal cysts. There may be drainage of malodorous keratinous and purulent debris. They are typically not infected. Treatment includes incision and drainage for fluctuant lesions or intralesional corticosteroid injection for early, nonfluctuant cases.
Allergic contact dermatitis to metal may be seen with implantable devices. Patch testing to various metal allergens can be helpful in determining if any allergy is present.
This case and photo were submitted by Michael Stierstorfer, MD, East Penn Dermatology, North Wales, Pa.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
Risk factors for foot ulcers differ for type 1 and type 2 diabetes
Danish researchers have linked multiple factors to higher risk of first-time diabetic foot ulcers (DFUs) in patients with type 1 and type 2 diabetes, although some of the factors –
according to the new study findings.The authors suggest that since clinical information gathered from patients during routine follow-up visits often includes mention of the risk factors for first-time DFU, it could form the basis of a risk stratification process for first-time DFU that can be integrated into the electronic record system and easily incorporated into routine care.
DFU is a significant complication for both type 1 and type 2 diabetes, but no previous research has stratified the risk factors for first-time DFUs by type of diabetes, emphasized the study authors, led by Sine Hangaard, MSc, of Steno Diabetes Center Copenhagen.
For the new study, the researchers tracked 5,588 patients with type 1 diabetes and 7,113 with type 2, all of whom were treated at a hospital clinic in Denmark between 2001 and 2015. The authors noted that the patients with type 2 disease who were treated at the center were clinically more complicated and had a longer disease duration than average type 2 patients, whereas the patients with type 1 diabetes did not differ from average type 1 patients.
Several factors boosted the risk of first-time DFU in both types of disease, including high or low levels of albumin excretion, advanced diabetic retinopathy, limited or nonexistent vibration sense, symptoms of neuropathy, and absence of foot pulses per univariable regression (all P less than .01). The researchers linked the neuropathy and absences of foot pulses to especially high spikes in risk.
Female gender was protective for type 1 and type 2 disease (hazard ratios, 0.7 and 0.5, respectively; P = .0000). Various body mass index levels seemed to have no impact on risk.
Three factors that posed a higher risk for first-time DFU in type 1 disease, but not type 2, were: smoking (HR, 1.4 vs. no smoking, P = .0220), age of 60-79 years (HR, 1.7 vs. age 40-59; P = .0000), cardiovascular disease (HR, 2.2 vs. no cardiovascular disease; P = .0000), and diabetes duration of between 5 and 20 years (HR, 2.2 vs. less than 5 years; P = .0027) or 20 years or more (HR, 5.2 vs. less than 5 years; P = .0000).
The authors noted that “25% of all patients with diabetes develop DFU during their lifetime, and DFUs precede 80% of all lower leg amputations in patients with diabetes.” In addition, DFU often occurs in feet already compromised by neuropathy or peripheral vascular disease, and is therefore associated with greater risk for infection, poorer outcomes, recurrent ulceration, amputation, and increased mortality. These risks underscore the need for the earliest-possible identification of first-time DFU and timely adoption of effective, preventative strategies, they wrote.
The study was not funded. Several of the authors reported that they own shares in Novo Nordisk.
SOURCE: Hangaard S et al. Diabetes Res Clin Pract. 2019 Apr 18;151:177-86.
Danish researchers have linked multiple factors to higher risk of first-time diabetic foot ulcers (DFUs) in patients with type 1 and type 2 diabetes, although some of the factors –
according to the new study findings.The authors suggest that since clinical information gathered from patients during routine follow-up visits often includes mention of the risk factors for first-time DFU, it could form the basis of a risk stratification process for first-time DFU that can be integrated into the electronic record system and easily incorporated into routine care.
DFU is a significant complication for both type 1 and type 2 diabetes, but no previous research has stratified the risk factors for first-time DFUs by type of diabetes, emphasized the study authors, led by Sine Hangaard, MSc, of Steno Diabetes Center Copenhagen.
For the new study, the researchers tracked 5,588 patients with type 1 diabetes and 7,113 with type 2, all of whom were treated at a hospital clinic in Denmark between 2001 and 2015. The authors noted that the patients with type 2 disease who were treated at the center were clinically more complicated and had a longer disease duration than average type 2 patients, whereas the patients with type 1 diabetes did not differ from average type 1 patients.
Several factors boosted the risk of first-time DFU in both types of disease, including high or low levels of albumin excretion, advanced diabetic retinopathy, limited or nonexistent vibration sense, symptoms of neuropathy, and absence of foot pulses per univariable regression (all P less than .01). The researchers linked the neuropathy and absences of foot pulses to especially high spikes in risk.
Female gender was protective for type 1 and type 2 disease (hazard ratios, 0.7 and 0.5, respectively; P = .0000). Various body mass index levels seemed to have no impact on risk.
Three factors that posed a higher risk for first-time DFU in type 1 disease, but not type 2, were: smoking (HR, 1.4 vs. no smoking, P = .0220), age of 60-79 years (HR, 1.7 vs. age 40-59; P = .0000), cardiovascular disease (HR, 2.2 vs. no cardiovascular disease; P = .0000), and diabetes duration of between 5 and 20 years (HR, 2.2 vs. less than 5 years; P = .0027) or 20 years or more (HR, 5.2 vs. less than 5 years; P = .0000).
The authors noted that “25% of all patients with diabetes develop DFU during their lifetime, and DFUs precede 80% of all lower leg amputations in patients with diabetes.” In addition, DFU often occurs in feet already compromised by neuropathy or peripheral vascular disease, and is therefore associated with greater risk for infection, poorer outcomes, recurrent ulceration, amputation, and increased mortality. These risks underscore the need for the earliest-possible identification of first-time DFU and timely adoption of effective, preventative strategies, they wrote.
The study was not funded. Several of the authors reported that they own shares in Novo Nordisk.
SOURCE: Hangaard S et al. Diabetes Res Clin Pract. 2019 Apr 18;151:177-86.
Danish researchers have linked multiple factors to higher risk of first-time diabetic foot ulcers (DFUs) in patients with type 1 and type 2 diabetes, although some of the factors –
according to the new study findings.The authors suggest that since clinical information gathered from patients during routine follow-up visits often includes mention of the risk factors for first-time DFU, it could form the basis of a risk stratification process for first-time DFU that can be integrated into the electronic record system and easily incorporated into routine care.
DFU is a significant complication for both type 1 and type 2 diabetes, but no previous research has stratified the risk factors for first-time DFUs by type of diabetes, emphasized the study authors, led by Sine Hangaard, MSc, of Steno Diabetes Center Copenhagen.
For the new study, the researchers tracked 5,588 patients with type 1 diabetes and 7,113 with type 2, all of whom were treated at a hospital clinic in Denmark between 2001 and 2015. The authors noted that the patients with type 2 disease who were treated at the center were clinically more complicated and had a longer disease duration than average type 2 patients, whereas the patients with type 1 diabetes did not differ from average type 1 patients.
Several factors boosted the risk of first-time DFU in both types of disease, including high or low levels of albumin excretion, advanced diabetic retinopathy, limited or nonexistent vibration sense, symptoms of neuropathy, and absence of foot pulses per univariable regression (all P less than .01). The researchers linked the neuropathy and absences of foot pulses to especially high spikes in risk.
Female gender was protective for type 1 and type 2 disease (hazard ratios, 0.7 and 0.5, respectively; P = .0000). Various body mass index levels seemed to have no impact on risk.
Three factors that posed a higher risk for first-time DFU in type 1 disease, but not type 2, were: smoking (HR, 1.4 vs. no smoking, P = .0220), age of 60-79 years (HR, 1.7 vs. age 40-59; P = .0000), cardiovascular disease (HR, 2.2 vs. no cardiovascular disease; P = .0000), and diabetes duration of between 5 and 20 years (HR, 2.2 vs. less than 5 years; P = .0027) or 20 years or more (HR, 5.2 vs. less than 5 years; P = .0000).
The authors noted that “25% of all patients with diabetes develop DFU during their lifetime, and DFUs precede 80% of all lower leg amputations in patients with diabetes.” In addition, DFU often occurs in feet already compromised by neuropathy or peripheral vascular disease, and is therefore associated with greater risk for infection, poorer outcomes, recurrent ulceration, amputation, and increased mortality. These risks underscore the need for the earliest-possible identification of first-time DFU and timely adoption of effective, preventative strategies, they wrote.
The study was not funded. Several of the authors reported that they own shares in Novo Nordisk.
SOURCE: Hangaard S et al. Diabetes Res Clin Pract. 2019 Apr 18;151:177-86.
FROM DIABETES RESEARCH AND CLINICAL PRACTICE
Asboe-Hansen Sign in Toxic Epidermal Necrolysis
To the Editor:
A 25-year-old woman with no notable medical history was admitted to the hospital for suspected Stevens-Johnson syndrome (SJS). The patient was started on amoxicillin 7 days prior to the skin eruption for prophylaxis before removal of an intrauterine device. On the day of admission, she reported ocular discomfort, dysphagia, and dysuria. She developed erythema of the conjunctivae, face, chest, and proximal upper extremities, as well as erosions of the vermilion lips. She presented to the local emergency department and was transferred to our institution for urgent dermatologic consultation. On physical examination by the dermatology service, the patient had erythematous macules coalescing into patches with overlying flaccid bullae, some denuded, involving the face, chest, abdomen, back (Figure 1), bilateral upper extremities, bilateral thighs, and labia majora and minora. Additionally, she had conjunctivitis, superficial erosions of the vermilion lips, and tense bullae of the palms and soles. On palpation of the flaccid bullae, the Asboe-Hansen sign was elicited (Figure 2 and video). A shave biopsy of the newly elicited bullae was performed. Pathology showed a subepidermal bulla with confluent necrosis of the epidermis and minimal inflammatory infiltrate. An additional shave biopsy of perilesional skin was obtained for direct immunofluorescence, which was negative for IgG, C3, IgM, and IgA. Based on the clinical presentation involving more than 30% of the patient’s body surface area (BSA) and the pathology findings, a diagnosis of toxic epidermal necrolysis (TEN) was made. The patient remained in the intensive care unit with a multidisciplinary team consisting of dermatology, ophthalmology, gynecology, gastroenterology, and the general surgery burn group. Following treatment with intravenous immunoglobulin, systemic corticosteroids, and aggressive wound care, the patient made a full recovery.
Toxic epidermal necrolysis is a rare, acute, life-threatening mucocutaneous disease within a spectrum of adverse cutaneous drug reactions. The estimated worldwide incidence of TEN is 0.4 to 1.9 per million individuals annually.1 Toxic epidermal necrolysis is clinically characterized by diffuse exfoliation of the skin and mucosae with flaccid bullae. These clinical features are a consequence of extensive keratinocyte death, leading to dermoepidermal junction dissociation. Commonly, there is a prodrome of fever, pharyngitis, and painful skin preceding the diffuse erythema and sloughing of skin and mucous membranes. Lesions typically first appear on the trunk and then follow a centrifugal spread, often sparing the distal aspects of the arms and legs.
Toxic epidermal necrolysis is part of a continuous spectrum with SJS. Less than 10% BSA involvement is considered SJS, 10% to 30% BSA involvement is SJS/TEN overlap, and more than 30% BSA detachment is TEN. Stevens-Johnson syndrome can progress to TEN. In TEN, the distribution of cutaneous lesions is more confluent, and mucosal involvement is more severe.2 The differential diagnosis may include staphylococcal scalded skin syndrome, drug-induced linear IgA bullous dermatosis, severe acute graft-vs-host disease, drug reaction with eosinophilia and systemic symptoms, and invasive fungal dermatitis. An accurate diagnosis of TEN is imperative, as the management and morbidity of these diseases are vastly different. Toxic epidermal necrolysis has an estimated mortality rate of 25% to 30%, with sepsis leading to multiorgan failure being the most common cause of death.3
Although the pathophysiology of TEN has yet to be fully elucidated, it is thought to be a T cell–mediated process with CD8+ cells acting as the primary means of keratinocyte death. An estimated 80% to 95% of cases are due to drug reactions.3 The medications that are most commonly associated with TEN include allopurinol, antibiotics, nonsteroidal anti-inflammatory drugs, and anticonvulsants. Symptoms typically begin 7 to 21 days after starting the drug. Less commonly, Mycoplasma pneumoniae, dengue virus, cytomegalovirus, and contrast medium have been reported as inciting factors for TEN.2
The diagnosis of TEN is established by correlating clinical features with a histopathologic examination obtained from a lesional skin biopsy. The classic cutaneous features of TEN begin as erythematous, flesh-colored, dusky to violaceous macules and/or morbilliform or targetoid lesions. These early lesions have the tendency to coalesce. The cutaneous findings will eventually progress into flaccid bullae, diffuse epidermal sloughing, and full-thickness skin necrosis.2,3 The evolution of skin lesions may be rapid or may take several days to develop. On palpation, the Nikolsky (lateral shearing of epidermis with minimal pressure) and Asboe-Hansen sign will be positive in patients with SJS/TEN, demonstrating that the associated blisters are flaccid and may be displaced peripherally.4 For an accurate diagnosis, the biopsy must contain full-thickness epidermis. It is imperative to choose a biopsy site from an acute blister, as old lesions of other diseases, such as erythema multiforme, will eventually become necrotic and mimic the histopathologic appearance of SJS/TEN, potentially leading to an incorrect diagnosis.4 Full-thickness epidermal necrosis has a high sensitivity but low specificity for TEN.3 The histologic features of TEN vary depending on the stage of the disease. Classic histologic findings include satellite necrosis of keratinocytes followed by full-thickness necrosis of keratinocytes and perivascular lymphoid infiltrates. The stratum corneum retains its original structure.4
The Asboe-Hansen sign, also known as the bulla spread sign, was originally described in 1960 as a diagnostic sign for pemphigus vulgaris.5 A positive Asboe-Hansen sign demonstrates the ability to enlarge a bulla in the lateral direction by applying perpendicular mechanical pressure to the roof of an intact bulla. The bulla is extended to adjacent nonblistered skin.6 A positive sign demonstrates decreased adhesion between keratinocytes or between the basal epidermal cells and the dermal connective tissue.5 In addition to pemphigus vulgaris, the Asboe-Hansen sign may be positive in TEN and SJS, as well as other diseases affecting the dermoepidermal junction including pemphigus foliaceus, pemphigus vegetans, and bullous pemphigoid. Asboe-Hansen5 made the argument that a fresh bulla should be biopsied if histopathologic diagnosis is necessary, as older bullae may exhibit epithelial cell regeneration and disturb an accurate diagnosis.
Accurate and early diagnosis of TEN is imperative, as prognosis is strongly correlated with the speed at which the offending drug is discontinued and appropriate medical treatment is initiated. Prompt withdrawal of the offending drug has been reported to reduce the risk for morbidity by 30% per day.7 Although classically associated with the pemphigus group of diseases, the Asboe-Hansen sign is of diagnostic value to the pathologist in diagnosing TEN by reproducing the same microscopic appearance of a fresh spontaneous blister. Due to the notable morbidity and mortality in SJS and TEN, the Asboe-Hansen sign should be attempted for the site of a lesional biopsy, as an accurate diagnosis relies on clinicopathologic correlation.
- Schwartz RA, McDonough PH, Lee BW, et al. Toxic epidermal necrolysis: part I. introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis. J Am Acad Dermatol. 2013;69:173.e1-173.e13.
- Frech LE, Prins C. Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. In: Bolognia J, Jorizzo J, Schaffer J, eds. Dermatology. 3rd ed. New York, NY: Elsevier; 2012:332-347.
- Schwartz RA, McDonough PH, Lee BW, et al. Toxic epidermal necrolysis: part II. prognosis, sequelae, diagnosis, differential diagnosis, prevention, and treatment. J Am Acad Dermatol. 2013;69:187.e1–187.e16.
- Elston D, Stratman E, Miller S. Skin biopsy. J Am Acad Dermatol. 2016;74:1-16.
- Asboe-Hansen G. Blister-spread induced by finger-pressure, a diagnostic sign in pemphigus. J Invest Dermatol. 1960;34:5-9.
- Ganapati S. Eponymous dermatological signs in bullous dermatoses. Indian J Dermatol. 2014;59:21-23.
- Garcia-Doval I, Lecleach L, Bocquet H, et al. Toxic epidermal necrolysis and Stevens-Johnson syndrome: does early withdrawal of causative drugs decrease the risk of death? Arch Dermatol. 2000;136:323-327.
To the Editor:
A 25-year-old woman with no notable medical history was admitted to the hospital for suspected Stevens-Johnson syndrome (SJS). The patient was started on amoxicillin 7 days prior to the skin eruption for prophylaxis before removal of an intrauterine device. On the day of admission, she reported ocular discomfort, dysphagia, and dysuria. She developed erythema of the conjunctivae, face, chest, and proximal upper extremities, as well as erosions of the vermilion lips. She presented to the local emergency department and was transferred to our institution for urgent dermatologic consultation. On physical examination by the dermatology service, the patient had erythematous macules coalescing into patches with overlying flaccid bullae, some denuded, involving the face, chest, abdomen, back (Figure 1), bilateral upper extremities, bilateral thighs, and labia majora and minora. Additionally, she had conjunctivitis, superficial erosions of the vermilion lips, and tense bullae of the palms and soles. On palpation of the flaccid bullae, the Asboe-Hansen sign was elicited (Figure 2 and video). A shave biopsy of the newly elicited bullae was performed. Pathology showed a subepidermal bulla with confluent necrosis of the epidermis and minimal inflammatory infiltrate. An additional shave biopsy of perilesional skin was obtained for direct immunofluorescence, which was negative for IgG, C3, IgM, and IgA. Based on the clinical presentation involving more than 30% of the patient’s body surface area (BSA) and the pathology findings, a diagnosis of toxic epidermal necrolysis (TEN) was made. The patient remained in the intensive care unit with a multidisciplinary team consisting of dermatology, ophthalmology, gynecology, gastroenterology, and the general surgery burn group. Following treatment with intravenous immunoglobulin, systemic corticosteroids, and aggressive wound care, the patient made a full recovery.
