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Age, skin cancer risks for ICI-induced bullous pemphigoid identified
that may result in treatment interruption or cessation.
Investigators in Boston report that among patients receiving ICIs, being aged 70 years or older and having skin cancer are both significant risk factors for bullous pemphigoid. On the plus side, ICI-induced bullous pemphigoid also appears to be a marker for improved tumor responses to therapy.
In a nested case-control study of 5,636 patients with cancer who received either a programmed death 1 inhibitor such as pembrolizumab (Keytruda) or nivolumab (Opdivo) or a cytotoxic T-lymphocyte–associated protein 4 inhibitor such as ipilimumab (Yervoy), 35 patients (0.6%) developed bullous pemphigoid. The study by Nicole R. LeBoeuf, MD, MPH, from Brigham and Women’s Hospital in Boston and colleagues was published online in JAMA Dermatology.
“What is interesting is that 0.6 is a small number, but we’re seeing bullous pemphigoid at considerably higher frequency than is expected in the general population,” Dr. LeBoeuf said in an interview.
And although bullous pemphigoid has the potential to disrupt ICI therapy, it also appears to be a marker for a favorable tumor response, the investigators found.
Their findings suggest that management of bullous pemphigoid for patients receiving ICIs should focus on early identification and management with therapies directed at the specific toxicity, Dr. LeBoeuf said.
“When you make a specific diagnosis like bullous pemphigoid, then you can treat that specific disease with very targeted therapies, such as omalizumab or dupilumab or rituximab – things that are not globally immune suppressing like steroid or other T-cell–depleting agents. Studies have shown that depleting B cells with anti-CD20 agents is not detrimental to immune checkpoint inhibitor therapy,” she said.
Dermatologic AEs common
About 40% of patients with cancer treated with ICIs experience immune-related dermatologic adverse events (AEs) that can range from mild rashes and hair and nail changes to uncommon but life-threatening complications, such as Stevens-Johnson syndrome, a form of toxic epidermal necrolysis, according to members of a European Academy of Dermatology and Venereology task force.
“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they wrote in a position statement on the management of ICI-derived dermatologic adverse events.
Dr. LeBoeuf and colleagues note that, while reported risk factors for idiopathic bullous pemphigoid include advanced age, type 2 diabetes, use of dipeptidyl peptidase-4 inhibitors, cerebrovascular disease, and neurocognitive disease, risk factors for bullous pemphigoid and other adverse dermatologic events associated with ICIs are less well known.
Study details
To identify risk factors for bullous pemphigoid in patients receiving ICI, the investigators performed a case-control study nested within a retrospective cohort study.
They evaluated records for all patients in the three Harvard-affiliated hospitals to identify patients with ICI-associated bullous pemphigoid from October 2014 through December 2020. Control persons were all patients in the Dana-Farber cancer registry who received ICIs during the study period.
The investigators chose age at ICI initiation (69 years and younger or 70 years and older), sex, ICI agents, and cancer type as potential risk factors.
They used propensity score matching based on age, cancer type, ICI agent, and number of ICI cycles to match two control persons with each case patient.
Of the 5,636 patients treated with ICIs during the study period, 35 (0.6%) developed bullous pemphigoid. The median age was 72.8 years, and 71.4% were men.
In a multivariate logistic regression model that included 2,955 patients with complete data in the cancer registry, factors significantly associated with developing bullous pemphigoid included age 70 years or older (odds ratio, 2.32; P = .01), having melanoma (OR, 3.21; P < .001), and having nonmelanoma skin cancer (OR, 8.32; P < .001).
In comparing the 35 case patients with their matched control patients, a complete or partial response at first restaging imaging was significantly associated with developing bullous pemphigoid (OR, 3.37; P = .01). In addition, there was a higher likelihood of tumor responses to ICIs among patients with bullous pemphigoid, compared with matched control patients (objective response rate, 82.9% vs. 61.4%; P = .03).
Prudent toxicity management
Ryan Sullivan, MD, who treats patients with skin cancer at Massachusetts General Hospital Cancer Center, Boston, but was not involved in the study, commented that the findings raise questions about the relationship between skin cancers and immune-related adverse events.
“It is compelling that bullous pemphigoid is a skin toxicity and is more common to happen in skin cancer patients,” he noted. “That’s a very interesting finding, and the reason that it’s interesting is that it’s harder to understand why a presumably antibody-mediated side effect would be more likely to have that cross-reactivity where the tumor started and where the toxicity happened,” he said in an interview.
He noted that the benefits of ICIs for patients with skin cancers far outweigh the risks of dermatologic adverse events such as bullous pemphigoid and that ICI-associated events require judicious management.
“This is true across the spectrum of toxicities: There are clear manifestations of toxicity that we should be more thoughtful about what’s driving them, more thoughtful about what it is, and more thoughtful about treating them, other than just pouring steroids into patients in industrial doses and hoping that everything’s going to be OK,” he said.
No funding source for the study was reported. Dr. LeBoeuf reported receiving grants from the National Institutes of Health National Cancer Institute during the conduct of the study and personal fees for serving as a consultant for several companies outside the study. Coauthor Arash Mostaghimi, MD, MPA, MPH, is associate editor of JAMA Dermatology but was not involved in study selection or evaluation for publication. Dr. Sullivan disclosed consulting for ICI makers Bristol-Myers Squibb and Merck.
A version of this article first appeared on Medscape.com.
that may result in treatment interruption or cessation.
Investigators in Boston report that among patients receiving ICIs, being aged 70 years or older and having skin cancer are both significant risk factors for bullous pemphigoid. On the plus side, ICI-induced bullous pemphigoid also appears to be a marker for improved tumor responses to therapy.
In a nested case-control study of 5,636 patients with cancer who received either a programmed death 1 inhibitor such as pembrolizumab (Keytruda) or nivolumab (Opdivo) or a cytotoxic T-lymphocyte–associated protein 4 inhibitor such as ipilimumab (Yervoy), 35 patients (0.6%) developed bullous pemphigoid. The study by Nicole R. LeBoeuf, MD, MPH, from Brigham and Women’s Hospital in Boston and colleagues was published online in JAMA Dermatology.
“What is interesting is that 0.6 is a small number, but we’re seeing bullous pemphigoid at considerably higher frequency than is expected in the general population,” Dr. LeBoeuf said in an interview.
And although bullous pemphigoid has the potential to disrupt ICI therapy, it also appears to be a marker for a favorable tumor response, the investigators found.
Their findings suggest that management of bullous pemphigoid for patients receiving ICIs should focus on early identification and management with therapies directed at the specific toxicity, Dr. LeBoeuf said.
“When you make a specific diagnosis like bullous pemphigoid, then you can treat that specific disease with very targeted therapies, such as omalizumab or dupilumab or rituximab – things that are not globally immune suppressing like steroid or other T-cell–depleting agents. Studies have shown that depleting B cells with anti-CD20 agents is not detrimental to immune checkpoint inhibitor therapy,” she said.
Dermatologic AEs common
About 40% of patients with cancer treated with ICIs experience immune-related dermatologic adverse events (AEs) that can range from mild rashes and hair and nail changes to uncommon but life-threatening complications, such as Stevens-Johnson syndrome, a form of toxic epidermal necrolysis, according to members of a European Academy of Dermatology and Venereology task force.
“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they wrote in a position statement on the management of ICI-derived dermatologic adverse events.
Dr. LeBoeuf and colleagues note that, while reported risk factors for idiopathic bullous pemphigoid include advanced age, type 2 diabetes, use of dipeptidyl peptidase-4 inhibitors, cerebrovascular disease, and neurocognitive disease, risk factors for bullous pemphigoid and other adverse dermatologic events associated with ICIs are less well known.
Study details
To identify risk factors for bullous pemphigoid in patients receiving ICI, the investigators performed a case-control study nested within a retrospective cohort study.
They evaluated records for all patients in the three Harvard-affiliated hospitals to identify patients with ICI-associated bullous pemphigoid from October 2014 through December 2020. Control persons were all patients in the Dana-Farber cancer registry who received ICIs during the study period.
The investigators chose age at ICI initiation (69 years and younger or 70 years and older), sex, ICI agents, and cancer type as potential risk factors.
They used propensity score matching based on age, cancer type, ICI agent, and number of ICI cycles to match two control persons with each case patient.
Of the 5,636 patients treated with ICIs during the study period, 35 (0.6%) developed bullous pemphigoid. The median age was 72.8 years, and 71.4% were men.
In a multivariate logistic regression model that included 2,955 patients with complete data in the cancer registry, factors significantly associated with developing bullous pemphigoid included age 70 years or older (odds ratio, 2.32; P = .01), having melanoma (OR, 3.21; P < .001), and having nonmelanoma skin cancer (OR, 8.32; P < .001).
In comparing the 35 case patients with their matched control patients, a complete or partial response at first restaging imaging was significantly associated with developing bullous pemphigoid (OR, 3.37; P = .01). In addition, there was a higher likelihood of tumor responses to ICIs among patients with bullous pemphigoid, compared with matched control patients (objective response rate, 82.9% vs. 61.4%; P = .03).
Prudent toxicity management
Ryan Sullivan, MD, who treats patients with skin cancer at Massachusetts General Hospital Cancer Center, Boston, but was not involved in the study, commented that the findings raise questions about the relationship between skin cancers and immune-related adverse events.
“It is compelling that bullous pemphigoid is a skin toxicity and is more common to happen in skin cancer patients,” he noted. “That’s a very interesting finding, and the reason that it’s interesting is that it’s harder to understand why a presumably antibody-mediated side effect would be more likely to have that cross-reactivity where the tumor started and where the toxicity happened,” he said in an interview.
He noted that the benefits of ICIs for patients with skin cancers far outweigh the risks of dermatologic adverse events such as bullous pemphigoid and that ICI-associated events require judicious management.
“This is true across the spectrum of toxicities: There are clear manifestations of toxicity that we should be more thoughtful about what’s driving them, more thoughtful about what it is, and more thoughtful about treating them, other than just pouring steroids into patients in industrial doses and hoping that everything’s going to be OK,” he said.
No funding source for the study was reported. Dr. LeBoeuf reported receiving grants from the National Institutes of Health National Cancer Institute during the conduct of the study and personal fees for serving as a consultant for several companies outside the study. Coauthor Arash Mostaghimi, MD, MPA, MPH, is associate editor of JAMA Dermatology but was not involved in study selection or evaluation for publication. Dr. Sullivan disclosed consulting for ICI makers Bristol-Myers Squibb and Merck.
A version of this article first appeared on Medscape.com.
that may result in treatment interruption or cessation.
Investigators in Boston report that among patients receiving ICIs, being aged 70 years or older and having skin cancer are both significant risk factors for bullous pemphigoid. On the plus side, ICI-induced bullous pemphigoid also appears to be a marker for improved tumor responses to therapy.
In a nested case-control study of 5,636 patients with cancer who received either a programmed death 1 inhibitor such as pembrolizumab (Keytruda) or nivolumab (Opdivo) or a cytotoxic T-lymphocyte–associated protein 4 inhibitor such as ipilimumab (Yervoy), 35 patients (0.6%) developed bullous pemphigoid. The study by Nicole R. LeBoeuf, MD, MPH, from Brigham and Women’s Hospital in Boston and colleagues was published online in JAMA Dermatology.
“What is interesting is that 0.6 is a small number, but we’re seeing bullous pemphigoid at considerably higher frequency than is expected in the general population,” Dr. LeBoeuf said in an interview.
And although bullous pemphigoid has the potential to disrupt ICI therapy, it also appears to be a marker for a favorable tumor response, the investigators found.
Their findings suggest that management of bullous pemphigoid for patients receiving ICIs should focus on early identification and management with therapies directed at the specific toxicity, Dr. LeBoeuf said.
“When you make a specific diagnosis like bullous pemphigoid, then you can treat that specific disease with very targeted therapies, such as omalizumab or dupilumab or rituximab – things that are not globally immune suppressing like steroid or other T-cell–depleting agents. Studies have shown that depleting B cells with anti-CD20 agents is not detrimental to immune checkpoint inhibitor therapy,” she said.
Dermatologic AEs common
About 40% of patients with cancer treated with ICIs experience immune-related dermatologic adverse events (AEs) that can range from mild rashes and hair and nail changes to uncommon but life-threatening complications, such as Stevens-Johnson syndrome, a form of toxic epidermal necrolysis, according to members of a European Academy of Dermatology and Venereology task force.
“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they wrote in a position statement on the management of ICI-derived dermatologic adverse events.
Dr. LeBoeuf and colleagues note that, while reported risk factors for idiopathic bullous pemphigoid include advanced age, type 2 diabetes, use of dipeptidyl peptidase-4 inhibitors, cerebrovascular disease, and neurocognitive disease, risk factors for bullous pemphigoid and other adverse dermatologic events associated with ICIs are less well known.
Study details
To identify risk factors for bullous pemphigoid in patients receiving ICI, the investigators performed a case-control study nested within a retrospective cohort study.
They evaluated records for all patients in the three Harvard-affiliated hospitals to identify patients with ICI-associated bullous pemphigoid from October 2014 through December 2020. Control persons were all patients in the Dana-Farber cancer registry who received ICIs during the study period.
The investigators chose age at ICI initiation (69 years and younger or 70 years and older), sex, ICI agents, and cancer type as potential risk factors.
They used propensity score matching based on age, cancer type, ICI agent, and number of ICI cycles to match two control persons with each case patient.
Of the 5,636 patients treated with ICIs during the study period, 35 (0.6%) developed bullous pemphigoid. The median age was 72.8 years, and 71.4% were men.
In a multivariate logistic regression model that included 2,955 patients with complete data in the cancer registry, factors significantly associated with developing bullous pemphigoid included age 70 years or older (odds ratio, 2.32; P = .01), having melanoma (OR, 3.21; P < .001), and having nonmelanoma skin cancer (OR, 8.32; P < .001).
