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Study validates use of new psoriatic arthritis prediction tool
Though it requires further validation, researchers led by rheumatologist Lihi Eder, MD, PhD, of the Women’s College Research Institute at Women’s College Hospital, Toronto, characterized the development and validation of PRESTO as “an important first step in the development and testing of interventional strategies that may ultimately halt disease progression,” they wrote in their study of the tool, which published in Arthritis & Rheumatology. Dr. Eder presented a summary of progress on the effort at the 2023 annual meeting of the Canadian Rheumatology Association.
To develop and validate the tool, the researchers evaluated 635 patients from the University of Toronto Psoriasis Cohort, which was launched in 2006 as a prospective longitudinal cohort study to examine risk factors for the development of PsA among patients with psoriasis. Patients enrolled in the cohort have a dermatologist-confirmed diagnosis of psoriasis and are assessed by a rheumatologist prior to enrollment to exclude those with inflammatory arthritis in the past or at the time of assessment.
To develop prediction models for PsA, Dr. Eder and colleagues used information from the patient cohort demographics, psoriasis characteristics, comorbidities, medications, and musculoskeletal symptoms. Next, they used multivariable logistic regression models adjusting for covariates, duration of psoriasis, and the log duration at risk to estimate the probability of developing PsA within 1-year and 5-year time windows from consecutive study visits.
The mean age of the study participants was 47 years, 76% were White, and 57% were male; and they had psoriasis for a mean of 16 years. The researchers found that 51 patients developed PsA during the 1-year follow-up, and 71 developed PsA during the 5-year follow-up. The risk of developing PsA within 1 year was associated with younger age, male sex, family history of psoriasis, back stiffness, nail pitting, joint stiffness, use of biologic medications, patient global health, and pain severity (area under the curve, 72.3).
In addition, the risk of developing PsA within 5 years was associated with morning stiffness, psoriatic nail lesions, psoriasis severity, fatigue, pain, and use of systemic non-biologic medication or phototherapy (AUC, 74.9). Calibration plots showed reasonable agreement between predicted and observed probabilities.
“Interestingly, several previously reported risk factors for PsA, such as HLA-B27, family history of PsA, uveitis, and flexural psoriasis, were not included in the risk prediction model due to their scarcity in our cohort,” the researchers wrote. “This finding may be due to immortal time bias which can complicate the development of risk prediction models for PsA. Genetic factors or their surrogates (e.g., family history of PsA) are associated with the development of PsA concurrently or shortly after the onset of psoriasis.”
They acknowledged certain limitations of the study, including its relatively small sample size and questionable generalizability of the study findings, “as most of the patients were recruited from dermatology clinics leading to overrepresentation of moderate-severe psoriasis. Therefore, PRESTO will require an external validation to assess its performance in other populations of psoriasis patients with different characteristics.”
Saakshi Khattri, MD, a board-certified dermatologist, rheumatologist, and internist at the Icahn School of Medicine at Mount Sinai, New York, who was not involved in the study and was asked to comment on the results, characterized the PRESTO tool as “an interesting step in the right direction, but it’s the first step.”
Since dermatologists are usually the first point of contact for psoriasis patients, she added, “a risk calculator can be helpful, but the question remains: When do we refer them to a rheumatologist? If the risk comes to 5%, is that a low risk that doesn’t need referral to rheumatology? I don’t think those questions have been answered here. From a rheumatology perspective, does the risk calculator help me decide when to intervene? At present, I’m not sure it does. Perhaps a higher score might make us intervene sooner if our clinical exam doesn’t show swollen or tender joints.”
Clinical exam findings and history she considers as a rheumatologist before making treatment recommendations include the following: Are there swollen and tender joints? Does the patient report morning stiffness for upwards of 30 minutes? Do they have enthesitis or dactylitis? Is there axial involvement? “Imaging can help if there isn’t anything on clinical exam and the history is compelling and/or the patient has risk factors for PsA,” she said.
The study’s finding of biologic use being associated with risk of developing PsA at year 1 but not at year 5 is “confusing,” Dr. Khattri added. “My concern is, will that now dissuade our moderate to severe psoriasis patients from using biologics to clear their psoriasis? We know that biologics are indicated for moderate to severe psoriasis. We also know psoriasis is associated with increased cardiovascular risk and there’s data to suggest that treatment with biologics with its resultant decrease in systemic inflammation can decrease cardiovascular risk.”
The study was supported by a New Investigator Grant from the Physician Services Incorporated Foundation. Dr. Eder disclosed that she is supported by the Canada Research Chair in Inflammatory Rheumatic Diseases. Dr. Khattri reported that she is a member of the advisory board for UCB, Janssen, AbbVie, Regeneron, Sanofi, Lilly, Argenx, and Arcutis. She has also received research funds from Incyte, AbbVie, Leo, Galderma, Pfizer, and Acelyrin.
Though it requires further validation, researchers led by rheumatologist Lihi Eder, MD, PhD, of the Women’s College Research Institute at Women’s College Hospital, Toronto, characterized the development and validation of PRESTO as “an important first step in the development and testing of interventional strategies that may ultimately halt disease progression,” they wrote in their study of the tool, which published in Arthritis & Rheumatology. Dr. Eder presented a summary of progress on the effort at the 2023 annual meeting of the Canadian Rheumatology Association.
To develop and validate the tool, the researchers evaluated 635 patients from the University of Toronto Psoriasis Cohort, which was launched in 2006 as a prospective longitudinal cohort study to examine risk factors for the development of PsA among patients with psoriasis. Patients enrolled in the cohort have a dermatologist-confirmed diagnosis of psoriasis and are assessed by a rheumatologist prior to enrollment to exclude those with inflammatory arthritis in the past or at the time of assessment.
To develop prediction models for PsA, Dr. Eder and colleagues used information from the patient cohort demographics, psoriasis characteristics, comorbidities, medications, and musculoskeletal symptoms. Next, they used multivariable logistic regression models adjusting for covariates, duration of psoriasis, and the log duration at risk to estimate the probability of developing PsA within 1-year and 5-year time windows from consecutive study visits.
The mean age of the study participants was 47 years, 76% were White, and 57% were male; and they had psoriasis for a mean of 16 years. The researchers found that 51 patients developed PsA during the 1-year follow-up, and 71 developed PsA during the 5-year follow-up. The risk of developing PsA within 1 year was associated with younger age, male sex, family history of psoriasis, back stiffness, nail pitting, joint stiffness, use of biologic medications, patient global health, and pain severity (area under the curve, 72.3).
In addition, the risk of developing PsA within 5 years was associated with morning stiffness, psoriatic nail lesions, psoriasis severity, fatigue, pain, and use of systemic non-biologic medication or phototherapy (AUC, 74.9). Calibration plots showed reasonable agreement between predicted and observed probabilities.
“Interestingly, several previously reported risk factors for PsA, such as HLA-B27, family history of PsA, uveitis, and flexural psoriasis, were not included in the risk prediction model due to their scarcity in our cohort,” the researchers wrote. “This finding may be due to immortal time bias which can complicate the development of risk prediction models for PsA. Genetic factors or their surrogates (e.g., family history of PsA) are associated with the development of PsA concurrently or shortly after the onset of psoriasis.”
They acknowledged certain limitations of the study, including its relatively small sample size and questionable generalizability of the study findings, “as most of the patients were recruited from dermatology clinics leading to overrepresentation of moderate-severe psoriasis. Therefore, PRESTO will require an external validation to assess its performance in other populations of psoriasis patients with different characteristics.”
Saakshi Khattri, MD, a board-certified dermatologist, rheumatologist, and internist at the Icahn School of Medicine at Mount Sinai, New York, who was not involved in the study and was asked to comment on the results, characterized the PRESTO tool as “an interesting step in the right direction, but it’s the first step.”
Since dermatologists are usually the first point of contact for psoriasis patients, she added, “a risk calculator can be helpful, but the question remains: When do we refer them to a rheumatologist? If the risk comes to 5%, is that a low risk that doesn’t need referral to rheumatology? I don’t think those questions have been answered here. From a rheumatology perspective, does the risk calculator help me decide when to intervene? At present, I’m not sure it does. Perhaps a higher score might make us intervene sooner if our clinical exam doesn’t show swollen or tender joints.”
Clinical exam findings and history she considers as a rheumatologist before making treatment recommendations include the following: Are there swollen and tender joints? Does the patient report morning stiffness for upwards of 30 minutes? Do they have enthesitis or dactylitis? Is there axial involvement? “Imaging can help if there isn’t anything on clinical exam and the history is compelling and/or the patient has risk factors for PsA,” she said.
The study’s finding of biologic use being associated with risk of developing PsA at year 1 but not at year 5 is “confusing,” Dr. Khattri added. “My concern is, will that now dissuade our moderate to severe psoriasis patients from using biologics to clear their psoriasis? We know that biologics are indicated for moderate to severe psoriasis. We also know psoriasis is associated with increased cardiovascular risk and there’s data to suggest that treatment with biologics with its resultant decrease in systemic inflammation can decrease cardiovascular risk.”
The study was supported by a New Investigator Grant from the Physician Services Incorporated Foundation. Dr. Eder disclosed that she is supported by the Canada Research Chair in Inflammatory Rheumatic Diseases. Dr. Khattri reported that she is a member of the advisory board for UCB, Janssen, AbbVie, Regeneron, Sanofi, Lilly, Argenx, and Arcutis. She has also received research funds from Incyte, AbbVie, Leo, Galderma, Pfizer, and Acelyrin.
Though it requires further validation, researchers led by rheumatologist Lihi Eder, MD, PhD, of the Women’s College Research Institute at Women’s College Hospital, Toronto, characterized the development and validation of PRESTO as “an important first step in the development and testing of interventional strategies that may ultimately halt disease progression,” they wrote in their study of the tool, which published in Arthritis & Rheumatology. Dr. Eder presented a summary of progress on the effort at the 2023 annual meeting of the Canadian Rheumatology Association.
To develop and validate the tool, the researchers evaluated 635 patients from the University of Toronto Psoriasis Cohort, which was launched in 2006 as a prospective longitudinal cohort study to examine risk factors for the development of PsA among patients with psoriasis. Patients enrolled in the cohort have a dermatologist-confirmed diagnosis of psoriasis and are assessed by a rheumatologist prior to enrollment to exclude those with inflammatory arthritis in the past or at the time of assessment.
To develop prediction models for PsA, Dr. Eder and colleagues used information from the patient cohort demographics, psoriasis characteristics, comorbidities, medications, and musculoskeletal symptoms. Next, they used multivariable logistic regression models adjusting for covariates, duration of psoriasis, and the log duration at risk to estimate the probability of developing PsA within 1-year and 5-year time windows from consecutive study visits.
The mean age of the study participants was 47 years, 76% were White, and 57% were male; and they had psoriasis for a mean of 16 years. The researchers found that 51 patients developed PsA during the 1-year follow-up, and 71 developed PsA during the 5-year follow-up. The risk of developing PsA within 1 year was associated with younger age, male sex, family history of psoriasis, back stiffness, nail pitting, joint stiffness, use of biologic medications, patient global health, and pain severity (area under the curve, 72.3).
In addition, the risk of developing PsA within 5 years was associated with morning stiffness, psoriatic nail lesions, psoriasis severity, fatigue, pain, and use of systemic non-biologic medication or phototherapy (AUC, 74.9). Calibration plots showed reasonable agreement between predicted and observed probabilities.
“Interestingly, several previously reported risk factors for PsA, such as HLA-B27, family history of PsA, uveitis, and flexural psoriasis, were not included in the risk prediction model due to their scarcity in our cohort,” the researchers wrote. “This finding may be due to immortal time bias which can complicate the development of risk prediction models for PsA. Genetic factors or their surrogates (e.g., family history of PsA) are associated with the development of PsA concurrently or shortly after the onset of psoriasis.”
They acknowledged certain limitations of the study, including its relatively small sample size and questionable generalizability of the study findings, “as most of the patients were recruited from dermatology clinics leading to overrepresentation of moderate-severe psoriasis. Therefore, PRESTO will require an external validation to assess its performance in other populations of psoriasis patients with different characteristics.”
Saakshi Khattri, MD, a board-certified dermatologist, rheumatologist, and internist at the Icahn School of Medicine at Mount Sinai, New York, who was not involved in the study and was asked to comment on the results, characterized the PRESTO tool as “an interesting step in the right direction, but it’s the first step.”
Since dermatologists are usually the first point of contact for psoriasis patients, she added, “a risk calculator can be helpful, but the question remains: When do we refer them to a rheumatologist? If the risk comes to 5%, is that a low risk that doesn’t need referral to rheumatology? I don’t think those questions have been answered here. From a rheumatology perspective, does the risk calculator help me decide when to intervene? At present, I’m not sure it does. Perhaps a higher score might make us intervene sooner if our clinical exam doesn’t show swollen or tender joints.”
Clinical exam findings and history she considers as a rheumatologist before making treatment recommendations include the following: Are there swollen and tender joints? Does the patient report morning stiffness for upwards of 30 minutes? Do they have enthesitis or dactylitis? Is there axial involvement? “Imaging can help if there isn’t anything on clinical exam and the history is compelling and/or the patient has risk factors for PsA,” she said.
The study’s finding of biologic use being associated with risk of developing PsA at year 1 but not at year 5 is “confusing,” Dr. Khattri added. “My concern is, will that now dissuade our moderate to severe psoriasis patients from using biologics to clear their psoriasis? We know that biologics are indicated for moderate to severe psoriasis. We also know psoriasis is associated with increased cardiovascular risk and there’s data to suggest that treatment with biologics with its resultant decrease in systemic inflammation can decrease cardiovascular risk.”
The study was supported by a New Investigator Grant from the Physician Services Incorporated Foundation. Dr. Eder disclosed that she is supported by the Canada Research Chair in Inflammatory Rheumatic Diseases. Dr. Khattri reported that she is a member of the advisory board for UCB, Janssen, AbbVie, Regeneron, Sanofi, Lilly, Argenx, and Arcutis. She has also received research funds from Incyte, AbbVie, Leo, Galderma, Pfizer, and Acelyrin.
FROM ARTHRITIS AND RHEUMATOLOGY
What's the diagnosis?
Given the characteristic clinical presentation, the most likely diagnosis is pilomatrixoma.
Pilomatrixomas are benign adnexal tumors that arise from immature matrix cells of the hair follicles located on dermal or subcutaneous tissue.
The cause of pilomatrixoma remains unclear. Recent studies have suggested that the development of pilomatrixoma are related to mutations in the Wnt signaling pathway, where beta-catenin gene (CTNNB1) mutation is the most frequently reported.1-4
Pilomatrixomas are more common in children and often present before 10 years of age.1,2,5 They commonly appear in head and neck, as well as upper extremities, trunk, and lower extremities.2,6
The clinical manifestations of pilomatrixomas are diverse and according to their appearance five classic clinical types are described: mass, pigmented, mixed, ulcerated, and keloid-like.2,3 The mass type is the predominant form, where it generally presents as a hard and freely mobile nodule covered by skin that may present a firm calcified protruding nodule. Other less common types include: lymphangiectasic, anetodermic, perforating, and bullous.2,6,7
Pilomatrixomas are mostly solitary, whereas multiple forms are reported to be associated with familial inheritance or syndromic conditions, such as myotonic dystrophy, Gardner syndrome, Turner’s syndrome, and Rubinstein-Taybi syndrome.2-4 However, children and adolescents occasionally present with multiple pilomatricomas with no associated syndrome.
On physical exam a helpful features for the diagnosis is the “teeter-totter sign,” which can be illustrated by pressing on one edge of the lesion that will cause the opposite edge to protrude from the skin. Another helpful tool is to use a light to transilluminate and the calcification produces a bluish opaque hue,8 as light cannot transmit through the calcification, often differentiating it from epidermal inclusion cysts or other noncalcified lesions.
What is the differential diagnosis?
Because of the diverse clinical presentations, pilomatrixomas are frequently misdiagnosed. The percentage of correct preoperative diagnosis reported is low, varying from 16% to 43% in different series.1,9-11 They most frequently are misdiagnosed as other types of cysts such as epidermal, dermoid, or sebaceous.2,3,5,12,13 Rapidly growing pilomatrixomas can be also be misdiagnosed as malignant soft-tissue tumors, cutaneous lymphoma, or sarcomas.5,13
When presenting with a classic history and physical features, diagnosis is clinical, and no further studies are recommended.14 To improve diagnostic accuracy when encountering unusual subtypes, imaging is recommended, including ultrasound. Ultrasound adds a high positive predictive value (95.56%).2 Generally, on ultrasound a pilomatrixoma is described as an oval, well-defined, heterogeneous, hyperechoic subcutaneous mass with or without posterior shadowing.2 The definitive diagnosis is, however, made by histopathologic examination.