Toxic epidermal necrolysis is a rare, acute, life-threatening mucocutaneous disease within a spectrum of adverse cutaneous drug reactions. The estimated worldwide incidence of TEN is 0.4 to 1.9 per million individuals annually.1 Toxic epidermal necrolysis is clinically characterized by diffuse exfoliation of the skin and mucosae with flaccid bullae. These clinical features are a consequence of extensive keratinocyte death, leading to dermoepidermal junction dissociation. Commonly, there is a prodrome of fever, pharyngitis, and painful skin preceding the diffuse erythema and sloughing of skin and mucous membranes. Lesions typically first appear on the trunk and then follow a centrifugal spread, often sparing the distal aspects of the arms and legs.
Toxic epidermal necrolysis is part of a continuous spectrum with SJS. Less than 10% BSA involvement is considered SJS, 10% to 30% BSA involvement is SJS/TEN overlap, and more than 30% BSA detachment is TEN. Stevens-Johnson syndrome can progress to TEN. In TEN, the distribution of cutaneous lesions is more confluent, and mucosal involvement is more severe.2 The differential diagnosis may include staphylococcal scalded skin syndrome, drug-induced linear IgA bullous dermatosis, severe acute graft-vs-host disease, drug reaction with eosinophilia and systemic symptoms, and invasive fungal dermatitis. An accurate diagnosis of TEN is imperative, as the management and morbidity of these diseases are vastly different. Toxic epidermal necrolysis has an estimated mortality rate of 25% to 30%, with sepsis leading to multiorgan failure being the most common cause of death.3
Although the pathophysiology of TEN has yet to be fully elucidated, it is thought to be a T cell–mediated process with CD8+ cells acting as the primary means of keratinocyte death. An estimated 80% to 95% of cases are due to drug reactions.3 The medications that are most commonly associated with TEN include allopurinol, antibiotics, nonsteroidal anti-inflammatory drugs, and anticonvulsants. Symptoms typically begin 7 to 21 days after starting the drug. Less commonly, Mycoplasma pneumoniae, dengue virus, cytomegalovirus, and contrast medium have been reported as inciting factors for TEN.2
The diagnosis of TEN is established by correlating clinical features with a histopathologic examination obtained from a lesional skin biopsy. The classic cutaneous features of TEN begin as erythematous, flesh-colored, dusky to violaceous macules and/or morbilliform or targetoid lesions. These early lesions have the tendency to coalesce. The cutaneous findings will eventually progress into flaccid bullae, diffuse epidermal sloughing, and full-thickness skin necrosis.2,3 The evolution of skin lesions may be rapid or may take several days to develop. On palpation, the Nikolsky (lateral shearing of epidermis with minimal pressure) and Asboe-Hansen sign will be positive in patients with SJS/TEN, demonstrating that the associated blisters are flaccid and may be displaced peripherally.4 For an accurate diagnosis, the biopsy must contain full-thickness epidermis. It is imperative to choose a biopsy site from an acute blister, as old lesions of other diseases, such as erythema multiforme, will eventually become necrotic and mimic the histopathologic appearance of SJS/TEN, potentially leading to an incorrect diagnosis.4 Full-thickness epidermal necrosis has a high sensitivity but low specificity for TEN.3 The histologic features of TEN vary depending on the stage of the disease. Classic histologic findings include satellite necrosis of keratinocytes followed by full-thickness necrosis of keratinocytes and perivascular lymphoid infiltrates. The stratum corneum retains its original structure.4
The Asboe-Hansen sign, also known as the bulla spread sign, was originally described in 1960 as a diagnostic sign for pemphigus vulgaris.5 A positive Asboe-Hansen sign demonstrates the ability to enlarge a bulla in the lateral direction by applying perpendicular mechanical pressure to the roof of an intact bulla. The bulla is extended to adjacent nonblistered skin.6 A positive sign demonstrates decreased adhesion between keratinocytes or between the basal epidermal cells and the dermal connective tissue.5 In addition to pemphigus vulgaris, the Asboe-Hansen sign may be positive in TEN and SJS, as well as other diseases affecting the dermoepidermal junction including pemphigus foliaceus, pemphigus vegetans, and bullous pemphigoid. Asboe-Hansen5 made the argument that a fresh bulla should be biopsied if histopathologic diagnosis is necessary, as older bullae may exhibit epithelial cell regeneration and disturb an accurate diagnosis.
Accurate and early diagnosis of TEN is imperative, as prognosis is strongly correlated with the speed at which the offending drug is discontinued and appropriate medical treatment is initiated. Prompt withdrawal of the offending drug has been reported to reduce the risk for morbidity by 30% per day.7 Although classically associated with the pemphigus group of diseases, the Asboe-Hansen sign is of diagnostic value to the pathologist in diagnosing TEN by reproducing the same microscopic appearance of a fresh spontaneous blister. Due to the notable morbidity and mortality in SJS and TEN, the Asboe-Hansen sign should be attempted for the site of a lesional biopsy, as an accurate diagnosis relies on clinicopathologic correlation.
To the Editor:
A 25-year-old woman with no notable medical history was admitted to the hospital for suspected Stevens-Johnson syndrome (SJS). The patient was started on amoxicillin 7 days prior to the skin eruption for prophylaxis before removal of an intrauterine device. On the day of admission, she reported ocular discomfort, dysphagia, and dysuria. She developed erythema of the conjunctivae, face, chest, and proximal upper extremities, as well as erosions of the vermilion lips. She presented to the local emergency department and was transferred to our institution for urgent dermatologic consultation. On physical examination by the dermatology service, the patient had erythematous macules coalescing into patches with overlying flaccid bullae, some denuded, involving the face, chest, abdomen, back (Figure 1), bilateral upper extremities, bilateral thighs, and labia majora and minora. Additionally, she had conjunctivitis, superficial erosions of the vermilion lips, and tense bullae of the palms and soles. On palpation of the flaccid bullae, the Asboe-Hansen sign was elicited (Figure 2 and video). A shave biopsy of the newly elicited bullae was performed. Pathology showed a subepidermal bulla with confluent necrosis of the epidermis and minimal inflammatory infiltrate. An additional shave biopsy of perilesional skin was obtained for direct immunofluorescence, which was negative for IgG, C3, IgM, and IgA. Based on the clinical presentation involving more than 30% of the patient’s body surface area (BSA) and the pathology findings, a diagnosis of toxic epidermal necrolysis (TEN) was made. The patient remained in the intensive care unit with a multidisciplinary team consisting of dermatology, ophthalmology, gynecology, gastroenterology, and the general surgery burn group. Following treatment with intravenous immunoglobulin, systemic corticosteroids, and aggressive wound care, the patient made a full recovery.
Toxic epidermal necrolysis is a rare, acute, life-threatening mucocutaneous disease within a spectrum of adverse cutaneous drug reactions. The estimated worldwide incidence of TEN is 0.4 to 1.9 per million individuals annually.1 Toxic epidermal necrolysis is clinically characterized by diffuse exfoliation of the skin and mucosae with flaccid bullae. These clinical features are a consequence of extensive keratinocyte death, leading to dermoepidermal junction dissociation. Commonly, there is a prodrome of fever, pharyngitis, and painful skin preceding the diffuse erythema and sloughing of skin and mucous membranes. Lesions typically first appear on the trunk and then follow a centrifugal spread, often sparing the distal aspects of the arms and legs.
Toxic epidermal necrolysis is part of a continuous spectrum with SJS. Less than 10% BSA involvement is considered SJS, 10% to 30% BSA involvement is SJS/TEN overlap, and more than 30% BSA detachment is TEN. Stevens-Johnson syndrome can progress to TEN. In TEN, the distribution of cutaneous lesions is more confluent, and mucosal involvement is more severe.2 The differential diagnosis may include staphylococcal scalded skin syndrome, drug-induced linear IgA bullous dermatosis, severe acute graft-vs-host disease, drug reaction with eosinophilia and systemic symptoms, and invasive fungal dermatitis. An accurate diagnosis of TEN is imperative, as the management and morbidity of these diseases are vastly different. Toxic epidermal necrolysis has an estimated mortality rate of 25% to 30%, with sepsis leading to multiorgan failure being the most common cause of death.3
Although the pathophysiology of TEN has yet to be fully elucidated, it is thought to be a T cell–mediated process with CD8+ cells acting as the primary means of keratinocyte death. An estimated 80% to 95% of cases are due to drug reactions.3 The medications that are most commonly associated with TEN include allopurinol, antibiotics, nonsteroidal anti-inflammatory drugs, and anticonvulsants. Symptoms typically begin 7 to 21 days after starting the drug. Less commonly, Mycoplasma pneumoniae, dengue virus, cytomegalovirus, and contrast medium have been reported as inciting factors for TEN.2
The diagnosis of TEN is established by correlating clinical features with a histopathologic examination obtained from a lesional skin biopsy. The classic cutaneous features of TEN begin as erythematous, flesh-colored, dusky to violaceous macules and/or morbilliform or targetoid lesions. These early lesions have the tendency to coalesce. The cutaneous findings will eventually progress into flaccid bullae, diffuse epidermal sloughing, and full-thickness skin necrosis.2,3 The evolution of skin lesions may be rapid or may take several days to develop. On palpation, the Nikolsky (lateral shearing of epidermis with minimal pressure) and Asboe-Hansen sign will be positive in patients with SJS/TEN, demonstrating that the associated blisters are flaccid and may be displaced peripherally.4 For an accurate diagnosis, the biopsy must contain full-thickness epidermis. It is imperative to choose a biopsy site from an acute blister, as old lesions of other diseases, such as erythema multiforme, will eventually become necrotic and mimic the histopathologic appearance of SJS/TEN, potentially leading to an incorrect diagnosis.4 Full-thickness epidermal necrosis has a high sensitivity but low specificity for TEN.3 The histologic features of TEN vary depending on the stage of the disease. Classic histologic findings include satellite necrosis of keratinocytes followed by full-thickness necrosis of keratinocytes and perivascular lymphoid infiltrates. The stratum corneum retains its original structure.4
The Asboe-Hansen sign, also known as the bulla spread sign, was originally described in 1960 as a diagnostic sign for pemphigus vulgaris.5 A positive Asboe-Hansen sign demonstrates the ability to enlarge a bulla in the lateral direction by applying perpendicular mechanical pressure to the roof of an intact bulla. The bulla is extended to adjacent nonblistered skin.6 A positive sign demonstrates decreased adhesion between keratinocytes or between the basal epidermal cells and the dermal connective tissue.5 In addition to pemphigus vulgaris, the Asboe-Hansen sign may be positive in TEN and SJS, as well as other diseases affecting the dermoepidermal junction including pemphigus foliaceus, pemphigus vegetans, and bullous pemphigoid. Asboe-Hansen5 made the argument that a fresh bulla should be biopsied if histopathologic diagnosis is necessary, as older bullae may exhibit epithelial cell regeneration and disturb an accurate diagnosis.
Accurate and early diagnosis of TEN is imperative, as prognosis is strongly correlated with the speed at which the offending drug is discontinued and appropriate medical treatment is initiated. Prompt withdrawal of the offending drug has been reported to reduce the risk for morbidity by 30% per day.7 Although classically associated with the pemphigus group of diseases, the Asboe-Hansen sign is of diagnostic value to the pathologist in diagnosing TEN by reproducing the same microscopic appearance of a fresh spontaneous blister. Due to the notable morbidity and mortality in SJS and TEN, the Asboe-Hansen sign should be attempted for the site of a lesional biopsy, as an accurate diagnosis relies on clinicopathologic correlation.
- Schwartz RA, McDonough PH, Lee BW, et al. Toxic epidermal necrolysis: part I. introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis. J Am Acad Dermatol. 2013;69:173.e1-173.e13.
- Frech LE, Prins C. Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. In: Bolognia J, Jorizzo J, Schaffer J, eds. Dermatology. 3rd ed. New York, NY: Elsevier; 2012:332-347.
- Schwartz RA, McDonough PH, Lee BW, et al. Toxic epidermal necrolysis: part II. prognosis, sequelae, diagnosis, differential diagnosis, prevention, and treatment. J Am Acad Dermatol. 2013;69:187.e1–187.e16.
- Elston D, Stratman E, Miller S. Skin biopsy. J Am Acad Dermatol. 2016;74:1-16.
- Asboe-Hansen G. Blister-spread induced by finger-pressure, a diagnostic sign in pemphigus. J Invest Dermatol. 1960;34:5-9.
- Ganapati S. Eponymous dermatological signs in bullous dermatoses. Indian J Dermatol. 2014;59:21-23.
- Garcia-Doval I, Lecleach L, Bocquet H, et al. Toxic epidermal necrolysis and Stevens-Johnson syndrome: does early withdrawal of causative drugs decrease the risk of death? Arch Dermatol. 2000;136:323-327.
- Schwartz RA, McDonough PH, Lee BW, et al. Toxic epidermal necrolysis: part I. introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis. J Am Acad Dermatol. 2013;69:173.e1-173.e13.
- Frech LE, Prins C. Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. In: Bolognia J, Jorizzo J, Schaffer J, eds. Dermatology. 3rd ed. New York, NY: Elsevier; 2012:332-347.
- Schwartz RA, McDonough PH, Lee BW, et al. Toxic epidermal necrolysis: part II. prognosis, sequelae, diagnosis, differential diagnosis, prevention, and treatment. J Am Acad Dermatol. 2013;69:187.e1–187.e16.
- Elston D, Stratman E, Miller S. Skin biopsy. J Am Acad Dermatol. 2016;74:1-16.
- Asboe-Hansen G. Blister-spread induced by finger-pressure, a diagnostic sign in pemphigus. J Invest Dermatol. 1960;34:5-9.
- Ganapati S. Eponymous dermatological signs in bullous dermatoses. Indian J Dermatol. 2014;59:21-23.
- Garcia-Doval I, Lecleach L, Bocquet H, et al. Toxic epidermal necrolysis and Stevens-Johnson syndrome: does early withdrawal of causative drugs decrease the risk of death? Arch Dermatol. 2000;136:323-327.
Practice Points
- Asboe-Hansen sign is a useful clinical tool for diagnosing toxic epidermal necrolysis (TEN).
- Asboe-Hansen sign can be employed to generate a fresh bulla for lesional skin biopsy in the evaluation of TEN.
Topical Natural Products in Managing Dermatologic Conditions: Observations and Recommendations
Patients seek healthy skin that conveys overall health and well-being. Cosmeceuticals claim to therapeutically affect the structure and function of the skin, and it is rational to hold them to scientific standards that substantiate efficacy claims.1 Notably, it is increasingly important to consider nature-based products in helping patients and consumers to achieve healthier skin. Despite the availability of sophisticated efficacy testing, explanations of the underlying physiologic and pharmacologic principles of nature-based products lag behind those of conventional formulations. In many instances, simple form and function information cannot adequately support their desired use and expected benefits. In addition, cosmetic regulations do not even permit structure-function claims that are allowed for dietary supplements.
Physicians whose patients want recommendations for nature-based products often do not know where to turn for definitive product and use information. Unlike prescription medications or even beauty-from-within dietary supplement products, natural cosmetics and cosmeceuticals are barred from communicating scientific evidence and experience of use to form proper opinions for recommendations. Without the benefit of full product labeling, physicians are left to mine sparse, confusing, and often contradictory literature in an effort to self-educate. Here, we share our experiences with patients, our operating knowledge base, and our recommendations for investigation to improve the available information and ensure practicing physicians have the information they need to appropriately recommend nature-based products.
General Observations Pertaining to Patients and Nature-Based Products
Ethnic and cultural customs and traditions have accepted and employed nature-based products for skin health for millennia (eTables 1–3).2-20 African and the derived Caribbean cultures frequently use shea butter, black soap, or coconut oil. East Asian ethnobotanical practices include the use of ginseng, green tea, almond, and angelica root in skin care. Indian culture employs Ayurvedic medicine principles that include herbal remedies comprised of ground chickpeas, rice, turmeric, neem, ashwagandha, moringa, and kutki. These cultural traditions continue into modern times, and patients regularly use these products. Modern social trends that focus on a healthy lifestyle also create demand for nature-based products for skin health. In our opinion, the current growing interest in nature-based products implies continued growth in their use as patients become more familiar and comfortable with them.
For beauty and skin health, a new trend has evolved in which the first source of advice is rarely a dermatologist. Social media, nonphysician influencers, and pseudoscience have created an authority previously reserved for dermatologists among patients and consumers. Bloggers and social media influencers, posting their individual real-world experiences, shape the perceptions of consumers and patients.21,22 Nonphysician influencers leverage their celebrity to provide guidance and advice on beauty and cosmetic tips.23 Much of the evidence supporting cosmetic and especially nature-based products for skin care and health often is believed to be less rigorous and of lower quality than that typically supporting physician recommendations.24-26
Nature-Based Products in Skin Health and Dermatologic Conditions
Patients turn to nature-based products for skin care and health for many reasons. The simplest reason is that they grew up with such products and continue their use. Many patients find nature-based products themselves, have favorable experiences, and seek advice on their efficacy and safety for continued use. Patients also use these products as part of a holistic approach to health in which diet and exercise coincide with the idea of ministering to the whole self instead of preventing or treating an illness. These nature-based treatment options fit their natural lifestyles. Patients sometimes express concerns about synthetic products that lead them to seek out nature-based products. Chemicals and preservatives (eg, parabens, sunscreens, nanoparticles) may evoke concerns about negative health consequences, which can be a cause of great anxiety to patients.