In comparing the 35 case patients with their matched control patients, a complete or partial response at first restaging imaging was significantly associated with developing bullous pemphigoid (OR, 3.37; P = .01). In addition, there was a higher likelihood of tumor responses to ICIs among patients with bullous pemphigoid, compared with matched control patients (objective response rate, 82.9% vs. 61.4%; P = .03).
Prudent toxicity management
Ryan Sullivan, MD, who treats patients with skin cancer at Massachusetts General Hospital Cancer Center, Boston, but was not involved in the study, commented that the findings raise questions about the relationship between skin cancers and immune-related adverse events.
“It is compelling that bullous pemphigoid is a skin toxicity and is more common to happen in skin cancer patients,” he noted. “That’s a very interesting finding, and the reason that it’s interesting is that it’s harder to understand why a presumably antibody-mediated side effect would be more likely to have that cross-reactivity where the tumor started and where the toxicity happened,” he said in an interview.
He noted that the benefits of ICIs for patients with skin cancers far outweigh the risks of dermatologic adverse events such as bullous pemphigoid and that ICI-associated events require judicious management.
“This is true across the spectrum of toxicities: There are clear manifestations of toxicity that we should be more thoughtful about what’s driving them, more thoughtful about what it is, and more thoughtful about treating them, other than just pouring steroids into patients in industrial doses and hoping that everything’s going to be OK,” he said.
No funding source for the study was reported. Dr. LeBoeuf reported receiving grants from the National Institutes of Health National Cancer Institute during the conduct of the study and personal fees for serving as a consultant for several companies outside the study. Coauthor Arash Mostaghimi, MD, MPA, MPH, is associate editor of JAMA Dermatology but was not involved in study selection or evaluation for publication. Dr. Sullivan disclosed consulting for ICI makers Bristol-Myers Squibb and Merck.
A version of this article first appeared on Medscape.com.
FROM JAMA DERMATOLOGY
24-year-old female presents with a 3-month history of nonpruritic rash
, typically characterized by symmetrical, nonblanching, purpuric, telangiectatic, and atrophic patches with a predilection for the lower extremities and buttocks.
Plaques are usually 1-3 cm in diameter and annular with punctate telangiectasias and cayenne pepper petechiae in the border. The annular patches may form concentric rings. It is most commonly seen in children and young females.
The etiology of Majocchi’s disease is largely unknown and idiopathic.
Triggers are not always detected but may be associated with viral infections, chronic comorbidities, and medications. Levofloxacin and isotretinoin have been described in as reports as causing PATM. Other medications reported to cause PPD include sedatives, stimulants, antibiotics, NSAIDS, and cardiovascular drugs.
Diagnosis of PATM is clinical and histopathologic. Direct immunofluorescence (DIF) may show fibrinogen, IgM, and/or C3 deposition in superficial dermal vessels. Histopathologic findings show lymphocytic infiltrate involving the superficial small vessels, extravasated red blood cells, and hemosiderin-laden macrophages.
There is no consensus regarding treatment with variable responses to proposed treatment based on reports and case studies. The first line of treatment is topical corticosteroids and compression hose. Additional treatments, including narrowband UVB phototherapy (NBUVB), griseofulvin, pentoxifylline, cyclosporine, colchicine, rutoside with ascorbic acid, and methotrexate, have been used with varying success.
In this patient, a punch biopsy was performed, which revealed lymphocytes and extravasated erythrocytes and siderophages in the dermis. She was treated with topical steroids with improvement. She started NBUVB, a short course of griseofulvin, and vitamin C supplements.
This case and the photos were photo submitted by Ms. Xu, of the University of California, San Diego, and Dr. Sateesh, of San Diego Family Dermatology. Dr. Donna Bilu Martin edited the column.
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].
References
1. Garcez A et al. An Bras Dermatol. Sep-Oct 2020;95(5):664-6. doi: 10.1016/j.abd.2020.02.007.
2. Asadbeigi S, Momtahen S. Pigmented purpuric dermatosis. PathologyOutlines.com website.
3. Martínez P et al. Actas Dermosifiliogr (Engl Ed). 2020 Apr;111(3):196-204. doi: 10.1016/j.ad.2019.02.013.
4. Hoesly FJ et al. Int J Dermatol. 2009 Oct;48(10):1129-33. doi: 10.1111/j.1365-4632.2009.04160.x.
, typically characterized by symmetrical, nonblanching, purpuric, telangiectatic, and atrophic patches with a predilection for the lower extremities and buttocks.
Plaques are usually 1-3 cm in diameter and annular with punctate telangiectasias and cayenne pepper petechiae in the border. The annular patches may form concentric rings. It is most commonly seen in children and young females.
The etiology of Majocchi’s disease is largely unknown and idiopathic.
Triggers are not always detected but may be associated with viral infections, chronic comorbidities, and medications. Levofloxacin and isotretinoin have been described in as reports as causing PATM. Other medications reported to cause PPD include sedatives, stimulants, antibiotics, NSAIDS, and cardiovascular drugs.
Diagnosis of PATM is clinical and histopathologic. Direct immunofluorescence (DIF) may show fibrinogen, IgM, and/or C3 deposition in superficial dermal vessels. Histopathologic findings show lymphocytic infiltrate involving the superficial small vessels, extravasated red blood cells, and hemosiderin-laden macrophages.
There is no consensus regarding treatment with variable responses to proposed treatment based on reports and case studies. The first line of treatment is topical corticosteroids and compression hose. Additional treatments, including narrowband UVB phototherapy (NBUVB), griseofulvin, pentoxifylline, cyclosporine, colchicine, rutoside with ascorbic acid, and methotrexate, have been used with varying success.
In this patient, a punch biopsy was performed, which revealed lymphocytes and extravasated erythrocytes and siderophages in the dermis. She was treated with topical steroids with improvement. She started NBUVB, a short course of griseofulvin, and vitamin C supplements.
This case and the photos were photo submitted by Ms. Xu, of the University of California, San Diego, and Dr. Sateesh, of San Diego Family Dermatology. Dr. Donna Bilu Martin edited the column.
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].
References
1. Garcez A et al. An Bras Dermatol. Sep-Oct 2020;95(5):664-6. doi: 10.1016/j.abd.2020.02.007.
2. Asadbeigi S, Momtahen S. Pigmented purpuric dermatosis. PathologyOutlines.com website.
3. Martínez P et al. Actas Dermosifiliogr (Engl Ed). 2020 Apr;111(3):196-204. doi: 10.1016/j.ad.2019.02.013.
4. Hoesly FJ et al. Int J Dermatol. 2009 Oct;48(10):1129-33. doi: 10.1111/j.1365-4632.2009.04160.x.
, typically characterized by symmetrical, nonblanching, purpuric, telangiectatic, and atrophic patches with a predilection for the lower extremities and buttocks.
Plaques are usually 1-3 cm in diameter and annular with punctate telangiectasias and cayenne pepper petechiae in the border. The annular patches may form concentric rings. It is most commonly seen in children and young females.
The etiology of Majocchi’s disease is largely unknown and idiopathic.
Triggers are not always detected but may be associated with viral infections, chronic comorbidities, and medications. Levofloxacin and isotretinoin have been described in as reports as causing PATM. Other medications reported to cause PPD include sedatives, stimulants, antibiotics, NSAIDS, and cardiovascular drugs.
Diagnosis of PATM is clinical and histopathologic. Direct immunofluorescence (DIF) may show fibrinogen, IgM, and/or C3 deposition in superficial dermal vessels. Histopathologic findings show lymphocytic infiltrate involving the superficial small vessels, extravasated red blood cells, and hemosiderin-laden macrophages.
There is no consensus regarding treatment with variable responses to proposed treatment based on reports and case studies. The first line of treatment is topical corticosteroids and compression hose. Additional treatments, including narrowband UVB phototherapy (NBUVB), griseofulvin, pentoxifylline, cyclosporine, colchicine, rutoside with ascorbic acid, and methotrexate, have been used with varying success.
In this patient, a punch biopsy was performed, which revealed lymphocytes and extravasated erythrocytes and siderophages in the dermis. She was treated with topical steroids with improvement. She started NBUVB, a short course of griseofulvin, and vitamin C supplements.
This case and the photos were photo submitted by Ms. Xu, of the University of California, San Diego, and Dr. Sateesh, of San Diego Family Dermatology. Dr. Donna Bilu Martin edited the column.
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].
References
1. Garcez A et al. An Bras Dermatol. Sep-Oct 2020;95(5):664-6. doi: 10.1016/j.abd.2020.02.007.
2. Asadbeigi S, Momtahen S. Pigmented purpuric dermatosis. PathologyOutlines.com website.
3. Martínez P et al. Actas Dermosifiliogr (Engl Ed). 2020 Apr;111(3):196-204. doi: 10.1016/j.ad.2019.02.013.
4. Hoesly FJ et al. Int J Dermatol. 2009 Oct;48(10):1129-33. doi: 10.1111/j.1365-4632.2009.04160.x.
A 14-year-old male presents to clinic with a new-onset rash of the hands
Photosensitivity due to doxycycline
As the patient’s rash presented in sun-exposed areas with both skin and nail changes, our patient was diagnosed with a phototoxic reaction to doxycycline, the oral antibiotic used to treat his acne.
Photosensitive cutaneous drug eruptions are reactions that occur after exposure to a medication and subsequent exposure to UV radiation or visible light. Reactions can be classified into two ways based on their mechanism of action: phototoxic or photoallergic.1 Phototoxic reactions are more common and are a result of direct keratinocyte damage and cellular necrosis. Many classes of medications may cause this adverse effect, but the tetracycline class of antibiotics is a common culprit.2 Photoallergic reactions are less common and are a result of a type IV immune reaction to the offending agent.1
Phototoxic reactions generally present shortly after sun or UV exposure with a photo-distributed eruption pattern.3 Commonly involved areas include the face, the neck, and the extensor surfaces of extremities, with sparing of relatively protected skin such as the upper eyelids and the skin folds.2 Erythema may initially develop in the exposed skin areas, followed by appearance of edema, vesicles, or bullae.1-3 The eruption may be painful and itchy, with some patients reporting severe pain.3
Doxycycline phototoxicity may also cause onycholysis of the nails.2 The reaction is dose dependent, with higher doses of medication leading to a higher likelihood of symptoms.1,2 It is also more prevalent in patients with Fitzpatrick skin type I and II. The usual UVA wavelength required to induce this reaction appears to be in the 320-400 nm range of the UV spectrum.4 By contrast, photoallergic reactions are dose independent, and require a sensitization period prior to the eruption.1 An eczematous eruption is most commonly seen with photoallergic reactions.3
Treatment of drug-induced photosensitivity reactions requires proper identification of the diagnosis and the offending agent, followed by cessation of the medication. If cessation is not possible, then lowering the dose can help to minimize worsening of the condition. However, for photoallergic reactions, the reaction is dose independent so switching to another tolerated agent is likely required. For persistent symptoms following medication withdrawal, topical or systemic steroids and oral antihistamine can help with symptom management.1 For patients with photo-onycholysis, treatment involves stopping the medication and waiting for the intact nail plate to grow.
Prevention is key in the management of photosensitivity reactions. Patients should be counseled about the increased risk of photosensitivity while on tetracycline medications and encouraged to engage in enhanced sun protection measures such as wearing sun protective hats and clothing, increasing use of sunscreen that provides mainly UVA but also UVB protection, and avoiding the sun during the midday when the UV index is highest.1-3
Dermatomyositis
Dermatomyositis is an autoimmune condition that presents with skin lesions as well as systemic findings such as myositis. The cutaneous findings are variable, but pathognomonic findings include Gottron papules of the hands, Gottron’s sign on the elbows, knees, and ankles, and the heliotrope rash of the face. Eighty percent of patients have myopathy presenting as muscle weakness, and commonly have elevated creatine kinase, aspartate transaminase, and alanine transaminase values.5 Diagnosis may be confirmed through skin or muscle biopsy, though antibody studies can also play a helpful role in diagnosis. Treatment is generally with oral corticosteroids or other immunosuppressants as well as sun protection.6 The rash seen in our patient could have been seen in patients with dermatomyositis, though it was not in the typical location on the knuckles (Gottron papules) as it also affected the lateral sides of the fingers.
Systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is an autoimmune condition characterized by systemic and cutaneous manifestations. Systemic symptoms may include weight loss, fever, fatigue, arthralgia, or arthritis; patients are at risk of renal, cardiovascular, pulmonary, and neurologic complications of SLE.7 The most common cutaneous finding is malar rash, though there are myriad dermatologic manifestations that can occur associated with photosensitivity. Diagnosis is made based on history, physical, and laboratory testing. Treatment options include NSAIDs, oral glucocorticoids, antimalarial drugs, and immunosuppressants.7 Though our patient exhibited photosensitivity, he had none of the systemic findings associated with SLE, making this diagnosis unlikely.
Allergic contact dermatitis
Allergic contact dermatitis (ACD) is a type IV hypersensitivity reaction, and may present as acute, subacute, or chronic dermatitis. The clinical findings vary based on chronicity. Acute ACD presents as pruritic erythematous papules and vesicles or bullae, similar to how it occurred in our patient, though our patient’s lesions were more tender than pruritic. Chronic ACD presents with erythematous lesions with pruritis, lichenification, scaling, and/or fissuring. Observing shapes or sharp demarcation of lesions may help with diagnosis. Patch testing is also useful in the diagnosis of ACD.
Treatment generally involves avoiding the offending agent with topical corticosteroids for symptom management.8
Polymorphous light eruption
Polymorphous light eruption (PLE) is a delayed, type IV hypersensitivity reaction to UV-induced antigens, though these antigens are unknown. PLE presents hours to days following solar or UV exposure and presents only in sun-exposed areas. Itching and burning are always present, but lesion morphology varies from erythema and papules to vesico-papules and blisters. Notably, PLE must be distinguished from drug photosensitivity through history. Treatment generally involves symptom management with topical steroids and sun protective measures for prevention.9 While PLE may present similarly to drug photosensitivity reactions, our patient’s use of a known phototoxic agent makes PLE a less likely diagnosis.