Pilomatrixomas do not spontaneously regress, therefore complete surgical resection is the standard treatment. During the follow-up period, very low recurrence rates have been reported, varying from 1.5% to 2% which generally occurs because of incomplete resection.2,3
Plexiform neurofibromas are usually congenital tumors of peripheral nerve sheath associated with neurofibromatosis type 1, often with a “bag of worms” feel on palpation. Epidermoid cysts generally present as dermal nodules often with a visible puncture, mobile on soft and mobile on palpation. Dermatofibromas present as firm, usually hyperpigmented papule or nodules that are fixed to subcutaneous tissue, thus often “dimpling” when pitched. Dermatofibrosarcoma protuberans is a rare soft-tissue sarcoma which presents as a firm, slow growing indurated plaques growing over months to years.
Conclusion
Pilomatrixomas are a benign adnexal tumor that sometimes can present as atypical forms such as this case. Diagnosis is usually based on clinical diagnosis, and transillumination can be a bedside clue. When the clinical diagnosis remains obscure an ultrasound can be helpful. The main aim of this case is to improve awareness of the variable presentations of pilomatrixomas and the importance of high level of suspicion supported by careful clinical evaluation.
Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Al-Nabti is a clinical fellow in the division of pediatric and adolescent dermatology, University of California, San Diego. Dr. Guelfand is a visiting dermatology resident in the division of pediaric and adolescent dermatology, University of Califonia, San Diego.
References
1. Jones CD et al. Am J Dermatopathol. 2018;40:631-41.
2. Hu JL et al. Arch Craniofac Surg. 2020;21(5):288-93.
3. Adhikari G and Jadhav GS. Cureus. 2022;14(2):22228.
4. Cóbar JP et al. J Surg Case Rep. 2023;2023(4):rjad182.
5. Schwarz Y et al. Int J Pediatr Otorhinolaryngol. 2016;85:148-53.
6. Kose D et al. J Cancer Res Ther. 2014;10(3):549-51.
7. Sabater-Abad J et al. Dermatol Online J. 2020;26(8):13030/qt4h16s45w.
8. Alkatan HM et al. Int J Surg Case Rep. 2021;84:106068.
9. Pant I et al. Indian J Dermatol. 2010;55:390-2.
10. Kaddu S et al. Am J Dermatopathol. 1996;18(4):333-8
11. Schwarz Y et al. Int J Pediatr Otorhinolaryngol. 2016;85:148-53.
12. Wang YN et al. Chin Med J (Engl). 2021;134(16):2011-2.
13. Yannoutsos A et al. Am J Dermatopathol. 2018;40(9):690-3.
14. Zhao A et al. Ear Nose Throat J. 2021;1455613211044778.
Given the characteristic clinical presentation, the most likely diagnosis is pilomatrixoma.
Pilomatrixomas are benign adnexal tumors that arise from immature matrix cells of the hair follicles located on dermal or subcutaneous tissue.
The cause of pilomatrixoma remains unclear. Recent studies have suggested that the development of pilomatrixoma are related to mutations in the Wnt signaling pathway, where beta-catenin gene (CTNNB1) mutation is the most frequently reported.1-4
Pilomatrixomas are more common in children and often present before 10 years of age.1,2,5 They commonly appear in head and neck, as well as upper extremities, trunk, and lower extremities.2,6
The clinical manifestations of pilomatrixomas are diverse and according to their appearance five classic clinical types are described: mass, pigmented, mixed, ulcerated, and keloid-like.2,3 The mass type is the predominant form, where it generally presents as a hard and freely mobile nodule covered by skin that may present a firm calcified protruding nodule. Other less common types include: lymphangiectasic, anetodermic, perforating, and bullous.2,6,7
Pilomatrixomas are mostly solitary, whereas multiple forms are reported to be associated with familial inheritance or syndromic conditions, such as myotonic dystrophy, Gardner syndrome, Turner’s syndrome, and Rubinstein-Taybi syndrome.2-4 However, children and adolescents occasionally present with multiple pilomatricomas with no associated syndrome.
On physical exam a helpful features for the diagnosis is the “teeter-totter sign,” which can be illustrated by pressing on one edge of the lesion that will cause the opposite edge to protrude from the skin. Another helpful tool is to use a light to transilluminate and the calcification produces a bluish opaque hue,8 as light cannot transmit through the calcification, often differentiating it from epidermal inclusion cysts or other noncalcified lesions.
What is the differential diagnosis?
Because of the diverse clinical presentations, pilomatrixomas are frequently misdiagnosed. The percentage of correct preoperative diagnosis reported is low, varying from 16% to 43% in different series.1,9-11 They most frequently are misdiagnosed as other types of cysts such as epidermal, dermoid, or sebaceous.2,3,5,12,13 Rapidly growing pilomatrixomas can be also be misdiagnosed as malignant soft-tissue tumors, cutaneous lymphoma, or sarcomas.5,13
When presenting with a classic history and physical features, diagnosis is clinical, and no further studies are recommended.14 To improve diagnostic accuracy when encountering unusual subtypes, imaging is recommended, including ultrasound. Ultrasound adds a high positive predictive value (95.56%).2 Generally, on ultrasound a pilomatrixoma is described as an oval, well-defined, heterogeneous, hyperechoic subcutaneous mass with or without posterior shadowing.2 The definitive diagnosis is, however, made by histopathologic examination.
Pilomatrixomas do not spontaneously regress, therefore complete surgical resection is the standard treatment. During the follow-up period, very low recurrence rates have been reported, varying from 1.5% to 2% which generally occurs because of incomplete resection.2,3
Plexiform neurofibromas are usually congenital tumors of peripheral nerve sheath associated with neurofibromatosis type 1, often with a “bag of worms” feel on palpation. Epidermoid cysts generally present as dermal nodules often with a visible puncture, mobile on soft and mobile on palpation. Dermatofibromas present as firm, usually hyperpigmented papule or nodules that are fixed to subcutaneous tissue, thus often “dimpling” when pitched. Dermatofibrosarcoma protuberans is a rare soft-tissue sarcoma which presents as a firm, slow growing indurated plaques growing over months to years.
Conclusion
Pilomatrixomas are a benign adnexal tumor that sometimes can present as atypical forms such as this case. Diagnosis is usually based on clinical diagnosis, and transillumination can be a bedside clue. When the clinical diagnosis remains obscure an ultrasound can be helpful. The main aim of this case is to improve awareness of the variable presentations of pilomatrixomas and the importance of high level of suspicion supported by careful clinical evaluation.
Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Al-Nabti is a clinical fellow in the division of pediatric and adolescent dermatology, University of California, San Diego. Dr. Guelfand is a visiting dermatology resident in the division of pediaric and adolescent dermatology, University of Califonia, San Diego.
References
1. Jones CD et al. Am J Dermatopathol. 2018;40:631-41.
2. Hu JL et al. Arch Craniofac Surg. 2020;21(5):288-93.
3. Adhikari G and Jadhav GS. Cureus. 2022;14(2):22228.
4. Cóbar JP et al. J Surg Case Rep. 2023;2023(4):rjad182.
5. Schwarz Y et al. Int J Pediatr Otorhinolaryngol. 2016;85:148-53.
6. Kose D et al. J Cancer Res Ther. 2014;10(3):549-51.
7. Sabater-Abad J et al. Dermatol Online J. 2020;26(8):13030/qt4h16s45w.
8. Alkatan HM et al. Int J Surg Case Rep. 2021;84:106068.
9. Pant I et al. Indian J Dermatol. 2010;55:390-2.
10. Kaddu S et al. Am J Dermatopathol. 1996;18(4):333-8
11. Schwarz Y et al. Int J Pediatr Otorhinolaryngol. 2016;85:148-53.
12. Wang YN et al. Chin Med J (Engl). 2021;134(16):2011-2.
13. Yannoutsos A et al. Am J Dermatopathol. 2018;40(9):690-3.
14. Zhao A et al. Ear Nose Throat J. 2021;1455613211044778.
Given the characteristic clinical presentation, the most likely diagnosis is pilomatrixoma.
Pilomatrixomas are benign adnexal tumors that arise from immature matrix cells of the hair follicles located on dermal or subcutaneous tissue.
The cause of pilomatrixoma remains unclear. Recent studies have suggested that the development of pilomatrixoma are related to mutations in the Wnt signaling pathway, where beta-catenin gene (CTNNB1) mutation is the most frequently reported.1-4
Pilomatrixomas are more common in children and often present before 10 years of age.1,2,5 They commonly appear in head and neck, as well as upper extremities, trunk, and lower extremities.2,6
The clinical manifestations of pilomatrixomas are diverse and according to their appearance five classic clinical types are described: mass, pigmented, mixed, ulcerated, and keloid-like.2,3 The mass type is the predominant form, where it generally presents as a hard and freely mobile nodule covered by skin that may present a firm calcified protruding nodule. Other less common types include: lymphangiectasic, anetodermic, perforating, and bullous.2,6,7
Pilomatrixomas are mostly solitary, whereas multiple forms are reported to be associated with familial inheritance or syndromic conditions, such as myotonic dystrophy, Gardner syndrome, Turner’s syndrome, and Rubinstein-Taybi syndrome.2-4 However, children and adolescents occasionally present with multiple pilomatricomas with no associated syndrome.
On physical exam a helpful features for the diagnosis is the “teeter-totter sign,” which can be illustrated by pressing on one edge of the lesion that will cause the opposite edge to protrude from the skin. Another helpful tool is to use a light to transilluminate and the calcification produces a bluish opaque hue,8 as light cannot transmit through the calcification, often differentiating it from epidermal inclusion cysts or other noncalcified lesions.
What is the differential diagnosis?
Because of the diverse clinical presentations, pilomatrixomas are frequently misdiagnosed. The percentage of correct preoperative diagnosis reported is low, varying from 16% to 43% in different series.1,9-11 They most frequently are misdiagnosed as other types of cysts such as epidermal, dermoid, or sebaceous.2,3,5,12,13 Rapidly growing pilomatrixomas can be also be misdiagnosed as malignant soft-tissue tumors, cutaneous lymphoma, or sarcomas.5,13
When presenting with a classic history and physical features, diagnosis is clinical, and no further studies are recommended.14 To improve diagnostic accuracy when encountering unusual subtypes, imaging is recommended, including ultrasound. Ultrasound adds a high positive predictive value (95.56%).2 Generally, on ultrasound a pilomatrixoma is described as an oval, well-defined, heterogeneous, hyperechoic subcutaneous mass with or without posterior shadowing.2 The definitive diagnosis is, however, made by histopathologic examination.
Pilomatrixomas do not spontaneously regress, therefore complete surgical resection is the standard treatment. During the follow-up period, very low recurrence rates have been reported, varying from 1.5% to 2% which generally occurs because of incomplete resection.2,3
Plexiform neurofibromas are usually congenital tumors of peripheral nerve sheath associated with neurofibromatosis type 1, often with a “bag of worms” feel on palpation. Epidermoid cysts generally present as dermal nodules often with a visible puncture, mobile on soft and mobile on palpation. Dermatofibromas present as firm, usually hyperpigmented papule or nodules that are fixed to subcutaneous tissue, thus often “dimpling” when pitched. Dermatofibrosarcoma protuberans is a rare soft-tissue sarcoma which presents as a firm, slow growing indurated plaques growing over months to years.
Conclusion
Pilomatrixomas are a benign adnexal tumor that sometimes can present as atypical forms such as this case. Diagnosis is usually based on clinical diagnosis, and transillumination can be a bedside clue. When the clinical diagnosis remains obscure an ultrasound can be helpful. The main aim of this case is to improve awareness of the variable presentations of pilomatrixomas and the importance of high level of suspicion supported by careful clinical evaluation.
Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Al-Nabti is a clinical fellow in the division of pediatric and adolescent dermatology, University of California, San Diego. Dr. Guelfand is a visiting dermatology resident in the division of pediaric and adolescent dermatology, University of Califonia, San Diego.
References
1. Jones CD et al. Am J Dermatopathol. 2018;40:631-41.
2. Hu JL et al. Arch Craniofac Surg. 2020;21(5):288-93.
3. Adhikari G and Jadhav GS. Cureus. 2022;14(2):22228.
4. Cóbar JP et al. J Surg Case Rep. 2023;2023(4):rjad182.
5. Schwarz Y et al. Int J Pediatr Otorhinolaryngol. 2016;85:148-53.
6. Kose D et al. J Cancer Res Ther. 2014;10(3):549-51.
7. Sabater-Abad J et al. Dermatol Online J. 2020;26(8):13030/qt4h16s45w.
8. Alkatan HM et al. Int J Surg Case Rep. 2021;84:106068.
9. Pant I et al. Indian J Dermatol. 2010;55:390-2.
10. Kaddu S et al. Am J Dermatopathol. 1996;18(4):333-8
11. Schwarz Y et al. Int J Pediatr Otorhinolaryngol. 2016;85:148-53.
12. Wang YN et al. Chin Med J (Engl). 2021;134(16):2011-2.
13. Yannoutsos A et al. Am J Dermatopathol. 2018;40(9):690-3.
14. Zhao A et al. Ear Nose Throat J. 2021;1455613211044778.
On physical exam there was a well-circumscribed skin-colored nodule measuring 3.1 x 3 cm that was tender on palpation. The nodule was mobile, with a firm, stony feel, and no punctum was visualized. Transillumination revealed a subtle bluish hue within the nodule.
Study highlights diagnostic challenges of differentiating lichen sclerosus from vitiligo
of cases.
Researchers who tallied symptoms and physical exam findings observed fewer statistically significant differences between LS and vitiligo patients than expected, and LS and vitiligo were sometimes misdiagnosed as each other.
“LS must be treated aggressively to prevent long-term sequelae such as permanent scarring and vulvar squamous cell carcinoma, making an accurate diagnosis crucial,” the authors write in a poster they presented at the annual meeting of the Society for Pediatric Dermatology.
LS is symptomatic and has multiple exam findings, but once treated or quiescent, the discoloration can persist and create diagnostic uncertainty, lead study author Kaiane Habeshian, MD, a pediatric dermatologist at Children’s National Hospital, Washington, told this news organization following the SPD meeting.
The diagnostic uncertainty is especially true in patients with darker skin tones, who may have vitiligoid LS, an LS variant that has overlapping features of both LS and vitiligo.
Vitiligoid LS “presents clinically as a depigmented symmetric white vulvar and perianal white patch, often with minimal signs of inflammation, but is symptomatic and appears consistent with LS on histopathology,” Dr. Habeshian said.
“In our experience, in patients with medium to dark skin tones, there is a variable amount of repigmentation after treating LS,” she added. “After use of high potency topical corticosteroids, some patients almost completely repigment, while others have minimal repigmentation, and this can fluctuate over time, sometimes independent of other signs or symptoms of a flare up. This can lead to diagnostic confusion. For example, if an LS patient is examined after treatment, and their symptoms have resolved, they may subsequently be given a diagnosis of vitiligo.”
In the study, Dr. Habeshian and her coauthors aimed to characterize differences in LS and vitiligo based on history, physical exam, and demographic findings at the time of the initial clinic visit. She and her colleagues extracted and reviewed the medical records of 98 patients with a diagnosis of LS or vitiligo who were seen at a joint pediatric dermatology-gynecology vulvar clinic over 6.8 years. The median and mean age of the study population at diagnosis was about 6 years, with ages ranging from 2 to 20. The team used descriptive statistics and Z tests for data analysis.
The researchers found that pruritus, constipation, and dysuria were the most common symptoms experienced by both LS and vitiligo patients. All were experienced more frequently by LS patients, but only pruritus reached statistical significance (P = .040). Other symptoms experienced only by LS patients included vulvar pain, bleeding, and pain with defecation.
Meanwhile, apart from hypopigmentation and erythema, all physical exam findings were more frequent in LS patients, compared with vitiligo patients, including fissures and purpura/petechiae, but only epidermal atrophy and figure-of-8 distribution of hypopigmentation reached statistical significance (P values of .047 and .036, respectively).
In other findings, LS and vitiligo were misdiagnosed as each other 15 times. Nearly half of the misdiagnoses (46.7%) were made in Black patients, who composed 38.8% of all patients in the study.
“I suspect that some vitiligo cases that were previously ‘misdiagnosed’ as LS were actually LS that just didn’t repigment and then were labeled as vitiligo in the chart,” Dr. Habeshian said.
“And some of those LS cases that previously were misdiagnosed as vitiligo likely had other more subtle LS findings that were missed (shininess and wrinkling of the skin, small fissures, constipation) or that were attributed to comorbid irritant contact dermatitis or another condition,” she said. “It was interesting to see that even in a vulvar dermatology clinic there can be confusion between these diagnoses because the literature on pediatric LS in darker skin tones is so sparse.”
She emphasized that a close exam and detailed history are needed to properly diagnose patients with anogenital skin conditions.