Nature-based products, when recommended by physicians, can fulfill important roles. As healthier alternatives, they can address health concerns in the belief that plant-based ingredients may be more compatible with overall health than synthetic ingredients. This compatibility may have resulted from the human species coevolving with plant species containing therapeutic utility, leading to the development of specific receptors for many natural products, such as digoxin from foxglove (Digitalis purpurea), opioids from poppies (Papaver somniferum), and cannabinoids (Cannabis sativa and hybrids). Natural products can become alternatives to synthetic products or adjuncts to prescription medications. Often, inclusion of nature-based products into a treatment plan enables patients to feel that they are a more integral part of the care team treating their conditions. By virtue of physician recommendations, patients may have expectations on product efficacy being as robust as prescription products with the safety profile of plant-based products. Patients should be advised to accept a realistic view of the efficacy and tolerability profiles. In the end, patients consider physician recommendations based on the assumption that they are credible and derived from experience and knowledge.
Physician Perceptions of Nature-Based Products
Physicians recommend nature-based products based on several factors. Central to the recommendation is an understanding, through appropriate documentation, that the product will be reasonably efficacious. Critical to this point, physicians must understand what ingredients are in nature-based products, their concentrations or amounts, and why they are present. However, our experience with nature-based products suggests that many of these factors are not met. Limited or unclear information on the efficacy of nature-based products fails to satisfy a physician’s need for adequate information to support recommendations. Although natural ingredients are listed on product labels, their intended benefit and efficacy characteristics often are unclear or poorly stated, in some cases resulting from improper labeling and in other cases due to claim restrictions imposed on cosmetics. In addition, insufficient details on formulation, such as type and percentages of oils, antioxidants, and vitamins, hinder the physician’s ability to identify and explain mechanisms that bring benefit to the patient. Universal benchmarks do not exist for amounts or concentrations of ingredients that are required for a stated benefit.27 Currently, no standards exist for assurances that product quality, control, and efficacy are consistently reproducible. For example, angel dusting is a practice that discloses that an active ingredient is present, yet these ingredients may be present in quantities that are insufficient to provide measurable benefit. Sourcing of ingredients also can be concerning, as they may not always meet manufacturer, physician, or patient expectations for characterization or efficacy.28,29 Dry testing, which is when a manufacturer contracts a laboratory to certify their ingredients without performing assays, has been increasingly reported in lay and botanical literature over the last few years.30
It is unknown if many nature-based products clinically exhibit their stated efficacy. Empirical evidence or well-conducted clinical studies on which to base recommendations of these products are limited. Individual natural ingredients, however, do have some supporting evidence of efficacy: shea butter moisturizes31; coconut oil exhibits anti-inflammatory properties32,33; and vinegar, yogurt, and diluted tea tree oil exhibit antibacterial properties in postprocedure care and fungal infections, and as adjuvants to prescription antibiotics in atopic dermatitis, acne, and rosacea.34-41 Honey also has been shown to improve wound healing and is even available as a medical device for wounds.42,43 Although nature-based products are an interesting alternative to synthetic products, they require a fulsome understanding of characteristics and efficacy properties to support physician recommendations.
Physician Recommendations
Physicians must be educated to understand when and how to recommend nature-based products. Although we recommend increased product information to guide physicians, current laws, including the Federal Food, Drug, and Cosmetic Act and the Fair Packaging and Labeling Act, are satisfactory from a regulatory standpoint.44 Here, we discuss the information physicians could use to support an informed recommendation of nature-based products.
A clear specific explanation of natural ingredient sources, their intended efficacy, and rigorous scientific clinical evidence supporting their use should be given. Manufacturers are needed to document and report the structure and function of natural ingredients, leading to a common understanding by practicing dermatologists.45 For this reason, manufacturers must provide nonambiguous and standardized methods and measures to demonstrate the mechanism of ingredient efficacy and the limits of safety and tolerability.
We recommend that manufacturers provide standardized transparency into the composition of nature-based formulations, including amounts and concentrations of ingredients; geographic sources; parts of plants used; and if extracted, what agent(s) this standard is based on (eg, hypericin in Saint-John’s-wort or kavalactones in kava kava). Most natural products contain an aqueous phase and therefore will likely require preservatives such as synthetic parabens or alcohols to avoid degradation. Unnecessary ingredients, including fragrances, fillers, and support chemicals, should be absent since inert agents may exhibit biologic effects, obscuring the boundary between active and inert. A clear explanation of the origins of these nature-based ingredients and the concentration, purity, and activity assessment should be provided. In the context of an authoritative review with standardized measures, labels that provide the common name, plant name, part used, how it was obtained, concentrations and/or amounts, and standardized activity measures can be helpful to the recommending physician, who will then know the efficacy patients should expect from the ingredients. They also can assess the expected tolerability based on the concentrations and their own experience managing a particular disorder, tempered by the patient’s experiences with prior therapies. Transparent and standardized labeling describing the formulation, quantities of ingredients, and intended activity will help inform expectations of efficacy.
We recommend clear preclinical and clinical demonstrations of the efficacy and benefits that are claimed by nature-based formulations. Properly designed placebo- or active-controlled, blinded, randomized studies with standardized measures and end points are recommended to determine efficacy and safety. These demonstrations of efficacy can provide physicians with credible evidence on which to base their recommendations and guide the use of products for the patient’s best experience. Given sufficient involvement from manufacturers and publication of the information in peer-reviewed journals, the relative benefits for each nature-based product can be cataloged as a resource for physicians.
Conclusion
Patients turn to nature-based products for many reasons. They have high expectations but also harbor concerns as to the efficacy of these products for skin and health care. Physicians seek to recommend nature-based products for these patients but often find themselves disadvantaged by limited published evidence and insufficient labeling information on composition and efficacy, which should support recommendations for use. To remedy this situation, we suggest research to allow a clear explanation of the activity of natural ingredients, clear demonstrations of the efficacy of nature-based formulas using clinical standardized measures and end points, and clear education and disclosure of ingredients contained within nature-based products.
Acknowledgments—Burt’s Bees (Durham, North Carolina) provided funding for editorial support by Medical Dynamics, Inc (New York, New York).
- Levin J, Momin SB. How much do we really know about our favorite cosmeceutical ingredients? J Clin Aesthet Dermatol. 2010;3:22-41.
- Ajala EO, Aberuagba F, Olaniyan AM, et al. Optimization of solvent extraction of shea butter (Vitellaria paradoxa) using response surface methodology and its characterization. J Food Sci Technol. 2016;53:730-738.
- Lin A, Nabatian A, Halverstam CP. Discovering black soap: a survey on the attitudes and practices of black soap users. J Clin Aesthet Dermatol. 2017;10:18-22.
- Lin TK, Zhong L, Santiago JL. Anti-inflammatory and skin barrier repair effects of topical application of some plant oils. Int J Mol Sci. 2017;19. pii:E70. doi:10.3390/ijms19010070.
- Dua K, Sheshala R, Ling TY, et al. Anti-inflammatory, antibacterial and analgesic potential of cocos nucifera linn.: a review. Antiinflamm Antiallergy Agents Med Chem. 2013;12:158-164.
- Hyun TK, Jang KI. Are berries useless by-products of ginseng? recent research on the potential health benefits of ginseng berry. EXCLI J. 2017;16:780-784.
- Truong VL, Bak MJ, Lee C, et al. Hair regenerative mechanisms of red ginseng oil and its major components in the testosterone-induced delay of anagen entry in C57BL/6 mice. Molecules. 2017;22. pii:E1505. doi:10.3390/molecules22091505.
- Hussain M, Habib Ur R, Akhtar L. Therapeutic benefits of green tea extract on various parameters in non-alcoholic fatty liver disease patients. Pak J Med Sci. 2017;33:931-936.
- Yi M, Fu J, Zhou L, et al. The effect of almond consumption on elements of endurance exercise performance in trained athletes. J Int Soc Sports Nutr. 2014;11:18.
- Sowndhararajan K, Deepa P, Kim M, et al. A review of the composition of the essential oils and biological activities of angelica species. Sci Pharm. 2017;85. pii:E33. doi:10.3390/scipharm85030033.
- Mahjour M, Khoushabi A, Noras M, et al. Effectiveness of Cicer arietinum in cutaneous problems: viewpoint of Avicenna and Razi. Curr Drug Discov Technol. 2018;15:243-250.
- Kanlayavattanakul M, Laurits N, Chaikul P. Jasmine rice panicle: a safe and efficient natural ingredient for skin aging treatments. J Ethnopharmacol. 2016;193:607-616.
- Aggarwal BB, Yuan W, Li S, et al. Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: identification of novel components of turmeric. Mol Nutr Food Res. 2013;57:1529-1542.
- Mohanty C, Sahoo SK. Curcumin and its topical formulations for wound healing applications. Drug Discov Today. 2017;22:1582-1592.
- Gupta SC, Prasad S, Tyagi AK, et al. Neem (Azadirachta indica): an Indian traditional panacea with modern molecular basis. Phytomedicine. 2017;34:14-20.
- Choudhary D, Bhattacharyya S, Bose S. Efficacy and safety of ashwagandha (Withania somnifera (L.) Dunal) root extract in improving memory and cognitive functions. J Diet Suppl. 2017;14:599-612.
- Halder B, Singh S, Thakur SS. Withania somnifera root extract has potent cytotoxic effect against human malignant melanoma cells. PLoS One. 2015;10:E0137498.
- Nadeem M, Imran M. Promising features of Moringa oleifera oil: recent updates and perspectives. Lipids Health Dis. 2016;15:212.
- Sultan P, Jan A, Pervaiz Q. Phytochemical studies for quantitative estimation of iridoid glycosides in Picrorhiza kurroa Royle. Bot Stud. 2016;57:7.
- Gianfaldoni S, Wollina U, Tirant M, et al. Herbal compounds for the treatment of vitiligo: a review. Open Access Maced J Med Sci. 2018;6:203-207.
- Diamantoglou M, Platz J, Vienken J. Cellulose carbamates and derivatives as hemocompatible membrane materials for hemodialysis. Artif Organs. 1999;23:15-22.
- Respiratory syncytial virus (RSV). Centers for Disease Control and Prevention website. http://www.cdc.gov/rsv/research/us-surveillance.html. Updated June 26, 2018. Accessed February 1, 2019.
- Dembo G, Park SB, Kharasch ED. Central nervous system concentrations of cyclooxygenase-2 inhibitors in humans. Anesthesiology. 2005;102:409-415.
- Fong P. CFTR-SLC26 transporter interactions in epithelia. Biophys Rev. 2012;4:107-116.
- Liu Z. How cosmeceuticals companies get away with pseudoscience. Pacific Standard website. https://psmag.com/environment/cosmetic-companies-get-away-pseudoscience-placebo-week-92455. Published October 15, 2014. Accessed February 1, 2019.
- Beyerstein BL. Alternative medicine and common errors of reasoning. Acad Med. 2001;76:230-237.
- Topical antimicrobial drug products for over-the-counter human use. US Food and Drug Administration website. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=333.310. Accessed February 1, 2019.
- Natural personal care. Natural Products Association website. https://www.npanational.org/certifications/natural-seal/natural-seal-personal-care/. Accessed March 27, 2019.
- Natural Cosmetics Standard. GFaW Web site. https://gfaw.eu/en/ncs-for-all-who-love-nature-and-cosmetics/ncs-information-for-consumer/. Accessed February 1, 2019.
- Brown PN, Betz JM, Jasch F. How to qualify an analytical laboratory for analysis of herbal dietary ingredients and avoid using a “dry lab”: a review of issues related to using a contract analytical laboratory by industry, academia, and regulatory agencies. HerbalGram. 2013:52-59.
- Oh MJ, Cho YH, Cha SY, et al. Novel phytoceramides containing fatty acids of diverse chain lengths are better than a single C18-ceramide N-stearoyl phytosphingosine to improve the physiological properties of human stratum corneum. Clin Cosmet Investig Dermatol. 2017;10:363-371.
- Famurewa AC, Aja PM, Maduagwuna EK, et al. Antioxidant and anti-inflammatory effects of virgin coconut oil supplementation abrogate acute chemotherapy oxidative nephrotoxicity induced by anticancer drug methotrexate in rats. Biomed Pharmacother. 2017;96:905-911.
- Intahphuak S, Khonsung P, Panthong A. Anti-inflammatory, analgesic, and antipyretic activities of virgin coconut oil. Pharm Biol. 2010;48:151-157.
- McKenna PJ, Lehr GS, Leist P, et al. Antiseptic effectiveness with fibroblast preservation. Ann Plast Surg. 1991;27:265-268.
- Brockow K, Grabenhorst P, Abeck D, et al. Effect of gentian violet, corticosteroid and tar preparations in Staphylococcus aureus-colonized atopic eczema. Dermatology. 1999;199:231-236.
- Larson D, Jacob SE. Tea tree oil. Dermatitis. 2012;23:48-49.
- Misner BD. A novel aromatic oil compound inhibits microbial overgrowth on feet: a case study. J Int Soc Sports Nutr. 2007;4:3.
- D’Auria FD, Laino L, Strippoli V, et al. In vitro activity of tea tree oil against Candida albicans mycelial conversion and other pathogenic fungi. J Chemother. 2001;13:377-383.
- Fuchs-Tarlovsky V, Marquez-Barba MF, Sriram K. Probiotics in dermatologic practice. Nutrition. 2016;32:289-295.
- Bowe W, Patel NB, Logan AC. Acne vulgaris, probiotics and the gut-brain-skin axis: from anecdote to translational medicine. Benef Microbes. 2014;5:185-199.
- Baquerizo Nole KL, Yim E, Keri JE. Probiotics and prebiotics in dermatology. J Am Acad Dermatol. 2014;71:814-821.
- Saikaly SK, Khachemoune A. Honey and wound healing: an update. Am J Clin Dermatol. 2017;18:237-251.
- Aziz Z, Abdul Rasool Hassan B. The effects of honey compared to silver sulfadiazine for the treatment of burns: a systematic review of randomized controlled trials. Burns. 2017;43:50-57.
- FDA authority over cosmetics: how cosmetics are not FDA-approved, but are FDA-regulated. US Food and Drug AdministrationWeb site. https://www.fda.gov/cosmetics/guidanceregulation/lawsregulations/ucm074162.htm. Updated July 24, 2018. Accessed February 1, 2019.
- Wohlrab J. Topical preparations and their use in dermatology. J Dtsch Dermatol Ges. 2016;4:1061-1070
Patients seek healthy skin that conveys overall health and well-being. Cosmeceuticals claim to therapeutically affect the structure and function of the skin, and it is rational to hold them to scientific standards that substantiate efficacy claims.1 Notably, it is increasingly important to consider nature-based products in helping patients and consumers to achieve healthier skin. Despite the availability of sophisticated efficacy testing, explanations of the underlying physiologic and pharmacologic principles of nature-based products lag behind those of conventional formulations. In many instances, simple form and function information cannot adequately support their desired use and expected benefits. In addition, cosmetic regulations do not even permit structure-function claims that are allowed for dietary supplements.
Physicians whose patients want recommendations for nature-based products often do not know where to turn for definitive product and use information. Unlike prescription medications or even beauty-from-within dietary supplement products, natural cosmetics and cosmeceuticals are barred from communicating scientific evidence and experience of use to form proper opinions for recommendations. Without the benefit of full product labeling, physicians are left to mine sparse, confusing, and often contradictory literature in an effort to self-educate. Here, we share our experiences with patients, our operating knowledge base, and our recommendations for investigation to improve the available information and ensure practicing physicians have the information they need to appropriately recommend nature-based products.
General Observations Pertaining to Patients and Nature-Based Products
Ethnic and cultural customs and traditions have accepted and employed nature-based products for skin health for millennia (eTables 1–3).2-20 African and the derived Caribbean cultures frequently use shea butter, black soap, or coconut oil. East Asian ethnobotanical practices include the use of ginseng, green tea, almond, and angelica root in skin care. Indian culture employs Ayurvedic medicine principles that include herbal remedies comprised of ground chickpeas, rice, turmeric, neem, ashwagandha, moringa, and kutki. These cultural traditions continue into modern times, and patients regularly use these products. Modern social trends that focus on a healthy lifestyle also create demand for nature-based products for skin health. In our opinion, the current growing interest in nature-based products implies continued growth in their use as patients become more familiar and comfortable with them.
For beauty and skin health, a new trend has evolved in which the first source of advice is rarely a dermatologist. Social media, nonphysician influencers, and pseudoscience have created an authority previously reserved for dermatologists among patients and consumers. Bloggers and social media influencers, posting their individual real-world experiences, shape the perceptions of consumers and patients.21,22 Nonphysician influencers leverage their celebrity to provide guidance and advice on beauty and cosmetic tips.23 Much of the evidence supporting cosmetic and especially nature-based products for skin care and health often is believed to be less rigorous and of lower quality than that typically supporting physician recommendations.24-26
Nature-Based Products in Skin Health and Dermatologic Conditions
Patients turn to nature-based products for skin care and health for many reasons. The simplest reason is that they grew up with such products and continue their use. Many patients find nature-based products themselves, have favorable experiences, and seek advice on their efficacy and safety for continued use. Patients also use these products as part of a holistic approach to health in which diet and exercise coincide with the idea of ministering to the whole self instead of preventing or treating an illness. These nature-based treatment options fit their natural lifestyles. Patients sometimes express concerns about synthetic products that lead them to seek out nature-based products. Chemicals and preservatives (eg, parabens, sunscreens, nanoparticles) may evoke concerns about negative health consequences, which can be a cause of great anxiety to patients.
Nature-based products, when recommended by physicians, can fulfill important roles. As healthier alternatives, they can address health concerns in the belief that plant-based ingredients may be more compatible with overall health than synthetic ingredients. This compatibility may have resulted from the human species coevolving with plant species containing therapeutic utility, leading to the development of specific receptors for many natural products, such as digoxin from foxglove (Digitalis purpurea), opioids from poppies (Papaver somniferum), and cannabinoids (Cannabis sativa and hybrids). Natural products can become alternatives to synthetic products or adjuncts to prescription medications. Often, inclusion of nature-based products into a treatment plan enables patients to feel that they are a more integral part of the care team treating their conditions. By virtue of physician recommendations, patients may have expectations on product efficacy being as robust as prescription products with the safety profile of plant-based products. Patients should be advised to accept a realistic view of the efficacy and tolerability profiles. In the end, patients consider physician recommendations based on the assumption that they are credible and derived from experience and knowledge.