Ms. Appiah is a pediatric dermatology research associate and medical student at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Neither Dr. Matiz nor Ms. Appiah has any relevant financial disclosures.
References
1. Montgomery S et al. Clin Dermatol. 2022;40(1):57-63.
2. Blakely KM et al. Drug Saf. 2019;42(7):827-47.
3. Goetze S et al. Skin Pharmacol Physiol. 2017;30(2):76-80.
4. Odorici G et al. Dermatol Ther. 2021;34(4):e14978.
5. DeWane ME et al. J Am Acad Dermatol. 2020;82(2):267-81.
6. Waldman R et al. J Am Acad Dermatol. 2020;82(2):283-96.
7. Kiriakidou M et al. Ann Intern Med. 2020;172(11):ITC81-ITC96.
8. Nassau S et al. Med Clin North Am. 2020;104(1):61-76.
9. Guarrera M. Adv Exp Med Biol. 2017;996:61-70.
Photosensitivity due to doxycycline
As the patient’s rash presented in sun-exposed areas with both skin and nail changes, our patient was diagnosed with a phototoxic reaction to doxycycline, the oral antibiotic used to treat his acne.
Photosensitive cutaneous drug eruptions are reactions that occur after exposure to a medication and subsequent exposure to UV radiation or visible light. Reactions can be classified into two ways based on their mechanism of action: phototoxic or photoallergic.1 Phototoxic reactions are more common and are a result of direct keratinocyte damage and cellular necrosis. Many classes of medications may cause this adverse effect, but the tetracycline class of antibiotics is a common culprit.2 Photoallergic reactions are less common and are a result of a type IV immune reaction to the offending agent.1
Phototoxic reactions generally present shortly after sun or UV exposure with a photo-distributed eruption pattern.3 Commonly involved areas include the face, the neck, and the extensor surfaces of extremities, with sparing of relatively protected skin such as the upper eyelids and the skin folds.2 Erythema may initially develop in the exposed skin areas, followed by appearance of edema, vesicles, or bullae.1-3 The eruption may be painful and itchy, with some patients reporting severe pain.3
Doxycycline phototoxicity may also cause onycholysis of the nails.2 The reaction is dose dependent, with higher doses of medication leading to a higher likelihood of symptoms.1,2 It is also more prevalent in patients with Fitzpatrick skin type I and II. The usual UVA wavelength required to induce this reaction appears to be in the 320-400 nm range of the UV spectrum.4 By contrast, photoallergic reactions are dose independent, and require a sensitization period prior to the eruption.1 An eczematous eruption is most commonly seen with photoallergic reactions.3
Treatment of drug-induced photosensitivity reactions requires proper identification of the diagnosis and the offending agent, followed by cessation of the medication. If cessation is not possible, then lowering the dose can help to minimize worsening of the condition. However, for photoallergic reactions, the reaction is dose independent so switching to another tolerated agent is likely required. For persistent symptoms following medication withdrawal, topical or systemic steroids and oral antihistamine can help with symptom management.1 For patients with photo-onycholysis, treatment involves stopping the medication and waiting for the intact nail plate to grow.
Prevention is key in the management of photosensitivity reactions. Patients should be counseled about the increased risk of photosensitivity while on tetracycline medications and encouraged to engage in enhanced sun protection measures such as wearing sun protective hats and clothing, increasing use of sunscreen that provides mainly UVA but also UVB protection, and avoiding the sun during the midday when the UV index is highest.1-3
Dermatomyositis
Dermatomyositis is an autoimmune condition that presents with skin lesions as well as systemic findings such as myositis. The cutaneous findings are variable, but pathognomonic findings include Gottron papules of the hands, Gottron’s sign on the elbows, knees, and ankles, and the heliotrope rash of the face. Eighty percent of patients have myopathy presenting as muscle weakness, and commonly have elevated creatine kinase, aspartate transaminase, and alanine transaminase values.5 Diagnosis may be confirmed through skin or muscle biopsy, though antibody studies can also play a helpful role in diagnosis. Treatment is generally with oral corticosteroids or other immunosuppressants as well as sun protection.6 The rash seen in our patient could have been seen in patients with dermatomyositis, though it was not in the typical location on the knuckles (Gottron papules) as it also affected the lateral sides of the fingers.
Systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is an autoimmune condition characterized by systemic and cutaneous manifestations. Systemic symptoms may include weight loss, fever, fatigue, arthralgia, or arthritis; patients are at risk of renal, cardiovascular, pulmonary, and neurologic complications of SLE.7 The most common cutaneous finding is malar rash, though there are myriad dermatologic manifestations that can occur associated with photosensitivity. Diagnosis is made based on history, physical, and laboratory testing. Treatment options include NSAIDs, oral glucocorticoids, antimalarial drugs, and immunosuppressants.7 Though our patient exhibited photosensitivity, he had none of the systemic findings associated with SLE, making this diagnosis unlikely.
Allergic contact dermatitis
Allergic contact dermatitis (ACD) is a type IV hypersensitivity reaction, and may present as acute, subacute, or chronic dermatitis. The clinical findings vary based on chronicity. Acute ACD presents as pruritic erythematous papules and vesicles or bullae, similar to how it occurred in our patient, though our patient’s lesions were more tender than pruritic. Chronic ACD presents with erythematous lesions with pruritis, lichenification, scaling, and/or fissuring. Observing shapes or sharp demarcation of lesions may help with diagnosis. Patch testing is also useful in the diagnosis of ACD.
Treatment generally involves avoiding the offending agent with topical corticosteroids for symptom management.8
Polymorphous light eruption
Polymorphous light eruption (PLE) is a delayed, type IV hypersensitivity reaction to UV-induced antigens, though these antigens are unknown. PLE presents hours to days following solar or UV exposure and presents only in sun-exposed areas. Itching and burning are always present, but lesion morphology varies from erythema and papules to vesico-papules and blisters. Notably, PLE must be distinguished from drug photosensitivity through history. Treatment generally involves symptom management with topical steroids and sun protective measures for prevention.9 While PLE may present similarly to drug photosensitivity reactions, our patient’s use of a known phototoxic agent makes PLE a less likely diagnosis.
Ms. Appiah is a pediatric dermatology research associate and medical student at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Neither Dr. Matiz nor Ms. Appiah has any relevant financial disclosures.
References
1. Montgomery S et al. Clin Dermatol. 2022;40(1):57-63.
2. Blakely KM et al. Drug Saf. 2019;42(7):827-47.
3. Goetze S et al. Skin Pharmacol Physiol. 2017;30(2):76-80.
4. Odorici G et al. Dermatol Ther. 2021;34(4):e14978.
5. DeWane ME et al. J Am Acad Dermatol. 2020;82(2):267-81.
6. Waldman R et al. J Am Acad Dermatol. 2020;82(2):283-96.
7. Kiriakidou M et al. Ann Intern Med. 2020;172(11):ITC81-ITC96.
8. Nassau S et al. Med Clin North Am. 2020;104(1):61-76.
9. Guarrera M. Adv Exp Med Biol. 2017;996:61-70.
Photosensitivity due to doxycycline
As the patient’s rash presented in sun-exposed areas with both skin and nail changes, our patient was diagnosed with a phototoxic reaction to doxycycline, the oral antibiotic used to treat his acne.
Photosensitive cutaneous drug eruptions are reactions that occur after exposure to a medication and subsequent exposure to UV radiation or visible light. Reactions can be classified into two ways based on their mechanism of action: phototoxic or photoallergic.1 Phototoxic reactions are more common and are a result of direct keratinocyte damage and cellular necrosis. Many classes of medications may cause this adverse effect, but the tetracycline class of antibiotics is a common culprit.2 Photoallergic reactions are less common and are a result of a type IV immune reaction to the offending agent.1
Phototoxic reactions generally present shortly after sun or UV exposure with a photo-distributed eruption pattern.3 Commonly involved areas include the face, the neck, and the extensor surfaces of extremities, with sparing of relatively protected skin such as the upper eyelids and the skin folds.2 Erythema may initially develop in the exposed skin areas, followed by appearance of edema, vesicles, or bullae.1-3 The eruption may be painful and itchy, with some patients reporting severe pain.3
Doxycycline phototoxicity may also cause onycholysis of the nails.2 The reaction is dose dependent, with higher doses of medication leading to a higher likelihood of symptoms.1,2 It is also more prevalent in patients with Fitzpatrick skin type I and II. The usual UVA wavelength required to induce this reaction appears to be in the 320-400 nm range of the UV spectrum.4 By contrast, photoallergic reactions are dose independent, and require a sensitization period prior to the eruption.1 An eczematous eruption is most commonly seen with photoallergic reactions.3
Treatment of drug-induced photosensitivity reactions requires proper identification of the diagnosis and the offending agent, followed by cessation of the medication. If cessation is not possible, then lowering the dose can help to minimize worsening of the condition. However, for photoallergic reactions, the reaction is dose independent so switching to another tolerated agent is likely required. For persistent symptoms following medication withdrawal, topical or systemic steroids and oral antihistamine can help with symptom management.1 For patients with photo-onycholysis, treatment involves stopping the medication and waiting for the intact nail plate to grow.
Prevention is key in the management of photosensitivity reactions. Patients should be counseled about the increased risk of photosensitivity while on tetracycline medications and encouraged to engage in enhanced sun protection measures such as wearing sun protective hats and clothing, increasing use of sunscreen that provides mainly UVA but also UVB protection, and avoiding the sun during the midday when the UV index is highest.1-3
Dermatomyositis
Dermatomyositis is an autoimmune condition that presents with skin lesions as well as systemic findings such as myositis. The cutaneous findings are variable, but pathognomonic findings include Gottron papules of the hands, Gottron’s sign on the elbows, knees, and ankles, and the heliotrope rash of the face. Eighty percent of patients have myopathy presenting as muscle weakness, and commonly have elevated creatine kinase, aspartate transaminase, and alanine transaminase values.5 Diagnosis may be confirmed through skin or muscle biopsy, though antibody studies can also play a helpful role in diagnosis. Treatment is generally with oral corticosteroids or other immunosuppressants as well as sun protection.6 The rash seen in our patient could have been seen in patients with dermatomyositis, though it was not in the typical location on the knuckles (Gottron papules) as it also affected the lateral sides of the fingers.
Systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is an autoimmune condition characterized by systemic and cutaneous manifestations. Systemic symptoms may include weight loss, fever, fatigue, arthralgia, or arthritis; patients are at risk of renal, cardiovascular, pulmonary, and neurologic complications of SLE.7 The most common cutaneous finding is malar rash, though there are myriad dermatologic manifestations that can occur associated with photosensitivity. Diagnosis is made based on history, physical, and laboratory testing. Treatment options include NSAIDs, oral glucocorticoids, antimalarial drugs, and immunosuppressants.7 Though our patient exhibited photosensitivity, he had none of the systemic findings associated with SLE, making this diagnosis unlikely.
Allergic contact dermatitis
Allergic contact dermatitis (ACD) is a type IV hypersensitivity reaction, and may present as acute, subacute, or chronic dermatitis. The clinical findings vary based on chronicity. Acute ACD presents as pruritic erythematous papules and vesicles or bullae, similar to how it occurred in our patient, though our patient’s lesions were more tender than pruritic. Chronic ACD presents with erythematous lesions with pruritis, lichenification, scaling, and/or fissuring. Observing shapes or sharp demarcation of lesions may help with diagnosis. Patch testing is also useful in the diagnosis of ACD.
Treatment generally involves avoiding the offending agent with topical corticosteroids for symptom management.8
Polymorphous light eruption
Polymorphous light eruption (PLE) is a delayed, type IV hypersensitivity reaction to UV-induced antigens, though these antigens are unknown. PLE presents hours to days following solar or UV exposure and presents only in sun-exposed areas. Itching and burning are always present, but lesion morphology varies from erythema and papules to vesico-papules and blisters. Notably, PLE must be distinguished from drug photosensitivity through history. Treatment generally involves symptom management with topical steroids and sun protective measures for prevention.9 While PLE may present similarly to drug photosensitivity reactions, our patient’s use of a known phototoxic agent makes PLE a less likely diagnosis.
Ms. Appiah is a pediatric dermatology research associate and medical student at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Neither Dr. Matiz nor Ms. Appiah has any relevant financial disclosures.
References
1. Montgomery S et al. Clin Dermatol. 2022;40(1):57-63.
2. Blakely KM et al. Drug Saf. 2019;42(7):827-47.
3. Goetze S et al. Skin Pharmacol Physiol. 2017;30(2):76-80.
4. Odorici G et al. Dermatol Ther. 2021;34(4):e14978.
5. DeWane ME et al. J Am Acad Dermatol. 2020;82(2):267-81.
6. Waldman R et al. J Am Acad Dermatol. 2020;82(2):283-96.
7. Kiriakidou M et al. Ann Intern Med. 2020;172(11):ITC81-ITC96.
8. Nassau S et al. Med Clin North Am. 2020;104(1):61-76.
9. Guarrera M. Adv Exp Med Biol. 2017;996:61-70.
He reported no hiking or gardening, no new topical products such as new sunscreens or lotions, and no new medications. The patient had a history of acne, for which he used over-the-counter benzoyl peroxide wash, adapalene gel, and an oral antibiotic for 3 months. His review of systems was negative for fevers, chills, muscle weakness, mouth sores, or joint pain and no prior rashes following sun exposure.
On physical exam he presented with pink plaques with thin vesicles on the dorsum of the hands that were more noticeable on the lateral aspect of both the first and second fingers (Figures 1 and 2). His nails also had a yellow discoloration.
CO2 laser excision therapy for hidradenitis suppurativa shows no keloid risk
BOSTON – The use of , new research shows.
“With keloids disproportionately affecting Black and other skin of color patients, denying treatment on a notion that lacks evidentiary support further potentiates the health disparities experienced by these marginalized groups,” the researchers reported at the Annual Meeting of the Skin of Color Society Scientific Symposium (SOCS) 2022. In their retrospective study of 129 patients with HS treated with CO2 laser, “there were no cases of keloid formation,” they say.