“Don’t forget to ask about constipation and urinary symptoms as well as psychosocial and, in the appropriate patient, sexual and reproductive function,” Dr. Habeshian said. “Based on my experience, pediatric LS is much more common in our community than the literature would suggest. Its psychosocial impact is tremendous but not well documented, particularly in pediatric patients. In my experience, the longer LS is misdiagnosed or mistreated, the more challenging it becomes to manage. You don’t want to miss LS.”
She acknowledged certain limitations of the study, including the fact that photographs were not available for review for many of the earlier years of the clinic. “Therefore, we had to depend on the diagnosis given at the time of the visit,” she said. “This likely accounts in part for the smaller number than expected of significant exam and history findings between LS and vitiligo. We need further studies utilizing a standardized approach to accurate diagnosis.”
Her coauthors were Nikita Menta, Aneka Khilnani, MS, and Tazim Dowlut-McElroy, MD. The researchers reported having no financial disclosures.
of cases.
Researchers who tallied symptoms and physical exam findings observed fewer statistically significant differences between LS and vitiligo patients than expected, and LS and vitiligo were sometimes misdiagnosed as each other.
“LS must be treated aggressively to prevent long-term sequelae such as permanent scarring and vulvar squamous cell carcinoma, making an accurate diagnosis crucial,” the authors write in a poster they presented at the annual meeting of the Society for Pediatric Dermatology.
LS is symptomatic and has multiple exam findings, but once treated or quiescent, the discoloration can persist and create diagnostic uncertainty, lead study author Kaiane Habeshian, MD, a pediatric dermatologist at Children’s National Hospital, Washington, told this news organization following the SPD meeting.
The diagnostic uncertainty is especially true in patients with darker skin tones, who may have vitiligoid LS, an LS variant that has overlapping features of both LS and vitiligo.
Vitiligoid LS “presents clinically as a depigmented symmetric white vulvar and perianal white patch, often with minimal signs of inflammation, but is symptomatic and appears consistent with LS on histopathology,” Dr. Habeshian said.
“In our experience, in patients with medium to dark skin tones, there is a variable amount of repigmentation after treating LS,” she added. “After use of high potency topical corticosteroids, some patients almost completely repigment, while others have minimal repigmentation, and this can fluctuate over time, sometimes independent of other signs or symptoms of a flare up. This can lead to diagnostic confusion. For example, if an LS patient is examined after treatment, and their symptoms have resolved, they may subsequently be given a diagnosis of vitiligo.”
In the study, Dr. Habeshian and her coauthors aimed to characterize differences in LS and vitiligo based on history, physical exam, and demographic findings at the time of the initial clinic visit. She and her colleagues extracted and reviewed the medical records of 98 patients with a diagnosis of LS or vitiligo who were seen at a joint pediatric dermatology-gynecology vulvar clinic over 6.8 years. The median and mean age of the study population at diagnosis was about 6 years, with ages ranging from 2 to 20. The team used descriptive statistics and Z tests for data analysis.
The researchers found that pruritus, constipation, and dysuria were the most common symptoms experienced by both LS and vitiligo patients. All were experienced more frequently by LS patients, but only pruritus reached statistical significance (P = .040). Other symptoms experienced only by LS patients included vulvar pain, bleeding, and pain with defecation.
Meanwhile, apart from hypopigmentation and erythema, all physical exam findings were more frequent in LS patients, compared with vitiligo patients, including fissures and purpura/petechiae, but only epidermal atrophy and figure-of-8 distribution of hypopigmentation reached statistical significance (P values of .047 and .036, respectively).
In other findings, LS and vitiligo were misdiagnosed as each other 15 times. Nearly half of the misdiagnoses (46.7%) were made in Black patients, who composed 38.8% of all patients in the study.
“I suspect that some vitiligo cases that were previously ‘misdiagnosed’ as LS were actually LS that just didn’t repigment and then were labeled as vitiligo in the chart,” Dr. Habeshian said.
“And some of those LS cases that previously were misdiagnosed as vitiligo likely had other more subtle LS findings that were missed (shininess and wrinkling of the skin, small fissures, constipation) or that were attributed to comorbid irritant contact dermatitis or another condition,” she said. “It was interesting to see that even in a vulvar dermatology clinic there can be confusion between these diagnoses because the literature on pediatric LS in darker skin tones is so sparse.”
She emphasized that a close exam and detailed history are needed to properly diagnose patients with anogenital skin conditions.
“Don’t forget to ask about constipation and urinary symptoms as well as psychosocial and, in the appropriate patient, sexual and reproductive function,” Dr. Habeshian said. “Based on my experience, pediatric LS is much more common in our community than the literature would suggest. Its psychosocial impact is tremendous but not well documented, particularly in pediatric patients. In my experience, the longer LS is misdiagnosed or mistreated, the more challenging it becomes to manage. You don’t want to miss LS.”
She acknowledged certain limitations of the study, including the fact that photographs were not available for review for many of the earlier years of the clinic. “Therefore, we had to depend on the diagnosis given at the time of the visit,” she said. “This likely accounts in part for the smaller number than expected of significant exam and history findings between LS and vitiligo. We need further studies utilizing a standardized approach to accurate diagnosis.”
Her coauthors were Nikita Menta, Aneka Khilnani, MS, and Tazim Dowlut-McElroy, MD. The researchers reported having no financial disclosures.
of cases.
Researchers who tallied symptoms and physical exam findings observed fewer statistically significant differences between LS and vitiligo patients than expected, and LS and vitiligo were sometimes misdiagnosed as each other.
“LS must be treated aggressively to prevent long-term sequelae such as permanent scarring and vulvar squamous cell carcinoma, making an accurate diagnosis crucial,” the authors write in a poster they presented at the annual meeting of the Society for Pediatric Dermatology.
LS is symptomatic and has multiple exam findings, but once treated or quiescent, the discoloration can persist and create diagnostic uncertainty, lead study author Kaiane Habeshian, MD, a pediatric dermatologist at Children’s National Hospital, Washington, told this news organization following the SPD meeting.
The diagnostic uncertainty is especially true in patients with darker skin tones, who may have vitiligoid LS, an LS variant that has overlapping features of both LS and vitiligo.
Vitiligoid LS “presents clinically as a depigmented symmetric white vulvar and perianal white patch, often with minimal signs of inflammation, but is symptomatic and appears consistent with LS on histopathology,” Dr. Habeshian said.
“In our experience, in patients with medium to dark skin tones, there is a variable amount of repigmentation after treating LS,” she added. “After use of high potency topical corticosteroids, some patients almost completely repigment, while others have minimal repigmentation, and this can fluctuate over time, sometimes independent of other signs or symptoms of a flare up. This can lead to diagnostic confusion. For example, if an LS patient is examined after treatment, and their symptoms have resolved, they may subsequently be given a diagnosis of vitiligo.”
In the study, Dr. Habeshian and her coauthors aimed to characterize differences in LS and vitiligo based on history, physical exam, and demographic findings at the time of the initial clinic visit. She and her colleagues extracted and reviewed the medical records of 98 patients with a diagnosis of LS or vitiligo who were seen at a joint pediatric dermatology-gynecology vulvar clinic over 6.8 years. The median and mean age of the study population at diagnosis was about 6 years, with ages ranging from 2 to 20. The team used descriptive statistics and Z tests for data analysis.
The researchers found that pruritus, constipation, and dysuria were the most common symptoms experienced by both LS and vitiligo patients. All were experienced more frequently by LS patients, but only pruritus reached statistical significance (P = .040). Other symptoms experienced only by LS patients included vulvar pain, bleeding, and pain with defecation.
Meanwhile, apart from hypopigmentation and erythema, all physical exam findings were more frequent in LS patients, compared with vitiligo patients, including fissures and purpura/petechiae, but only epidermal atrophy and figure-of-8 distribution of hypopigmentation reached statistical significance (P values of .047 and .036, respectively).
In other findings, LS and vitiligo were misdiagnosed as each other 15 times. Nearly half of the misdiagnoses (46.7%) were made in Black patients, who composed 38.8% of all patients in the study.
“I suspect that some vitiligo cases that were previously ‘misdiagnosed’ as LS were actually LS that just didn’t repigment and then were labeled as vitiligo in the chart,” Dr. Habeshian said.
“And some of those LS cases that previously were misdiagnosed as vitiligo likely had other more subtle LS findings that were missed (shininess and wrinkling of the skin, small fissures, constipation) or that were attributed to comorbid irritant contact dermatitis or another condition,” she said. “It was interesting to see that even in a vulvar dermatology clinic there can be confusion between these diagnoses because the literature on pediatric LS in darker skin tones is so sparse.”
She emphasized that a close exam and detailed history are needed to properly diagnose patients with anogenital skin conditions.
“Don’t forget to ask about constipation and urinary symptoms as well as psychosocial and, in the appropriate patient, sexual and reproductive function,” Dr. Habeshian said. “Based on my experience, pediatric LS is much more common in our community than the literature would suggest. Its psychosocial impact is tremendous but not well documented, particularly in pediatric patients. In my experience, the longer LS is misdiagnosed or mistreated, the more challenging it becomes to manage. You don’t want to miss LS.”
She acknowledged certain limitations of the study, including the fact that photographs were not available for review for many of the earlier years of the clinic. “Therefore, we had to depend on the diagnosis given at the time of the visit,” she said. “This likely accounts in part for the smaller number than expected of significant exam and history findings between LS and vitiligo. We need further studies utilizing a standardized approach to accurate diagnosis.”
Her coauthors were Nikita Menta, Aneka Khilnani, MS, and Tazim Dowlut-McElroy, MD. The researchers reported having no financial disclosures.
FROM SPD 2023
Autoantibody against enteric nervous system protein linked to GI dysfunction in systemic sclerosis
(SSc), new research suggests. Researchers also found that gephyrin is expressed in the patient’s enteric nervous system (ENS), which regulates gut motility.
“While there are many antibodies that are helpful in identifying patients at risk for extraintestinal complications of this disease, markers that identify patients at higher risk for gastrointestinal complications are limited. Furthermore, the biological mechanisms that cause and perpetuate the progression of gastrointestinal disease in scleroderma are not well understood, making it challenging to distinguish between patients whose gastrointestinal disease will progress from those whose GI disease will remain stable/mild,” Zsuzsanna H. McMahan, MD, MHS, told this news organization in an email. Dr. McMahan is co–first author on the study along with Subhash Kulkarni, PhD. They conducted the research with colleagues when they both worked at Johns Hopkins University in Baltimore, Md.
When asked for comment, Kimberly Lakin, MD, MS, assistant professor of medicine at Weill Cornell Medicine and a rheumatologist at Hospital for Special Surgery, New York, called the study “interesting and novel.”
“Not only did [antigephyrin antibodies] correlate with the presence of lower GI symptoms, but also higher levels of antibodies correlated with worse lower GI symptoms. This suggests that not only could this antibody be used to predict who may have constipation and potentially need more aggressive GI interventions, but it may also be useful in quantifying GI severity in systemic sclerosis, although more research is still needed,” said Dr. Lakin, who was not involved with the research.
The study was published online in Arthritis & Rheumatology.
In the cross-sectional study, researchers identified gephyrin as an autoantigen in sera from a single patient with SSc by isolating it from immunoprecipitations performed with murine myenteric plexus neuron lysates, and then characterizing it by mass spectrometry and validating it in further assays. That patient had GI dysfunction but no defined SSc-associated autoantibodies.
Dr. McMahan and colleagues then investigated the prevalence of the autoantibody by screening the sera of 188 patients with SSc who presented consecutively to the Johns Hopkins Scleroderma Center between April 2016 and August 2017, as well as 40 controls, and compared GI symptom severity between antibody-positive and antibody-negative patients with SSc.
A total of 16 (8.5%) of the 188 patients with SSc had antigephyrin antibodies, compared with none of the controls. Of these 16 patients, 4 had no other defined SSc antibodies. In the SSc cohort, severe constipation was more common in antigephyrin antibody–positive patients, compared with antibody-negative patients (46% vs. 15%). Antibody-positive patients also had higher constipation scores, and severe distension and bloating occurred in the antibody-positive group more than twice as often (54% vs. 25%).
Patients with severe constipation, distention, and bloating had higher antigephyrin antibody levels. After adjusting for confounders such as disease duration, patients with severe constipation were nearly five times as likely (odds ratio, 4.74; P = .010) to be antigephyrin antibody–positive, and patients with severe distention and bloating were nearly four times as likely (OR, 3.71; P = .027) to be antibody-positive.
Last, the authors showed via immunohistochemistry that gephyrin is expressed in the myenteric ganglia of human GI tissue.
“Gastrointestinal function is highly regulated by the ENS, so it is interesting that antibodies that target a protein expressed by ENS cells (gephyrin) were identified in patients with scleroderma who have severe lower bowel dysfunction,” said Dr. McMahan, who is associate professor in the division of rheumatology and codirector of the scleroderma program at the University of Texas Health Science Center at Houston. “Gephyrin is a key mediator of normal communications between nerves in the gut, so it is tantalizing to speculate that autoimmune-mediated disruption (e.g., an inhibitory or blocking antibody) in neural (ENS) communications in the gut might lead to impaired bowel transit and prominent constipation.”
The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and other NIH grants, as well as the Scleroderma Research Foundation, Rheumatology Research Foundation, Jerome L. Greene Foundation, Martha McCrory Professorship, and Chresanthe Stauraluakis Memorial Discovery Fund. The study authors and Dr. Lakin report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(SSc), new research suggests. Researchers also found that gephyrin is expressed in the patient’s enteric nervous system (ENS), which regulates gut motility.
“While there are many antibodies that are helpful in identifying patients at risk for extraintestinal complications of this disease, markers that identify patients at higher risk for gastrointestinal complications are limited. Furthermore, the biological mechanisms that cause and perpetuate the progression of gastrointestinal disease in scleroderma are not well understood, making it challenging to distinguish between patients whose gastrointestinal disease will progress from those whose GI disease will remain stable/mild,” Zsuzsanna H. McMahan, MD, MHS, told this news organization in an email. Dr. McMahan is co–first author on the study along with Subhash Kulkarni, PhD. They conducted the research with colleagues when they both worked at Johns Hopkins University in Baltimore, Md.
When asked for comment, Kimberly Lakin, MD, MS, assistant professor of medicine at Weill Cornell Medicine and a rheumatologist at Hospital for Special Surgery, New York, called the study “interesting and novel.”
“Not only did [antigephyrin antibodies] correlate with the presence of lower GI symptoms, but also higher levels of antibodies correlated with worse lower GI symptoms. This suggests that not only could this antibody be used to predict who may have constipation and potentially need more aggressive GI interventions, but it may also be useful in quantifying GI severity in systemic sclerosis, although more research is still needed,” said Dr. Lakin, who was not involved with the research.
The study was published online in Arthritis & Rheumatology.
In the cross-sectional study, researchers identified gephyrin as an autoantigen in sera from a single patient with SSc by isolating it from immunoprecipitations performed with murine myenteric plexus neuron lysates, and then characterizing it by mass spectrometry and validating it in further assays. That patient had GI dysfunction but no defined SSc-associated autoantibodies.
Dr. McMahan and colleagues then investigated the prevalence of the autoantibody by screening the sera of 188 patients with SSc who presented consecutively to the Johns Hopkins Scleroderma Center between April 2016 and August 2017, as well as 40 controls, and compared GI symptom severity between antibody-positive and antibody-negative patients with SSc.
A total of 16 (8.5%) of the 188 patients with SSc had antigephyrin antibodies, compared with none of the controls. Of these 16 patients, 4 had no other defined SSc antibodies. In the SSc cohort, severe constipation was more common in antigephyrin antibody–positive patients, compared with antibody-negative patients (46% vs. 15%). Antibody-positive patients also had higher constipation scores, and severe distension and bloating occurred in the antibody-positive group more than twice as often (54% vs. 25%).
Patients with severe constipation, distention, and bloating had higher antigephyrin antibody levels. After adjusting for confounders such as disease duration, patients with severe constipation were nearly five times as likely (odds ratio, 4.74; P = .010) to be antigephyrin antibody–positive, and patients with severe distention and bloating were nearly four times as likely (OR, 3.71; P = .027) to be antibody-positive.
Last, the authors showed via immunohistochemistry that gephyrin is expressed in the myenteric ganglia of human GI tissue.
“Gastrointestinal function is highly regulated by the ENS, so it is interesting that antibodies that target a protein expressed by ENS cells (gephyrin) were identified in patients with scleroderma who have severe lower bowel dysfunction,” said Dr. McMahan, who is associate professor in the division of rheumatology and codirector of the scleroderma program at the University of Texas Health Science Center at Houston. “Gephyrin is a key mediator of normal communications between nerves in the gut, so it is tantalizing to speculate that autoimmune-mediated disruption (e.g., an inhibitory or blocking antibody) in neural (ENS) communications in the gut might lead to impaired bowel transit and prominent constipation.”