Physician Perceptions of Nature-Based Products
Physicians recommend nature-based products based on several factors. Central to the recommendation is an understanding, through appropriate documentation, that the product will be reasonably efficacious. Critical to this point, physicians must understand what ingredients are in nature-based products, their concentrations or amounts, and why they are present. However, our experience with nature-based products suggests that many of these factors are not met. Limited or unclear information on the efficacy of nature-based products fails to satisfy a physician’s need for adequate information to support recommendations. Although natural ingredients are listed on product labels, their intended benefit and efficacy characteristics often are unclear or poorly stated, in some cases resulting from improper labeling and in other cases due to claim restrictions imposed on cosmetics. In addition, insufficient details on formulation, such as type and percentages of oils, antioxidants, and vitamins, hinder the physician’s ability to identify and explain mechanisms that bring benefit to the patient. Universal benchmarks do not exist for amounts or concentrations of ingredients that are required for a stated benefit.27 Currently, no standards exist for assurances that product quality, control, and efficacy are consistently reproducible. For example, angel dusting is a practice that discloses that an active ingredient is present, yet these ingredients may be present in quantities that are insufficient to provide measurable benefit. Sourcing of ingredients also can be concerning, as they may not always meet manufacturer, physician, or patient expectations for characterization or efficacy.28,29 Dry testing, which is when a manufacturer contracts a laboratory to certify their ingredients without performing assays, has been increasingly reported in lay and botanical literature over the last few years.30
It is unknown if many nature-based products clinically exhibit their stated efficacy. Empirical evidence or well-conducted clinical studies on which to base recommendations of these products are limited. Individual natural ingredients, however, do have some supporting evidence of efficacy: shea butter moisturizes31; coconut oil exhibits anti-inflammatory properties32,33; and vinegar, yogurt, and diluted tea tree oil exhibit antibacterial properties in postprocedure care and fungal infections, and as adjuvants to prescription antibiotics in atopic dermatitis, acne, and rosacea.34-41 Honey also has been shown to improve wound healing and is even available as a medical device for wounds.42,43 Although nature-based products are an interesting alternative to synthetic products, they require a fulsome understanding of characteristics and efficacy properties to support physician recommendations.
Physician Recommendations
Physicians must be educated to understand when and how to recommend nature-based products. Although we recommend increased product information to guide physicians, current laws, including the Federal Food, Drug, and Cosmetic Act and the Fair Packaging and Labeling Act, are satisfactory from a regulatory standpoint.44 Here, we discuss the information physicians could use to support an informed recommendation of nature-based products.
A clear specific explanation of natural ingredient sources, their intended efficacy, and rigorous scientific clinical evidence supporting their use should be given. Manufacturers are needed to document and report the structure and function of natural ingredients, leading to a common understanding by practicing dermatologists.45 For this reason, manufacturers must provide nonambiguous and standardized methods and measures to demonstrate the mechanism of ingredient efficacy and the limits of safety and tolerability.
We recommend that manufacturers provide standardized transparency into the composition of nature-based formulations, including amounts and concentrations of ingredients; geographic sources; parts of plants used; and if extracted, what agent(s) this standard is based on (eg, hypericin in Saint-John’s-wort or kavalactones in kava kava). Most natural products contain an aqueous phase and therefore will likely require preservatives such as synthetic parabens or alcohols to avoid degradation. Unnecessary ingredients, including fragrances, fillers, and support chemicals, should be absent since inert agents may exhibit biologic effects, obscuring the boundary between active and inert. A clear explanation of the origins of these nature-based ingredients and the concentration, purity, and activity assessment should be provided. In the context of an authoritative review with standardized measures, labels that provide the common name, plant name, part used, how it was obtained, concentrations and/or amounts, and standardized activity measures can be helpful to the recommending physician, who will then know the efficacy patients should expect from the ingredients. They also can assess the expected tolerability based on the concentrations and their own experience managing a particular disorder, tempered by the patient’s experiences with prior therapies. Transparent and standardized labeling describing the formulation, quantities of ingredients, and intended activity will help inform expectations of efficacy.
We recommend clear preclinical and clinical demonstrations of the efficacy and benefits that are claimed by nature-based formulations. Properly designed placebo- or active-controlled, blinded, randomized studies with standardized measures and end points are recommended to determine efficacy and safety. These demonstrations of efficacy can provide physicians with credible evidence on which to base their recommendations and guide the use of products for the patient’s best experience. Given sufficient involvement from manufacturers and publication of the information in peer-reviewed journals, the relative benefits for each nature-based product can be cataloged as a resource for physicians.
Conclusion
Patients turn to nature-based products for many reasons. They have high expectations but also harbor concerns as to the efficacy of these products for skin and health care. Physicians seek to recommend nature-based products for these patients but often find themselves disadvantaged by limited published evidence and insufficient labeling information on composition and efficacy, which should support recommendations for use. To remedy this situation, we suggest research to allow a clear explanation of the activity of natural ingredients, clear demonstrations of the efficacy of nature-based formulas using clinical standardized measures and end points, and clear education and disclosure of ingredients contained within nature-based products.
Acknowledgments—Burt’s Bees (Durham, North Carolina) provided funding for editorial support by Medical Dynamics, Inc (New York, New York).
Patients seek healthy skin that conveys overall health and well-being. Cosmeceuticals claim to therapeutically affect the structure and function of the skin, and it is rational to hold them to scientific standards that substantiate efficacy claims.1 Notably, it is increasingly important to consider nature-based products in helping patients and consumers to achieve healthier skin. Despite the availability of sophisticated efficacy testing, explanations of the underlying physiologic and pharmacologic principles of nature-based products lag behind those of conventional formulations. In many instances, simple form and function information cannot adequately support their desired use and expected benefits. In addition, cosmetic regulations do not even permit structure-function claims that are allowed for dietary supplements.
Physicians whose patients want recommendations for nature-based products often do not know where to turn for definitive product and use information. Unlike prescription medications or even beauty-from-within dietary supplement products, natural cosmetics and cosmeceuticals are barred from communicating scientific evidence and experience of use to form proper opinions for recommendations. Without the benefit of full product labeling, physicians are left to mine sparse, confusing, and often contradictory literature in an effort to self-educate. Here, we share our experiences with patients, our operating knowledge base, and our recommendations for investigation to improve the available information and ensure practicing physicians have the information they need to appropriately recommend nature-based products.
General Observations Pertaining to Patients and Nature-Based Products
Ethnic and cultural customs and traditions have accepted and employed nature-based products for skin health for millennia (eTables 1–3).2-20 African and the derived Caribbean cultures frequently use shea butter, black soap, or coconut oil. East Asian ethnobotanical practices include the use of ginseng, green tea, almond, and angelica root in skin care. Indian culture employs Ayurvedic medicine principles that include herbal remedies comprised of ground chickpeas, rice, turmeric, neem, ashwagandha, moringa, and kutki. These cultural traditions continue into modern times, and patients regularly use these products. Modern social trends that focus on a healthy lifestyle also create demand for nature-based products for skin health. In our opinion, the current growing interest in nature-based products implies continued growth in their use as patients become more familiar and comfortable with them.
For beauty and skin health, a new trend has evolved in which the first source of advice is rarely a dermatologist. Social media, nonphysician influencers, and pseudoscience have created an authority previously reserved for dermatologists among patients and consumers. Bloggers and social media influencers, posting their individual real-world experiences, shape the perceptions of consumers and patients.21,22 Nonphysician influencers leverage their celebrity to provide guidance and advice on beauty and cosmetic tips.23 Much of the evidence supporting cosmetic and especially nature-based products for skin care and health often is believed to be less rigorous and of lower quality than that typically supporting physician recommendations.24-26
Nature-Based Products in Skin Health and Dermatologic Conditions
Patients turn to nature-based products for skin care and health for many reasons. The simplest reason is that they grew up with such products and continue their use. Many patients find nature-based products themselves, have favorable experiences, and seek advice on their efficacy and safety for continued use. Patients also use these products as part of a holistic approach to health in which diet and exercise coincide with the idea of ministering to the whole self instead of preventing or treating an illness. These nature-based treatment options fit their natural lifestyles. Patients sometimes express concerns about synthetic products that lead them to seek out nature-based products. Chemicals and preservatives (eg, parabens, sunscreens, nanoparticles) may evoke concerns about negative health consequences, which can be a cause of great anxiety to patients.
Nature-based products, when recommended by physicians, can fulfill important roles. As healthier alternatives, they can address health concerns in the belief that plant-based ingredients may be more compatible with overall health than synthetic ingredients. This compatibility may have resulted from the human species coevolving with plant species containing therapeutic utility, leading to the development of specific receptors for many natural products, such as digoxin from foxglove (Digitalis purpurea), opioids from poppies (Papaver somniferum), and cannabinoids (Cannabis sativa and hybrids). Natural products can become alternatives to synthetic products or adjuncts to prescription medications. Often, inclusion of nature-based products into a treatment plan enables patients to feel that they are a more integral part of the care team treating their conditions. By virtue of physician recommendations, patients may have expectations on product efficacy being as robust as prescription products with the safety profile of plant-based products. Patients should be advised to accept a realistic view of the efficacy and tolerability profiles. In the end, patients consider physician recommendations based on the assumption that they are credible and derived from experience and knowledge.
Physician Perceptions of Nature-Based Products
Physicians recommend nature-based products based on several factors. Central to the recommendation is an understanding, through appropriate documentation, that the product will be reasonably efficacious. Critical to this point, physicians must understand what ingredients are in nature-based products, their concentrations or amounts, and why they are present. However, our experience with nature-based products suggests that many of these factors are not met. Limited or unclear information on the efficacy of nature-based products fails to satisfy a physician’s need for adequate information to support recommendations. Although natural ingredients are listed on product labels, their intended benefit and efficacy characteristics often are unclear or poorly stated, in some cases resulting from improper labeling and in other cases due to claim restrictions imposed on cosmetics. In addition, insufficient details on formulation, such as type and percentages of oils, antioxidants, and vitamins, hinder the physician’s ability to identify and explain mechanisms that bring benefit to the patient. Universal benchmarks do not exist for amounts or concentrations of ingredients that are required for a stated benefit.27 Currently, no standards exist for assurances that product quality, control, and efficacy are consistently reproducible. For example, angel dusting is a practice that discloses that an active ingredient is present, yet these ingredients may be present in quantities that are insufficient to provide measurable benefit. Sourcing of ingredients also can be concerning, as they may not always meet manufacturer, physician, or patient expectations for characterization or efficacy.28,29 Dry testing, which is when a manufacturer contracts a laboratory to certify their ingredients without performing assays, has been increasingly reported in lay and botanical literature over the last few years.30
It is unknown if many nature-based products clinically exhibit their stated efficacy. Empirical evidence or well-conducted clinical studies on which to base recommendations of these products are limited. Individual natural ingredients, however, do have some supporting evidence of efficacy: shea butter moisturizes31; coconut oil exhibits anti-inflammatory properties32,33; and vinegar, yogurt, and diluted tea tree oil exhibit antibacterial properties in postprocedure care and fungal infections, and as adjuvants to prescription antibiotics in atopic dermatitis, acne, and rosacea.34-41 Honey also has been shown to improve wound healing and is even available as a medical device for wounds.42,43 Although nature-based products are an interesting alternative to synthetic products, they require a fulsome understanding of characteristics and efficacy properties to support physician recommendations.
Physician Recommendations
Physicians must be educated to understand when and how to recommend nature-based products. Although we recommend increased product information to guide physicians, current laws, including the Federal Food, Drug, and Cosmetic Act and the Fair Packaging and Labeling Act, are satisfactory from a regulatory standpoint.44 Here, we discuss the information physicians could use to support an informed recommendation of nature-based products.
A clear specific explanation of natural ingredient sources, their intended efficacy, and rigorous scientific clinical evidence supporting their use should be given. Manufacturers are needed to document and report the structure and function of natural ingredients, leading to a common understanding by practicing dermatologists.45 For this reason, manufacturers must provide nonambiguous and standardized methods and measures to demonstrate the mechanism of ingredient efficacy and the limits of safety and tolerability.
We recommend that manufacturers provide standardized transparency into the composition of nature-based formulations, including amounts and concentrations of ingredients; geographic sources; parts of plants used; and if extracted, what agent(s) this standard is based on (eg, hypericin in Saint-John’s-wort or kavalactones in kava kava). Most natural products contain an aqueous phase and therefore will likely require preservatives such as synthetic parabens or alcohols to avoid degradation. Unnecessary ingredients, including fragrances, fillers, and support chemicals, should be absent since inert agents may exhibit biologic effects, obscuring the boundary between active and inert. A clear explanation of the origins of these nature-based ingredients and the concentration, purity, and activity assessment should be provided. In the context of an authoritative review with standardized measures, labels that provide the common name, plant name, part used, how it was obtained, concentrations and/or amounts, and standardized activity measures can be helpful to the recommending physician, who will then know the efficacy patients should expect from the ingredients. They also can assess the expected tolerability based on the concentrations and their own experience managing a particular disorder, tempered by the patient’s experiences with prior therapies. Transparent and standardized labeling describing the formulation, quantities of ingredients, and intended activity will help inform expectations of efficacy.
We recommend clear preclinical and clinical demonstrations of the efficacy and benefits that are claimed by nature-based formulations. Properly designed placebo- or active-controlled, blinded, randomized studies with standardized measures and end points are recommended to determine efficacy and safety. These demonstrations of efficacy can provide physicians with credible evidence on which to base their recommendations and guide the use of products for the patient’s best experience. Given sufficient involvement from manufacturers and publication of the information in peer-reviewed journals, the relative benefits for each nature-based product can be cataloged as a resource for physicians.
Conclusion
Patients turn to nature-based products for many reasons. They have high expectations but also harbor concerns as to the efficacy of these products for skin and health care. Physicians seek to recommend nature-based products for these patients but often find themselves disadvantaged by limited published evidence and insufficient labeling information on composition and efficacy, which should support recommendations for use. To remedy this situation, we suggest research to allow a clear explanation of the activity of natural ingredients, clear demonstrations of the efficacy of nature-based formulas using clinical standardized measures and end points, and clear education and disclosure of ingredients contained within nature-based products.
Acknowledgments—Burt’s Bees (Durham, North Carolina) provided funding for editorial support by Medical Dynamics, Inc (New York, New York).
- Levin J, Momin SB. How much do we really know about our favorite cosmeceutical ingredients? J Clin Aesthet Dermatol. 2010;3:22-41.
- Ajala EO, Aberuagba F, Olaniyan AM, et al. Optimization of solvent extraction of shea butter (Vitellaria paradoxa) using response surface methodology and its characterization. J Food Sci Technol. 2016;53:730-738.
- Lin A, Nabatian A, Halverstam CP. Discovering black soap: a survey on the attitudes and practices of black soap users. J Clin Aesthet Dermatol. 2017;10:18-22.
- Lin TK, Zhong L, Santiago JL. Anti-inflammatory and skin barrier repair effects of topical application of some plant oils. Int J Mol Sci. 2017;19. pii:E70. doi:10.3390/ijms19010070.
- Dua K, Sheshala R, Ling TY, et al. Anti-inflammatory, antibacterial and analgesic potential of cocos nucifera linn.: a review. Antiinflamm Antiallergy Agents Med Chem. 2013;12:158-164.
- Hyun TK, Jang KI. Are berries useless by-products of ginseng? recent research on the potential health benefits of ginseng berry. EXCLI J. 2017;16:780-784.
- Truong VL, Bak MJ, Lee C, et al. Hair regenerative mechanisms of red ginseng oil and its major components in the testosterone-induced delay of anagen entry in C57BL/6 mice. Molecules. 2017;22. pii:E1505. doi:10.3390/molecules22091505.
- Hussain M, Habib Ur R, Akhtar L. Therapeutic benefits of green tea extract on various parameters in non-alcoholic fatty liver disease patients. Pak J Med Sci. 2017;33:931-936.
- Yi M, Fu J, Zhou L, et al. The effect of almond consumption on elements of endurance exercise performance in trained athletes. J Int Soc Sports Nutr. 2014;11:18.
- Sowndhararajan K, Deepa P, Kim M, et al. A review of the composition of the essential oils and biological activities of angelica species. Sci Pharm. 2017;85. pii:E33. doi:10.3390/scipharm85030033.
- Mahjour M, Khoushabi A, Noras M, et al. Effectiveness of Cicer arietinum in cutaneous problems: viewpoint of Avicenna and Razi. Curr Drug Discov Technol. 2018;15:243-250.
- Kanlayavattanakul M, Laurits N, Chaikul P. Jasmine rice panicle: a safe and efficient natural ingredient for skin aging treatments. J Ethnopharmacol. 2016;193:607-616.
- Aggarwal BB, Yuan W, Li S, et al. Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: identification of novel components of turmeric. Mol Nutr Food Res. 2013;57:1529-1542.
- Mohanty C, Sahoo SK. Curcumin and its topical formulations for wound healing applications. Drug Discov Today. 2017;22:1582-1592.
- Gupta SC, Prasad S, Tyagi AK, et al. Neem (Azadirachta indica): an Indian traditional panacea with modern molecular basis. Phytomedicine. 2017;34:14-20.
- Choudhary D, Bhattacharyya S, Bose S. Efficacy and safety of ashwagandha (Withania somnifera (L.) Dunal) root extract in improving memory and cognitive functions. J Diet Suppl. 2017;14:599-612.