HS, a potentially debilitating chronic inflammatory condition that involves painful nodules, boils, and abscesses, is often refractory to standard treatment. CO2 laser excision therapy has yielded favorable outcomes in some studies.
Although CO2 laser therapy is also used to treat keloids, some clinicians hesitate to use this treatment in these patients because of concerns that its use for treating HS could trigger the development of keloids.
“Many patients come in telling us they were denied [CO2 laser] surgery due to keloids,” senior author Iltefat Hamzavi, MD, a senior staff physician in the Department of Dermatology at the Henry Ford Health System, Detroit, told this news organization.
Although patients with HS are commonly treated with CO2 laser excision in his department, this treatment approach “is underused nationally,” he said.
“Of note, the sinus tunnels of hidradenitis suppurativa can look like keloids, so this might drive surgeons away from treating [those] lesions,” Dr. Hamzavi said.
To further evaluate the risk of developing keloids with the treatment, Dr. Hamzavi and his colleagues conducted a retrospective review of 129 patients with HS treated at Henry Ford who had undergone follicular destruction with CO2 laser between 2014 and 2021; 102 (79%) patients were female. The mean age was about 38 years (range, 15-78 years).
Of the patients, almost half were Black, almost 40% were White, 5% were Asian, and 3% were of unknown ethnicity.
Medical records of nine patients included diagnoses of keloids or hypertrophic scars. Further review indicated that none of the diagnoses were for keloids but were for hypertrophic scars, hypertrophic granulation tissue, an HS nodule, or contracture scar, the authors report.
“While the emergence of hypertrophic scars, hypertrophic granulation tissue, and scar contracture following CO2 laser excision therapy for hidradenitis suppurativa has been documented in the literature, existing evidence does not support postoperative keloid formation,” the authors conclude.
Because healing time with CO2 laser treatment is prolonged and there is an increase in risk of adverse events, Dr. Hamzavi underscored that “safety protocols for CO2 lasers should be followed, and wound prep instructions should be provided along with counseling on healing times.”
Regarding patient selection, he noted that “the disease should be medically stable with reduction in drainage to help control postop bleeding risk.”
The findings of the study are supported by a recent systematic review that compared outcomes and adverse effects of treatment with ablative laser therapies with nonablative lasers for skin resurfacing. The review included 34 studies and involved 1,093 patients. The conditions that were treated ranged from photodamage and acne scars to HS and post-traumatic scarring from basal cell carcinoma excision.
That review found that overall, rates of adverse events were higher with nonablative therapies (12.2%, 31 events), compared with ablative laser therapy, such as with CO2 laser (8.28%, 81 events). In addition, when transient events were excluded, ablative lasers were associated with fewer complications overall, compared with nonablative lasers (2.56% vs. 7.48%).
The authors conclude: “It is our hope that this study will facilitate continued research in this domain in an effort to combat these inequities and improve access to CO2 excision or standardized excisional therapy for hidradenitis suppurativa treatment.”
Dr. Hamzavi and the other authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON – The use of , new research shows.
“With keloids disproportionately affecting Black and other skin of color patients, denying treatment on a notion that lacks evidentiary support further potentiates the health disparities experienced by these marginalized groups,” the researchers reported at the Annual Meeting of the Skin of Color Society Scientific Symposium (SOCS) 2022. In their retrospective study of 129 patients with HS treated with CO2 laser, “there were no cases of keloid formation,” they say.
HS, a potentially debilitating chronic inflammatory condition that involves painful nodules, boils, and abscesses, is often refractory to standard treatment. CO2 laser excision therapy has yielded favorable outcomes in some studies.
Although CO2 laser therapy is also used to treat keloids, some clinicians hesitate to use this treatment in these patients because of concerns that its use for treating HS could trigger the development of keloids.
“Many patients come in telling us they were denied [CO2 laser] surgery due to keloids,” senior author Iltefat Hamzavi, MD, a senior staff physician in the Department of Dermatology at the Henry Ford Health System, Detroit, told this news organization.
Although patients with HS are commonly treated with CO2 laser excision in his department, this treatment approach “is underused nationally,” he said.
“Of note, the sinus tunnels of hidradenitis suppurativa can look like keloids, so this might drive surgeons away from treating [those] lesions,” Dr. Hamzavi said.
To further evaluate the risk of developing keloids with the treatment, Dr. Hamzavi and his colleagues conducted a retrospective review of 129 patients with HS treated at Henry Ford who had undergone follicular destruction with CO2 laser between 2014 and 2021; 102 (79%) patients were female. The mean age was about 38 years (range, 15-78 years).
Of the patients, almost half were Black, almost 40% were White, 5% were Asian, and 3% were of unknown ethnicity.
Medical records of nine patients included diagnoses of keloids or hypertrophic scars. Further review indicated that none of the diagnoses were for keloids but were for hypertrophic scars, hypertrophic granulation tissue, an HS nodule, or contracture scar, the authors report.
“While the emergence of hypertrophic scars, hypertrophic granulation tissue, and scar contracture following CO2 laser excision therapy for hidradenitis suppurativa has been documented in the literature, existing evidence does not support postoperative keloid formation,” the authors conclude.
Because healing time with CO2 laser treatment is prolonged and there is an increase in risk of adverse events, Dr. Hamzavi underscored that “safety protocols for CO2 lasers should be followed, and wound prep instructions should be provided along with counseling on healing times.”
Regarding patient selection, he noted that “the disease should be medically stable with reduction in drainage to help control postop bleeding risk.”
The findings of the study are supported by a recent systematic review that compared outcomes and adverse effects of treatment with ablative laser therapies with nonablative lasers for skin resurfacing. The review included 34 studies and involved 1,093 patients. The conditions that were treated ranged from photodamage and acne scars to HS and post-traumatic scarring from basal cell carcinoma excision.
That review found that overall, rates of adverse events were higher with nonablative therapies (12.2%, 31 events), compared with ablative laser therapy, such as with CO2 laser (8.28%, 81 events). In addition, when transient events were excluded, ablative lasers were associated with fewer complications overall, compared with nonablative lasers (2.56% vs. 7.48%).
The authors conclude: “It is our hope that this study will facilitate continued research in this domain in an effort to combat these inequities and improve access to CO2 excision or standardized excisional therapy for hidradenitis suppurativa treatment.”
Dr. Hamzavi and the other authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BOSTON – The use of , new research shows.
“With keloids disproportionately affecting Black and other skin of color patients, denying treatment on a notion that lacks evidentiary support further potentiates the health disparities experienced by these marginalized groups,” the researchers reported at the Annual Meeting of the Skin of Color Society Scientific Symposium (SOCS) 2022. In their retrospective study of 129 patients with HS treated with CO2 laser, “there were no cases of keloid formation,” they say.
HS, a potentially debilitating chronic inflammatory condition that involves painful nodules, boils, and abscesses, is often refractory to standard treatment. CO2 laser excision therapy has yielded favorable outcomes in some studies.
Although CO2 laser therapy is also used to treat keloids, some clinicians hesitate to use this treatment in these patients because of concerns that its use for treating HS could trigger the development of keloids.
“Many patients come in telling us they were denied [CO2 laser] surgery due to keloids,” senior author Iltefat Hamzavi, MD, a senior staff physician in the Department of Dermatology at the Henry Ford Health System, Detroit, told this news organization.
Although patients with HS are commonly treated with CO2 laser excision in his department, this treatment approach “is underused nationally,” he said.
“Of note, the sinus tunnels of hidradenitis suppurativa can look like keloids, so this might drive surgeons away from treating [those] lesions,” Dr. Hamzavi said.
To further evaluate the risk of developing keloids with the treatment, Dr. Hamzavi and his colleagues conducted a retrospective review of 129 patients with HS treated at Henry Ford who had undergone follicular destruction with CO2 laser between 2014 and 2021; 102 (79%) patients were female. The mean age was about 38 years (range, 15-78 years).
Of the patients, almost half were Black, almost 40% were White, 5% were Asian, and 3% were of unknown ethnicity.
Medical records of nine patients included diagnoses of keloids or hypertrophic scars. Further review indicated that none of the diagnoses were for keloids but were for hypertrophic scars, hypertrophic granulation tissue, an HS nodule, or contracture scar, the authors report.
“While the emergence of hypertrophic scars, hypertrophic granulation tissue, and scar contracture following CO2 laser excision therapy for hidradenitis suppurativa has been documented in the literature, existing evidence does not support postoperative keloid formation,” the authors conclude.
Because healing time with CO2 laser treatment is prolonged and there is an increase in risk of adverse events, Dr. Hamzavi underscored that “safety protocols for CO2 lasers should be followed, and wound prep instructions should be provided along with counseling on healing times.”
Regarding patient selection, he noted that “the disease should be medically stable with reduction in drainage to help control postop bleeding risk.”
The findings of the study are supported by a recent systematic review that compared outcomes and adverse effects of treatment with ablative laser therapies with nonablative lasers for skin resurfacing. The review included 34 studies and involved 1,093 patients. The conditions that were treated ranged from photodamage and acne scars to HS and post-traumatic scarring from basal cell carcinoma excision.
That review found that overall, rates of adverse events were higher with nonablative therapies (12.2%, 31 events), compared with ablative laser therapy, such as with CO2 laser (8.28%, 81 events). In addition, when transient events were excluded, ablative lasers were associated with fewer complications overall, compared with nonablative lasers (2.56% vs. 7.48%).
The authors conclude: “It is our hope that this study will facilitate continued research in this domain in an effort to combat these inequities and improve access to CO2 excision or standardized excisional therapy for hidradenitis suppurativa treatment.”
Dr. Hamzavi and the other authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT SOCS 2022
For pemphigus, rituximab is first line, expert says
BOSTON – . This drug is more rapidly effective, more likely to provide sustained remission, better tolerated, and lowers health care costs, according to an expert summary at the annual meeting of the American Academy of Dermatology.
With rituximab “we are not only able to offer better efficacy, earlier and longer remissions, less side effects, less risk of relapse after a response, but it is actually cheaper,” reported Erin X. Wei, MD, director of the Bullous Diseases Clinic at Brigham and Women’s Hospital, Boston.
There are many treatments that reduce the inflammatory component of pemphigus. Corticosteroids, doxycycline, mycophenolate mofetil, azathioprine, and methotrexate are among those options commonly considered in the early control of this rare and potentially fatal autoimmune blistering disease of the skin, mouth, and other tissues.
Not all of these options have been compared directly in controlled trials, but Dr. Wei indicated that the preponderance of evidence is now on the side of rituximab as a first-line choice. For example, in the multicenter Ritux 3 trial, which compared a tapered regimen of prednisone alone to rituximab combined with a shorter and lower-dose prednisone taper in patients with pemphigus, complete response rates off therapy at 2 years were 89% in the rituximab group versus 34% in the group that received prednisone alone.
“This was quite a remarkable difference,” said Dr. Wei, who noted that remissions overall occurred faster in the rituximab group and were more durable once achieved.
No other treatment option has demonstrated this degree of relative benefit over corticosteroids, according to Dr. Wei. She said there is evidence that mycophenolate mofetil acts more rapidly, but it has not been shown to be superior for sustained complete response. Nor has azathioprine provided a clear advantage over steroids. There are no well-conducted comparisons of methotrexate and prednisone, according to Dr. Wei, assistant professor at Harvard Medical School, Boston.
Corticosteroids, doxycycline, and immunomodulators have been characterized as mainstays of early treatment in pemphigus, but Dr. Wei argued that the evidence supports starting with the most effective therapy first. There are many advantages to suppressing disease activity “as soon as possible” after diagnosis.
Early control “is associated with a more sustained remission, lower overall steroid use, and better quality of life,” said Dr. Wei, listing the hazards of starting with less effective therapy, and explaining why she has moved to rituximab as a first-line choice. According to her, there are data to support these advantages.
“Several studies have observed that rituximab, within the first 6 months of disease onset, is associated with a higher rate of complete response and a longer duration of complete response,” Dr. Wei said.
Intravenous immunoglobulin (IVIG) therapy is effective in many patients but less reliable, and it has other disadvantages relative to rituximab as a first-line therapy.
“IVIG in pemphigus works quickly when it works, but it is more expensive and it is more of an ongoing therapy relative to rituximab,” said Dr. Wei, referring to the lower likelihood of IVIG to provide sustained remissions.
The price of rituximab is high relative to prednisone or other immunomodulators, but management costs are ultimately reduced because of better disease control, according to Dr. Wei. She cited a Canadian study published several years ago in which health care costs in the 6 months prior to rituximab were compared to costs over 6 months after it was initiated.
In this cohort of 89 patients with pemphigus or pemphigoid, the average cost per patient for 6 months of care prior to starting rituximab was $42,231 in Canadian dollars. After treatment was started, the cost fell to $29,423, a 30% reduction, over the next 6 months.
“It takes rituximab up to 3 months or sometimes even longer to achieve its greatest benefit, making these results even more impressive,” Dr. Wei said.
The activity of rituximab to suppress autoreactive B-cells can be monitored with antidesmoglein autoantibody levels and by measuring CD20-positive cell percentages. Unlike severity of disease at baseline, which Dr. Wei said is not a reliable predictor of relapse risk, these can guide steroid tapering.
“If the patient is not making new autoantibodies, then tapering steroids can be considered safe,” Dr. Wei said.
One small case series cited by Dr. Wei has suggested that rituximab might be effectively employed as a maintenance therapy for pemphigus. The maintenance treatment, which initially consisted of 1 g of rituximab every 6 months, was evaluated in 11 patients with a history of severe and frequent relapses.
In this group, rituximab was first employed to achieve a complete response. The maintenance was initiated when patients were in remission. In some patients, the maintenance dose interval was extended to once every 12 months over time. During a mean follow-up of 4 years, all 11 patients remained in complete remission.
“This was a remarkable result,” said Dr. Wei, who noted that there were no serious adverse events associated with rituximab maintenance over this period. This cannot be considered a routine strategy without a large patient experience, according to Dr. Wei, but it does provide another piece of evidence that rituximab is effective and well tolerated.