The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and other NIH grants, as well as the Scleroderma Research Foundation, Rheumatology Research Foundation, Jerome L. Greene Foundation, Martha McCrory Professorship, and Chresanthe Stauraluakis Memorial Discovery Fund. The study authors and Dr. Lakin report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(SSc), new research suggests. Researchers also found that gephyrin is expressed in the patient’s enteric nervous system (ENS), which regulates gut motility.
“While there are many antibodies that are helpful in identifying patients at risk for extraintestinal complications of this disease, markers that identify patients at higher risk for gastrointestinal complications are limited. Furthermore, the biological mechanisms that cause and perpetuate the progression of gastrointestinal disease in scleroderma are not well understood, making it challenging to distinguish between patients whose gastrointestinal disease will progress from those whose GI disease will remain stable/mild,” Zsuzsanna H. McMahan, MD, MHS, told this news organization in an email. Dr. McMahan is co–first author on the study along with Subhash Kulkarni, PhD. They conducted the research with colleagues when they both worked at Johns Hopkins University in Baltimore, Md.
When asked for comment, Kimberly Lakin, MD, MS, assistant professor of medicine at Weill Cornell Medicine and a rheumatologist at Hospital for Special Surgery, New York, called the study “interesting and novel.”
“Not only did [antigephyrin antibodies] correlate with the presence of lower GI symptoms, but also higher levels of antibodies correlated with worse lower GI symptoms. This suggests that not only could this antibody be used to predict who may have constipation and potentially need more aggressive GI interventions, but it may also be useful in quantifying GI severity in systemic sclerosis, although more research is still needed,” said Dr. Lakin, who was not involved with the research.
The study was published online in Arthritis & Rheumatology.
In the cross-sectional study, researchers identified gephyrin as an autoantigen in sera from a single patient with SSc by isolating it from immunoprecipitations performed with murine myenteric plexus neuron lysates, and then characterizing it by mass spectrometry and validating it in further assays. That patient had GI dysfunction but no defined SSc-associated autoantibodies.
Dr. McMahan and colleagues then investigated the prevalence of the autoantibody by screening the sera of 188 patients with SSc who presented consecutively to the Johns Hopkins Scleroderma Center between April 2016 and August 2017, as well as 40 controls, and compared GI symptom severity between antibody-positive and antibody-negative patients with SSc.
A total of 16 (8.5%) of the 188 patients with SSc had antigephyrin antibodies, compared with none of the controls. Of these 16 patients, 4 had no other defined SSc antibodies. In the SSc cohort, severe constipation was more common in antigephyrin antibody–positive patients, compared with antibody-negative patients (46% vs. 15%). Antibody-positive patients also had higher constipation scores, and severe distension and bloating occurred in the antibody-positive group more than twice as often (54% vs. 25%).
Patients with severe constipation, distention, and bloating had higher antigephyrin antibody levels. After adjusting for confounders such as disease duration, patients with severe constipation were nearly five times as likely (odds ratio, 4.74; P = .010) to be antigephyrin antibody–positive, and patients with severe distention and bloating were nearly four times as likely (OR, 3.71; P = .027) to be antibody-positive.
Last, the authors showed via immunohistochemistry that gephyrin is expressed in the myenteric ganglia of human GI tissue.
“Gastrointestinal function is highly regulated by the ENS, so it is interesting that antibodies that target a protein expressed by ENS cells (gephyrin) were identified in patients with scleroderma who have severe lower bowel dysfunction,” said Dr. McMahan, who is associate professor in the division of rheumatology and codirector of the scleroderma program at the University of Texas Health Science Center at Houston. “Gephyrin is a key mediator of normal communications between nerves in the gut, so it is tantalizing to speculate that autoimmune-mediated disruption (e.g., an inhibitory or blocking antibody) in neural (ENS) communications in the gut might lead to impaired bowel transit and prominent constipation.”
The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and other NIH grants, as well as the Scleroderma Research Foundation, Rheumatology Research Foundation, Jerome L. Greene Foundation, Martha McCrory Professorship, and Chresanthe Stauraluakis Memorial Discovery Fund. The study authors and Dr. Lakin report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ARTHRITIS & RHEUMATOLOGY
A 45-year-old White woman with no significant medical history presented with a 1-month history of lesions on the nose and right cheek
Cultures for bacteria, varicella zoster virus, herpes simplex virus, and mpox virus were all negative. A biopsy revealed suprabasilar acantholysis with follicular involvement in association with blister formation and inflammation. Direct immunofluorescence was positive for suprabasilar IgG and C3 deposition, consistent with pemphigus vulgaris (PV).
. There is likely a genetic predisposition. Medications that may induce pemphigus include penicillamine, nifedipine, or captopril.
Clinically, flaccid blistering lesions are present that may be cutaneous and/or mucosal. Bullae can progress to erosions and crusting, which then heal with pigment alteration but not scarring. The most commonly affected sites are the mouth, intertriginous areas, face, and neck. Mucosal lesions may involve the lips, esophagus, conjunctiva, and genitals.
Biopsy for histology and direct immunofluorescence is important in distinguishing between PV and other blistering disorders. Up to 75% of patients with active disease also have a positive indirect immunofluorescence with circulating IgG.
Treatment is generally immunosuppressive. Systemic therapy usually begins with prednisone and then is transitioned to a steroid-sparing agent such as mycophenolate mofetil. Other steroid-sparing agents include azathioprine, methotrexate, cyclophosphamide, and intravenous immunoglobulin. Secondary infections are possible and should be treated. Topical therapies aimed at reducing pain, especially in mucosal lesions, can be beneficial.
This case and the photos are from Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, 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].
Cultures for bacteria, varicella zoster virus, herpes simplex virus, and mpox virus were all negative. A biopsy revealed suprabasilar acantholysis with follicular involvement in association with blister formation and inflammation. Direct immunofluorescence was positive for suprabasilar IgG and C3 deposition, consistent with pemphigus vulgaris (PV).
. There is likely a genetic predisposition. Medications that may induce pemphigus include penicillamine, nifedipine, or captopril.
Clinically, flaccid blistering lesions are present that may be cutaneous and/or mucosal. Bullae can progress to erosions and crusting, which then heal with pigment alteration but not scarring. The most commonly affected sites are the mouth, intertriginous areas, face, and neck. Mucosal lesions may involve the lips, esophagus, conjunctiva, and genitals.
Biopsy for histology and direct immunofluorescence is important in distinguishing between PV and other blistering disorders. Up to 75% of patients with active disease also have a positive indirect immunofluorescence with circulating IgG.
Treatment is generally immunosuppressive. Systemic therapy usually begins with prednisone and then is transitioned to a steroid-sparing agent such as mycophenolate mofetil. Other steroid-sparing agents include azathioprine, methotrexate, cyclophosphamide, and intravenous immunoglobulin. Secondary infections are possible and should be treated. Topical therapies aimed at reducing pain, especially in mucosal lesions, can be beneficial.
This case and the photos are from Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, 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].
Cultures for bacteria, varicella zoster virus, herpes simplex virus, and mpox virus were all negative. A biopsy revealed suprabasilar acantholysis with follicular involvement in association with blister formation and inflammation. Direct immunofluorescence was positive for suprabasilar IgG and C3 deposition, consistent with pemphigus vulgaris (PV).
. There is likely a genetic predisposition. Medications that may induce pemphigus include penicillamine, nifedipine, or captopril.
Clinically, flaccid blistering lesions are present that may be cutaneous and/or mucosal. Bullae can progress to erosions and crusting, which then heal with pigment alteration but not scarring. The most commonly affected sites are the mouth, intertriginous areas, face, and neck. Mucosal lesions may involve the lips, esophagus, conjunctiva, and genitals.
Biopsy for histology and direct immunofluorescence is important in distinguishing between PV and other blistering disorders. Up to 75% of patients with active disease also have a positive indirect immunofluorescence with circulating IgG.
Treatment is generally immunosuppressive. Systemic therapy usually begins with prednisone and then is transitioned to a steroid-sparing agent such as mycophenolate mofetil. Other steroid-sparing agents include azathioprine, methotrexate, cyclophosphamide, and intravenous immunoglobulin. Secondary infections are possible and should be treated. Topical therapies aimed at reducing pain, especially in mucosal lesions, can be beneficial.
This case and the photos are from Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, 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].
Black women weigh emerging risks of ‘creamy crack’ hair straighteners
Deanna Denham Hughes was stunned when she was diagnosed with ovarian cancer in 2022. She was only 32. She had no family history of cancer, and tests found no genetic link. Ms. Hughes wondered why she, an otherwise healthy Black mother of two, would develop a malignancy known as a “silent killer.”
After emergency surgery to remove the mass, along with her ovaries, uterus, fallopian tubes, and appendix, Ms. Hughes said, she saw an Instagram post in which a woman with uterine cancer linked her condition to chemical hair straighteners.
“I almost fell over,” she said from her home in Smyrna, Ga.
When Ms. Hughes was about 4, her mother began applying a chemical straightener, or relaxer, to her hair every 6-8 weeks. “It burned, and it smelled awful,” Ms. Hughes recalled. “But it was just part of our routine to ‘deal with my hair.’ ”
The routine continued until she went to college and met other Black women who wore their hair naturally. Soon, Ms. Hughes quit relaxers.
Social and economic pressures have long compelled Black girls and women to straighten their hair to conform to Eurocentric beauty standards. But chemical straighteners are stinky and costly and sometimes cause painful scalp burns. Mounting evidence now shows they could be a health hazard.
Relaxers can contain carcinogens, such as formaldehyde-releasing agents, phthalates, and other endocrine-disrupting compounds, according to National Institutes of Health studies. The compounds can mimic the body’s hormones and have been linked to breast, uterine, and ovarian cancers, studies show.
African American women’s often frequent and lifelong application of chemical relaxers to their hair and scalp might explain why hormone-related cancers kill disproportionately more Black than White women, say researchers and cancer doctors.
“What’s in these products is harmful,” said Tamarra James-Todd, PhD, an epidemiology professor at Harvard T.H. Chan School of Public Health, Boston, who has studied straightening products for the past 20 years.
She believes manufacturers, policymakers, and physicians should warn consumers that relaxers might cause cancer and other health problems.
But regulators have been slow to act, physicians have been reluctant to take up the cause, and racism continues to dictate fashion standards that make it tough for women to quit relaxers, products so addictive they’re known as “creamy crack.”
Michelle Obama straightened her hair when Barack Obama served as president because she believed Americans were “not ready” to see her in braids, the former first lady said after leaving the White House. The U.S. military still prohibited popular Black hairstyles such as dreadlocks and twists while the nation’s first Black president was in office.
California in 2019 became the first of nearly two dozen states to ban race-based hair discrimination. Last year, the U.S. House of Representatives passed similar legislation, known as the CROWN Act, for Creating a Respectful and Open World for Natural Hair. But the bill failed in the Senate.
The need for legislation underscores the challenges Black girls and women face at school and in the workplace.
“You have to pick your struggles,” said Atlanta-based surgical oncologist Ryland J. Gore, MD. She informs her breast cancer patients about the increased cancer risk from relaxers. Despite her knowledge, however, Dr. Gore continues to use chemical straighteners on her own hair, as she has since she was about 7 years old.
“Your hair tells a story,” she said.
In conversations with patients, Dr. Gore sometimes talks about how African American women once wove messages into their braids about the route to take on the Underground Railroad as they sought freedom from slavery.
“It’s just a deep discussion,” one that touches on culture, history, and research into current hairstyling practices, she said. “The data is out there. So patients should be warned, and then they can make a decision.”
The first hint of a connection between hair products and health issues surfaced in the 1990s. Doctors began seeing signs of sexual maturation in Black babies and young girls who developed breasts and pubic hair after using shampoo containing estrogen or placental extract. When the girls stopped using the shampoo, the hair and breast development receded, according to a study published in the journal Clinical Pediatrics in 1998.
Since then, Dr. James-Todd and other researchers have linked chemicals in hair products to a variety of health issues more prevalent among Black women – from early puberty to preterm birth, obesity, and diabetes.
In recent years, researchers have focused on a possible connection between ingredients in chemical relaxers and hormone-related cancers, like the one Ms. Hughes developed, which tend to be more aggressive and deadly in Black women.
A 2017 study found White women who used chemical relaxers were nearly twice as likely to develop breast cancer as those who did not use them. Because the vast majority of the Black study participants used relaxers, researchers could not effectively test the association in Black women, said lead author Adana Llanos, PhD, associate professor of epidemiology at Columbia University’s Mailman School of Public Health, New York.
Researchers did test it in 2020.
The so-called Sister Study, a landmark National Institute of Environmental Health Sciences investigation into the causes of breast cancer and related diseases, followed 50,000 U.S. women whose sisters had been diagnosed with breast cancer and who were cancer-free when they enrolled. Regardless of race, women who reported using relaxers in the prior year were 18% more likely to be diagnosed with breast cancer. Those who used relaxers at least every 5-8 weeks had a 31% higher breast cancer risk.
Nearly 75% of the Black sisters used relaxers in the prior year, compared with 3% of the non-Hispanic White sisters. Three-quarters of Black women self-reported using the straighteners as adolescents, and frequent use of chemical straighteners during adolescence raised the risk of premenopausal breast cancer, a 2021 NIH-funded study in the International Journal of Cancer found.
Another 2021 analysis of the Sister Study data showed sisters who self-reported that they frequently used relaxers or pressing products doubled their ovarian cancer risk. In 2022, another study found frequent use more than doubled uterine cancer risk.
After researchers discovered the link with uterine cancer, some called for policy changes and other measures to reduce exposure to chemical relaxers.
“It is time to intervene,” Dr. Llanos and her colleagues wrote in a Journal of the National Cancer Institute editorial accompanying the uterine cancer analysis. While acknowledging the need for more research, they issued a “call for action.”
No one can say that using permanent hair straighteners will give you cancer, Dr. Llanos said in an interview. “That’s not how cancer works,” she said, noting that some smokers never develop lung cancer, despite tobacco use being a known risk factor.
The body of research linking hair straighteners and cancer is more limited, said Dr. Llanos, who quit using chemical relaxers 15 years ago. But, she asked rhetorically, “Do we need to do the research for 50 more years to know that chemical relaxers are harmful?”
Charlotte R. Gamble, MD, a gynecological oncologist whose Washington, D.C., practice includes Black women with uterine and ovarian cancer, said she and her colleagues see the uterine cancer study findings as worthy of further exploration – but not yet worthy of discussion with patients.
“The jury’s out for me personally,” she said. “There’s so much more data that’s needed.”
Meanwhile, Dr. James-Todd and other researchers believe they have built a solid body of evidence.
“There are enough things we do know to begin taking action, developing interventions, providing useful information to clinicians and patients and the general public,” said Traci N. Bethea, PhD, assistant professor in the Office of Minority Health and Health Disparities Research at Georgetown University.
Responsibility for regulating personal-care products, including chemical hair straighteners and hair dyes – which also have been linked to hormone-related cancers – lies with the Food and Drug Administration. But the FDA does not subject personal-care products to the same approval process it uses for food and drugs. The FDA restricts only 11 categories of chemicals used in cosmetics, while concerns about health effects have prompted the European Union to restrict the use of at least 2,400 substances.
In March, Reps. Ayanna Pressley (D-Mass.) and Shontel Brown (D-Ohio) asked the FDA to investigate the potential health threat posed by chemical relaxers. An FDA representative said the agency would look into it.
Natural hairstyles are enjoying a resurgence among Black girls and women, but many continue to rely on the creamy crack, said Dede Teteh, DrPH, assistant professor of public health at Chapman University, Irvine, Calif.
She had her first straightening perm at 8 and has struggled to withdraw from relaxers as an adult, said Dr. Teteh, who now wears locs. Not long ago, she considered chemically straightening her hair for an academic job interview because she didn’t want her hair to “be a hindrance” when she appeared before White professors.
Dr. Teteh led “The Cost of Beauty,” a hair-health research project published in 2017. She and her team interviewed 91 Black women in Southern California. Some became “combative” at the idea of quitting relaxers and claimed “everything can cause cancer.”
Their reactions speak to the challenges Black women face in America, Dr. Teteh said.
“It’s not that people do not want to hear the information related to their health,” she said. “But they want people to share the information in a way that it’s really empathetic to the plight of being Black here in the United States.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.
Deanna Denham Hughes was stunned when she was diagnosed with ovarian cancer in 2022. She was only 32. She had no family history of cancer, and tests found no genetic link. Ms. Hughes wondered why she, an otherwise healthy Black mother of two, would develop a malignancy known as a “silent killer.”
After emergency surgery to remove the mass, along with her ovaries, uterus, fallopian tubes, and appendix, Ms. Hughes said, she saw an Instagram post in which a woman with uterine cancer linked her condition to chemical hair straighteners.
“I almost fell over,” she said from her home in Smyrna, Ga.