- Halder B, Singh S, Thakur SS. Withania somnifera root extract has potent cytotoxic effect against human malignant melanoma cells. PLoS One. 2015;10:E0137498.
- Nadeem M, Imran M. Promising features of Moringa oleifera oil: recent updates and perspectives. Lipids Health Dis. 2016;15:212.
- Sultan P, Jan A, Pervaiz Q. Phytochemical studies for quantitative estimation of iridoid glycosides in Picrorhiza kurroa Royle. Bot Stud. 2016;57:7.
- Gianfaldoni S, Wollina U, Tirant M, et al. Herbal compounds for the treatment of vitiligo: a review. Open Access Maced J Med Sci. 2018;6:203-207.
- Diamantoglou M, Platz J, Vienken J. Cellulose carbamates and derivatives as hemocompatible membrane materials for hemodialysis. Artif Organs. 1999;23:15-22.
- Respiratory syncytial virus (RSV). Centers for Disease Control and Prevention website. http://www.cdc.gov/rsv/research/us-surveillance.html. Updated June 26, 2018. Accessed February 1, 2019.
- Dembo G, Park SB, Kharasch ED. Central nervous system concentrations of cyclooxygenase-2 inhibitors in humans. Anesthesiology. 2005;102:409-415.
- Fong P. CFTR-SLC26 transporter interactions in epithelia. Biophys Rev. 2012;4:107-116.
- Liu Z. How cosmeceuticals companies get away with pseudoscience. Pacific Standard website. https://psmag.com/environment/cosmetic-companies-get-away-pseudoscience-placebo-week-92455. Published October 15, 2014. Accessed February 1, 2019.
- Beyerstein BL. Alternative medicine and common errors of reasoning. Acad Med. 2001;76:230-237.
- Topical antimicrobial drug products for over-the-counter human use. US Food and Drug Administration website. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=333.310. Accessed February 1, 2019.
- Natural personal care. Natural Products Association website. https://www.npanational.org/certifications/natural-seal/natural-seal-personal-care/. Accessed March 27, 2019.
- Natural Cosmetics Standard. GFaW Web site. https://gfaw.eu/en/ncs-for-all-who-love-nature-and-cosmetics/ncs-information-for-consumer/. Accessed February 1, 2019.
- Brown PN, Betz JM, Jasch F. How to qualify an analytical laboratory for analysis of herbal dietary ingredients and avoid using a “dry lab”: a review of issues related to using a contract analytical laboratory by industry, academia, and regulatory agencies. HerbalGram. 2013:52-59.
- Oh MJ, Cho YH, Cha SY, et al. Novel phytoceramides containing fatty acids of diverse chain lengths are better than a single C18-ceramide N-stearoyl phytosphingosine to improve the physiological properties of human stratum corneum. Clin Cosmet Investig Dermatol. 2017;10:363-371.
- Famurewa AC, Aja PM, Maduagwuna EK, et al. Antioxidant and anti-inflammatory effects of virgin coconut oil supplementation abrogate acute chemotherapy oxidative nephrotoxicity induced by anticancer drug methotrexate in rats. Biomed Pharmacother. 2017;96:905-911.
- Intahphuak S, Khonsung P, Panthong A. Anti-inflammatory, analgesic, and antipyretic activities of virgin coconut oil. Pharm Biol. 2010;48:151-157.
- McKenna PJ, Lehr GS, Leist P, et al. Antiseptic effectiveness with fibroblast preservation. Ann Plast Surg. 1991;27:265-268.
- Brockow K, Grabenhorst P, Abeck D, et al. Effect of gentian violet, corticosteroid and tar preparations in Staphylococcus aureus-colonized atopic eczema. Dermatology. 1999;199:231-236.
- Larson D, Jacob SE. Tea tree oil. Dermatitis. 2012;23:48-49.
- Misner BD. A novel aromatic oil compound inhibits microbial overgrowth on feet: a case study. J Int Soc Sports Nutr. 2007;4:3.
- D’Auria FD, Laino L, Strippoli V, et al. In vitro activity of tea tree oil against Candida albicans mycelial conversion and other pathogenic fungi. J Chemother. 2001;13:377-383.
- Fuchs-Tarlovsky V, Marquez-Barba MF, Sriram K. Probiotics in dermatologic practice. Nutrition. 2016;32:289-295.
- Bowe W, Patel NB, Logan AC. Acne vulgaris, probiotics and the gut-brain-skin axis: from anecdote to translational medicine. Benef Microbes. 2014;5:185-199.
- Baquerizo Nole KL, Yim E, Keri JE. Probiotics and prebiotics in dermatology. J Am Acad Dermatol. 2014;71:814-821.
- Saikaly SK, Khachemoune A. Honey and wound healing: an update. Am J Clin Dermatol. 2017;18:237-251.
- Aziz Z, Abdul Rasool Hassan B. The effects of honey compared to silver sulfadiazine for the treatment of burns: a systematic review of randomized controlled trials. Burns. 2017;43:50-57.
- FDA authority over cosmetics: how cosmetics are not FDA-approved, but are FDA-regulated. US Food and Drug AdministrationWeb site. https://www.fda.gov/cosmetics/guidanceregulation/lawsregulations/ucm074162.htm. Updated July 24, 2018. Accessed February 1, 2019.
- Wohlrab J. Topical preparations and their use in dermatology. J Dtsch Dermatol Ges. 2016;4:1061-1070
- Levin J, Momin SB. How much do we really know about our favorite cosmeceutical ingredients? J Clin Aesthet Dermatol. 2010;3:22-41.
- Ajala EO, Aberuagba F, Olaniyan AM, et al. Optimization of solvent extraction of shea butter (Vitellaria paradoxa) using response surface methodology and its characterization. J Food Sci Technol. 2016;53:730-738.
- Lin A, Nabatian A, Halverstam CP. Discovering black soap: a survey on the attitudes and practices of black soap users. J Clin Aesthet Dermatol. 2017;10:18-22.
- Lin TK, Zhong L, Santiago JL. Anti-inflammatory and skin barrier repair effects of topical application of some plant oils. Int J Mol Sci. 2017;19. pii:E70. doi:10.3390/ijms19010070.
- Dua K, Sheshala R, Ling TY, et al. Anti-inflammatory, antibacterial and analgesic potential of cocos nucifera linn.: a review. Antiinflamm Antiallergy Agents Med Chem. 2013;12:158-164.
- Hyun TK, Jang KI. Are berries useless by-products of ginseng? recent research on the potential health benefits of ginseng berry. EXCLI J. 2017;16:780-784.
- Truong VL, Bak MJ, Lee C, et al. Hair regenerative mechanisms of red ginseng oil and its major components in the testosterone-induced delay of anagen entry in C57BL/6 mice. Molecules. 2017;22. pii:E1505. doi:10.3390/molecules22091505.
- Hussain M, Habib Ur R, Akhtar L. Therapeutic benefits of green tea extract on various parameters in non-alcoholic fatty liver disease patients. Pak J Med Sci. 2017;33:931-936.
- Yi M, Fu J, Zhou L, et al. The effect of almond consumption on elements of endurance exercise performance in trained athletes. J Int Soc Sports Nutr. 2014;11:18.
- Sowndhararajan K, Deepa P, Kim M, et al. A review of the composition of the essential oils and biological activities of angelica species. Sci Pharm. 2017;85. pii:E33. doi:10.3390/scipharm85030033.
- Mahjour M, Khoushabi A, Noras M, et al. Effectiveness of Cicer arietinum in cutaneous problems: viewpoint of Avicenna and Razi. Curr Drug Discov Technol. 2018;15:243-250.
- Kanlayavattanakul M, Laurits N, Chaikul P. Jasmine rice panicle: a safe and efficient natural ingredient for skin aging treatments. J Ethnopharmacol. 2016;193:607-616.
- Aggarwal BB, Yuan W, Li S, et al. Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: identification of novel components of turmeric. Mol Nutr Food Res. 2013;57:1529-1542.
- Mohanty C, Sahoo SK. Curcumin and its topical formulations for wound healing applications. Drug Discov Today. 2017;22:1582-1592.
- Gupta SC, Prasad S, Tyagi AK, et al. Neem (Azadirachta indica): an Indian traditional panacea with modern molecular basis. Phytomedicine. 2017;34:14-20.
- Choudhary D, Bhattacharyya S, Bose S. Efficacy and safety of ashwagandha (Withania somnifera (L.) Dunal) root extract in improving memory and cognitive functions. J Diet Suppl. 2017;14:599-612.
- Halder B, Singh S, Thakur SS. Withania somnifera root extract has potent cytotoxic effect against human malignant melanoma cells. PLoS One. 2015;10:E0137498.
- Nadeem M, Imran M. Promising features of Moringa oleifera oil: recent updates and perspectives. Lipids Health Dis. 2016;15:212.
- Sultan P, Jan A, Pervaiz Q. Phytochemical studies for quantitative estimation of iridoid glycosides in Picrorhiza kurroa Royle. Bot Stud. 2016;57:7.
- Gianfaldoni S, Wollina U, Tirant M, et al. Herbal compounds for the treatment of vitiligo: a review. Open Access Maced J Med Sci. 2018;6:203-207.
- Diamantoglou M, Platz J, Vienken J. Cellulose carbamates and derivatives as hemocompatible membrane materials for hemodialysis. Artif Organs. 1999;23:15-22.
- Respiratory syncytial virus (RSV). Centers for Disease Control and Prevention website. http://www.cdc.gov/rsv/research/us-surveillance.html. Updated June 26, 2018. Accessed February 1, 2019.
- Dembo G, Park SB, Kharasch ED. Central nervous system concentrations of cyclooxygenase-2 inhibitors in humans. Anesthesiology. 2005;102:409-415.
- Fong P. CFTR-SLC26 transporter interactions in epithelia. Biophys Rev. 2012;4:107-116.
- Liu Z. How cosmeceuticals companies get away with pseudoscience. Pacific Standard website. https://psmag.com/environment/cosmetic-companies-get-away-pseudoscience-placebo-week-92455. Published October 15, 2014. Accessed February 1, 2019.
- Beyerstein BL. Alternative medicine and common errors of reasoning. Acad Med. 2001;76:230-237.
- Topical antimicrobial drug products for over-the-counter human use. US Food and Drug Administration website. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=333.310. Accessed February 1, 2019.
- Natural personal care. Natural Products Association website. https://www.npanational.org/certifications/natural-seal/natural-seal-personal-care/. Accessed March 27, 2019.
- Natural Cosmetics Standard. GFaW Web site. https://gfaw.eu/en/ncs-for-all-who-love-nature-and-cosmetics/ncs-information-for-consumer/. Accessed February 1, 2019.
- Brown PN, Betz JM, Jasch F. How to qualify an analytical laboratory for analysis of herbal dietary ingredients and avoid using a “dry lab”: a review of issues related to using a contract analytical laboratory by industry, academia, and regulatory agencies. HerbalGram. 2013:52-59.
- Oh MJ, Cho YH, Cha SY, et al. Novel phytoceramides containing fatty acids of diverse chain lengths are better than a single C18-ceramide N-stearoyl phytosphingosine to improve the physiological properties of human stratum corneum. Clin Cosmet Investig Dermatol. 2017;10:363-371.
- Famurewa AC, Aja PM, Maduagwuna EK, et al. Antioxidant and anti-inflammatory effects of virgin coconut oil supplementation abrogate acute chemotherapy oxidative nephrotoxicity induced by anticancer drug methotrexate in rats. Biomed Pharmacother. 2017;96:905-911.
- Intahphuak S, Khonsung P, Panthong A. Anti-inflammatory, analgesic, and antipyretic activities of virgin coconut oil. Pharm Biol. 2010;48:151-157.
- McKenna PJ, Lehr GS, Leist P, et al. Antiseptic effectiveness with fibroblast preservation. Ann Plast Surg. 1991;27:265-268.
- Brockow K, Grabenhorst P, Abeck D, et al. Effect of gentian violet, corticosteroid and tar preparations in Staphylococcus aureus-colonized atopic eczema. Dermatology. 1999;199:231-236.
- Larson D, Jacob SE. Tea tree oil. Dermatitis. 2012;23:48-49.
- Misner BD. A novel aromatic oil compound inhibits microbial overgrowth on feet: a case study. J Int Soc Sports Nutr. 2007;4:3.
- D’Auria FD, Laino L, Strippoli V, et al. In vitro activity of tea tree oil against Candida albicans mycelial conversion and other pathogenic fungi. J Chemother. 2001;13:377-383.
- Fuchs-Tarlovsky V, Marquez-Barba MF, Sriram K. Probiotics in dermatologic practice. Nutrition. 2016;32:289-295.
- Bowe W, Patel NB, Logan AC. Acne vulgaris, probiotics and the gut-brain-skin axis: from anecdote to translational medicine. Benef Microbes. 2014;5:185-199.
- Baquerizo Nole KL, Yim E, Keri JE. Probiotics and prebiotics in dermatology. J Am Acad Dermatol. 2014;71:814-821.
- Saikaly SK, Khachemoune A. Honey and wound healing: an update. Am J Clin Dermatol. 2017;18:237-251.
- Aziz Z, Abdul Rasool Hassan B. The effects of honey compared to silver sulfadiazine for the treatment of burns: a systematic review of randomized controlled trials. Burns. 2017;43:50-57.
- FDA authority over cosmetics: how cosmetics are not FDA-approved, but are FDA-regulated. US Food and Drug AdministrationWeb site. https://www.fda.gov/cosmetics/guidanceregulation/lawsregulations/ucm074162.htm. Updated July 24, 2018. Accessed February 1, 2019.
- Wohlrab J. Topical preparations and their use in dermatology. J Dtsch Dermatol Ges. 2016;4:1061-1070
Practice Points
- Patients are increasingly interested in and asking for nature-based products and formulations to manage dermatologic conditions.
- Physicians can satisfy patient interests with nature-based formulations that are as beneficial or more so than synthetic formulations because of the physiologic activity of the ingredients within these formulations.
- Physicians should have resources available to them that adequately educate on nature-based ingredients and how to recommend them.
What’s Eating You? Millipede Burns
Clinical Presentation
Millipedes secrete a noxious toxin implicated in millipede burns. The toxic substance is benzoquinone, a strong irritant secreted from the repugnatorial glands contained in each segment of the arthropod (Figure 1). This compound serves as a natural insect repellant, acting as the millipede’s defense mechanism from potential predators.1 On human skin, benzoquinone causes localized pigmentary changes most commonly presenting on the feet and toes. Local lesions may be associated with pain or burning, but there are no known reports of adverse systemic effects.2 Affected patients experience cutaneous pigmentary changes, which may be dark red, blue, or black, and spontaneously resolve over time.2 The degree of pigment change may be associated with duration of skin contact with the toxin. The affected areas may resemble burns, dermatitis, or skin necrosis. More distal lesions may present similarly to blue toe syndrome or acute arterial occlusion but can be differentiated by the presence of intact peripheral pulses and lack of temperature discrepancy between the feet.3,4 Histologic evaluation of the lesions generally reveals nonspecific full-thickness epidermal necrosis, making clinical suspicion and physical examination paramount to the diagnosis of millipede burns.5
Diagnostic Difficulties
Accurate diagnosis of millipede burns is more difficult when the burn involves an unusual site. The most common site of involvement is the foot (Figure 2), followed by other commonly exposed areas such as the arms, face, and eyes.2,3,6,7 Covered parts of the body are much less commonly affected, requiring the arthropod to gain access via infiltration of clothing, often when hanging on a clothesline. In these cases, burns may be mistaken for child abuse, especially if certain areas of the body are involved, such as the groin and genitals.2 The well-defined arcuate lesions of the burns may resemble injuries from a wire or belt to the unsuspecting observer.
Conclusion
Although millipedes often are regarded as harmless, they are capable of causing adverse reactions through the secretion of toxic chemicals. Millipede burns cause localized pigmentary changes that may be associated with pain or burning in some patients. Because these burns may resemble child abuse in pediatric patients, physicians should be aware of this diagnosis when unusual parts of the body are involved.
- Kuwahara Y, Omura H, Tanabe T. 2-Nitroethenylbenzenes as naturalproducts in millipede defense secretions. Naturwissenschaften. 2002;89:308-310.
- De Capitani EM, Vieira RJ, Bucaretchi F, et al. Human accidents involving Rhinocricus spp., a common millipede genus observed in urban areas of Brazil. Clin Toxicol (Phila). 2011;49:187-190.
- Heeren Neto AS, Bernardes Filho F, Martins G. Skin lesions simulating blue toe syndrome caused by prolonged contact with a millipede. Rev Soc Bras Med Trop. 2014;47:257-258.
- Lima CA, Cardoso JL, Magela A, et al. Exogenous pigmentation in toes feigning ischemia of the extremities: a diagnostic challenge brought by arthropods of the Diplopoda class (“millipedes”). An Bras Dermatol. 2010;85:391-392.
- Dar NR, Raza N, Rehman SB. Millipede burn at an unusual site mimicking child abuse in an 8-year-old girl. Clin Pediatr (Phila). 2008;47:490-492.
- Hendrickson RG. Millipede exposure. Clin Toxicol (Phila). 2005;43:211-212.
- Verma AK, Bourke B. Millipede burn masquerading as trash foot in a paediatric patient [published online October 29, 2013]. ANZ J Surg. 2014;84:388-390.