There are no guidelines from a major organization that establish an evidence-based treatment algorithm for pemphigus, but Dr. Wei is not alone in considering early initiation of the most effective therapy as the best approach to sustained control.
“I agree that rituximab is a good first-line option for pemphigus patients,” said Kara Heelan, MBBCh, MD, a consultant dermatologist at the Royal Marsden and Lister Hospital, London. She was the first author of the cost-effectiveness study that Dr. Wei cited. The study was published when she was an associate in the division of dermatology at the University of Toronto.
By calling rituximab “a good” option rather than a potential standard, Dr. Heelan appeared to be more circumspect than Dr. Wei about its central role in the care of pemphigus, but she did agree in an interview that this agent “has been shown to be cost-effective.” In her study, this was an advantage attributed to relative efficacy and safety that reduced use of health care resources.
A version of this article first appeared on Medscape.com.
BOSTON – . This drug is more rapidly effective, more likely to provide sustained remission, better tolerated, and lowers health care costs, according to an expert summary at the annual meeting of the American Academy of Dermatology.
With rituximab “we are not only able to offer better efficacy, earlier and longer remissions, less side effects, less risk of relapse after a response, but it is actually cheaper,” reported Erin X. Wei, MD, director of the Bullous Diseases Clinic at Brigham and Women’s Hospital, Boston.
There are many treatments that reduce the inflammatory component of pemphigus. Corticosteroids, doxycycline, mycophenolate mofetil, azathioprine, and methotrexate are among those options commonly considered in the early control of this rare and potentially fatal autoimmune blistering disease of the skin, mouth, and other tissues.
Not all of these options have been compared directly in controlled trials, but Dr. Wei indicated that the preponderance of evidence is now on the side of rituximab as a first-line choice. For example, in the multicenter Ritux 3 trial, which compared a tapered regimen of prednisone alone to rituximab combined with a shorter and lower-dose prednisone taper in patients with pemphigus, complete response rates off therapy at 2 years were 89% in the rituximab group versus 34% in the group that received prednisone alone.
“This was quite a remarkable difference,” said Dr. Wei, who noted that remissions overall occurred faster in the rituximab group and were more durable once achieved.
No other treatment option has demonstrated this degree of relative benefit over corticosteroids, according to Dr. Wei. She said there is evidence that mycophenolate mofetil acts more rapidly, but it has not been shown to be superior for sustained complete response. Nor has azathioprine provided a clear advantage over steroids. There are no well-conducted comparisons of methotrexate and prednisone, according to Dr. Wei, assistant professor at Harvard Medical School, Boston.
Corticosteroids, doxycycline, and immunomodulators have been characterized as mainstays of early treatment in pemphigus, but Dr. Wei argued that the evidence supports starting with the most effective therapy first. There are many advantages to suppressing disease activity “as soon as possible” after diagnosis.
Early control “is associated with a more sustained remission, lower overall steroid use, and better quality of life,” said Dr. Wei, listing the hazards of starting with less effective therapy, and explaining why she has moved to rituximab as a first-line choice. According to her, there are data to support these advantages.
“Several studies have observed that rituximab, within the first 6 months of disease onset, is associated with a higher rate of complete response and a longer duration of complete response,” Dr. Wei said.
Intravenous immunoglobulin (IVIG) therapy is effective in many patients but less reliable, and it has other disadvantages relative to rituximab as a first-line therapy.
“IVIG in pemphigus works quickly when it works, but it is more expensive and it is more of an ongoing therapy relative to rituximab,” said Dr. Wei, referring to the lower likelihood of IVIG to provide sustained remissions.
The price of rituximab is high relative to prednisone or other immunomodulators, but management costs are ultimately reduced because of better disease control, according to Dr. Wei. She cited a Canadian study published several years ago in which health care costs in the 6 months prior to rituximab were compared to costs over 6 months after it was initiated.
In this cohort of 89 patients with pemphigus or pemphigoid, the average cost per patient for 6 months of care prior to starting rituximab was $42,231 in Canadian dollars. After treatment was started, the cost fell to $29,423, a 30% reduction, over the next 6 months.
“It takes rituximab up to 3 months or sometimes even longer to achieve its greatest benefit, making these results even more impressive,” Dr. Wei said.
The activity of rituximab to suppress autoreactive B-cells can be monitored with antidesmoglein autoantibody levels and by measuring CD20-positive cell percentages. Unlike severity of disease at baseline, which Dr. Wei said is not a reliable predictor of relapse risk, these can guide steroid tapering.
“If the patient is not making new autoantibodies, then tapering steroids can be considered safe,” Dr. Wei said.
One small case series cited by Dr. Wei has suggested that rituximab might be effectively employed as a maintenance therapy for pemphigus. The maintenance treatment, which initially consisted of 1 g of rituximab every 6 months, was evaluated in 11 patients with a history of severe and frequent relapses.
In this group, rituximab was first employed to achieve a complete response. The maintenance was initiated when patients were in remission. In some patients, the maintenance dose interval was extended to once every 12 months over time. During a mean follow-up of 4 years, all 11 patients remained in complete remission.
“This was a remarkable result,” said Dr. Wei, who noted that there were no serious adverse events associated with rituximab maintenance over this period. This cannot be considered a routine strategy without a large patient experience, according to Dr. Wei, but it does provide another piece of evidence that rituximab is effective and well tolerated.
There are no guidelines from a major organization that establish an evidence-based treatment algorithm for pemphigus, but Dr. Wei is not alone in considering early initiation of the most effective therapy as the best approach to sustained control.
“I agree that rituximab is a good first-line option for pemphigus patients,” said Kara Heelan, MBBCh, MD, a consultant dermatologist at the Royal Marsden and Lister Hospital, London. She was the first author of the cost-effectiveness study that Dr. Wei cited. The study was published when she was an associate in the division of dermatology at the University of Toronto.
By calling rituximab “a good” option rather than a potential standard, Dr. Heelan appeared to be more circumspect than Dr. Wei about its central role in the care of pemphigus, but she did agree in an interview that this agent “has been shown to be cost-effective.” In her study, this was an advantage attributed to relative efficacy and safety that reduced use of health care resources.
A version of this article first appeared on Medscape.com.
BOSTON – . This drug is more rapidly effective, more likely to provide sustained remission, better tolerated, and lowers health care costs, according to an expert summary at the annual meeting of the American Academy of Dermatology.
With rituximab “we are not only able to offer better efficacy, earlier and longer remissions, less side effects, less risk of relapse after a response, but it is actually cheaper,” reported Erin X. Wei, MD, director of the Bullous Diseases Clinic at Brigham and Women’s Hospital, Boston.
There are many treatments that reduce the inflammatory component of pemphigus. Corticosteroids, doxycycline, mycophenolate mofetil, azathioprine, and methotrexate are among those options commonly considered in the early control of this rare and potentially fatal autoimmune blistering disease of the skin, mouth, and other tissues.
Not all of these options have been compared directly in controlled trials, but Dr. Wei indicated that the preponderance of evidence is now on the side of rituximab as a first-line choice. For example, in the multicenter Ritux 3 trial, which compared a tapered regimen of prednisone alone to rituximab combined with a shorter and lower-dose prednisone taper in patients with pemphigus, complete response rates off therapy at 2 years were 89% in the rituximab group versus 34% in the group that received prednisone alone.
“This was quite a remarkable difference,” said Dr. Wei, who noted that remissions overall occurred faster in the rituximab group and were more durable once achieved.
No other treatment option has demonstrated this degree of relative benefit over corticosteroids, according to Dr. Wei. She said there is evidence that mycophenolate mofetil acts more rapidly, but it has not been shown to be superior for sustained complete response. Nor has azathioprine provided a clear advantage over steroids. There are no well-conducted comparisons of methotrexate and prednisone, according to Dr. Wei, assistant professor at Harvard Medical School, Boston.
Corticosteroids, doxycycline, and immunomodulators have been characterized as mainstays of early treatment in pemphigus, but Dr. Wei argued that the evidence supports starting with the most effective therapy first. There are many advantages to suppressing disease activity “as soon as possible” after diagnosis.
Early control “is associated with a more sustained remission, lower overall steroid use, and better quality of life,” said Dr. Wei, listing the hazards of starting with less effective therapy, and explaining why she has moved to rituximab as a first-line choice. According to her, there are data to support these advantages.
“Several studies have observed that rituximab, within the first 6 months of disease onset, is associated with a higher rate of complete response and a longer duration of complete response,” Dr. Wei said.
Intravenous immunoglobulin (IVIG) therapy is effective in many patients but less reliable, and it has other disadvantages relative to rituximab as a first-line therapy.
“IVIG in pemphigus works quickly when it works, but it is more expensive and it is more of an ongoing therapy relative to rituximab,” said Dr. Wei, referring to the lower likelihood of IVIG to provide sustained remissions.
The price of rituximab is high relative to prednisone or other immunomodulators, but management costs are ultimately reduced because of better disease control, according to Dr. Wei. She cited a Canadian study published several years ago in which health care costs in the 6 months prior to rituximab were compared to costs over 6 months after it was initiated.
In this cohort of 89 patients with pemphigus or pemphigoid, the average cost per patient for 6 months of care prior to starting rituximab was $42,231 in Canadian dollars. After treatment was started, the cost fell to $29,423, a 30% reduction, over the next 6 months.
“It takes rituximab up to 3 months or sometimes even longer to achieve its greatest benefit, making these results even more impressive,” Dr. Wei said.
The activity of rituximab to suppress autoreactive B-cells can be monitored with antidesmoglein autoantibody levels and by measuring CD20-positive cell percentages. Unlike severity of disease at baseline, which Dr. Wei said is not a reliable predictor of relapse risk, these can guide steroid tapering.
“If the patient is not making new autoantibodies, then tapering steroids can be considered safe,” Dr. Wei said.
One small case series cited by Dr. Wei has suggested that rituximab might be effectively employed as a maintenance therapy for pemphigus. The maintenance treatment, which initially consisted of 1 g of rituximab every 6 months, was evaluated in 11 patients with a history of severe and frequent relapses.
In this group, rituximab was first employed to achieve a complete response. The maintenance was initiated when patients were in remission. In some patients, the maintenance dose interval was extended to once every 12 months over time. During a mean follow-up of 4 years, all 11 patients remained in complete remission.
“This was a remarkable result,” said Dr. Wei, who noted that there were no serious adverse events associated with rituximab maintenance over this period. This cannot be considered a routine strategy without a large patient experience, according to Dr. Wei, but it does provide another piece of evidence that rituximab is effective and well tolerated.
There are no guidelines from a major organization that establish an evidence-based treatment algorithm for pemphigus, but Dr. Wei is not alone in considering early initiation of the most effective therapy as the best approach to sustained control.
“I agree that rituximab is a good first-line option for pemphigus patients,” said Kara Heelan, MBBCh, MD, a consultant dermatologist at the Royal Marsden and Lister Hospital, London. She was the first author of the cost-effectiveness study that Dr. Wei cited. The study was published when she was an associate in the division of dermatology at the University of Toronto.
By calling rituximab “a good” option rather than a potential standard, Dr. Heelan appeared to be more circumspect than Dr. Wei about its central role in the care of pemphigus, but she did agree in an interview that this agent “has been shown to be cost-effective.” In her study, this was an advantage attributed to relative efficacy and safety that reduced use of health care resources.
A version of this article first appeared on Medscape.com.
AT AAD 2022
Dupilumab treats itch and clears lesions in prurigo nodularis patients
BOSTON – of treatment, in a phase 3 trial presented at the American Academy of Dermatology 2022 Annual Meeting.
There are currently no Food and Drug Administration–approved systemic therapies for PN. Although several treatments for the disease are used off label for the condition, such as ultraviolet light therapy and immunosuppressive agents, moderate to severe PN is usually difficult to control, noted Gil Yosipovitch, MD, director of the Miami Itch Center at the University of Miami Miller School of Medicine, Florida. He led the research and presented the findings at the conference.
“Many dermatologists feel very uncomfortable dealing with these patients because they suffer from chronicity, they are miserable, and previously, the drugs didn’t work well,” Dr. Yosipovitch told this news organization. The results from this trial “are very promising,” he said. “It opens a new field of treatment for itchy conditions.”
The trial, named LIBERTY-PN PRIME2, enrolled patients aged 18-80 who had been living with PN for at least 3 months. Patients had at least 20 lesions at baseline as well as severe itch, defined as a score of 7 or greater on the Worst Itch Numerical Rating Scale (WI-NRS). The scale ranges from 0 (no itch) to 10 (worst itch imaginable). Participants also had a history of treatment failure with medium to super-potent topical corticosteroids (TCSs), or treatment with TCSs was not medically advisable for them.
The randomized, double-blinded study enrolled 160 adults with PN. Of those, 78 were assigned to the treatment arm and received a 600-mg loading dose of dupilumab, administered subcutaneously, followed by 300-mg doses every 2 weeks for 24 weeks; 82 patients were allocated to receive placebo.
During the study, 25 patients in the placebo arm discontinued treatment. In the treatment arm, one patient was not treated and two discontinued treatment due to lack of efficacy.
The primary endpoint of the study was a reduction of at least 4 points on the WI-NRS at 12 weeks. Secondary endpoints included at least a 4-point WI-NRS reduction at 24 weeks and clear to nearly clear skin, defined as having a score of 0 or 1 on the Investigator’s Global Assessment PN-Stage (IGN PN-S). The scale ranges from 0 (clear) to 4 (severe).
At 12 weeks, 37.2% of patients given dupilumab reported a reduction of at least 4 points in WI-NRS, compared with 22.0% of patients given placebo (P = .0216). By 24 weeks, 57.7% of adults who received dupilumab achieved a greater than or equal to 4-point reduction in WI-NRS, compared with 19.5% of those who received placebo (P < .0001). Additionally, 44.9% of participants in the treatment arm achieved a score of 0 or 1 on the IGA PN-S, compared with 15.9% of those in the placebo arm (P < .0001).