When Ms. Hughes was about 4, her mother began applying a chemical straightener, or relaxer, to her hair every 6-8 weeks. “It burned, and it smelled awful,” Ms. Hughes recalled. “But it was just part of our routine to ‘deal with my hair.’ ”
The routine continued until she went to college and met other Black women who wore their hair naturally. Soon, Ms. Hughes quit relaxers.
Social and economic pressures have long compelled Black girls and women to straighten their hair to conform to Eurocentric beauty standards. But chemical straighteners are stinky and costly and sometimes cause painful scalp burns. Mounting evidence now shows they could be a health hazard.
Relaxers can contain carcinogens, such as formaldehyde-releasing agents, phthalates, and other endocrine-disrupting compounds, according to National Institutes of Health studies. The compounds can mimic the body’s hormones and have been linked to breast, uterine, and ovarian cancers, studies show.
African American women’s often frequent and lifelong application of chemical relaxers to their hair and scalp might explain why hormone-related cancers kill disproportionately more Black than White women, say researchers and cancer doctors.
“What’s in these products is harmful,” said Tamarra James-Todd, PhD, an epidemiology professor at Harvard T.H. Chan School of Public Health, Boston, who has studied straightening products for the past 20 years.
She believes manufacturers, policymakers, and physicians should warn consumers that relaxers might cause cancer and other health problems.
But regulators have been slow to act, physicians have been reluctant to take up the cause, and racism continues to dictate fashion standards that make it tough for women to quit relaxers, products so addictive they’re known as “creamy crack.”
Michelle Obama straightened her hair when Barack Obama served as president because she believed Americans were “not ready” to see her in braids, the former first lady said after leaving the White House. The U.S. military still prohibited popular Black hairstyles such as dreadlocks and twists while the nation’s first Black president was in office.
California in 2019 became the first of nearly two dozen states to ban race-based hair discrimination. Last year, the U.S. House of Representatives passed similar legislation, known as the CROWN Act, for Creating a Respectful and Open World for Natural Hair. But the bill failed in the Senate.
The need for legislation underscores the challenges Black girls and women face at school and in the workplace.
“You have to pick your struggles,” said Atlanta-based surgical oncologist Ryland J. Gore, MD. She informs her breast cancer patients about the increased cancer risk from relaxers. Despite her knowledge, however, Dr. Gore continues to use chemical straighteners on her own hair, as she has since she was about 7 years old.
“Your hair tells a story,” she said.
In conversations with patients, Dr. Gore sometimes talks about how African American women once wove messages into their braids about the route to take on the Underground Railroad as they sought freedom from slavery.
“It’s just a deep discussion,” one that touches on culture, history, and research into current hairstyling practices, she said. “The data is out there. So patients should be warned, and then they can make a decision.”
The first hint of a connection between hair products and health issues surfaced in the 1990s. Doctors began seeing signs of sexual maturation in Black babies and young girls who developed breasts and pubic hair after using shampoo containing estrogen or placental extract. When the girls stopped using the shampoo, the hair and breast development receded, according to a study published in the journal Clinical Pediatrics in 1998.
Since then, Dr. James-Todd and other researchers have linked chemicals in hair products to a variety of health issues more prevalent among Black women – from early puberty to preterm birth, obesity, and diabetes.
In recent years, researchers have focused on a possible connection between ingredients in chemical relaxers and hormone-related cancers, like the one Ms. Hughes developed, which tend to be more aggressive and deadly in Black women.
A 2017 study found White women who used chemical relaxers were nearly twice as likely to develop breast cancer as those who did not use them. Because the vast majority of the Black study participants used relaxers, researchers could not effectively test the association in Black women, said lead author Adana Llanos, PhD, associate professor of epidemiology at Columbia University’s Mailman School of Public Health, New York.
Researchers did test it in 2020.
The so-called Sister Study, a landmark National Institute of Environmental Health Sciences investigation into the causes of breast cancer and related diseases, followed 50,000 U.S. women whose sisters had been diagnosed with breast cancer and who were cancer-free when they enrolled. Regardless of race, women who reported using relaxers in the prior year were 18% more likely to be diagnosed with breast cancer. Those who used relaxers at least every 5-8 weeks had a 31% higher breast cancer risk.
Nearly 75% of the Black sisters used relaxers in the prior year, compared with 3% of the non-Hispanic White sisters. Three-quarters of Black women self-reported using the straighteners as adolescents, and frequent use of chemical straighteners during adolescence raised the risk of premenopausal breast cancer, a 2021 NIH-funded study in the International Journal of Cancer found.
Another 2021 analysis of the Sister Study data showed sisters who self-reported that they frequently used relaxers or pressing products doubled their ovarian cancer risk. In 2022, another study found frequent use more than doubled uterine cancer risk.
After researchers discovered the link with uterine cancer, some called for policy changes and other measures to reduce exposure to chemical relaxers.
“It is time to intervene,” Dr. Llanos and her colleagues wrote in a Journal of the National Cancer Institute editorial accompanying the uterine cancer analysis. While acknowledging the need for more research, they issued a “call for action.”
No one can say that using permanent hair straighteners will give you cancer, Dr. Llanos said in an interview. “That’s not how cancer works,” she said, noting that some smokers never develop lung cancer, despite tobacco use being a known risk factor.
The body of research linking hair straighteners and cancer is more limited, said Dr. Llanos, who quit using chemical relaxers 15 years ago. But, she asked rhetorically, “Do we need to do the research for 50 more years to know that chemical relaxers are harmful?”
Charlotte R. Gamble, MD, a gynecological oncologist whose Washington, D.C., practice includes Black women with uterine and ovarian cancer, said she and her colleagues see the uterine cancer study findings as worthy of further exploration – but not yet worthy of discussion with patients.
“The jury’s out for me personally,” she said. “There’s so much more data that’s needed.”
Meanwhile, Dr. James-Todd and other researchers believe they have built a solid body of evidence.
“There are enough things we do know to begin taking action, developing interventions, providing useful information to clinicians and patients and the general public,” said Traci N. Bethea, PhD, assistant professor in the Office of Minority Health and Health Disparities Research at Georgetown University.
Responsibility for regulating personal-care products, including chemical hair straighteners and hair dyes – which also have been linked to hormone-related cancers – lies with the Food and Drug Administration. But the FDA does not subject personal-care products to the same approval process it uses for food and drugs. The FDA restricts only 11 categories of chemicals used in cosmetics, while concerns about health effects have prompted the European Union to restrict the use of at least 2,400 substances.
In March, Reps. Ayanna Pressley (D-Mass.) and Shontel Brown (D-Ohio) asked the FDA to investigate the potential health threat posed by chemical relaxers. An FDA representative said the agency would look into it.
Natural hairstyles are enjoying a resurgence among Black girls and women, but many continue to rely on the creamy crack, said Dede Teteh, DrPH, assistant professor of public health at Chapman University, Irvine, Calif.
She had her first straightening perm at 8 and has struggled to withdraw from relaxers as an adult, said Dr. Teteh, who now wears locs. Not long ago, she considered chemically straightening her hair for an academic job interview because she didn’t want her hair to “be a hindrance” when she appeared before White professors.
Dr. Teteh led “The Cost of Beauty,” a hair-health research project published in 2017. She and her team interviewed 91 Black women in Southern California. Some became “combative” at the idea of quitting relaxers and claimed “everything can cause cancer.”
Their reactions speak to the challenges Black women face in America, Dr. Teteh said.
“It’s not that people do not want to hear the information related to their health,” she said. “But they want people to share the information in a way that it’s really empathetic to the plight of being Black here in the United States.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.
Deanna Denham Hughes was stunned when she was diagnosed with ovarian cancer in 2022. She was only 32. She had no family history of cancer, and tests found no genetic link. Ms. Hughes wondered why she, an otherwise healthy Black mother of two, would develop a malignancy known as a “silent killer.”
After emergency surgery to remove the mass, along with her ovaries, uterus, fallopian tubes, and appendix, Ms. Hughes said, she saw an Instagram post in which a woman with uterine cancer linked her condition to chemical hair straighteners.
“I almost fell over,” she said from her home in Smyrna, Ga.
When Ms. Hughes was about 4, her mother began applying a chemical straightener, or relaxer, to her hair every 6-8 weeks. “It burned, and it smelled awful,” Ms. Hughes recalled. “But it was just part of our routine to ‘deal with my hair.’ ”
The routine continued until she went to college and met other Black women who wore their hair naturally. Soon, Ms. Hughes quit relaxers.
Social and economic pressures have long compelled Black girls and women to straighten their hair to conform to Eurocentric beauty standards. But chemical straighteners are stinky and costly and sometimes cause painful scalp burns. Mounting evidence now shows they could be a health hazard.
Relaxers can contain carcinogens, such as formaldehyde-releasing agents, phthalates, and other endocrine-disrupting compounds, according to National Institutes of Health studies. The compounds can mimic the body’s hormones and have been linked to breast, uterine, and ovarian cancers, studies show.
African American women’s often frequent and lifelong application of chemical relaxers to their hair and scalp might explain why hormone-related cancers kill disproportionately more Black than White women, say researchers and cancer doctors.
“What’s in these products is harmful,” said Tamarra James-Todd, PhD, an epidemiology professor at Harvard T.H. Chan School of Public Health, Boston, who has studied straightening products for the past 20 years.
She believes manufacturers, policymakers, and physicians should warn consumers that relaxers might cause cancer and other health problems.
But regulators have been slow to act, physicians have been reluctant to take up the cause, and racism continues to dictate fashion standards that make it tough for women to quit relaxers, products so addictive they’re known as “creamy crack.”
Michelle Obama straightened her hair when Barack Obama served as president because she believed Americans were “not ready” to see her in braids, the former first lady said after leaving the White House. The U.S. military still prohibited popular Black hairstyles such as dreadlocks and twists while the nation’s first Black president was in office.
California in 2019 became the first of nearly two dozen states to ban race-based hair discrimination. Last year, the U.S. House of Representatives passed similar legislation, known as the CROWN Act, for Creating a Respectful and Open World for Natural Hair. But the bill failed in the Senate.
The need for legislation underscores the challenges Black girls and women face at school and in the workplace.
“You have to pick your struggles,” said Atlanta-based surgical oncologist Ryland J. Gore, MD. She informs her breast cancer patients about the increased cancer risk from relaxers. Despite her knowledge, however, Dr. Gore continues to use chemical straighteners on her own hair, as she has since she was about 7 years old.
“Your hair tells a story,” she said.
In conversations with patients, Dr. Gore sometimes talks about how African American women once wove messages into their braids about the route to take on the Underground Railroad as they sought freedom from slavery.
“It’s just a deep discussion,” one that touches on culture, history, and research into current hairstyling practices, she said. “The data is out there. So patients should be warned, and then they can make a decision.”
The first hint of a connection between hair products and health issues surfaced in the 1990s. Doctors began seeing signs of sexual maturation in Black babies and young girls who developed breasts and pubic hair after using shampoo containing estrogen or placental extract. When the girls stopped using the shampoo, the hair and breast development receded, according to a study published in the journal Clinical Pediatrics in 1998.
Since then, Dr. James-Todd and other researchers have linked chemicals in hair products to a variety of health issues more prevalent among Black women – from early puberty to preterm birth, obesity, and diabetes.
In recent years, researchers have focused on a possible connection between ingredients in chemical relaxers and hormone-related cancers, like the one Ms. Hughes developed, which tend to be more aggressive and deadly in Black women.
A 2017 study found White women who used chemical relaxers were nearly twice as likely to develop breast cancer as those who did not use them. Because the vast majority of the Black study participants used relaxers, researchers could not effectively test the association in Black women, said lead author Adana Llanos, PhD, associate professor of epidemiology at Columbia University’s Mailman School of Public Health, New York.
Researchers did test it in 2020.
The so-called Sister Study, a landmark National Institute of Environmental Health Sciences investigation into the causes of breast cancer and related diseases, followed 50,000 U.S. women whose sisters had been diagnosed with breast cancer and who were cancer-free when they enrolled. Regardless of race, women who reported using relaxers in the prior year were 18% more likely to be diagnosed with breast cancer. Those who used relaxers at least every 5-8 weeks had a 31% higher breast cancer risk.
Nearly 75% of the Black sisters used relaxers in the prior year, compared with 3% of the non-Hispanic White sisters. Three-quarters of Black women self-reported using the straighteners as adolescents, and frequent use of chemical straighteners during adolescence raised the risk of premenopausal breast cancer, a 2021 NIH-funded study in the International Journal of Cancer found.
Another 2021 analysis of the Sister Study data showed sisters who self-reported that they frequently used relaxers or pressing products doubled their ovarian cancer risk. In 2022, another study found frequent use more than doubled uterine cancer risk.
After researchers discovered the link with uterine cancer, some called for policy changes and other measures to reduce exposure to chemical relaxers.
“It is time to intervene,” Dr. Llanos and her colleagues wrote in a Journal of the National Cancer Institute editorial accompanying the uterine cancer analysis. While acknowledging the need for more research, they issued a “call for action.”
No one can say that using permanent hair straighteners will give you cancer, Dr. Llanos said in an interview. “That’s not how cancer works,” she said, noting that some smokers never develop lung cancer, despite tobacco use being a known risk factor.
The body of research linking hair straighteners and cancer is more limited, said Dr. Llanos, who quit using chemical relaxers 15 years ago. But, she asked rhetorically, “Do we need to do the research for 50 more years to know that chemical relaxers are harmful?”
Charlotte R. Gamble, MD, a gynecological oncologist whose Washington, D.C., practice includes Black women with uterine and ovarian cancer, said she and her colleagues see the uterine cancer study findings as worthy of further exploration – but not yet worthy of discussion with patients.
“The jury’s out for me personally,” she said. “There’s so much more data that’s needed.”
Meanwhile, Dr. James-Todd and other researchers believe they have built a solid body of evidence.
“There are enough things we do know to begin taking action, developing interventions, providing useful information to clinicians and patients and the general public,” said Traci N. Bethea, PhD, assistant professor in the Office of Minority Health and Health Disparities Research at Georgetown University.
Responsibility for regulating personal-care products, including chemical hair straighteners and hair dyes – which also have been linked to hormone-related cancers – lies with the Food and Drug Administration. But the FDA does not subject personal-care products to the same approval process it uses for food and drugs. The FDA restricts only 11 categories of chemicals used in cosmetics, while concerns about health effects have prompted the European Union to restrict the use of at least 2,400 substances.
In March, Reps. Ayanna Pressley (D-Mass.) and Shontel Brown (D-Ohio) asked the FDA to investigate the potential health threat posed by chemical relaxers. An FDA representative said the agency would look into it.
Natural hairstyles are enjoying a resurgence among Black girls and women, but many continue to rely on the creamy crack, said Dede Teteh, DrPH, assistant professor of public health at Chapman University, Irvine, Calif.
She had her first straightening perm at 8 and has struggled to withdraw from relaxers as an adult, said Dr. Teteh, who now wears locs. Not long ago, she considered chemically straightening her hair for an academic job interview because she didn’t want her hair to “be a hindrance” when she appeared before White professors.
Dr. Teteh led “The Cost of Beauty,” a hair-health research project published in 2017. She and her team interviewed 91 Black women in Southern California. Some became “combative” at the idea of quitting relaxers and claimed “everything can cause cancer.”
Their reactions speak to the challenges Black women face in America, Dr. Teteh said.
“It’s not that people do not want to hear the information related to their health,” she said. “But they want people to share the information in a way that it’s really empathetic to the plight of being Black here in the United States.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.
Many users of skin-lightening product unaware of risks
, a recent cross-sectional survey suggests.
Skin lightening – which uses chemicals to lighten dark areas of skin or to generally lighten skin tone – poses a health risk from potentially unsafe formulations, the authors write in the International Journal of Women’s Dermatology.
Skin lightening is “influenced by colorism, the system of inequality that affords opportunities and privileges to lighter-skinned individuals across racial/ethnic groups,” they add. “Women, in particular, are vulnerable as media and popular culture propagate beauty standards that lighter skin can elevate physical appearance and social acceptance.”
“It is important to recognize that the primary motivator for skin lightening is most often dermatological disease but that, less frequently, it can be colorism,” senior study author Roopal V. Kundu, MD, professor of dermatology and founding director of the Northwestern Center for Ethnic Skin and Hair at Northwestern University, Chicago, said in an email interview.
Skin lightening is a growing, multibillion-dollar, largely unregulated, global industry. Rates have been estimated at 27% in South Africa, 40% in China and South Korea, 77% in Nigeria, but U.S. rates are unknown.
To investigate skin-lightening habits and the role colorism plays in skin-lightening practices in the United States, Dr. Kundu and her colleagues sent an online survey to 578 adults with darker skin who participated in ResearchMatch, a national health registry supported by the National Institutes of Health that connects volunteers with research studies they choose to take part in.
Of the 455 people who completed the 19-item anonymous questionnaire, 238 (52.3%) identified as Black or African American, 83 (18.2%) as Asian, 84 (18.5%) as multiracial, 31 (6.8%) as Hispanic, 14 (3.1%) as American Indian or Alaska Native, and 5 (1.1%) as other. Overall, 364 (80.0%) were women.