Clinical Presentation
Millipedes secrete a noxious toxin implicated in millipede burns. The toxic substance is benzoquinone, a strong irritant secreted from the repugnatorial glands contained in each segment of the arthropod (Figure 1). This compound serves as a natural insect repellant, acting as the millipede’s defense mechanism from potential predators.1 On human skin, benzoquinone causes localized pigmentary changes most commonly presenting on the feet and toes. Local lesions may be associated with pain or burning, but there are no known reports of adverse systemic effects.2 Affected patients experience cutaneous pigmentary changes, which may be dark red, blue, or black, and spontaneously resolve over time.2 The degree of pigment change may be associated with duration of skin contact with the toxin. The affected areas may resemble burns, dermatitis, or skin necrosis. More distal lesions may present similarly to blue toe syndrome or acute arterial occlusion but can be differentiated by the presence of intact peripheral pulses and lack of temperature discrepancy between the feet.3,4 Histologic evaluation of the lesions generally reveals nonspecific full-thickness epidermal necrosis, making clinical suspicion and physical examination paramount to the diagnosis of millipede burns.5
Diagnostic Difficulties
Accurate diagnosis of millipede burns is more difficult when the burn involves an unusual site. The most common site of involvement is the foot (Figure 2), followed by other commonly exposed areas such as the arms, face, and eyes.2,3,6,7 Covered parts of the body are much less commonly affected, requiring the arthropod to gain access via infiltration of clothing, often when hanging on a clothesline. In these cases, burns may be mistaken for child abuse, especially if certain areas of the body are involved, such as the groin and genitals.2 The well-defined arcuate lesions of the burns may resemble injuries from a wire or belt to the unsuspecting observer.
Conclusion
Although millipedes often are regarded as harmless, they are capable of causing adverse reactions through the secretion of toxic chemicals. Millipede burns cause localized pigmentary changes that may be associated with pain or burning in some patients. Because these burns may resemble child abuse in pediatric patients, physicians should be aware of this diagnosis when unusual parts of the body are involved.
Clinical Presentation
Millipedes secrete a noxious toxin implicated in millipede burns. The toxic substance is benzoquinone, a strong irritant secreted from the repugnatorial glands contained in each segment of the arthropod (Figure 1). This compound serves as a natural insect repellant, acting as the millipede’s defense mechanism from potential predators.1 On human skin, benzoquinone causes localized pigmentary changes most commonly presenting on the feet and toes. Local lesions may be associated with pain or burning, but there are no known reports of adverse systemic effects.2 Affected patients experience cutaneous pigmentary changes, which may be dark red, blue, or black, and spontaneously resolve over time.2 The degree of pigment change may be associated with duration of skin contact with the toxin. The affected areas may resemble burns, dermatitis, or skin necrosis. More distal lesions may present similarly to blue toe syndrome or acute arterial occlusion but can be differentiated by the presence of intact peripheral pulses and lack of temperature discrepancy between the feet.3,4 Histologic evaluation of the lesions generally reveals nonspecific full-thickness epidermal necrosis, making clinical suspicion and physical examination paramount to the diagnosis of millipede burns.5
Diagnostic Difficulties
Accurate diagnosis of millipede burns is more difficult when the burn involves an unusual site. The most common site of involvement is the foot (Figure 2), followed by other commonly exposed areas such as the arms, face, and eyes.2,3,6,7 Covered parts of the body are much less commonly affected, requiring the arthropod to gain access via infiltration of clothing, often when hanging on a clothesline. In these cases, burns may be mistaken for child abuse, especially if certain areas of the body are involved, such as the groin and genitals.2 The well-defined arcuate lesions of the burns may resemble injuries from a wire or belt to the unsuspecting observer.
Conclusion
Although millipedes often are regarded as harmless, they are capable of causing adverse reactions through the secretion of toxic chemicals. Millipede burns cause localized pigmentary changes that may be associated with pain or burning in some patients. Because these burns may resemble child abuse in pediatric patients, physicians should be aware of this diagnosis when unusual parts of the body are involved.
- Kuwahara Y, Omura H, Tanabe T. 2-Nitroethenylbenzenes as naturalproducts in millipede defense secretions. Naturwissenschaften. 2002;89:308-310.
- De Capitani EM, Vieira RJ, Bucaretchi F, et al. Human accidents involving Rhinocricus spp., a common millipede genus observed in urban areas of Brazil. Clin Toxicol (Phila). 2011;49:187-190.
- Heeren Neto AS, Bernardes Filho F, Martins G. Skin lesions simulating blue toe syndrome caused by prolonged contact with a millipede. Rev Soc Bras Med Trop. 2014;47:257-258.
- Lima CA, Cardoso JL, Magela A, et al. Exogenous pigmentation in toes feigning ischemia of the extremities: a diagnostic challenge brought by arthropods of the Diplopoda class (“millipedes”). An Bras Dermatol. 2010;85:391-392.
- Dar NR, Raza N, Rehman SB. Millipede burn at an unusual site mimicking child abuse in an 8-year-old girl. Clin Pediatr (Phila). 2008;47:490-492.
- Hendrickson RG. Millipede exposure. Clin Toxicol (Phila). 2005;43:211-212.
- Verma AK, Bourke B. Millipede burn masquerading as trash foot in a paediatric patient [published online October 29, 2013]. ANZ J Surg. 2014;84:388-390.
- Kuwahara Y, Omura H, Tanabe T. 2-Nitroethenylbenzenes as naturalproducts in millipede defense secretions. Naturwissenschaften. 2002;89:308-310.
- De Capitani EM, Vieira RJ, Bucaretchi F, et al. Human accidents involving Rhinocricus spp., a common millipede genus observed in urban areas of Brazil. Clin Toxicol (Phila). 2011;49:187-190.
- Heeren Neto AS, Bernardes Filho F, Martins G. Skin lesions simulating blue toe syndrome caused by prolonged contact with a millipede. Rev Soc Bras Med Trop. 2014;47:257-258.
- Lima CA, Cardoso JL, Magela A, et al. Exogenous pigmentation in toes feigning ischemia of the extremities: a diagnostic challenge brought by arthropods of the Diplopoda class (“millipedes”). An Bras Dermatol. 2010;85:391-392.
- Dar NR, Raza N, Rehman SB. Millipede burn at an unusual site mimicking child abuse in an 8-year-old girl. Clin Pediatr (Phila). 2008;47:490-492.
- Hendrickson RG. Millipede exposure. Clin Toxicol (Phila). 2005;43:211-212.
- Verma AK, Bourke B. Millipede burn masquerading as trash foot in a paediatric patient [published online October 29, 2013]. ANZ J Surg. 2014;84:388-390.
Practice Points
- The most common site of involvement of millipede burns is the foot, followed by other commonly exposed areas such as the arms, face, and eyes. Covered parts of the body are much less commonly affected.
- Millipede burns may resemble child abuse in pediatric patients; therefore, physicians should be aware of this diagnosis when unusual parts of the body are involved.
At what diameter does a scar form after a full-thickness wound?
DENVER – A clinically identifiable scar occurs after full-thickness skin wounds greater than 400-500 mcm in diameter, while wounds of smaller diameter heal with no clinically perceptible scar.
The findings come from a Amanda H. Champlain, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery. “The size threshold at which a full-thickness skin wound can heal without scarring had not been determined prior to this study.”
Dr. Champlain, a fellow at Massachusetts General Hospital and The Wellman Center for Photomedicine, both in Boston, and her colleagues designed a way to evaluate healing responses and safety after collecting skin microbiopsies of different sizes from preabdominoplasty skin. According to the study abstract, the concept “is based on fractional photothermolysis in which a multitude of small, full-thickness thermal burns are produced by a laser on the skin with rapid healing and no scarring.” Measures included the Patient and Observer Scar Assessment Scale (POSAS), donor site pain scale, subject satisfaction survey, and an assessment of side effects, clinical photographs, and histology.
Preliminary data are available for five subjects. The POSAS-Observer scale ranges from 5 to 50 while the POSAS-Patient scale ranges from 6 to 60. The researchers observed that average final POSAS-Observer scores were 5.6 for scars 200 mcm in diameter, 5.2 for scars 400 mcm in diameter, 7.0 for scars 500 mcm in diameter, 6.8 for scars 600 mcm in diameter, 8.2 for scars 800 mcm in diameter, 9.6 for scars 1 mm in diameter, and 13.2 for those 2 mm in diameter. Meanwhile, the average final POSAS-Subject scores were 6.0 for scars 200 mcm in diameter, 6.0 for scars 400 mcm in diameter, 6.6 for scars 500 mcm in diameter, 6.4 for those 600 mcm in diameter, 7.2 for scars 800 mcm in diameter, 7.4 for scars 1 mm in diameter, and 10.0 for those 2 mm in diameter.
The maximum donor site pain reported was 4 out of 10 in one subject. “The procedure was very well tolerated by the subjects,” Dr. Champlain said. “They healed quickly, and the majority were happy with the cosmetic outcome regardless of the diameter of the microbiopsy used.”
The most common side effects of the study procedures included mild bleeding, scabbing, redness, and hyper/hypopigmentation. “The majority of study participants strongly agree that the study procedure was safe, tolerable, and cosmetically sound,” she said.
Dr. Champlain does not have any disclosures, but she said that the study was funded by the Department of Defense.
DENVER – A clinically identifiable scar occurs after full-thickness skin wounds greater than 400-500 mcm in diameter, while wounds of smaller diameter heal with no clinically perceptible scar.
The findings come from a Amanda H. Champlain, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery. “The size threshold at which a full-thickness skin wound can heal without scarring had not been determined prior to this study.”
Dr. Champlain, a fellow at Massachusetts General Hospital and The Wellman Center for Photomedicine, both in Boston, and her colleagues designed a way to evaluate healing responses and safety after collecting skin microbiopsies of different sizes from preabdominoplasty skin. According to the study abstract, the concept “is based on fractional photothermolysis in which a multitude of small, full-thickness thermal burns are produced by a laser on the skin with rapid healing and no scarring.” Measures included the Patient and Observer Scar Assessment Scale (POSAS), donor site pain scale, subject satisfaction survey, and an assessment of side effects, clinical photographs, and histology.
Preliminary data are available for five subjects. The POSAS-Observer scale ranges from 5 to 50 while the POSAS-Patient scale ranges from 6 to 60. The researchers observed that average final POSAS-Observer scores were 5.6 for scars 200 mcm in diameter, 5.2 for scars 400 mcm in diameter, 7.0 for scars 500 mcm in diameter, 6.8 for scars 600 mcm in diameter, 8.2 for scars 800 mcm in diameter, 9.6 for scars 1 mm in diameter, and 13.2 for those 2 mm in diameter. Meanwhile, the average final POSAS-Subject scores were 6.0 for scars 200 mcm in diameter, 6.0 for scars 400 mcm in diameter, 6.6 for scars 500 mcm in diameter, 6.4 for those 600 mcm in diameter, 7.2 for scars 800 mcm in diameter, 7.4 for scars 1 mm in diameter, and 10.0 for those 2 mm in diameter.
The maximum donor site pain reported was 4 out of 10 in one subject. “The procedure was very well tolerated by the subjects,” Dr. Champlain said. “They healed quickly, and the majority were happy with the cosmetic outcome regardless of the diameter of the microbiopsy used.”
The most common side effects of the study procedures included mild bleeding, scabbing, redness, and hyper/hypopigmentation. “The majority of study participants strongly agree that the study procedure was safe, tolerable, and cosmetically sound,” she said.
Dr. Champlain does not have any disclosures, but she said that the study was funded by the Department of Defense.
DENVER – A clinically identifiable scar occurs after full-thickness skin wounds greater than 400-500 mcm in diameter, while wounds of smaller diameter heal with no clinically perceptible scar.
The findings come from a Amanda H. Champlain, MD, said in an interview in advance of the annual conference of the American Society for Laser Medicine and Surgery. “The size threshold at which a full-thickness skin wound can heal without scarring had not been determined prior to this study.”
Dr. Champlain, a fellow at Massachusetts General Hospital and The Wellman Center for Photomedicine, both in Boston, and her colleagues designed a way to evaluate healing responses and safety after collecting skin microbiopsies of different sizes from preabdominoplasty skin. According to the study abstract, the concept “is based on fractional photothermolysis in which a multitude of small, full-thickness thermal burns are produced by a laser on the skin with rapid healing and no scarring.” Measures included the Patient and Observer Scar Assessment Scale (POSAS), donor site pain scale, subject satisfaction survey, and an assessment of side effects, clinical photographs, and histology.
Preliminary data are available for five subjects. The POSAS-Observer scale ranges from 5 to 50 while the POSAS-Patient scale ranges from 6 to 60. The researchers observed that average final POSAS-Observer scores were 5.6 for scars 200 mcm in diameter, 5.2 for scars 400 mcm in diameter, 7.0 for scars 500 mcm in diameter, 6.8 for scars 600 mcm in diameter, 8.2 for scars 800 mcm in diameter, 9.6 for scars 1 mm in diameter, and 13.2 for those 2 mm in diameter. Meanwhile, the average final POSAS-Subject scores were 6.0 for scars 200 mcm in diameter, 6.0 for scars 400 mcm in diameter, 6.6 for scars 500 mcm in diameter, 6.4 for those 600 mcm in diameter, 7.2 for scars 800 mcm in diameter, 7.4 for scars 1 mm in diameter, and 10.0 for those 2 mm in diameter.
The maximum donor site pain reported was 4 out of 10 in one subject. “The procedure was very well tolerated by the subjects,” Dr. Champlain said. “They healed quickly, and the majority were happy with the cosmetic outcome regardless of the diameter of the microbiopsy used.”
The most common side effects of the study procedures included mild bleeding, scabbing, redness, and hyper/hypopigmentation. “The majority of study participants strongly agree that the study procedure was safe, tolerable, and cosmetically sound,” she said.
Dr. Champlain does not have any disclosures, but she said that the study was funded by the Department of Defense.
REPORTING FROM ASLMS 2019
Key clinical point: Collecting skin microbiopsies of different sizes from preabdominoplasty skin is safe and highly tolerable.
Major finding: Full-thickness skin wounds greater than 400-500 mcm in diameter heal with a clinically identifiable scar.
Study details: A pilot trial in five individuals that set out to determine the biopsy size limit at which healing occurs without a scar, as well as demonstrate the safety of performing multiple skin microbiopsies.
Disclosures: Dr. Champlain does not have any disclosures, but she said that the study was funded by the Department of Defense.
Umbilical cord allograft may boost diabetic foot ulcer healing
Dehydrated human umbilical cord allograft may have benefit over alginate wound dressings as a treatment for chronic, nonhealing diabetic foot ulcers (DFU), findings from an industry-funded, randomized controlled study suggest.
The findings “provide additional evidence of the safety and efficacy of dehydrated placental tissues,” wrote William Tettelbach, MD, and his colleagues. Their report is in International Wound Journal.
The burden of diabetic foot disease in the United States is immense. A 2014 study estimated that treatment of DFUs alone cost public and private insurers as much as $13 billion per year (Diabetes Care. 2014;37(3):651-8).
MiMedx, which funded the new study, has developed a product called EpiCord to protect the DFU wound site. The product’s website describes it as a “unique, thick membrane derived from umbilical cord” that’s “minimally manipulated, dehydrated, [and] non-viable” (www.mimedx.com/epicord). The study authors noted that “immunogenicity of placental tissue lends credence to its use as an allograft material for difficult-to-heal wounds.”
For the new study, which was conducted from 2016 to 2018 and led by Dr. Tettelbach, an infectious disease specialist who is now an employee of MiMedx, the researchers enlisted 155 adult patients with stubborn DFUs at 11 centers in the United States.
All the ulcers had 30% or less wound area reduction after 14 days of standard care. The majority of patients (81%) were male; 63% were obese, 43% were smokers, and 17% had a prior amputation.
The patients were randomly assigned to receive a weekly application of EpiCord (n = 101) or treatment with an alginate wound dressing (n = 54) in addition to standard care. The percentage of patients whose wounds healed completely by 12 weeks later was higher in the study group than in those who were treated with alginate dressings (70% vs. 48%, respectively; P = .0089), per an intent-to-treat analysis.
The researchers also focused purely on patients who had received adequate debridement (107/155 ulcers, 69%). Of those ulcers, 64/67 (96%), in the study group healed completely at 12 weeks, compared with 26/40 (65%) of the alginate group (P less than .0001.)
The researchers did not notice any adverse effects related to either dressing.
According to the study, the findings regarding EpiCord are comparable with a sister study of a similar product by the same company that was tested in diabetic lower-extremity ulcers. That study, of a product called EpiFix, was published in the same issue of the journal (Int Wound J. 2019 Feb;16[1]:19-29).
“A thicker and more durable allograft such as EpiCord may be a good choice for implantation into deeper wounds and in situations where suturing the allograft in place is desired,” the authors wrote of the EpiCord study.
MiMedx provided research funding to all of the authors.
SOURCE: Tettelbach W et al. Int Wound J. 2019;16(1):122-130. doi: 10.1111/iwj.12976.
Dehydrated human umbilical cord allograft may have benefit over alginate wound dressings as a treatment for chronic, nonhealing diabetic foot ulcers (DFU), findings from an industry-funded, randomized controlled study suggest.
The findings “provide additional evidence of the safety and efficacy of dehydrated placental tissues,” wrote William Tettelbach, MD, and his colleagues. Their report is in International Wound Journal.
The burden of diabetic foot disease in the United States is immense. A 2014 study estimated that treatment of DFUs alone cost public and private insurers as much as $13 billion per year (Diabetes Care. 2014;37(3):651-8).
MiMedx, which funded the new study, has developed a product called EpiCord to protect the DFU wound site. The product’s website describes it as a “unique, thick membrane derived from umbilical cord” that’s “minimally manipulated, dehydrated, [and] non-viable” (www.mimedx.com/epicord). The study authors noted that “immunogenicity of placental tissue lends credence to its use as an allograft material for difficult-to-heal wounds.”
For the new study, which was conducted from 2016 to 2018 and led by Dr. Tettelbach, an infectious disease specialist who is now an employee of MiMedx, the researchers enlisted 155 adult patients with stubborn DFUs at 11 centers in the United States.
All the ulcers had 30% or less wound area reduction after 14 days of standard care. The majority of patients (81%) were male; 63% were obese, 43% were smokers, and 17% had a prior amputation.