Forty-four participants who received dupilumab (57.1%) and 42 participants who received placebo (51.2%) reported at least one treatment-emergent adverse event (TEAE) during the study, though none of these events were serious. The most common TEAE in the study was headache, occurring in five patients taking placebo and four patients receiving dupilumab. In the dupilumab group, there were five cases of herpes virus infection, four non-herpes skin infections, and three cases of conjunctivitis. In the placebo group, seven non-herpes skin infections were reported.
Sanofi and Regeneron, who jointly developed dupilumab, plan to file for regulatory approval for dupilumab for PN “around the world” in the first half of this year, according to a press release.
“It’s great news and a step in the right direction,” Sarina Elmariah, MD, PhD, a dermatologist at Massachusetts General Hospital and instructor of dermatology at Harvard Medical School, both in Boston, told this news organization. She was not involved with the research.
“We’re finally starting to shed light on this condition and its pathogenesis,” she said. She noted that other potential therapeutics for PN are also in development. “It’s reflective of the fact that we are making strides in this area.”
Sanofi and Regeneron Pharmaceuticals sponsored the LIBERTY-PN PRIME2 trial. Dr. Yosipovitch has reported financial relationships with Bellus Health, Eli Lilly, Galderma, GSK, Kiniksa Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, and Trevi Therapeutics. Dr. Elmariah is on the advisory boards of Sanofi, Galderma, and Trevi Therapeutics.
A version of this article first appeared on Medscape.com.
BOSTON – of treatment, in a phase 3 trial presented at the American Academy of Dermatology 2022 Annual Meeting.
There are currently no Food and Drug Administration–approved systemic therapies for PN. Although several treatments for the disease are used off label for the condition, such as ultraviolet light therapy and immunosuppressive agents, moderate to severe PN is usually difficult to control, noted Gil Yosipovitch, MD, director of the Miami Itch Center at the University of Miami Miller School of Medicine, Florida. He led the research and presented the findings at the conference.
“Many dermatologists feel very uncomfortable dealing with these patients because they suffer from chronicity, they are miserable, and previously, the drugs didn’t work well,” Dr. Yosipovitch told this news organization. The results from this trial “are very promising,” he said. “It opens a new field of treatment for itchy conditions.”
The trial, named LIBERTY-PN PRIME2, enrolled patients aged 18-80 who had been living with PN for at least 3 months. Patients had at least 20 lesions at baseline as well as severe itch, defined as a score of 7 or greater on the Worst Itch Numerical Rating Scale (WI-NRS). The scale ranges from 0 (no itch) to 10 (worst itch imaginable). Participants also had a history of treatment failure with medium to super-potent topical corticosteroids (TCSs), or treatment with TCSs was not medically advisable for them.
The randomized, double-blinded study enrolled 160 adults with PN. Of those, 78 were assigned to the treatment arm and received a 600-mg loading dose of dupilumab, administered subcutaneously, followed by 300-mg doses every 2 weeks for 24 weeks; 82 patients were allocated to receive placebo.
During the study, 25 patients in the placebo arm discontinued treatment. In the treatment arm, one patient was not treated and two discontinued treatment due to lack of efficacy.
The primary endpoint of the study was a reduction of at least 4 points on the WI-NRS at 12 weeks. Secondary endpoints included at least a 4-point WI-NRS reduction at 24 weeks and clear to nearly clear skin, defined as having a score of 0 or 1 on the Investigator’s Global Assessment PN-Stage (IGN PN-S). The scale ranges from 0 (clear) to 4 (severe).
At 12 weeks, 37.2% of patients given dupilumab reported a reduction of at least 4 points in WI-NRS, compared with 22.0% of patients given placebo (P = .0216). By 24 weeks, 57.7% of adults who received dupilumab achieved a greater than or equal to 4-point reduction in WI-NRS, compared with 19.5% of those who received placebo (P < .0001). Additionally, 44.9% of participants in the treatment arm achieved a score of 0 or 1 on the IGA PN-S, compared with 15.9% of those in the placebo arm (P < .0001).
Forty-four participants who received dupilumab (57.1%) and 42 participants who received placebo (51.2%) reported at least one treatment-emergent adverse event (TEAE) during the study, though none of these events were serious. The most common TEAE in the study was headache, occurring in five patients taking placebo and four patients receiving dupilumab. In the dupilumab group, there were five cases of herpes virus infection, four non-herpes skin infections, and three cases of conjunctivitis. In the placebo group, seven non-herpes skin infections were reported.
Sanofi and Regeneron, who jointly developed dupilumab, plan to file for regulatory approval for dupilumab for PN “around the world” in the first half of this year, according to a press release.
“It’s great news and a step in the right direction,” Sarina Elmariah, MD, PhD, a dermatologist at Massachusetts General Hospital and instructor of dermatology at Harvard Medical School, both in Boston, told this news organization. She was not involved with the research.
“We’re finally starting to shed light on this condition and its pathogenesis,” she said. She noted that other potential therapeutics for PN are also in development. “It’s reflective of the fact that we are making strides in this area.”
Sanofi and Regeneron Pharmaceuticals sponsored the LIBERTY-PN PRIME2 trial. Dr. Yosipovitch has reported financial relationships with Bellus Health, Eli Lilly, Galderma, GSK, Kiniksa Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, and Trevi Therapeutics. Dr. Elmariah is on the advisory boards of Sanofi, Galderma, and Trevi Therapeutics.
A version of this article first appeared on Medscape.com.
BOSTON – of treatment, in a phase 3 trial presented at the American Academy of Dermatology 2022 Annual Meeting.
There are currently no Food and Drug Administration–approved systemic therapies for PN. Although several treatments for the disease are used off label for the condition, such as ultraviolet light therapy and immunosuppressive agents, moderate to severe PN is usually difficult to control, noted Gil Yosipovitch, MD, director of the Miami Itch Center at the University of Miami Miller School of Medicine, Florida. He led the research and presented the findings at the conference.
“Many dermatologists feel very uncomfortable dealing with these patients because they suffer from chronicity, they are miserable, and previously, the drugs didn’t work well,” Dr. Yosipovitch told this news organization. The results from this trial “are very promising,” he said. “It opens a new field of treatment for itchy conditions.”
The trial, named LIBERTY-PN PRIME2, enrolled patients aged 18-80 who had been living with PN for at least 3 months. Patients had at least 20 lesions at baseline as well as severe itch, defined as a score of 7 or greater on the Worst Itch Numerical Rating Scale (WI-NRS). The scale ranges from 0 (no itch) to 10 (worst itch imaginable). Participants also had a history of treatment failure with medium to super-potent topical corticosteroids (TCSs), or treatment with TCSs was not medically advisable for them.
The randomized, double-blinded study enrolled 160 adults with PN. Of those, 78 were assigned to the treatment arm and received a 600-mg loading dose of dupilumab, administered subcutaneously, followed by 300-mg doses every 2 weeks for 24 weeks; 82 patients were allocated to receive placebo.
During the study, 25 patients in the placebo arm discontinued treatment. In the treatment arm, one patient was not treated and two discontinued treatment due to lack of efficacy.
The primary endpoint of the study was a reduction of at least 4 points on the WI-NRS at 12 weeks. Secondary endpoints included at least a 4-point WI-NRS reduction at 24 weeks and clear to nearly clear skin, defined as having a score of 0 or 1 on the Investigator’s Global Assessment PN-Stage (IGN PN-S). The scale ranges from 0 (clear) to 4 (severe).
At 12 weeks, 37.2% of patients given dupilumab reported a reduction of at least 4 points in WI-NRS, compared with 22.0% of patients given placebo (P = .0216). By 24 weeks, 57.7% of adults who received dupilumab achieved a greater than or equal to 4-point reduction in WI-NRS, compared with 19.5% of those who received placebo (P < .0001). Additionally, 44.9% of participants in the treatment arm achieved a score of 0 or 1 on the IGA PN-S, compared with 15.9% of those in the placebo arm (P < .0001).
Forty-four participants who received dupilumab (57.1%) and 42 participants who received placebo (51.2%) reported at least one treatment-emergent adverse event (TEAE) during the study, though none of these events were serious. The most common TEAE in the study was headache, occurring in five patients taking placebo and four patients receiving dupilumab. In the dupilumab group, there were five cases of herpes virus infection, four non-herpes skin infections, and three cases of conjunctivitis. In the placebo group, seven non-herpes skin infections were reported.
Sanofi and Regeneron, who jointly developed dupilumab, plan to file for regulatory approval for dupilumab for PN “around the world” in the first half of this year, according to a press release.
“It’s great news and a step in the right direction,” Sarina Elmariah, MD, PhD, a dermatologist at Massachusetts General Hospital and instructor of dermatology at Harvard Medical School, both in Boston, told this news organization. She was not involved with the research.
“We’re finally starting to shed light on this condition and its pathogenesis,” she said. She noted that other potential therapeutics for PN are also in development. “It’s reflective of the fact that we are making strides in this area.”
Sanofi and Regeneron Pharmaceuticals sponsored the LIBERTY-PN PRIME2 trial. Dr. Yosipovitch has reported financial relationships with Bellus Health, Eli Lilly, Galderma, GSK, Kiniksa Pharmaceuticals, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, and Trevi Therapeutics. Dr. Elmariah is on the advisory boards of Sanofi, Galderma, and Trevi Therapeutics.
A version of this article first appeared on Medscape.com.
AT AAD 2022
Novel isotretinoin ointment for congenital ichthyosis shows promise
BOSTON – , results from a phase 2b study demonstrated.
“Patients with these deficiencies have generally had very limited treatment options, including lifelong use of emollients and keratolytics, and in severe cases, systemic retinoids,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said at a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. “There is currently no [Food and Drug Administration]-approved drug for CI. So, imagine your patients and their parents, and the frustration they must feel.”
In a study known as CONTROL, he and his colleagues evaluated the effect of TMB-001 on two subtypes of congenital ichthyosis: X-linked recessive ichthyosis (XLRI) and autosomal recessive congenital ichthyosis–lamellar ichthyosis (ARCI-LI). Of the two, the most common is XLRI, which has an estimated incidence of 1:3,000 and is caused by a deficiency of steroid sulfatase, resulting in cholesterol sulfate accumulation in the stratum corneum, retained corneodesmosomes, and reduced corneocyte desquamation, Dr. Bunick said.
ARCI-LI is rarer, with a prevalence of 1:100,000, and has been linked to mutations in six genes, most commonly TGM1, resulting in enzyme inactivation and deficient cross-linking of cornified cell envelope proteins.
TMB-001 is a proprietary, novel, topical isotretinoin formulation to treat CI that is being developed by Timber Pharmaceuticals. It uses a patented “IPEG” technology isotretinoin delivery system designed specifically for patients with CI. In a prior phase 2a study, TMB-001 0.1% and 0.2% ointment twice a day demonstrated greater improvement in ≥ 1 and ≥ 2 Investigator Global Assessment (IGA) scores compared with vehicle. Scaling in all patients treated with TMB-001 was considered clear, almost clear, or mild at 8 weeks, and no concerning safety signals were observed.
For the current trial, 33 patients with genetically confirmed XLRI/ARCI-LI and ≥ 2 (out of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with a ≥ 3 scaling score were randomized 1:1:1 to TMB-001 0.05%, TMB-001 0.1%, or vehicle twice daily for 12 weeks. Primary and secondary efficacy endpoints were reduction of ≥ 50% compared with baseline in VIIS-scaling (VIIS-50) and a ≥ 2-grade reduction in the Investigator Global Assessment (IGA)–scaling score compared with baseline. The patients ranged in age from 9 to 80 years, the majority were White, and their baseline body surface area (BSA) affected ranged from 28% to 38%.
Of the 33 patients, 11 patients received TMB-001 0.05%, 10 received TMB-001 0.1%, and 12 received the vehicle.
Among all patients, 55% had ARCI-LI and 45% had XLRI subtypes, and those with ARCI-LI had greater prior use of corticosteroid, emollient, and oral/topical retinoids. Overall, 100%, 50%, and 75% of patients with XLRI and 100%, 33%, and 17% of patients with ARCI-LI achieved VIIS-50 after receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
An improvement of a ≥ 2-grade IGA score was observed in 100%, 50%, and 25% of patients with XLRI and 100%, 67%, and none of patients with ARCI-LI who received TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
Dr. Bunick reported that there were no serious adverse events, no hospitalizations, and no patient deaths. Six patients discontinued treatment, five because of participant withdrawal and one because of physician withdrawal. The four most common treatment-emergent adverse events were erythema (21%), pruritus (21%), pain (15%) and dermatitis (12%).
“These results support ongoing investigation of TMB-001 as a promising alternative to systemic retinoids for participants with CI,” Dr. Bunick concluded. He noted that while he is not privy to details of TMB-001’s IPEG delivery system, “the way they have used polyethylene glycol to encapsulate the isotretinoin allows for greater barrier penetration and reduces a lot of the tolerability issues that are seen with other topical retinoids.” In his view, “that is providing this retinoid a greater chance of success. The patented delivery system is not only designed to help the isotretinoin do its job, but also to provide that stability and the ability to compound it, which have been barriers to success in the past.”
Phase 3 trials of the agent are scheduled to begin in June of 2022.
Amy S. Paller, MD, professor and chair of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that she was impressed that no significant changes from baseline laboratory clinical assessments were observed. “If that’s true, then we don’t have to be monitoring these patients in the same way as with systemic agents,” said Dr. Paller, who was involved in the phase 2a proof-of-concept trial of TMB-001. “I think that deserves more investigation. Hopefully that will be looked at in the phase 3 trial.”
Dr. Bunick reported having no disclosures related to his presentation. Dr. Paller disclosed that she is consultant to and/or an investigator for numerous pharmaceutical companies.
*A change correcting the age range of the patients in the study was made on 3/29/22.
BOSTON – , results from a phase 2b study demonstrated.
“Patients with these deficiencies have generally had very limited treatment options, including lifelong use of emollients and keratolytics, and in severe cases, systemic retinoids,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said at a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. “There is currently no [Food and Drug Administration]-approved drug for CI. So, imagine your patients and their parents, and the frustration they must feel.”