The survey asked about demographics, colorism attitudes, skin tone satisfaction, and skin-lightening product use. To assess colorism attitudes, the researchers asked respondents to rate six colorism statements on a Likert scale of 1 (strongly disagree) to 5 (strongly agree). The statements included “Lighter skin tone increases one’s self-esteem,” and “Lighter skin tone increases one’s chance of having a romantic relationship or getting married.” The researchers also asked them to rate their skin satisfaction levels on a Likert scale from 1 (very unsatisfied) to 5 (very satisfied).
Used mostly to treat skin conditions
Despite a lack of medical input, about three-quarters of people who used skin-lightening products reported using them for medical conditions, and around one-quarter used them for general lightening, the researchers report.
Of all respondents, 97 (21.3%) reported using skin-lightening agents. Of them, 71 (73.2%) used them to treat a skin condition such as acne, melasma, or postinflammatory hyperpigmentation, and 26 (26.8% of skin-lightening product users; 5.7% of all respondents) used them for generalized skin lightening.
The 97 users mostly obtained skin-lightening products from chain pharmacy and grocery stores, and also from community beauty stores, abroad, online, and medical providers, while two made them at home.
Skin-lightening product use did not differ with age, gender, race or ethnicity, education level, or immigration status.
Only 22 (22.7%) of the product users consulted a medical provider before using the products, and only 14 (14.4%) received skin-lightening products from medical providers.
In addition, 44 respondents (45.4%) could not identify the active ingredient in their skin-lightening products, but 34 (35.1%) reported using hydroquinone-based products. Other reported active ingredients included ascorbic acid, glycolic acid, salicylic acid, niacinamide, steroids, and mercury.
The face (86 people or 88.7%) and neck (37 or 38.1%) were the most common application sites.
Skin-lightening users were more likely to report that lighter skin was more beautiful and that it increased self-esteem and romantic prospects (P < .001 for all).
Elma Baron, MD, professor of dermatology at Case Western Reserve University, Cleveland, advised doctors to remind patients to consult a dermatologist before they use skin-lightening agents. “A dermatologist can evaluate whether there is a true indication for skin-lightening agents and explain the benefits, risks, and limitations of common skin-lightening formulations.
“When dealing with hyperpigmentation, clinicians should remember that ultraviolet light is a potent stimulus for melanogenesis,” added Dr. Baron by email. She was not involved in the study. “Wearing hats and other sun-protective clothing, using sunscreen, and avoiding sunlight during peak hours must always be emphasized.”
Amy J. McMichael, MD, professor of dermatology at Wake Forest University, Winston-Salem, N.C., often sees patients who try products based on persuasive advertising, not scientific benefit, she said by email.
“The findings are important, because many primary care providers and dermatologists do not realize that patients will use skin-lightening agents simply to provide a glow and in an attempt to attain complexion blending,” added Dr. McMichael, also not involved in the study.
She encouraged doctors to understand what motivates their patients to use skin-lightening agents, so they can effectively communicate what works and what does not work for their condition, as well as inform them about potential risks.
Strengths of the study, Dr. McMichael said, are the number of people surveyed and the inclusion of colorism data not typically gathered in studies of skin-lightening product use. Limitations include whether the reported conditions were what people actually had, and that, with over 50% of respondents being Black, the results may not be generalizable to other groups.
“Colorism is complex,” Dr. Kundu noted. “Dermatologists need to recognize how colorism impacts their patients, so they can provide them with culturally mindful care and deter them from using potentially harmful products.”
Illegal products may still be available
Dr. McMichael would like to know how many of these patients used products containing > 4%-strength hydroquinone, because they “can be dangerous, and patients don’t understand how these higher-strength medications can damage the skin.”
“Following the Coronavirus Aid, Relief, and Economic Security [CARES] Act of 2020, over-the-counter hydroquinone sales were prohibited in the U.S.,” the authors write. In 2022, the Food and Drug Administration issued warning letters to 12 companies that sold products containing unsafe concentrations of hydroquinone, because of concerns about swelling, rashes, and discoloration. Hydroquinone has also been linked with skin cancer.
“However, this study demonstrates that consumers in the U.S. may still have access to hydroquinone formulations,” the authors caution.
At its Skin Facts! Resources website, the FDA warns about potentially harmful over-the-counter skin-lightening products containing hydroquinone or mercury and recommends using only prescribed products. The information site was created by the FDA Office of Minority Health and Health Equity.
The study authors, Dr. Baron, and Dr. McMichael report no relevant financial relationships. The study did not receive external funding. All experts commented by email.
, a recent cross-sectional survey suggests.
Skin lightening – which uses chemicals to lighten dark areas of skin or to generally lighten skin tone – poses a health risk from potentially unsafe formulations, the authors write in the International Journal of Women’s Dermatology.
Skin lightening is “influenced by colorism, the system of inequality that affords opportunities and privileges to lighter-skinned individuals across racial/ethnic groups,” they add. “Women, in particular, are vulnerable as media and popular culture propagate beauty standards that lighter skin can elevate physical appearance and social acceptance.”
“It is important to recognize that the primary motivator for skin lightening is most often dermatological disease but that, less frequently, it can be colorism,” senior study author Roopal V. Kundu, MD, professor of dermatology and founding director of the Northwestern Center for Ethnic Skin and Hair at Northwestern University, Chicago, said in an email interview.
Skin lightening is a growing, multibillion-dollar, largely unregulated, global industry. Rates have been estimated at 27% in South Africa, 40% in China and South Korea, 77% in Nigeria, but U.S. rates are unknown.
To investigate skin-lightening habits and the role colorism plays in skin-lightening practices in the United States, Dr. Kundu and her colleagues sent an online survey to 578 adults with darker skin who participated in ResearchMatch, a national health registry supported by the National Institutes of Health that connects volunteers with research studies they choose to take part in.
Of the 455 people who completed the 19-item anonymous questionnaire, 238 (52.3%) identified as Black or African American, 83 (18.2%) as Asian, 84 (18.5%) as multiracial, 31 (6.8%) as Hispanic, 14 (3.1%) as American Indian or Alaska Native, and 5 (1.1%) as other. Overall, 364 (80.0%) were women.
The survey asked about demographics, colorism attitudes, skin tone satisfaction, and skin-lightening product use. To assess colorism attitudes, the researchers asked respondents to rate six colorism statements on a Likert scale of 1 (strongly disagree) to 5 (strongly agree). The statements included “Lighter skin tone increases one’s self-esteem,” and “Lighter skin tone increases one’s chance of having a romantic relationship or getting married.” The researchers also asked them to rate their skin satisfaction levels on a Likert scale from 1 (very unsatisfied) to 5 (very satisfied).
Used mostly to treat skin conditions
Despite a lack of medical input, about three-quarters of people who used skin-lightening products reported using them for medical conditions, and around one-quarter used them for general lightening, the researchers report.
Of all respondents, 97 (21.3%) reported using skin-lightening agents. Of them, 71 (73.2%) used them to treat a skin condition such as acne, melasma, or postinflammatory hyperpigmentation, and 26 (26.8% of skin-lightening product users; 5.7% of all respondents) used them for generalized skin lightening.
The 97 users mostly obtained skin-lightening products from chain pharmacy and grocery stores, and also from community beauty stores, abroad, online, and medical providers, while two made them at home.
Skin-lightening product use did not differ with age, gender, race or ethnicity, education level, or immigration status.
Only 22 (22.7%) of the product users consulted a medical provider before using the products, and only 14 (14.4%) received skin-lightening products from medical providers.
In addition, 44 respondents (45.4%) could not identify the active ingredient in their skin-lightening products, but 34 (35.1%) reported using hydroquinone-based products. Other reported active ingredients included ascorbic acid, glycolic acid, salicylic acid, niacinamide, steroids, and mercury.
The face (86 people or 88.7%) and neck (37 or 38.1%) were the most common application sites.
Skin-lightening users were more likely to report that lighter skin was more beautiful and that it increased self-esteem and romantic prospects (P < .001 for all).
Elma Baron, MD, professor of dermatology at Case Western Reserve University, Cleveland, advised doctors to remind patients to consult a dermatologist before they use skin-lightening agents. “A dermatologist can evaluate whether there is a true indication for skin-lightening agents and explain the benefits, risks, and limitations of common skin-lightening formulations.
“When dealing with hyperpigmentation, clinicians should remember that ultraviolet light is a potent stimulus for melanogenesis,” added Dr. Baron by email. She was not involved in the study. “Wearing hats and other sun-protective clothing, using sunscreen, and avoiding sunlight during peak hours must always be emphasized.”
Amy J. McMichael, MD, professor of dermatology at Wake Forest University, Winston-Salem, N.C., often sees patients who try products based on persuasive advertising, not scientific benefit, she said by email.
“The findings are important, because many primary care providers and dermatologists do not realize that patients will use skin-lightening agents simply to provide a glow and in an attempt to attain complexion blending,” added Dr. McMichael, also not involved in the study.
She encouraged doctors to understand what motivates their patients to use skin-lightening agents, so they can effectively communicate what works and what does not work for their condition, as well as inform them about potential risks.
Strengths of the study, Dr. McMichael said, are the number of people surveyed and the inclusion of colorism data not typically gathered in studies of skin-lightening product use. Limitations include whether the reported conditions were what people actually had, and that, with over 50% of respondents being Black, the results may not be generalizable to other groups.
“Colorism is complex,” Dr. Kundu noted. “Dermatologists need to recognize how colorism impacts their patients, so they can provide them with culturally mindful care and deter them from using potentially harmful products.”
Illegal products may still be available
Dr. McMichael would like to know how many of these patients used products containing > 4%-strength hydroquinone, because they “can be dangerous, and patients don’t understand how these higher-strength medications can damage the skin.”
“Following the Coronavirus Aid, Relief, and Economic Security [CARES] Act of 2020, over-the-counter hydroquinone sales were prohibited in the U.S.,” the authors write. In 2022, the Food and Drug Administration issued warning letters to 12 companies that sold products containing unsafe concentrations of hydroquinone, because of concerns about swelling, rashes, and discoloration. Hydroquinone has also been linked with skin cancer.
“However, this study demonstrates that consumers in the U.S. may still have access to hydroquinone formulations,” the authors caution.
At its Skin Facts! Resources website, the FDA warns about potentially harmful over-the-counter skin-lightening products containing hydroquinone or mercury and recommends using only prescribed products. The information site was created by the FDA Office of Minority Health and Health Equity.
The study authors, Dr. Baron, and Dr. McMichael report no relevant financial relationships. The study did not receive external funding. All experts commented by email.
, a recent cross-sectional survey suggests.
Skin lightening – which uses chemicals to lighten dark areas of skin or to generally lighten skin tone – poses a health risk from potentially unsafe formulations, the authors write in the International Journal of Women’s Dermatology.
Skin lightening is “influenced by colorism, the system of inequality that affords opportunities and privileges to lighter-skinned individuals across racial/ethnic groups,” they add. “Women, in particular, are vulnerable as media and popular culture propagate beauty standards that lighter skin can elevate physical appearance and social acceptance.”
“It is important to recognize that the primary motivator for skin lightening is most often dermatological disease but that, less frequently, it can be colorism,” senior study author Roopal V. Kundu, MD, professor of dermatology and founding director of the Northwestern Center for Ethnic Skin and Hair at Northwestern University, Chicago, said in an email interview.
Skin lightening is a growing, multibillion-dollar, largely unregulated, global industry. Rates have been estimated at 27% in South Africa, 40% in China and South Korea, 77% in Nigeria, but U.S. rates are unknown.
To investigate skin-lightening habits and the role colorism plays in skin-lightening practices in the United States, Dr. Kundu and her colleagues sent an online survey to 578 adults with darker skin who participated in ResearchMatch, a national health registry supported by the National Institutes of Health that connects volunteers with research studies they choose to take part in.
Of the 455 people who completed the 19-item anonymous questionnaire, 238 (52.3%) identified as Black or African American, 83 (18.2%) as Asian, 84 (18.5%) as multiracial, 31 (6.8%) as Hispanic, 14 (3.1%) as American Indian or Alaska Native, and 5 (1.1%) as other. Overall, 364 (80.0%) were women.
The survey asked about demographics, colorism attitudes, skin tone satisfaction, and skin-lightening product use. To assess colorism attitudes, the researchers asked respondents to rate six colorism statements on a Likert scale of 1 (strongly disagree) to 5 (strongly agree). The statements included “Lighter skin tone increases one’s self-esteem,” and “Lighter skin tone increases one’s chance of having a romantic relationship or getting married.” The researchers also asked them to rate their skin satisfaction levels on a Likert scale from 1 (very unsatisfied) to 5 (very satisfied).
Used mostly to treat skin conditions
Despite a lack of medical input, about three-quarters of people who used skin-lightening products reported using them for medical conditions, and around one-quarter used them for general lightening, the researchers report.
Of all respondents, 97 (21.3%) reported using skin-lightening agents. Of them, 71 (73.2%) used them to treat a skin condition such as acne, melasma, or postinflammatory hyperpigmentation, and 26 (26.8% of skin-lightening product users; 5.7% of all respondents) used them for generalized skin lightening.
The 97 users mostly obtained skin-lightening products from chain pharmacy and grocery stores, and also from community beauty stores, abroad, online, and medical providers, while two made them at home.
Skin-lightening product use did not differ with age, gender, race or ethnicity, education level, or immigration status.
Only 22 (22.7%) of the product users consulted a medical provider before using the products, and only 14 (14.4%) received skin-lightening products from medical providers.
In addition, 44 respondents (45.4%) could not identify the active ingredient in their skin-lightening products, but 34 (35.1%) reported using hydroquinone-based products. Other reported active ingredients included ascorbic acid, glycolic acid, salicylic acid, niacinamide, steroids, and mercury.
The face (86 people or 88.7%) and neck (37 or 38.1%) were the most common application sites.
Skin-lightening users were more likely to report that lighter skin was more beautiful and that it increased self-esteem and romantic prospects (P < .001 for all).
Elma Baron, MD, professor of dermatology at Case Western Reserve University, Cleveland, advised doctors to remind patients to consult a dermatologist before they use skin-lightening agents. “A dermatologist can evaluate whether there is a true indication for skin-lightening agents and explain the benefits, risks, and limitations of common skin-lightening formulations.
“When dealing with hyperpigmentation, clinicians should remember that ultraviolet light is a potent stimulus for melanogenesis,” added Dr. Baron by email. She was not involved in the study. “Wearing hats and other sun-protective clothing, using sunscreen, and avoiding sunlight during peak hours must always be emphasized.”
Amy J. McMichael, MD, professor of dermatology at Wake Forest University, Winston-Salem, N.C., often sees patients who try products based on persuasive advertising, not scientific benefit, she said by email.
“The findings are important, because many primary care providers and dermatologists do not realize that patients will use skin-lightening agents simply to provide a glow and in an attempt to attain complexion blending,” added Dr. McMichael, also not involved in the study.
She encouraged doctors to understand what motivates their patients to use skin-lightening agents, so they can effectively communicate what works and what does not work for their condition, as well as inform them about potential risks.
Strengths of the study, Dr. McMichael said, are the number of people surveyed and the inclusion of colorism data not typically gathered in studies of skin-lightening product use. Limitations include whether the reported conditions were what people actually had, and that, with over 50% of respondents being Black, the results may not be generalizable to other groups.
“Colorism is complex,” Dr. Kundu noted. “Dermatologists need to recognize how colorism impacts their patients, so they can provide them with culturally mindful care and deter them from using potentially harmful products.”
Illegal products may still be available
Dr. McMichael would like to know how many of these patients used products containing > 4%-strength hydroquinone, because they “can be dangerous, and patients don’t understand how these higher-strength medications can damage the skin.”
“Following the Coronavirus Aid, Relief, and Economic Security [CARES] Act of 2020, over-the-counter hydroquinone sales were prohibited in the U.S.,” the authors write. In 2022, the Food and Drug Administration issued warning letters to 12 companies that sold products containing unsafe concentrations of hydroquinone, because of concerns about swelling, rashes, and discoloration. Hydroquinone has also been linked with skin cancer.
“However, this study demonstrates that consumers in the U.S. may still have access to hydroquinone formulations,” the authors caution.
At its Skin Facts! Resources website, the FDA warns about potentially harmful over-the-counter skin-lightening products containing hydroquinone or mercury and recommends using only prescribed products. The information site was created by the FDA Office of Minority Health and Health Equity.
The study authors, Dr. Baron, and Dr. McMichael report no relevant financial relationships. The study did not receive external funding. All experts commented by email.
FROM THE INTERNATIONAL JOURNAL OF WOMEN’S DERMATOLOGY
Rosacea look-alike
Although it’s easy to jump to the conclusion that facial erythema is rosacea, there are multiple other conditions that can lead to reddening of the face. In this case, excessive sun exposure had resulted in a diffuse actinic change of the malar and lateral aspects of this patient’s face. The palpably rough lesions were actinic keratoses.