The patients were randomly assigned to receive a weekly application of EpiCord (n = 101) or treatment with an alginate wound dressing (n = 54) in addition to standard care. The percentage of patients whose wounds healed completely by 12 weeks later was higher in the study group than in those who were treated with alginate dressings (70% vs. 48%, respectively; P = .0089), per an intent-to-treat analysis.
The researchers also focused purely on patients who had received adequate debridement (107/155 ulcers, 69%). Of those ulcers, 64/67 (96%), in the study group healed completely at 12 weeks, compared with 26/40 (65%) of the alginate group (P less than .0001.)
The researchers did not notice any adverse effects related to either dressing.
According to the study, the findings regarding EpiCord are comparable with a sister study of a similar product by the same company that was tested in diabetic lower-extremity ulcers. That study, of a product called EpiFix, was published in the same issue of the journal (Int Wound J. 2019 Feb;16[1]:19-29).
“A thicker and more durable allograft such as EpiCord may be a good choice for implantation into deeper wounds and in situations where suturing the allograft in place is desired,” the authors wrote of the EpiCord study.
MiMedx provided research funding to all of the authors.
SOURCE: Tettelbach W et al. Int Wound J. 2019;16(1):122-130. doi: 10.1111/iwj.12976.
Dehydrated human umbilical cord allograft may have benefit over alginate wound dressings as a treatment for chronic, nonhealing diabetic foot ulcers (DFU), findings from an industry-funded, randomized controlled study suggest.
The findings “provide additional evidence of the safety and efficacy of dehydrated placental tissues,” wrote William Tettelbach, MD, and his colleagues. Their report is in International Wound Journal.
The burden of diabetic foot disease in the United States is immense. A 2014 study estimated that treatment of DFUs alone cost public and private insurers as much as $13 billion per year (Diabetes Care. 2014;37(3):651-8).
MiMedx, which funded the new study, has developed a product called EpiCord to protect the DFU wound site. The product’s website describes it as a “unique, thick membrane derived from umbilical cord” that’s “minimally manipulated, dehydrated, [and] non-viable” (www.mimedx.com/epicord). The study authors noted that “immunogenicity of placental tissue lends credence to its use as an allograft material for difficult-to-heal wounds.”
For the new study, which was conducted from 2016 to 2018 and led by Dr. Tettelbach, an infectious disease specialist who is now an employee of MiMedx, the researchers enlisted 155 adult patients with stubborn DFUs at 11 centers in the United States.
All the ulcers had 30% or less wound area reduction after 14 days of standard care. The majority of patients (81%) were male; 63% were obese, 43% were smokers, and 17% had a prior amputation.
The patients were randomly assigned to receive a weekly application of EpiCord (n = 101) or treatment with an alginate wound dressing (n = 54) in addition to standard care. The percentage of patients whose wounds healed completely by 12 weeks later was higher in the study group than in those who were treated with alginate dressings (70% vs. 48%, respectively; P = .0089), per an intent-to-treat analysis.
The researchers also focused purely on patients who had received adequate debridement (107/155 ulcers, 69%). Of those ulcers, 64/67 (96%), in the study group healed completely at 12 weeks, compared with 26/40 (65%) of the alginate group (P less than .0001.)
The researchers did not notice any adverse effects related to either dressing.
According to the study, the findings regarding EpiCord are comparable with a sister study of a similar product by the same company that was tested in diabetic lower-extremity ulcers. That study, of a product called EpiFix, was published in the same issue of the journal (Int Wound J. 2019 Feb;16[1]:19-29).
“A thicker and more durable allograft such as EpiCord may be a good choice for implantation into deeper wounds and in situations where suturing the allograft in place is desired,” the authors wrote of the EpiCord study.
MiMedx provided research funding to all of the authors.
SOURCE: Tettelbach W et al. Int Wound J. 2019;16(1):122-130. doi: 10.1111/iwj.12976.
FROM INTERNATIONAL WOUND JOURNAL
Aquatic Antagonists: Stingray Injury Update
Incidence and Characteristics
Stingrays are dorsoventrally flattened, diamond-shaped fish with light-colored ventral and dark-colored dorsal surfaces. They have strong pectoral wings that allow them to swim forward and backward and even launch off waves.3 Stingrays range in size from the palm of a human hand to 6.5 ft in width. They possess 1 or more spines (2.5 to >30 cm in length) that are disguised by much longer tails.6,7 They often are encountered accidentally because they bury themselves in the sand or mud of shallow coastal waters or rivers with only their eyes and tails exposed to fool prey and avoid predators.
Injury Clinical Presentation
Stingray injuries typically involve the lower legs, ankles, or feet after stepping on a stingray.8 Fishermen can present with injuries of the upper extremities after handling fish with their hands.9 Other rarer injuries occur when individuals are swimming alongside stingrays or when stingrays catapult off waves into moving boats.10,11 Stingrays impale victims by using their tails to direct a retroserrate barb composed of a strong cartilaginous material called vasodentin. The barb releases venom by breaking through the venom-containing integumentary sheath that encapsulates it. Stingray venom contains phosphodiesterase, serotonin, and 5′-nucleotidase. It causes severe pain, vasoconstriction, ischemia, and poor wound healing, along with systemic effects such as disorientation, syncope, seizures, salivation, nausea, vomiting, abdominal pain, diarrhea, muscle cramps or fasciculations, pruritus, allergic reaction, hypotension, cardiac arrhythmias, dyspnea, paralysis, and possibly death.1,8,12,13
Management
Pain Relief
As with many marine envenomations, immersion in hot but not scalding water can inactivate venom and reduce symptoms.8,9 In one retrospective review, 52 of 75 (69%) patients reporting to a California poison center with stingray injuries had improvement in pain within 1 hour of hot water immersion before any analgesics were instituted.8 In another review, 65 of 74 (88%) patients presenting to a California emergency department within 24 hours of sustaining a stingray injury had complete relief of pain within 30 minutes of hot water immersion. Patients who received analgesics in addition to hot water immersion did not require a second dose.9 In concordance with these studies, we suggest immersing areas affected by stingray injuries in hot water (temperature, 43.3°C to 46.1°C [110°F–115°F]; or as close to this range as tolerated) until pain subsides.8,9,14 Ice packs are an alternative to hot water immersion that may be more readily available to patients. If pain does not resolve following hot water immersion or application of an ice pack, additional analgesics and xylocaine without epinephrine may be helpful.9,15
Infection
One major complication of stingray injuries is infection.8,9 Many bacterial species reside in stingray mucus, the marine environment, or on human skin that may be introduced during a single injury. Marine envenomations can involve organisms such as Vibrio, Aeromonas, and Mycobacterium species, which often are resistant to antibiotic prophylaxis covering common causes of soft-tissue infection such as Staphylococcus and Streptococcus species.8,9,16,17 Additionally, physicians should cover for Clostridium species and ensure patients are up-to-date on vaccinations because severe cases of tetanus following stingray injuries have been reported.18 Lastly, fungal infections including fusariosis have been reported following stingray injuries and should be considered if a patient develops an infection.19
Several authors support the use of prophylactic broad-spectrum antibiotics in all but mild stingray injuries.8,9,20,21 Although no standardized definition exists, mild injuries generally represent patients with superficial lacerations or less, while deeper lacerations and puncture wounds require prophylaxis. Several authors agree on the use of fluoroquinolone antibiotics (eg, ciprofloxacin 500 mg twice daily) for 5 to 7 days following severe stingray injuries.1,9,13,22 Other proposed antibiotic regimens include trimethoprim-sulfamethoxazole (160/800 mg twice daily) or tetracycline (500 mg 4 times daily) for 7 days.13 Failure of ciprofloxacin therapy after 7 days has been reported, with resolution of infection after treatment with an intravenous cephalosporin for 7 days.20 Failure of trimethoprim-sulfamethoxazole therapy also has been reported, with one case requiring levofloxacin for a much longer course.21 Clinical follow-up remains essential after prescribing prophylactic antibiotics, as resistance is common.
Foreign Bodies
Stingray injuries also are often complicated by foreign bodies or retained spines.3,8 Although these complications are less severe than infection, all wounds should be explored for material under local anesthesia. Furthermore, there has been support for thorough debridement of necrotic tissue with referral to a hand specialist for deeper injuries to the hands as well as referral to a foot and ankle specialist for deeper injuries of the lower extremities.23,24 More serious injuries with penetration of vital structures, such as through the chest or abdomen, require immediate exploration in an operating room.1,24
Imaging
Routine imaging of stingray injuries remains controversial. In a case series of 119 patients presenting to a California emergency department with stingray injuries, Clark et al9 found that radiographs were not helpful. This finding likely is due in part to an inability to detect hypodense material such as integumentary or glandular tissue via radiography.3 However, radiographs have been used to identify retained stingray barbs in select cases in which retained barbs are suspected.2,25 Lastly, ultrasonography potentially may offer a better first choice when a barb is not readily apparent; magnetic resonance imaging may be indicated for more involved areas and for further visualization of suspected hypodense material, though at a higher expense.2,9
Biopsy
Biopsies of stingray injuries are rarely performed, and the findings are not well characterized. One case biopsied 2 months after injury showed a large zone of paucicellular necrosis with superficial ulceration and granulomatous inflammation. The stingray venom was most likely responsible for the pattern of necrosis noted in the biopsy.21
Avoidance and Prevention
Patients traveling to areas of the world inhabited by stingrays should receive counseling on how to avoid injury. Prior to entry, individuals can throw stones or use a long stick to clear their walking or swimming areas of venomous fish.26 Polarized sunglasses may help spot stingrays in shallow water. Furthermore, wading through water with a shuffling gait can help individuals avoid stepping directly on a stingray and also warns stingrays that someone is in the area. Individuals who spend more time in coastal waters or river systems inhabited by stingrays may invest in protective stingray gear such as leg guards or specialized wading boots.26 Lastly, fishermen should be advised to avoid handling stingrays with their hands and instead cut their fishing line to release the fish.
- Aurbach PS. Envenomations by aquatic vertebrates. In: Auerbach PS. Wilderness Medicine. 5th ed. St. Louis, MO: Mosby; 2007:1730-1749.
- Robins CR, Ray GC. A Field Guide to Atlantic Coast Fishes. New York, NY: Houghton Mifflin Company; 1986.
- Diaz JH. The evaluation, management, and prevention of stingray injuries in travelers. J Travel Med. 2008;15:102-109.
- Haddad V Jr, Neto DG, de Paula Neto JB, et al. Freshwater stingrays: study of epidemiologic, clinical and therapeutic aspects based on 84 envenomings in humans and some enzymatic activities of the venom. Toxicon. 2004;43:287-294.
- Marinkelle CJ. Accidents by venomous animals in Colombia. Ind Med Surg. 1966;35:988-992.
- Last PR, White WT, Caire JN, et al. Sharks and Rays of Borneo. Collingwood VIC, Australia: CSIRO Publishing; 2010.
- Mebs D. Venomous and Poisonous Animals: A Handbook for Biologists, Toxicologists and Toxinologists, Physicians and Pharmacists. Boca Raton, FL: CRC Press; 2002.
- Clark AT, Clark RF, Cantrell FL. A retrospective review of the presentation and treatment of stingray stings reported to a poison control system. Am J Ther. 2017;24:E177-E180.
- Clark RF, Girard RH, Rao D, et al. Stingray envenomation: a retrospective review of clinical presentation and treatment in 119 cases. J Emerg Med. 2007;33:33-37.
- Mahjoubi L, Joyeux A, Delambre JF, et al. Near-death thoracic trauma caused by a stingray in the Indian Ocean. Semin Thorac Cardiovasc Surg. 2017;29:262-263.
- Parra MW, Constantini EN, Rodas EB. Surviving a transfixing cardiac injury caused by a stingray barb. J Thorac Cardiovasc Surg. 2010;139:E115-E116.
- Dos Santos JC, Grund LZ, Seibert CS, et al. Stingray venom activates IL-33 producing cardiomyocytes, but not mast cell, to promote acute neutrophil-mediated injury. Sci Rep. 2017;7:7912.
- Auerbach PS, Norris RL. Marine envenomation. In: Longo DL, Kasper SL, Jameson JL, et al, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill; 2012:144-148.
- Cook MD, Matteucci MJ, Lall R, et al. Stingray envenomation. J Emerg Med. 2006;30:345-347.
- Bowers RC, Mustain MV. Disorders due to physical & environmental agents. In: Humphries RL, Stone C, eds. CURRENT Diagnosis & Treatment Emergency Medicine. 7th ed. New York, NY: McGraw-Hill; 2011:835-861.
- Domingos MO, Franzolin MR, dos Anjos MT, et al. The influence of environmental bacteria in freshwater stingray wound-healing. Toxicon. 2011;58:147-153.
- Auerbach PS, Yajko DM, Nassos PS, et al. Bacteriology of the marine environment: implications for clinical therapy. Ann Emerg Med. 1987;16:643-649.
- Torrez PP, Quiroga MM, Said R, et al. Tetanus after envenomations caused by freshwater stingrays. Toxicon. 2015;97:32-35.
- Hiemenz JW, Kennedy B, Kwon-Chung KJ. Invasive fusariosis associated with an injury by a stingray barb. J Med Vet Mycol. 1990;28:209-213.
- da Silva NJ Jr, Ferreira KR, Pinto RN, et al. A severe accident caused by an ocellate river stingray (Potamotrygon motoro) in central Brazil: how well do we really understand stingray venom chemistry, envenomation, and therapeutics? Toxins (Basel). 2015;7:2272-2288.
- Tartar D, Limova M, North J. Clinical and histopathologic findings in cutaneous sting ray wounds: a case report. Dermatol Online J. 2013;19:19261.
- Jarvis HC, Matheny LM, Clanton TO. Stingray injury to the webspace of the foot. Orthopedics. 2012;35:E762-E765.
- Trickett R, Whitaker IS, Boyce DE. Sting-ray injuries to the hand: case report, literature review and a suggested algorithm for management. J Plast Reconstruct Aesthet Surg. 2009;62:E270-E273.
- Fernandez I, Valladolid G, Varon J, et al. Encounters with venomous sea-life. J Emerg Med. 2011;40:103-112.
- O’Malley GF, O’Malley RN, Pham O, et al. Retained stingray barb and the importance of imaging. Wilderness Environ Med. 2015;26:375-379.
- How to protect yourself from stingrays. Howcast website. https://www.howcast.com/videos/228034-how-to-protect-yourself-from-stingrays/. Accessed July 12, 2018.
Incidence and Characteristics
Stingrays are dorsoventrally flattened, diamond-shaped fish with light-colored ventral and dark-colored dorsal surfaces. They have strong pectoral wings that allow them to swim forward and backward and even launch off waves.3 Stingrays range in size from the palm of a human hand to 6.5 ft in width. They possess 1 or more spines (2.5 to >30 cm in length) that are disguised by much longer tails.6,7 They often are encountered accidentally because they bury themselves in the sand or mud of shallow coastal waters or rivers with only their eyes and tails exposed to fool prey and avoid predators.
Injury Clinical Presentation
Stingray injuries typically involve the lower legs, ankles, or feet after stepping on a stingray.8 Fishermen can present with injuries of the upper extremities after handling fish with their hands.9 Other rarer injuries occur when individuals are swimming alongside stingrays or when stingrays catapult off waves into moving boats.10,11 Stingrays impale victims by using their tails to direct a retroserrate barb composed of a strong cartilaginous material called vasodentin. The barb releases venom by breaking through the venom-containing integumentary sheath that encapsulates it. Stingray venom contains phosphodiesterase, serotonin, and 5′-nucleotidase. It causes severe pain, vasoconstriction, ischemia, and poor wound healing, along with systemic effects such as disorientation, syncope, seizures, salivation, nausea, vomiting, abdominal pain, diarrhea, muscle cramps or fasciculations, pruritus, allergic reaction, hypotension, cardiac arrhythmias, dyspnea, paralysis, and possibly death.1,8,12,13
Management
Pain Relief
As with many marine envenomations, immersion in hot but not scalding water can inactivate venom and reduce symptoms.8,9 In one retrospective review, 52 of 75 (69%) patients reporting to a California poison center with stingray injuries had improvement in pain within 1 hour of hot water immersion before any analgesics were instituted.8 In another review, 65 of 74 (88%) patients presenting to a California emergency department within 24 hours of sustaining a stingray injury had complete relief of pain within 30 minutes of hot water immersion. Patients who received analgesics in addition to hot water immersion did not require a second dose.9 In concordance with these studies, we suggest immersing areas affected by stingray injuries in hot water (temperature, 43.3°C to 46.1°C [110°F–115°F]; or as close to this range as tolerated) until pain subsides.8,9,14 Ice packs are an alternative to hot water immersion that may be more readily available to patients. If pain does not resolve following hot water immersion or application of an ice pack, additional analgesics and xylocaine without epinephrine may be helpful.9,15
Infection
One major complication of stingray injuries is infection.8,9 Many bacterial species reside in stingray mucus, the marine environment, or on human skin that may be introduced during a single injury. Marine envenomations can involve organisms such as Vibrio, Aeromonas, and Mycobacterium species, which often are resistant to antibiotic prophylaxis covering common causes of soft-tissue infection such as Staphylococcus and Streptococcus species.8,9,16,17 Additionally, physicians should cover for Clostridium species and ensure patients are up-to-date on vaccinations because severe cases of tetanus following stingray injuries have been reported.18 Lastly, fungal infections including fusariosis have been reported following stingray injuries and should be considered if a patient develops an infection.19
Several authors support the use of prophylactic broad-spectrum antibiotics in all but mild stingray injuries.8,9,20,21 Although no standardized definition exists, mild injuries generally represent patients with superficial lacerations or less, while deeper lacerations and puncture wounds require prophylaxis. Several authors agree on the use of fluoroquinolone antibiotics (eg, ciprofloxacin 500 mg twice daily) for 5 to 7 days following severe stingray injuries.1,9,13,22 Other proposed antibiotic regimens include trimethoprim-sulfamethoxazole (160/800 mg twice daily) or tetracycline (500 mg 4 times daily) for 7 days.13 Failure of ciprofloxacin therapy after 7 days has been reported, with resolution of infection after treatment with an intravenous cephalosporin for 7 days.20 Failure of trimethoprim-sulfamethoxazole therapy also has been reported, with one case requiring levofloxacin for a much longer course.21 Clinical follow-up remains essential after prescribing prophylactic antibiotics, as resistance is common.