In a study known as CONTROL, he and his colleagues evaluated the effect of TMB-001 on two subtypes of congenital ichthyosis: X-linked recessive ichthyosis (XLRI) and autosomal recessive congenital ichthyosis–lamellar ichthyosis (ARCI-LI). Of the two, the most common is XLRI, which has an estimated incidence of 1:3,000 and is caused by a deficiency of steroid sulfatase, resulting in cholesterol sulfate accumulation in the stratum corneum, retained corneodesmosomes, and reduced corneocyte desquamation, Dr. Bunick said.
ARCI-LI is rarer, with a prevalence of 1:100,000, and has been linked to mutations in six genes, most commonly TGM1, resulting in enzyme inactivation and deficient cross-linking of cornified cell envelope proteins.
TMB-001 is a proprietary, novel, topical isotretinoin formulation to treat CI that is being developed by Timber Pharmaceuticals. It uses a patented “IPEG” technology isotretinoin delivery system designed specifically for patients with CI. In a prior phase 2a study, TMB-001 0.1% and 0.2% ointment twice a day demonstrated greater improvement in ≥ 1 and ≥ 2 Investigator Global Assessment (IGA) scores compared with vehicle. Scaling in all patients treated with TMB-001 was considered clear, almost clear, or mild at 8 weeks, and no concerning safety signals were observed.
For the current trial, 33 patients with genetically confirmed XLRI/ARCI-LI and ≥ 2 (out of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with a ≥ 3 scaling score were randomized 1:1:1 to TMB-001 0.05%, TMB-001 0.1%, or vehicle twice daily for 12 weeks. Primary and secondary efficacy endpoints were reduction of ≥ 50% compared with baseline in VIIS-scaling (VIIS-50) and a ≥ 2-grade reduction in the Investigator Global Assessment (IGA)–scaling score compared with baseline. The patients ranged in age from 9 to 80 years, the majority were White, and their baseline body surface area (BSA) affected ranged from 28% to 38%.
Of the 33 patients, 11 patients received TMB-001 0.05%, 10 received TMB-001 0.1%, and 12 received the vehicle.
Among all patients, 55% had ARCI-LI and 45% had XLRI subtypes, and those with ARCI-LI had greater prior use of corticosteroid, emollient, and oral/topical retinoids. Overall, 100%, 50%, and 75% of patients with XLRI and 100%, 33%, and 17% of patients with ARCI-LI achieved VIIS-50 after receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
An improvement of a ≥ 2-grade IGA score was observed in 100%, 50%, and 25% of patients with XLRI and 100%, 67%, and none of patients with ARCI-LI who received TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
Dr. Bunick reported that there were no serious adverse events, no hospitalizations, and no patient deaths. Six patients discontinued treatment, five because of participant withdrawal and one because of physician withdrawal. The four most common treatment-emergent adverse events were erythema (21%), pruritus (21%), pain (15%) and dermatitis (12%).
“These results support ongoing investigation of TMB-001 as a promising alternative to systemic retinoids for participants with CI,” Dr. Bunick concluded. He noted that while he is not privy to details of TMB-001’s IPEG delivery system, “the way they have used polyethylene glycol to encapsulate the isotretinoin allows for greater barrier penetration and reduces a lot of the tolerability issues that are seen with other topical retinoids.” In his view, “that is providing this retinoid a greater chance of success. The patented delivery system is not only designed to help the isotretinoin do its job, but also to provide that stability and the ability to compound it, which have been barriers to success in the past.”
Phase 3 trials of the agent are scheduled to begin in June of 2022.
Amy S. Paller, MD, professor and chair of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that she was impressed that no significant changes from baseline laboratory clinical assessments were observed. “If that’s true, then we don’t have to be monitoring these patients in the same way as with systemic agents,” said Dr. Paller, who was involved in the phase 2a proof-of-concept trial of TMB-001. “I think that deserves more investigation. Hopefully that will be looked at in the phase 3 trial.”
Dr. Bunick reported having no disclosures related to his presentation. Dr. Paller disclosed that she is consultant to and/or an investigator for numerous pharmaceutical companies.
*A change correcting the age range of the patients in the study was made on 3/29/22.
BOSTON – , results from a phase 2b study demonstrated.
“Patients with these deficiencies have generally had very limited treatment options, including lifelong use of emollients and keratolytics, and in severe cases, systemic retinoids,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said at a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. “There is currently no [Food and Drug Administration]-approved drug for CI. So, imagine your patients and their parents, and the frustration they must feel.”
In a study known as CONTROL, he and his colleagues evaluated the effect of TMB-001 on two subtypes of congenital ichthyosis: X-linked recessive ichthyosis (XLRI) and autosomal recessive congenital ichthyosis–lamellar ichthyosis (ARCI-LI). Of the two, the most common is XLRI, which has an estimated incidence of 1:3,000 and is caused by a deficiency of steroid sulfatase, resulting in cholesterol sulfate accumulation in the stratum corneum, retained corneodesmosomes, and reduced corneocyte desquamation, Dr. Bunick said.
ARCI-LI is rarer, with a prevalence of 1:100,000, and has been linked to mutations in six genes, most commonly TGM1, resulting in enzyme inactivation and deficient cross-linking of cornified cell envelope proteins.
TMB-001 is a proprietary, novel, topical isotretinoin formulation to treat CI that is being developed by Timber Pharmaceuticals. It uses a patented “IPEG” technology isotretinoin delivery system designed specifically for patients with CI. In a prior phase 2a study, TMB-001 0.1% and 0.2% ointment twice a day demonstrated greater improvement in ≥ 1 and ≥ 2 Investigator Global Assessment (IGA) scores compared with vehicle. Scaling in all patients treated with TMB-001 was considered clear, almost clear, or mild at 8 weeks, and no concerning safety signals were observed.
For the current trial, 33 patients with genetically confirmed XLRI/ARCI-LI and ≥ 2 (out of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with a ≥ 3 scaling score were randomized 1:1:1 to TMB-001 0.05%, TMB-001 0.1%, or vehicle twice daily for 12 weeks. Primary and secondary efficacy endpoints were reduction of ≥ 50% compared with baseline in VIIS-scaling (VIIS-50) and a ≥ 2-grade reduction in the Investigator Global Assessment (IGA)–scaling score compared with baseline. The patients ranged in age from 9 to 80 years, the majority were White, and their baseline body surface area (BSA) affected ranged from 28% to 38%.
Of the 33 patients, 11 patients received TMB-001 0.05%, 10 received TMB-001 0.1%, and 12 received the vehicle.
Among all patients, 55% had ARCI-LI and 45% had XLRI subtypes, and those with ARCI-LI had greater prior use of corticosteroid, emollient, and oral/topical retinoids. Overall, 100%, 50%, and 75% of patients with XLRI and 100%, 33%, and 17% of patients with ARCI-LI achieved VIIS-50 after receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
An improvement of a ≥ 2-grade IGA score was observed in 100%, 50%, and 25% of patients with XLRI and 100%, 67%, and none of patients with ARCI-LI who received TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.
Dr. Bunick reported that there were no serious adverse events, no hospitalizations, and no patient deaths. Six patients discontinued treatment, five because of participant withdrawal and one because of physician withdrawal. The four most common treatment-emergent adverse events were erythema (21%), pruritus (21%), pain (15%) and dermatitis (12%).
“These results support ongoing investigation of TMB-001 as a promising alternative to systemic retinoids for participants with CI,” Dr. Bunick concluded. He noted that while he is not privy to details of TMB-001’s IPEG delivery system, “the way they have used polyethylene glycol to encapsulate the isotretinoin allows for greater barrier penetration and reduces a lot of the tolerability issues that are seen with other topical retinoids.” In his view, “that is providing this retinoid a greater chance of success. The patented delivery system is not only designed to help the isotretinoin do its job, but also to provide that stability and the ability to compound it, which have been barriers to success in the past.”
Phase 3 trials of the agent are scheduled to begin in June of 2022.
Amy S. Paller, MD, professor and chair of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that she was impressed that no significant changes from baseline laboratory clinical assessments were observed. “If that’s true, then we don’t have to be monitoring these patients in the same way as with systemic agents,” said Dr. Paller, who was involved in the phase 2a proof-of-concept trial of TMB-001. “I think that deserves more investigation. Hopefully that will be looked at in the phase 3 trial.”
Dr. Bunick reported having no disclosures related to his presentation. Dr. Paller disclosed that she is consultant to and/or an investigator for numerous pharmaceutical companies.
*A change correcting the age range of the patients in the study was made on 3/29/22.
AT AAD 2022
Adverse skin effects of cancer immunotherapy reviewed
Immune checkpoint inhibitors (ICIs) have unquestionably revolutionized the care of patients with malignant melanoma, non-small cell lung cancer, and other types of cancer.
, according to members of a European Academy of Dermatology and Venereology (EADV) task force.
“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they write in a position statement on the management of ICI-derived dermatologic adverse events.
Recommendations from the EADV “Dermatology for Cancer Patients” task force have been published in the Journal of the European Academy of Dermatology and Venereology.
Task force members developed the recommendations based on clinical experience from published data and came up with specific recommendations for treating cutaneous toxicities associated with dermatologic immune-related adverse events (dirAEs) that occur in patients receiving immunotherapy with an ICI.
ICIs include the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab (Yervoy, Bristol Myers Squibb), and inhibitors of programmed death protein 1 (PD-1) and its ligand (PD-L1), including nivolumab (Opdivo, Bristol Myers Squibb), pembrolizumab (Keytruda, Merck), and other agents.
“The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients’ relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment,” they write.
The recommendations are in line with those included in a 2021 update of the American Society of Clinical Oncology (ASCO) guidelines on the management of irAEs in patients treated with ICIs across the whole range of organ systems, said Milan J. Anadkat, MD, professor of dermatology and director of dermatology clinical trials at Washington University School of Medicine, St. Louis. Dr. Anadkat was a coauthor of the ASCO guideline update.
Although the European recommendations focus only on dermatologic side effects of ICIs in patients with cancer, “that doesn’t diminish their importance. They do a good job of summarizing how to approach and how to manage it depending on the severity of the toxicities and the various types of toxicities,” he told this news organization.
Having a paper focused exclusively on the dermatologic side effects of ICIs allows the inclusion of photographs that can help clinicians identify specific conditions that may require referral to a dermatologist, he said.
Both Dr. Anadkat and the authors of the European recommendations noted that dermatologic irAEs are more common with CTLA-4 inhibition than with PD-1/PD-L1 inhibition.
“It has to do with where the target is,” Dr. Anadkat said. “CTLA-4 inhibition works on a central aspect of the immune system, so it’s a much less specific site, whereas PD-1 affects an interaction at the site of the tumor cell itself, so it’s a little more specific.”
Pruritus
ICI-induced pruritus can occur without apparent skin changes, they write, noting that in a recent study of patients with dirAEs, about one-third had isolated pruritus.
The task force members cite a meta-analysis indicating a pruritus incidence of 13.2% for patients treated with nivolumab and 20.2% for patients treated with pembrolizumab but respective grade 3 pruritus rates of only 0.5% and 2.3%. The reported incidence of pruritus with ipilimumab was 47% in a different study.
Recommended treatments include topical moisturizers with or without medium-to-high potency corticosteroids for grade 1 reactions, non-sedating histamines and/or GABA agonists such as pregabalin, or gabapentin for grade 2 pruritus, and suspension of ICIs until pruritus improves in patients with grade 3 pruritus.
Maculopapular rash
Maculopapular or eczema-like rashes may occur in up to 68% of patients who receive a CTLA-4 inhibitor and up to 20% of those who receive a PD1/PD-L1 inhibitor, the authors note. Rashes commonly appear within 3-6 weeks of initiating therapy.
“The clinical presentation is nonspecific and consists of a rapid onset of multiple minimally scaly, erythematous macules and papules, congregating into plaques. Lesions are mostly located on trunk and extensor surfaces of the extremities and the face is generally spared,” they write.
Maculopapular rashes are typically accompanied by itching but could be asymptomatic, they noted.
Mild (grade 1) rashes may respond to moisturizers and topical potent or super-potent corticosteroids. Patients with grade 2 rash should also receive oral antihistamines. Systemic corticosteroids may be considered for patients with grade 3 rashes but only after other dirAEs that may require specific management, such as psoriasis, are ruled out.
Psoriasis-like rash
The most common form of psoriasis seen in patients treated with ICIs is psoriasis vulgaris with plaques, but other clinical variants are also seen, the authors note.
“Topical agents (corticosteroids, Vitamin D analogues) are prescribed in Grades 1/2 and supplementary” to systemic treatment for patients with grade 3 or recalcitrant lesions, they write. “If skin-directed therapies fail to provide symptomatic control,” systemic treatment and narrow band UVB phototherapy “should be considered,” they add.
Evidence regarding the use of systemic therapies to treat psoriasis-like rash associated with ICIs is sparse. Acitretin can be safely used in patients with cancer. Low-dose methotrexate is also safe to use except in patients with non-melanoma skin cancers. Cyclosporine, however, should be avoided because of the potential for tumor-promoting effects, they emphasized.
The recommendations also cover treatment of lichen planus-like and vitiligo-like rashes, as well as hair and nail changes, autoimmune bullous disorders, and oral mucosal dirAEs.
In addition, the recommendations cover severe cutaneous adverse reactions as well as serious, potentially life-threatening dirAEs, including Stevens-Johnson syndrome/TEN, acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS).
“The dose of corticosteroids may be adapted to the severity of DRESS. The therapeutic benefit of systemic corticosteroids in the management of SJS/TEN remains controversial, and some authors favor treatment with cyclosporine. However, the use of corticosteroids in this context of ICI treatment appears reasonable and should be proposed. Short courses of steroids seem also effective in AGEP,” the task force members write.