Actinic keratoses are caused by exposure to ultraviolet radiation. These lesions are premalignant and common. Areas of the body at greatest risk include those not typically covered by clothing (eg, face, hands, arms, ears, forehead, and top of the scalp—especially in individuals with hair loss). There is a range of estimates regarding the percentage of actinic keratoses that will progress to squamous cell carcinoma in situ, and then invasive squamous cell carcinoma. One study determined that 10% of actinic keratoses progress to squamous cell carcinoma over the course of 2 years.1
In patients with broad areas of multiple clinically palpable lesions with rough sandpapery texture or visible white scale, there are likely preclinical lesions in the same areas. With so many lesions, field therapy of the entire region is often performed instead of treating the lesions 1 at a time.
There are multiple topical agents for field therapy, including 5-fluorouracil, diclofenac gel, and imiquimod gel.2 Since significant erythema and inflammation usually follow application of the topical agent, clinicians may want to have patients treat in segments to make the process more tolerable.
5-fluorouracil has a complete clearance rate (CCR) of 75% to 90% and is usually applied twice daily for 2 weeks, although there are multiple different protocols. Diclofenac has a CCR of 58% over a 60- to 90-day course, and imiquimod has a CCR of 54% after a 120-day course. Photodynamic therapy (PDT) has the advantage of a single treatment but a CCR of 38%. PDT may be advantageous for a patient who has difficulty applying topical medication over a period of weeks.
Niacinamide has been shown to help with skin repair and reduce the risk of additional nonmelanoma skin cancers (NMSC) by 23% and additional actinic keratoses by about 15% in individuals with a history of actinic keratoses or NMSC.3 In contrast to niacin, niacinamide does not cause flushing. Niacinamide is used long term; if discontinued, it no longer confers benefit in helping the skin repair itself.
The patient in this case was prescribed topical 5% fluorouracil cream to be applied twice daily to the malar regions bilaterally for 2 weeks and, if not inflamed by 2 weeks, to extend the treatment until there is robust inflammation (but not to exceed 3 weeks). He was scheduled to follow up in 3 months for reexamination. He was also advised to start taking niacinamide 500 mg twice daily to reduce his risk of additional precancerous and cancerous skin lesions and counseled on the importance of sunscreen, hats, and sun-protective clothing.
Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.
- Fuchs A, Marmur E. The kinetics of skin cancer: progression of actinic keratosis to squamous cell carcinoma. Dermatol Surg. 2007;33:1099-1101. doi: 10.1111/j.1524-4725.2007.33224.x
- Jansen MHE, Kessels JPHM, Nelemans PJ, et al. Randomized trial of four treatment approaches for actinic keratosis. N Engl J Med. 2019;380:935-946. doi: 10.1056/NEJMoa1811850
- Starr P. Oral nicotinamide prevents common skin cancers in high-risk patients, reduces costs. Am Health Drug Benefits. 2015;8(spec issue):13-14.
Although it’s easy to jump to the conclusion that facial erythema is rosacea, there are multiple other conditions that can lead to reddening of the face. In this case, excessive sun exposure had resulted in a diffuse actinic change of the malar and lateral aspects of this patient’s face. The palpably rough lesions were actinic keratoses.
Actinic keratoses are caused by exposure to ultraviolet radiation. These lesions are premalignant and common. Areas of the body at greatest risk include those not typically covered by clothing (eg, face, hands, arms, ears, forehead, and top of the scalp—especially in individuals with hair loss). There is a range of estimates regarding the percentage of actinic keratoses that will progress to squamous cell carcinoma in situ, and then invasive squamous cell carcinoma. One study determined that 10% of actinic keratoses progress to squamous cell carcinoma over the course of 2 years.1
In patients with broad areas of multiple clinically palpable lesions with rough sandpapery texture or visible white scale, there are likely preclinical lesions in the same areas. With so many lesions, field therapy of the entire region is often performed instead of treating the lesions 1 at a time.
There are multiple topical agents for field therapy, including 5-fluorouracil, diclofenac gel, and imiquimod gel.2 Since significant erythema and inflammation usually follow application of the topical agent, clinicians may want to have patients treat in segments to make the process more tolerable.
5-fluorouracil has a complete clearance rate (CCR) of 75% to 90% and is usually applied twice daily for 2 weeks, although there are multiple different protocols. Diclofenac has a CCR of 58% over a 60- to 90-day course, and imiquimod has a CCR of 54% after a 120-day course. Photodynamic therapy (PDT) has the advantage of a single treatment but a CCR of 38%. PDT may be advantageous for a patient who has difficulty applying topical medication over a period of weeks.
Niacinamide has been shown to help with skin repair and reduce the risk of additional nonmelanoma skin cancers (NMSC) by 23% and additional actinic keratoses by about 15% in individuals with a history of actinic keratoses or NMSC.3 In contrast to niacin, niacinamide does not cause flushing. Niacinamide is used long term; if discontinued, it no longer confers benefit in helping the skin repair itself.
The patient in this case was prescribed topical 5% fluorouracil cream to be applied twice daily to the malar regions bilaterally for 2 weeks and, if not inflamed by 2 weeks, to extend the treatment until there is robust inflammation (but not to exceed 3 weeks). He was scheduled to follow up in 3 months for reexamination. He was also advised to start taking niacinamide 500 mg twice daily to reduce his risk of additional precancerous and cancerous skin lesions and counseled on the importance of sunscreen, hats, and sun-protective clothing.
Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.
Although it’s easy to jump to the conclusion that facial erythema is rosacea, there are multiple other conditions that can lead to reddening of the face. In this case, excessive sun exposure had resulted in a diffuse actinic change of the malar and lateral aspects of this patient’s face. The palpably rough lesions were actinic keratoses.
Actinic keratoses are caused by exposure to ultraviolet radiation. These lesions are premalignant and common. Areas of the body at greatest risk include those not typically covered by clothing (eg, face, hands, arms, ears, forehead, and top of the scalp—especially in individuals with hair loss). There is a range of estimates regarding the percentage of actinic keratoses that will progress to squamous cell carcinoma in situ, and then invasive squamous cell carcinoma. One study determined that 10% of actinic keratoses progress to squamous cell carcinoma over the course of 2 years.1
In patients with broad areas of multiple clinically palpable lesions with rough sandpapery texture or visible white scale, there are likely preclinical lesions in the same areas. With so many lesions, field therapy of the entire region is often performed instead of treating the lesions 1 at a time.
There are multiple topical agents for field therapy, including 5-fluorouracil, diclofenac gel, and imiquimod gel.2 Since significant erythema and inflammation usually follow application of the topical agent, clinicians may want to have patients treat in segments to make the process more tolerable.
5-fluorouracil has a complete clearance rate (CCR) of 75% to 90% and is usually applied twice daily for 2 weeks, although there are multiple different protocols. Diclofenac has a CCR of 58% over a 60- to 90-day course, and imiquimod has a CCR of 54% after a 120-day course. Photodynamic therapy (PDT) has the advantage of a single treatment but a CCR of 38%. PDT may be advantageous for a patient who has difficulty applying topical medication over a period of weeks.
Niacinamide has been shown to help with skin repair and reduce the risk of additional nonmelanoma skin cancers (NMSC) by 23% and additional actinic keratoses by about 15% in individuals with a history of actinic keratoses or NMSC.3 In contrast to niacin, niacinamide does not cause flushing. Niacinamide is used long term; if discontinued, it no longer confers benefit in helping the skin repair itself.
The patient in this case was prescribed topical 5% fluorouracil cream to be applied twice daily to the malar regions bilaterally for 2 weeks and, if not inflamed by 2 weeks, to extend the treatment until there is robust inflammation (but not to exceed 3 weeks). He was scheduled to follow up in 3 months for reexamination. He was also advised to start taking niacinamide 500 mg twice daily to reduce his risk of additional precancerous and cancerous skin lesions and counseled on the importance of sunscreen, hats, and sun-protective clothing.
Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker, MD School of Medicine, Kalamazoo.
- Fuchs A, Marmur E. The kinetics of skin cancer: progression of actinic keratosis to squamous cell carcinoma. Dermatol Surg. 2007;33:1099-1101. doi: 10.1111/j.1524-4725.2007.33224.x
- Jansen MHE, Kessels JPHM, Nelemans PJ, et al. Randomized trial of four treatment approaches for actinic keratosis. N Engl J Med. 2019;380:935-946. doi: 10.1056/NEJMoa1811850
- Starr P. Oral nicotinamide prevents common skin cancers in high-risk patients, reduces costs. Am Health Drug Benefits. 2015;8(spec issue):13-14.
- Fuchs A, Marmur E. The kinetics of skin cancer: progression of actinic keratosis to squamous cell carcinoma. Dermatol Surg. 2007;33:1099-1101. doi: 10.1111/j.1524-4725.2007.33224.x
- Jansen MHE, Kessels JPHM, Nelemans PJ, et al. Randomized trial of four treatment approaches for actinic keratosis. N Engl J Med. 2019;380:935-946. doi: 10.1056/NEJMoa1811850
- Starr P. Oral nicotinamide prevents common skin cancers in high-risk patients, reduces costs. Am Health Drug Benefits. 2015;8(spec issue):13-14.
Skin reactions common at insulin pump infusion sites
new research suggests.
Insulin pump use is increasingly common, but many patients experience infusion-site failure that in some cases leads to discontinuation. In a novel investigation, researchers at the University of Washington, Seattle, used biopsies and noninvasive imaging to compare insulin pump sites with control sites in 30 patients. Several differences were found at pump sites in comparison with control sites, including fibrosis, inflammation, eosinophils, and increased vessel density.
“These findings support allergic sensitization as a potentially common reaction at [insulin pump] sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing,” wrote Andrea Kalus, MD, of the university’s dermatology division, and colleagues. The findings were published recently in Diabetes Care.
The inflammatory response, they wrote, “may result in tissue changes responsible for the infusion-site failures seen frequently in clinical practice.”
Such infusion site problems represent an “Achilles heel” of these otherwise highly beneficial devices, lead author Irl Hirsch, MD, professor of medicine in the division of metabolism, endocrinology, and nutrition, said in a statement. “It doesn’t really matter how good the technology is. We still don’t understand what is happening with the infusion sites, much less to [be able to] fix it.”
Significant differences between pump and nonpump sites
In the cross-sectional study, Dr. Kalus and colleagues used noninvasive optical coherence tomography (OCT) immediately prior to performing punch biopsies at three sites: the site currently in active use, the “recovery site” used 3-5 days prior to the procedures, and control sites never used for pump infusion. Punch biopsies were also performed at those sites.
The mean age of the patients was 48.3 years, the mean diabetes duration was 30.4 years, and the mean duration of pump use was 15.8 years. Nearly all patients (93.3%) reported itchiness at the site, and 76.7% reported skin redness.
Of the 25 patients for whom OCT imaging was successful, statistical analysis showed significant differences in vascular area density and the optical attenuation coefficient, a surrogate for skin inflammation, between the pump and control sites and between recovery sites and current pump sites. The greater vessel density is likely a result of injury and repair related to catheter insertion, the authors said.
In the biopsy samples, both current and recovery sites showed increased fibrosis, fibrin, inflammation, fat necrosis, vascularity, and eosinophils, compared with the control sites, but no significant differences were found between current and recovery sites.
Eosinophils: ‘The most surprising histologic finding’
Eosinophils were found in 73% of skin biopsy specimens from current sites and in 75% of specimens from recovery sites, compared with none from the control sites (for both, P < .01). In all study participants, eosinophils were found in at least one current and/or recovery infusion site deep in the dermis near the interface with fat. The number of eosinophils ranged from 0 to 31 per high-power field, with a median of 4.
The number of eosinophils didn’t vary by type of insulin or brand of pump, but higher counts were seen in those who had used pumps for less than 10 years, compared with more than 20 years (P = .02).
The prevalence and degree of eosinophils were “the most surprising histologic finding,” the authors wrote, adding that “eosinophils are not typically present as a component of resident inflammatory cells in the skin.”
While eosinophils may be present in normal wound healing, “the absolute number and density of eosinophil in these samples support a delayed-type hypersensitivity response, which is typically observed between 2 and 7 days after exposure to an allergen. ... Eosinophils are often correlated with symptoms of itchiness and likely explain the high percentage of participants who reported itchiness in this study,” Dr. Kalus and colleagues wrote.
Correlation found between inflammation and glycemic control
All participants used the Dexcom G6 continuous glucose monitor as part of their usual care. Inflammation scores were positively correlated with insulin dose (P = .009) and were negatively correlated with time in range (P = .01).
No other OCT or biopsy findings differed by duration of pump use, previous use of animal insulin, or type of insulin.
The reason for these findings is unclear, Dr. Hirsch said. “How much was the catheter or the insulin causing the irritation around the sites? How much was it from the preservatives, or is this because of the insulin pump itself? All these questions need to be answered in future studies. ... The real goal of all of this is to minimize skin damage and improve the experience for our patients.”
The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Hirsch reported grants and contracts from Insulet, Medtronic, and Dexcom outside the submitted work; consulting fees from Abbott Diabetes Care, Lifescan, and Hagar outside the submitted work; and honoraria for lectures, presentations, participation on speaker’s bureaus, manuscript writing, or educational events as section editor for UpToDate outside the submitted work. Dr. Kalus has no disclosures.
A version of this article first appeared on Medscape.com.
new research suggests.
Insulin pump use is increasingly common, but many patients experience infusion-site failure that in some cases leads to discontinuation. In a novel investigation, researchers at the University of Washington, Seattle, used biopsies and noninvasive imaging to compare insulin pump sites with control sites in 30 patients. Several differences were found at pump sites in comparison with control sites, including fibrosis, inflammation, eosinophils, and increased vessel density.
“These findings support allergic sensitization as a potentially common reaction at [insulin pump] sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing,” wrote Andrea Kalus, MD, of the university’s dermatology division, and colleagues. The findings were published recently in Diabetes Care.
The inflammatory response, they wrote, “may result in tissue changes responsible for the infusion-site failures seen frequently in clinical practice.”
Such infusion site problems represent an “Achilles heel” of these otherwise highly beneficial devices, lead author Irl Hirsch, MD, professor of medicine in the division of metabolism, endocrinology, and nutrition, said in a statement. “It doesn’t really matter how good the technology is. We still don’t understand what is happening with the infusion sites, much less to [be able to] fix it.”
Significant differences between pump and nonpump sites
In the cross-sectional study, Dr. Kalus and colleagues used noninvasive optical coherence tomography (OCT) immediately prior to performing punch biopsies at three sites: the site currently in active use, the “recovery site” used 3-5 days prior to the procedures, and control sites never used for pump infusion. Punch biopsies were also performed at those sites.
The mean age of the patients was 48.3 years, the mean diabetes duration was 30.4 years, and the mean duration of pump use was 15.8 years. Nearly all patients (93.3%) reported itchiness at the site, and 76.7% reported skin redness.
Of the 25 patients for whom OCT imaging was successful, statistical analysis showed significant differences in vascular area density and the optical attenuation coefficient, a surrogate for skin inflammation, between the pump and control sites and between recovery sites and current pump sites. The greater vessel density is likely a result of injury and repair related to catheter insertion, the authors said.
In the biopsy samples, both current and recovery sites showed increased fibrosis, fibrin, inflammation, fat necrosis, vascularity, and eosinophils, compared with the control sites, but no significant differences were found between current and recovery sites.
Eosinophils: ‘The most surprising histologic finding’
Eosinophils were found in 73% of skin biopsy specimens from current sites and in 75% of specimens from recovery sites, compared with none from the control sites (for both, P < .01). In all study participants, eosinophils were found in at least one current and/or recovery infusion site deep in the dermis near the interface with fat. The number of eosinophils ranged from 0 to 31 per high-power field, with a median of 4.
The number of eosinophils didn’t vary by type of insulin or brand of pump, but higher counts were seen in those who had used pumps for less than 10 years, compared with more than 20 years (P = .02).
The prevalence and degree of eosinophils were “the most surprising histologic finding,” the authors wrote, adding that “eosinophils are not typically present as a component of resident inflammatory cells in the skin.”
While eosinophils may be present in normal wound healing, “the absolute number and density of eosinophil in these samples support a delayed-type hypersensitivity response, which is typically observed between 2 and 7 days after exposure to an allergen. ... Eosinophils are often correlated with symptoms of itchiness and likely explain the high percentage of participants who reported itchiness in this study,” Dr. Kalus and colleagues wrote.
Correlation found between inflammation and glycemic control
All participants used the Dexcom G6 continuous glucose monitor as part of their usual care. Inflammation scores were positively correlated with insulin dose (P = .009) and were negatively correlated with time in range (P = .01).
No other OCT or biopsy findings differed by duration of pump use, previous use of animal insulin, or type of insulin.