Foreign Bodies
Stingray injuries also are often complicated by foreign bodies or retained spines.3,8 Although these complications are less severe than infection, all wounds should be explored for material under local anesthesia. Furthermore, there has been support for thorough debridement of necrotic tissue with referral to a hand specialist for deeper injuries to the hands as well as referral to a foot and ankle specialist for deeper injuries of the lower extremities.23,24 More serious injuries with penetration of vital structures, such as through the chest or abdomen, require immediate exploration in an operating room.1,24
Imaging
Routine imaging of stingray injuries remains controversial. In a case series of 119 patients presenting to a California emergency department with stingray injuries, Clark et al9 found that radiographs were not helpful. This finding likely is due in part to an inability to detect hypodense material such as integumentary or glandular tissue via radiography.3 However, radiographs have been used to identify retained stingray barbs in select cases in which retained barbs are suspected.2,25 Lastly, ultrasonography potentially may offer a better first choice when a barb is not readily apparent; magnetic resonance imaging may be indicated for more involved areas and for further visualization of suspected hypodense material, though at a higher expense.2,9
Biopsy
Biopsies of stingray injuries are rarely performed, and the findings are not well characterized. One case biopsied 2 months after injury showed a large zone of paucicellular necrosis with superficial ulceration and granulomatous inflammation. The stingray venom was most likely responsible for the pattern of necrosis noted in the biopsy.21
Avoidance and Prevention
Patients traveling to areas of the world inhabited by stingrays should receive counseling on how to avoid injury. Prior to entry, individuals can throw stones or use a long stick to clear their walking or swimming areas of venomous fish.26 Polarized sunglasses may help spot stingrays in shallow water. Furthermore, wading through water with a shuffling gait can help individuals avoid stepping directly on a stingray and also warns stingrays that someone is in the area. Individuals who spend more time in coastal waters or river systems inhabited by stingrays may invest in protective stingray gear such as leg guards or specialized wading boots.26 Lastly, fishermen should be advised to avoid handling stingrays with their hands and instead cut their fishing line to release the fish.
Incidence and Characteristics
Stingrays are dorsoventrally flattened, diamond-shaped fish with light-colored ventral and dark-colored dorsal surfaces. They have strong pectoral wings that allow them to swim forward and backward and even launch off waves.3 Stingrays range in size from the palm of a human hand to 6.5 ft in width. They possess 1 or more spines (2.5 to >30 cm in length) that are disguised by much longer tails.6,7 They often are encountered accidentally because they bury themselves in the sand or mud of shallow coastal waters or rivers with only their eyes and tails exposed to fool prey and avoid predators.
Injury Clinical Presentation
Stingray injuries typically involve the lower legs, ankles, or feet after stepping on a stingray.8 Fishermen can present with injuries of the upper extremities after handling fish with their hands.9 Other rarer injuries occur when individuals are swimming alongside stingrays or when stingrays catapult off waves into moving boats.10,11 Stingrays impale victims by using their tails to direct a retroserrate barb composed of a strong cartilaginous material called vasodentin. The barb releases venom by breaking through the venom-containing integumentary sheath that encapsulates it. Stingray venom contains phosphodiesterase, serotonin, and 5′-nucleotidase. It causes severe pain, vasoconstriction, ischemia, and poor wound healing, along with systemic effects such as disorientation, syncope, seizures, salivation, nausea, vomiting, abdominal pain, diarrhea, muscle cramps or fasciculations, pruritus, allergic reaction, hypotension, cardiac arrhythmias, dyspnea, paralysis, and possibly death.1,8,12,13
Management
Pain Relief
As with many marine envenomations, immersion in hot but not scalding water can inactivate venom and reduce symptoms.8,9 In one retrospective review, 52 of 75 (69%) patients reporting to a California poison center with stingray injuries had improvement in pain within 1 hour of hot water immersion before any analgesics were instituted.8 In another review, 65 of 74 (88%) patients presenting to a California emergency department within 24 hours of sustaining a stingray injury had complete relief of pain within 30 minutes of hot water immersion. Patients who received analgesics in addition to hot water immersion did not require a second dose.9 In concordance with these studies, we suggest immersing areas affected by stingray injuries in hot water (temperature, 43.3°C to 46.1°C [110°F–115°F]; or as close to this range as tolerated) until pain subsides.8,9,14 Ice packs are an alternative to hot water immersion that may be more readily available to patients. If pain does not resolve following hot water immersion or application of an ice pack, additional analgesics and xylocaine without epinephrine may be helpful.9,15
Infection
One major complication of stingray injuries is infection.8,9 Many bacterial species reside in stingray mucus, the marine environment, or on human skin that may be introduced during a single injury. Marine envenomations can involve organisms such as Vibrio, Aeromonas, and Mycobacterium species, which often are resistant to antibiotic prophylaxis covering common causes of soft-tissue infection such as Staphylococcus and Streptococcus species.8,9,16,17 Additionally, physicians should cover for Clostridium species and ensure patients are up-to-date on vaccinations because severe cases of tetanus following stingray injuries have been reported.18 Lastly, fungal infections including fusariosis have been reported following stingray injuries and should be considered if a patient develops an infection.19
Several authors support the use of prophylactic broad-spectrum antibiotics in all but mild stingray injuries.8,9,20,21 Although no standardized definition exists, mild injuries generally represent patients with superficial lacerations or less, while deeper lacerations and puncture wounds require prophylaxis. Several authors agree on the use of fluoroquinolone antibiotics (eg, ciprofloxacin 500 mg twice daily) for 5 to 7 days following severe stingray injuries.1,9,13,22 Other proposed antibiotic regimens include trimethoprim-sulfamethoxazole (160/800 mg twice daily) or tetracycline (500 mg 4 times daily) for 7 days.13 Failure of ciprofloxacin therapy after 7 days has been reported, with resolution of infection after treatment with an intravenous cephalosporin for 7 days.20 Failure of trimethoprim-sulfamethoxazole therapy also has been reported, with one case requiring levofloxacin for a much longer course.21 Clinical follow-up remains essential after prescribing prophylactic antibiotics, as resistance is common.
Foreign Bodies
Stingray injuries also are often complicated by foreign bodies or retained spines.3,8 Although these complications are less severe than infection, all wounds should be explored for material under local anesthesia. Furthermore, there has been support for thorough debridement of necrotic tissue with referral to a hand specialist for deeper injuries to the hands as well as referral to a foot and ankle specialist for deeper injuries of the lower extremities.23,24 More serious injuries with penetration of vital structures, such as through the chest or abdomen, require immediate exploration in an operating room.1,24
Imaging
Routine imaging of stingray injuries remains controversial. In a case series of 119 patients presenting to a California emergency department with stingray injuries, Clark et al9 found that radiographs were not helpful. This finding likely is due in part to an inability to detect hypodense material such as integumentary or glandular tissue via radiography.3 However, radiographs have been used to identify retained stingray barbs in select cases in which retained barbs are suspected.2,25 Lastly, ultrasonography potentially may offer a better first choice when a barb is not readily apparent; magnetic resonance imaging may be indicated for more involved areas and for further visualization of suspected hypodense material, though at a higher expense.2,9
Biopsy
Biopsies of stingray injuries are rarely performed, and the findings are not well characterized. One case biopsied 2 months after injury showed a large zone of paucicellular necrosis with superficial ulceration and granulomatous inflammation. The stingray venom was most likely responsible for the pattern of necrosis noted in the biopsy.21
Avoidance and Prevention
Patients traveling to areas of the world inhabited by stingrays should receive counseling on how to avoid injury. Prior to entry, individuals can throw stones or use a long stick to clear their walking or swimming areas of venomous fish.26 Polarized sunglasses may help spot stingrays in shallow water. Furthermore, wading through water with a shuffling gait can help individuals avoid stepping directly on a stingray and also warns stingrays that someone is in the area. Individuals who spend more time in coastal waters or river systems inhabited by stingrays may invest in protective stingray gear such as leg guards or specialized wading boots.26 Lastly, fishermen should be advised to avoid handling stingrays with their hands and instead cut their fishing line to release the fish.
- Aurbach PS. Envenomations by aquatic vertebrates. In: Auerbach PS. Wilderness Medicine. 5th ed. St. Louis, MO: Mosby; 2007:1730-1749.
- Robins CR, Ray GC. A Field Guide to Atlantic Coast Fishes. New York, NY: Houghton Mifflin Company; 1986.
- Diaz JH. The evaluation, management, and prevention of stingray injuries in travelers. J Travel Med. 2008;15:102-109.
- Haddad V Jr, Neto DG, de Paula Neto JB, et al. Freshwater stingrays: study of epidemiologic, clinical and therapeutic aspects based on 84 envenomings in humans and some enzymatic activities of the venom. Toxicon. 2004;43:287-294.
- Marinkelle CJ. Accidents by venomous animals in Colombia. Ind Med Surg. 1966;35:988-992.
- Last PR, White WT, Caire JN, et al. Sharks and Rays of Borneo. Collingwood VIC, Australia: CSIRO Publishing; 2010.
- Mebs D. Venomous and Poisonous Animals: A Handbook for Biologists, Toxicologists and Toxinologists, Physicians and Pharmacists. Boca Raton, FL: CRC Press; 2002.
- Clark AT, Clark RF, Cantrell FL. A retrospective review of the presentation and treatment of stingray stings reported to a poison control system. Am J Ther. 2017;24:E177-E180.
- Clark RF, Girard RH, Rao D, et al. Stingray envenomation: a retrospective review of clinical presentation and treatment in 119 cases. J Emerg Med. 2007;33:33-37.
- Mahjoubi L, Joyeux A, Delambre JF, et al. Near-death thoracic trauma caused by a stingray in the Indian Ocean. Semin Thorac Cardiovasc Surg. 2017;29:262-263.
- Parra MW, Constantini EN, Rodas EB. Surviving a transfixing cardiac injury caused by a stingray barb. J Thorac Cardiovasc Surg. 2010;139:E115-E116.
- Dos Santos JC, Grund LZ, Seibert CS, et al. Stingray venom activates IL-33 producing cardiomyocytes, but not mast cell, to promote acute neutrophil-mediated injury. Sci Rep. 2017;7:7912.
- Auerbach PS, Norris RL. Marine envenomation. In: Longo DL, Kasper SL, Jameson JL, et al, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill; 2012:144-148.
- Cook MD, Matteucci MJ, Lall R, et al. Stingray envenomation. J Emerg Med. 2006;30:345-347.
- Bowers RC, Mustain MV. Disorders due to physical & environmental agents. In: Humphries RL, Stone C, eds. CURRENT Diagnosis & Treatment Emergency Medicine. 7th ed. New York, NY: McGraw-Hill; 2011:835-861.
- Domingos MO, Franzolin MR, dos Anjos MT, et al. The influence of environmental bacteria in freshwater stingray wound-healing. Toxicon. 2011;58:147-153.
- Auerbach PS, Yajko DM, Nassos PS, et al. Bacteriology of the marine environment: implications for clinical therapy. Ann Emerg Med. 1987;16:643-649.
- Torrez PP, Quiroga MM, Said R, et al. Tetanus after envenomations caused by freshwater stingrays. Toxicon. 2015;97:32-35.
- Hiemenz JW, Kennedy B, Kwon-Chung KJ. Invasive fusariosis associated with an injury by a stingray barb. J Med Vet Mycol. 1990;28:209-213.
- da Silva NJ Jr, Ferreira KR, Pinto RN, et al. A severe accident caused by an ocellate river stingray (Potamotrygon motoro) in central Brazil: how well do we really understand stingray venom chemistry, envenomation, and therapeutics? Toxins (Basel). 2015;7:2272-2288.
- Tartar D, Limova M, North J. Clinical and histopathologic findings in cutaneous sting ray wounds: a case report. Dermatol Online J. 2013;19:19261.
- Jarvis HC, Matheny LM, Clanton TO. Stingray injury to the webspace of the foot. Orthopedics. 2012;35:E762-E765.
- Trickett R, Whitaker IS, Boyce DE. Sting-ray injuries to the hand: case report, literature review and a suggested algorithm for management. J Plast Reconstruct Aesthet Surg. 2009;62:E270-E273.
- Fernandez I, Valladolid G, Varon J, et al. Encounters with venomous sea-life. J Emerg Med. 2011;40:103-112.
- O’Malley GF, O’Malley RN, Pham O, et al. Retained stingray barb and the importance of imaging. Wilderness Environ Med. 2015;26:375-379.
- How to protect yourself from stingrays. Howcast website. https://www.howcast.com/videos/228034-how-to-protect-yourself-from-stingrays/. Accessed July 12, 2018.
- Aurbach PS. Envenomations by aquatic vertebrates. In: Auerbach PS. Wilderness Medicine. 5th ed. St. Louis, MO: Mosby; 2007:1730-1749.
- Robins CR, Ray GC. A Field Guide to Atlantic Coast Fishes. New York, NY: Houghton Mifflin Company; 1986.
- Diaz JH. The evaluation, management, and prevention of stingray injuries in travelers. J Travel Med. 2008;15:102-109.
- Haddad V Jr, Neto DG, de Paula Neto JB, et al. Freshwater stingrays: study of epidemiologic, clinical and therapeutic aspects based on 84 envenomings in humans and some enzymatic activities of the venom. Toxicon. 2004;43:287-294.
- Marinkelle CJ. Accidents by venomous animals in Colombia. Ind Med Surg. 1966;35:988-992.
- Last PR, White WT, Caire JN, et al. Sharks and Rays of Borneo. Collingwood VIC, Australia: CSIRO Publishing; 2010.
- Mebs D. Venomous and Poisonous Animals: A Handbook for Biologists, Toxicologists and Toxinologists, Physicians and Pharmacists. Boca Raton, FL: CRC Press; 2002.
- Clark AT, Clark RF, Cantrell FL. A retrospective review of the presentation and treatment of stingray stings reported to a poison control system. Am J Ther. 2017;24:E177-E180.
- Clark RF, Girard RH, Rao D, et al. Stingray envenomation: a retrospective review of clinical presentation and treatment in 119 cases. J Emerg Med. 2007;33:33-37.
- Mahjoubi L, Joyeux A, Delambre JF, et al. Near-death thoracic trauma caused by a stingray in the Indian Ocean. Semin Thorac Cardiovasc Surg. 2017;29:262-263.
- Parra MW, Constantini EN, Rodas EB. Surviving a transfixing cardiac injury caused by a stingray barb. J Thorac Cardiovasc Surg. 2010;139:E115-E116.
- Dos Santos JC, Grund LZ, Seibert CS, et al. Stingray venom activates IL-33 producing cardiomyocytes, but not mast cell, to promote acute neutrophil-mediated injury. Sci Rep. 2017;7:7912.
- Auerbach PS, Norris RL. Marine envenomation. In: Longo DL, Kasper SL, Jameson JL, et al, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill; 2012:144-148.
- Cook MD, Matteucci MJ, Lall R, et al. Stingray envenomation. J Emerg Med. 2006;30:345-347.
- Bowers RC, Mustain MV. Disorders due to physical & environmental agents. In: Humphries RL, Stone C, eds. CURRENT Diagnosis & Treatment Emergency Medicine. 7th ed. New York, NY: McGraw-Hill; 2011:835-861.
- Domingos MO, Franzolin MR, dos Anjos MT, et al. The influence of environmental bacteria in freshwater stingray wound-healing. Toxicon. 2011;58:147-153.
- Auerbach PS, Yajko DM, Nassos PS, et al. Bacteriology of the marine environment: implications for clinical therapy. Ann Emerg Med. 1987;16:643-649.
- Torrez PP, Quiroga MM, Said R, et al. Tetanus after envenomations caused by freshwater stingrays. Toxicon. 2015;97:32-35.
- Hiemenz JW, Kennedy B, Kwon-Chung KJ. Invasive fusariosis associated with an injury by a stingray barb. J Med Vet Mycol. 1990;28:209-213.
- da Silva NJ Jr, Ferreira KR, Pinto RN, et al. A severe accident caused by an ocellate river stingray (Potamotrygon motoro) in central Brazil: how well do we really understand stingray venom chemistry, envenomation, and therapeutics? Toxins (Basel). 2015;7:2272-2288.
- Tartar D, Limova M, North J. Clinical and histopathologic findings in cutaneous sting ray wounds: a case report. Dermatol Online J. 2013;19:19261.
- Jarvis HC, Matheny LM, Clanton TO. Stingray injury to the webspace of the foot. Orthopedics. 2012;35:E762-E765.
- Trickett R, Whitaker IS, Boyce DE. Sting-ray injuries to the hand: case report, literature review and a suggested algorithm for management. J Plast Reconstruct Aesthet Surg. 2009;62:E270-E273.
- Fernandez I, Valladolid G, Varon J, et al. Encounters with venomous sea-life. J Emerg Med. 2011;40:103-112.
- O’Malley GF, O’Malley RN, Pham O, et al. Retained stingray barb and the importance of imaging. Wilderness Environ Med. 2015;26:375-379.
- How to protect yourself from stingrays. Howcast website. https://www.howcast.com/videos/228034-how-to-protect-yourself-from-stingrays/. Accessed July 12, 2018.
Practice Points
- Acute pain associated with stingray injuries can be treated with hot water immersion.
- Stingray injuries are prone to secondary infection and poor wound healing.