The reason for these findings is unclear, Dr. Hirsch said. “How much was the catheter or the insulin causing the irritation around the sites? How much was it from the preservatives, or is this because of the insulin pump itself? All these questions need to be answered in future studies. ... The real goal of all of this is to minimize skin damage and improve the experience for our patients.”
The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Hirsch reported grants and contracts from Insulet, Medtronic, and Dexcom outside the submitted work; consulting fees from Abbott Diabetes Care, Lifescan, and Hagar outside the submitted work; and honoraria for lectures, presentations, participation on speaker’s bureaus, manuscript writing, or educational events as section editor for UpToDate outside the submitted work. Dr. Kalus has no disclosures.
A version of this article first appeared on Medscape.com.
new research suggests.
Insulin pump use is increasingly common, but many patients experience infusion-site failure that in some cases leads to discontinuation. In a novel investigation, researchers at the University of Washington, Seattle, used biopsies and noninvasive imaging to compare insulin pump sites with control sites in 30 patients. Several differences were found at pump sites in comparison with control sites, including fibrosis, inflammation, eosinophils, and increased vessel density.
“These findings support allergic sensitization as a potentially common reaction at [insulin pump] sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing,” wrote Andrea Kalus, MD, of the university’s dermatology division, and colleagues. The findings were published recently in Diabetes Care.
The inflammatory response, they wrote, “may result in tissue changes responsible for the infusion-site failures seen frequently in clinical practice.”
Such infusion site problems represent an “Achilles heel” of these otherwise highly beneficial devices, lead author Irl Hirsch, MD, professor of medicine in the division of metabolism, endocrinology, and nutrition, said in a statement. “It doesn’t really matter how good the technology is. We still don’t understand what is happening with the infusion sites, much less to [be able to] fix it.”
Significant differences between pump and nonpump sites
In the cross-sectional study, Dr. Kalus and colleagues used noninvasive optical coherence tomography (OCT) immediately prior to performing punch biopsies at three sites: the site currently in active use, the “recovery site” used 3-5 days prior to the procedures, and control sites never used for pump infusion. Punch biopsies were also performed at those sites.
The mean age of the patients was 48.3 years, the mean diabetes duration was 30.4 years, and the mean duration of pump use was 15.8 years. Nearly all patients (93.3%) reported itchiness at the site, and 76.7% reported skin redness.
Of the 25 patients for whom OCT imaging was successful, statistical analysis showed significant differences in vascular area density and the optical attenuation coefficient, a surrogate for skin inflammation, between the pump and control sites and between recovery sites and current pump sites. The greater vessel density is likely a result of injury and repair related to catheter insertion, the authors said.
In the biopsy samples, both current and recovery sites showed increased fibrosis, fibrin, inflammation, fat necrosis, vascularity, and eosinophils, compared with the control sites, but no significant differences were found between current and recovery sites.
Eosinophils: ‘The most surprising histologic finding’
Eosinophils were found in 73% of skin biopsy specimens from current sites and in 75% of specimens from recovery sites, compared with none from the control sites (for both, P < .01). In all study participants, eosinophils were found in at least one current and/or recovery infusion site deep in the dermis near the interface with fat. The number of eosinophils ranged from 0 to 31 per high-power field, with a median of 4.
The number of eosinophils didn’t vary by type of insulin or brand of pump, but higher counts were seen in those who had used pumps for less than 10 years, compared with more than 20 years (P = .02).
The prevalence and degree of eosinophils were “the most surprising histologic finding,” the authors wrote, adding that “eosinophils are not typically present as a component of resident inflammatory cells in the skin.”
While eosinophils may be present in normal wound healing, “the absolute number and density of eosinophil in these samples support a delayed-type hypersensitivity response, which is typically observed between 2 and 7 days after exposure to an allergen. ... Eosinophils are often correlated with symptoms of itchiness and likely explain the high percentage of participants who reported itchiness in this study,” Dr. Kalus and colleagues wrote.
Correlation found between inflammation and glycemic control
All participants used the Dexcom G6 continuous glucose monitor as part of their usual care. Inflammation scores were positively correlated with insulin dose (P = .009) and were negatively correlated with time in range (P = .01).
No other OCT or biopsy findings differed by duration of pump use, previous use of animal insulin, or type of insulin.
The reason for these findings is unclear, Dr. Hirsch said. “How much was the catheter or the insulin causing the irritation around the sites? How much was it from the preservatives, or is this because of the insulin pump itself? All these questions need to be answered in future studies. ... The real goal of all of this is to minimize skin damage and improve the experience for our patients.”
The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Hirsch reported grants and contracts from Insulet, Medtronic, and Dexcom outside the submitted work; consulting fees from Abbott Diabetes Care, Lifescan, and Hagar outside the submitted work; and honoraria for lectures, presentations, participation on speaker’s bureaus, manuscript writing, or educational events as section editor for UpToDate outside the submitted work. Dr. Kalus has no disclosures.
A version of this article first appeared on Medscape.com.
FROM DIABETES CARE
Roflumilast cream appears safe, effective for children with psoriasis, researchers report
In patients aged 2-11 years, roflumilast cream was well tolerated and improved signs and symptoms of psoriasis over 4 weeks, according to results from a pair of phase two studies.
“Limited topical treatments are approved for children younger than 12 years old with psoriasis,” researchers led by Adelaide A. Hebert, MD, wrote in their abstract. The results were presented during a poster session at the annual meeting of the Society for Pediatric Dermatology.
Roflumilast cream 0.3% (Zoryve) is a once-daily, topical nonsteroidal treatment from Arcutis Biotherapeutics. A phosphodiesterase-4 inhibitor, it was approved by the Food and Drug Administration in 2022 for mild, moderate and severe psoriasis in individuals aged 12 and older, including intertriginous psoriasis.
For the analysis, Dr. Hebert, chief of pediatric dermatology at the University of Texas, Houston, and colleagues conducted two 4-week, phase 2, open-label safety studies of roflumilast cream 0.3%.
One, study 216, enrolled 10 children aged 2-5, and all but one were Black. The other, study 215, enrolled 20 children aged 6-11, and half were Black and nearly half were White. At baseline, patients had 2% or greater body surface area (BSA) involvement and an Investigator Global Assessment (IGA) score of at least mild.
Caregivers applied roflumilast cream to all affected areas once daily for 28 days. The researchers collected pharmacokinetic samples at week 2 and week 4. The primary endpoints were pharmacokinetic, safety, and tolerability.
Efficacy was evaluated as exploratory endpoints: An IGA of clear or almost clear plus a 2-grade or more improvement from baseline, a 50% or greater improvement and a 75% or greater improvement on the Psoriasis Area and Severity Index (PASI-50 and PASI-75), a 4-point or greater reduction in the Worst Itch–Numeric Rating Scale (WI-NRS) in patients with a baseline score of 4 or greater, a mean change from baseline in BSA, and improvement in the Children’s Dermatology Life Quality Index (CDLQI).
At baseline, the mean BSA was similar for patients enrolled in studies 216 and 215 (9.6% and 8.8%, respectively), and 80% of all patients had baseline IGA of moderate. By week 2, the mean roflumilast and N-oxide predose plasma concentrations among patients in the younger group were 2.15 and 22.4 ng/mL, compared with 3.15 and 28.9 ng/mL among those in the older group. At week 4, the mean roflumilast and N-oxide predose concentrations were 2.04 and 15.8 ng/mL in the younger group (study 216), compared with 1.68 and 15.7 ng/mL in the older group (study 215).
As for efficacy, 90% and 40% of patients in studies 216 and 215 achieved IGA success at week 4, respectively, while 90% and 50% achieved PASI-75, 90% and 40% achieved WI-NRS success, and the mean BSA reductions at week 4 were 79.1% and 44.4%. Meanwhile, one younger patient in study 216 reported a treatment-emergent adverse event (TEAE) of headache, which was considered mild, while four older patients in study 215 reported 8 TEAEs, which were considered mild and ranged from back pain to nasal congestion.
“The rapid onset of action was surprising but exceedingly rewarding for the subjects enrolled in the study,” Dr. Hebert told this news organization after the meeting. “The PASI scores and itch scores were markedly improved at the end of the 4-week clinical trial. Patient and parents alike were pleased to use a steroid-free option with once-daily application and rapid onset of action to help control plaque psoriasis.”
In the poster abstract, she and her coauthors concluded that “under maximal use conditions in children aged 2-11 years, roflumilast cream 0.3% was well tolerated and improved signs and symptoms of psoriasis with measured improvements in IGA score, PASI score, BSA involvement, CDLQI, and WI-NRS. Overall, pharmacokinetics, safety, tolerability, and efficacy in patients aged 2-11 years were consistent with prior results in adults and adolescents.”
The study was funded by Arcutis Biotherapeutics. Dr. Hebert reported that she is an investigator for Arcutis. About half the coauthors are employees of Arcutis, and the other half disclosed grants, research funding and/or honoraria from the company. Research grants from the company for this study were paid to the McGovern Medical School at the University of Texas.
In patients aged 2-11 years, roflumilast cream was well tolerated and improved signs and symptoms of psoriasis over 4 weeks, according to results from a pair of phase two studies.
“Limited topical treatments are approved for children younger than 12 years old with psoriasis,” researchers led by Adelaide A. Hebert, MD, wrote in their abstract. The results were presented during a poster session at the annual meeting of the Society for Pediatric Dermatology.
Roflumilast cream 0.3% (Zoryve) is a once-daily, topical nonsteroidal treatment from Arcutis Biotherapeutics. A phosphodiesterase-4 inhibitor, it was approved by the Food and Drug Administration in 2022 for mild, moderate and severe psoriasis in individuals aged 12 and older, including intertriginous psoriasis.
For the analysis, Dr. Hebert, chief of pediatric dermatology at the University of Texas, Houston, and colleagues conducted two 4-week, phase 2, open-label safety studies of roflumilast cream 0.3%.
One, study 216, enrolled 10 children aged 2-5, and all but one were Black. The other, study 215, enrolled 20 children aged 6-11, and half were Black and nearly half were White. At baseline, patients had 2% or greater body surface area (BSA) involvement and an Investigator Global Assessment (IGA) score of at least mild.
Caregivers applied roflumilast cream to all affected areas once daily for 28 days. The researchers collected pharmacokinetic samples at week 2 and week 4. The primary endpoints were pharmacokinetic, safety, and tolerability.
Efficacy was evaluated as exploratory endpoints: An IGA of clear or almost clear plus a 2-grade or more improvement from baseline, a 50% or greater improvement and a 75% or greater improvement on the Psoriasis Area and Severity Index (PASI-50 and PASI-75), a 4-point or greater reduction in the Worst Itch–Numeric Rating Scale (WI-NRS) in patients with a baseline score of 4 or greater, a mean change from baseline in BSA, and improvement in the Children’s Dermatology Life Quality Index (CDLQI).
At baseline, the mean BSA was similar for patients enrolled in studies 216 and 215 (9.6% and 8.8%, respectively), and 80% of all patients had baseline IGA of moderate. By week 2, the mean roflumilast and N-oxide predose plasma concentrations among patients in the younger group were 2.15 and 22.4 ng/mL, compared with 3.15 and 28.9 ng/mL among those in the older group. At week 4, the mean roflumilast and N-oxide predose concentrations were 2.04 and 15.8 ng/mL in the younger group (study 216), compared with 1.68 and 15.7 ng/mL in the older group (study 215).
As for efficacy, 90% and 40% of patients in studies 216 and 215 achieved IGA success at week 4, respectively, while 90% and 50% achieved PASI-75, 90% and 40% achieved WI-NRS success, and the mean BSA reductions at week 4 were 79.1% and 44.4%. Meanwhile, one younger patient in study 216 reported a treatment-emergent adverse event (TEAE) of headache, which was considered mild, while four older patients in study 215 reported 8 TEAEs, which were considered mild and ranged from back pain to nasal congestion.
“The rapid onset of action was surprising but exceedingly rewarding for the subjects enrolled in the study,” Dr. Hebert told this news organization after the meeting. “The PASI scores and itch scores were markedly improved at the end of the 4-week clinical trial. Patient and parents alike were pleased to use a steroid-free option with once-daily application and rapid onset of action to help control plaque psoriasis.”
In the poster abstract, she and her coauthors concluded that “under maximal use conditions in children aged 2-11 years, roflumilast cream 0.3% was well tolerated and improved signs and symptoms of psoriasis with measured improvements in IGA score, PASI score, BSA involvement, CDLQI, and WI-NRS. Overall, pharmacokinetics, safety, tolerability, and efficacy in patients aged 2-11 years were consistent with prior results in adults and adolescents.”
The study was funded by Arcutis Biotherapeutics. Dr. Hebert reported that she is an investigator for Arcutis. About half the coauthors are employees of Arcutis, and the other half disclosed grants, research funding and/or honoraria from the company. Research grants from the company for this study were paid to the McGovern Medical School at the University of Texas.
In patients aged 2-11 years, roflumilast cream was well tolerated and improved signs and symptoms of psoriasis over 4 weeks, according to results from a pair of phase two studies.
“Limited topical treatments are approved for children younger than 12 years old with psoriasis,” researchers led by Adelaide A. Hebert, MD, wrote in their abstract. The results were presented during a poster session at the annual meeting of the Society for Pediatric Dermatology.
Roflumilast cream 0.3% (Zoryve) is a once-daily, topical nonsteroidal treatment from Arcutis Biotherapeutics. A phosphodiesterase-4 inhibitor, it was approved by the Food and Drug Administration in 2022 for mild, moderate and severe psoriasis in individuals aged 12 and older, including intertriginous psoriasis.
For the analysis, Dr. Hebert, chief of pediatric dermatology at the University of Texas, Houston, and colleagues conducted two 4-week, phase 2, open-label safety studies of roflumilast cream 0.3%.
One, study 216, enrolled 10 children aged 2-5, and all but one were Black. The other, study 215, enrolled 20 children aged 6-11, and half were Black and nearly half were White. At baseline, patients had 2% or greater body surface area (BSA) involvement and an Investigator Global Assessment (IGA) score of at least mild.
Caregivers applied roflumilast cream to all affected areas once daily for 28 days. The researchers collected pharmacokinetic samples at week 2 and week 4. The primary endpoints were pharmacokinetic, safety, and tolerability.
Efficacy was evaluated as exploratory endpoints: An IGA of clear or almost clear plus a 2-grade or more improvement from baseline, a 50% or greater improvement and a 75% or greater improvement on the Psoriasis Area and Severity Index (PASI-50 and PASI-75), a 4-point or greater reduction in the Worst Itch–Numeric Rating Scale (WI-NRS) in patients with a baseline score of 4 or greater, a mean change from baseline in BSA, and improvement in the Children’s Dermatology Life Quality Index (CDLQI).
At baseline, the mean BSA was similar for patients enrolled in studies 216 and 215 (9.6% and 8.8%, respectively), and 80% of all patients had baseline IGA of moderate. By week 2, the mean roflumilast and N-oxide predose plasma concentrations among patients in the younger group were 2.15 and 22.4 ng/mL, compared with 3.15 and 28.9 ng/mL among those in the older group. At week 4, the mean roflumilast and N-oxide predose concentrations were 2.04 and 15.8 ng/mL in the younger group (study 216), compared with 1.68 and 15.7 ng/mL in the older group (study 215).
As for efficacy, 90% and 40% of patients in studies 216 and 215 achieved IGA success at week 4, respectively, while 90% and 50% achieved PASI-75, 90% and 40% achieved WI-NRS success, and the mean BSA reductions at week 4 were 79.1% and 44.4%. Meanwhile, one younger patient in study 216 reported a treatment-emergent adverse event (TEAE) of headache, which was considered mild, while four older patients in study 215 reported 8 TEAEs, which were considered mild and ranged from back pain to nasal congestion.
“The rapid onset of action was surprising but exceedingly rewarding for the subjects enrolled in the study,” Dr. Hebert told this news organization after the meeting. “The PASI scores and itch scores were markedly improved at the end of the 4-week clinical trial. Patient and parents alike were pleased to use a steroid-free option with once-daily application and rapid onset of action to help control plaque psoriasis.”
In the poster abstract, she and her coauthors concluded that “under maximal use conditions in children aged 2-11 years, roflumilast cream 0.3% was well tolerated and improved signs and symptoms of psoriasis with measured improvements in IGA score, PASI score, BSA involvement, CDLQI, and WI-NRS. Overall, pharmacokinetics, safety, tolerability, and efficacy in patients aged 2-11 years were consistent with prior results in adults and adolescents.”
The study was funded by Arcutis Biotherapeutics. Dr. Hebert reported that she is an investigator for Arcutis. About half the coauthors are employees of Arcutis, and the other half disclosed grants, research funding and/or honoraria from the company. Research grants from the company for this study were paid to the McGovern Medical School at the University of Texas.
FROM SPD 2023