The recommendations did not have outside funding. Of the 19 authors, 6 disclosed relationships with various pharmaceutical companies, including AbbVie, Leo Pharma, Boehringer Ingelheim, Bristol Myers Squibb, and/or Janssen. Dr. Anadkat disclosed previous relationships with Merck, Bristol Myers Squibb, and current relationships with others.
A version of this article first appeared on Medscape.com.
Immune checkpoint inhibitors (ICIs) have unquestionably revolutionized the care of patients with malignant melanoma, non-small cell lung cancer, and other types of cancer.
, according to members of a European Academy of Dermatology and Venereology (EADV) task force.
“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they write in a position statement on the management of ICI-derived dermatologic adverse events.
Recommendations from the EADV “Dermatology for Cancer Patients” task force have been published in the Journal of the European Academy of Dermatology and Venereology.
Task force members developed the recommendations based on clinical experience from published data and came up with specific recommendations for treating cutaneous toxicities associated with dermatologic immune-related adverse events (dirAEs) that occur in patients receiving immunotherapy with an ICI.
ICIs include the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab (Yervoy, Bristol Myers Squibb), and inhibitors of programmed death protein 1 (PD-1) and its ligand (PD-L1), including nivolumab (Opdivo, Bristol Myers Squibb), pembrolizumab (Keytruda, Merck), and other agents.
“The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients’ relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment,” they write.
The recommendations are in line with those included in a 2021 update of the American Society of Clinical Oncology (ASCO) guidelines on the management of irAEs in patients treated with ICIs across the whole range of organ systems, said Milan J. Anadkat, MD, professor of dermatology and director of dermatology clinical trials at Washington University School of Medicine, St. Louis. Dr. Anadkat was a coauthor of the ASCO guideline update.
Although the European recommendations focus only on dermatologic side effects of ICIs in patients with cancer, “that doesn’t diminish their importance. They do a good job of summarizing how to approach and how to manage it depending on the severity of the toxicities and the various types of toxicities,” he told this news organization.
Having a paper focused exclusively on the dermatologic side effects of ICIs allows the inclusion of photographs that can help clinicians identify specific conditions that may require referral to a dermatologist, he said.
Both Dr. Anadkat and the authors of the European recommendations noted that dermatologic irAEs are more common with CTLA-4 inhibition than with PD-1/PD-L1 inhibition.
“It has to do with where the target is,” Dr. Anadkat said. “CTLA-4 inhibition works on a central aspect of the immune system, so it’s a much less specific site, whereas PD-1 affects an interaction at the site of the tumor cell itself, so it’s a little more specific.”
Pruritus
ICI-induced pruritus can occur without apparent skin changes, they write, noting that in a recent study of patients with dirAEs, about one-third had isolated pruritus.
The task force members cite a meta-analysis indicating a pruritus incidence of 13.2% for patients treated with nivolumab and 20.2% for patients treated with pembrolizumab but respective grade 3 pruritus rates of only 0.5% and 2.3%. The reported incidence of pruritus with ipilimumab was 47% in a different study.
Recommended treatments include topical moisturizers with or without medium-to-high potency corticosteroids for grade 1 reactions, non-sedating histamines and/or GABA agonists such as pregabalin, or gabapentin for grade 2 pruritus, and suspension of ICIs until pruritus improves in patients with grade 3 pruritus.
Maculopapular rash
Maculopapular or eczema-like rashes may occur in up to 68% of patients who receive a CTLA-4 inhibitor and up to 20% of those who receive a PD1/PD-L1 inhibitor, the authors note. Rashes commonly appear within 3-6 weeks of initiating therapy.
“The clinical presentation is nonspecific and consists of a rapid onset of multiple minimally scaly, erythematous macules and papules, congregating into plaques. Lesions are mostly located on trunk and extensor surfaces of the extremities and the face is generally spared,” they write.
Maculopapular rashes are typically accompanied by itching but could be asymptomatic, they noted.
Mild (grade 1) rashes may respond to moisturizers and topical potent or super-potent corticosteroids. Patients with grade 2 rash should also receive oral antihistamines. Systemic corticosteroids may be considered for patients with grade 3 rashes but only after other dirAEs that may require specific management, such as psoriasis, are ruled out.
Psoriasis-like rash
The most common form of psoriasis seen in patients treated with ICIs is psoriasis vulgaris with plaques, but other clinical variants are also seen, the authors note.
“Topical agents (corticosteroids, Vitamin D analogues) are prescribed in Grades 1/2 and supplementary” to systemic treatment for patients with grade 3 or recalcitrant lesions, they write. “If skin-directed therapies fail to provide symptomatic control,” systemic treatment and narrow band UVB phototherapy “should be considered,” they add.
Evidence regarding the use of systemic therapies to treat psoriasis-like rash associated with ICIs is sparse. Acitretin can be safely used in patients with cancer. Low-dose methotrexate is also safe to use except in patients with non-melanoma skin cancers. Cyclosporine, however, should be avoided because of the potential for tumor-promoting effects, they emphasized.
The recommendations also cover treatment of lichen planus-like and vitiligo-like rashes, as well as hair and nail changes, autoimmune bullous disorders, and oral mucosal dirAEs.
In addition, the recommendations cover severe cutaneous adverse reactions as well as serious, potentially life-threatening dirAEs, including Stevens-Johnson syndrome/TEN, acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS).
“The dose of corticosteroids may be adapted to the severity of DRESS. The therapeutic benefit of systemic corticosteroids in the management of SJS/TEN remains controversial, and some authors favor treatment with cyclosporine. However, the use of corticosteroids in this context of ICI treatment appears reasonable and should be proposed. Short courses of steroids seem also effective in AGEP,” the task force members write.
The recommendations did not have outside funding. Of the 19 authors, 6 disclosed relationships with various pharmaceutical companies, including AbbVie, Leo Pharma, Boehringer Ingelheim, Bristol Myers Squibb, and/or Janssen. Dr. Anadkat disclosed previous relationships with Merck, Bristol Myers Squibb, and current relationships with others.
A version of this article first appeared on Medscape.com.
Immune checkpoint inhibitors (ICIs) have unquestionably revolutionized the care of patients with malignant melanoma, non-small cell lung cancer, and other types of cancer.
, according to members of a European Academy of Dermatology and Venereology (EADV) task force.
“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they write in a position statement on the management of ICI-derived dermatologic adverse events.
Recommendations from the EADV “Dermatology for Cancer Patients” task force have been published in the Journal of the European Academy of Dermatology and Venereology.
Task force members developed the recommendations based on clinical experience from published data and came up with specific recommendations for treating cutaneous toxicities associated with dermatologic immune-related adverse events (dirAEs) that occur in patients receiving immunotherapy with an ICI.
ICIs include the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab (Yervoy, Bristol Myers Squibb), and inhibitors of programmed death protein 1 (PD-1) and its ligand (PD-L1), including nivolumab (Opdivo, Bristol Myers Squibb), pembrolizumab (Keytruda, Merck), and other agents.
“The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients’ relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment,” they write.
The recommendations are in line with those included in a 2021 update of the American Society of Clinical Oncology (ASCO) guidelines on the management of irAEs in patients treated with ICIs across the whole range of organ systems, said Milan J. Anadkat, MD, professor of dermatology and director of dermatology clinical trials at Washington University School of Medicine, St. Louis. Dr. Anadkat was a coauthor of the ASCO guideline update.
Although the European recommendations focus only on dermatologic side effects of ICIs in patients with cancer, “that doesn’t diminish their importance. They do a good job of summarizing how to approach and how to manage it depending on the severity of the toxicities and the various types of toxicities,” he told this news organization.
Having a paper focused exclusively on the dermatologic side effects of ICIs allows the inclusion of photographs that can help clinicians identify specific conditions that may require referral to a dermatologist, he said.
Both Dr. Anadkat and the authors of the European recommendations noted that dermatologic irAEs are more common with CTLA-4 inhibition than with PD-1/PD-L1 inhibition.
“It has to do with where the target is,” Dr. Anadkat said. “CTLA-4 inhibition works on a central aspect of the immune system, so it’s a much less specific site, whereas PD-1 affects an interaction at the site of the tumor cell itself, so it’s a little more specific.”
Pruritus
ICI-induced pruritus can occur without apparent skin changes, they write, noting that in a recent study of patients with dirAEs, about one-third had isolated pruritus.
The task force members cite a meta-analysis indicating a pruritus incidence of 13.2% for patients treated with nivolumab and 20.2% for patients treated with pembrolizumab but respective grade 3 pruritus rates of only 0.5% and 2.3%. The reported incidence of pruritus with ipilimumab was 47% in a different study.
Recommended treatments include topical moisturizers with or without medium-to-high potency corticosteroids for grade 1 reactions, non-sedating histamines and/or GABA agonists such as pregabalin, or gabapentin for grade 2 pruritus, and suspension of ICIs until pruritus improves in patients with grade 3 pruritus.
Maculopapular rash
Maculopapular or eczema-like rashes may occur in up to 68% of patients who receive a CTLA-4 inhibitor and up to 20% of those who receive a PD1/PD-L1 inhibitor, the authors note. Rashes commonly appear within 3-6 weeks of initiating therapy.
“The clinical presentation is nonspecific and consists of a rapid onset of multiple minimally scaly, erythematous macules and papules, congregating into plaques. Lesions are mostly located on trunk and extensor surfaces of the extremities and the face is generally spared,” they write.
Maculopapular rashes are typically accompanied by itching but could be asymptomatic, they noted.
Mild (grade 1) rashes may respond to moisturizers and topical potent or super-potent corticosteroids. Patients with grade 2 rash should also receive oral antihistamines. Systemic corticosteroids may be considered for patients with grade 3 rashes but only after other dirAEs that may require specific management, such as psoriasis, are ruled out.
Psoriasis-like rash
The most common form of psoriasis seen in patients treated with ICIs is psoriasis vulgaris with plaques, but other clinical variants are also seen, the authors note.
“Topical agents (corticosteroids, Vitamin D analogues) are prescribed in Grades 1/2 and supplementary” to systemic treatment for patients with grade 3 or recalcitrant lesions, they write. “If skin-directed therapies fail to provide symptomatic control,” systemic treatment and narrow band UVB phototherapy “should be considered,” they add.
Evidence regarding the use of systemic therapies to treat psoriasis-like rash associated with ICIs is sparse. Acitretin can be safely used in patients with cancer. Low-dose methotrexate is also safe to use except in patients with non-melanoma skin cancers. Cyclosporine, however, should be avoided because of the potential for tumor-promoting effects, they emphasized.
The recommendations also cover treatment of lichen planus-like and vitiligo-like rashes, as well as hair and nail changes, autoimmune bullous disorders, and oral mucosal dirAEs.
In addition, the recommendations cover severe cutaneous adverse reactions as well as serious, potentially life-threatening dirAEs, including Stevens-Johnson syndrome/TEN, acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS).
“The dose of corticosteroids may be adapted to the severity of DRESS. The therapeutic benefit of systemic corticosteroids in the management of SJS/TEN remains controversial, and some authors favor treatment with cyclosporine. However, the use of corticosteroids in this context of ICI treatment appears reasonable and should be proposed. Short courses of steroids seem also effective in AGEP,” the task force members write.
The recommendations did not have outside funding. Of the 19 authors, 6 disclosed relationships with various pharmaceutical companies, including AbbVie, Leo Pharma, Boehringer Ingelheim, Bristol Myers Squibb, and/or Janssen. Dr. Anadkat disclosed previous relationships with Merck, Bristol Myers Squibb, and current relationships with others.
A version of this article first appeared on Medscape.com.
A 31-year-old female presented with a burning rash on upper arms, groin, and axillae
The exact cause is unknown, but possible causes include medications, dental amalgam fillings, or an autoimmune reaction. Drugs implicated in causing LP include beta-blockers, methyldopa, penicillamine, quinidine, and quinine. A meta-analysis of case-control studies show a statistically significant association between hepatitis C infection and LP patients; thus, all patients presenting with LP should be screened for hepatitis.1 Individuals of all age groups and races can be affected by LP, but it is predominantly observed in middle-aged adults. Women are also twice as likely to get oral lichen planus.2
Atrophic lichen planus, the least common form of LP, presents as flat, violaceous papules with an atrophic, pale center. Although these papules can be found anywhere on the body, they most commonly affect the trunk and/or legs on areas of the skin previously affected by classical lichen planus.3 In most cases, LP is diagnosed by observing its clinical features. A biopsy is recommended to confirm the diagnosis for more atypical cases.
Histopathology reveals thinning of the epidermis with flattening of the rete ridges, vacuolar degeneration of the basal layer, and a lichenoid mononuclear infiltrate in the papillary dermis.
If the patient is diagnosed with LP but experiences no symptoms, treatment is not needed as LP may resolve spontaneously within 1-2 years. Recurrences are common, however. Lesions may heal with hyperpigmentation. Possible treatments that can help relieve symptoms of pruritus are high potency topical corticosteroids, calcineurin inhibitors, and antihistamines. In more severe and widespread cases, lesions may respond well to systemic corticosteroids or intralesional steroid injections.4 Phototherapy is reported to be effective as well. Acitretin, isotretinoin, methotrexate, hydroxychloroquine, and mycophenolate mofetil are all described in the literature. It is important to note that LP on mucous membranes may be more persistent and resistant to treatment.1
In this patient, a punch biopsy was performed, confirming the diagnosis. The patient was treated with topical and intralesional steroids, as well as a course of prednisone, and her lesions improved with treatment. Hepatitis serologies were negative.
This case and photo were submitted by Ms. Erras of the University of California, San Diego, and Dr. Sateesh, of San Diego Family Dermatology, and edited by Donna Bilu Martin, MD.
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].
References
1. Usatine R, Tinitigan M. Am Fam Physician. 2011 Jul 1;84(1):53-602.
2. Lichen planus, Johns Hopkins Medicine. [Cited 2022 Mar 13.]
3. Atrophic lichen planus, Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. [Cited 2022 Mar 13.]
4. ”Atrophic lichen planus,” Medscape, 2004 Feb 1. [Cited 2022 Mar 13.]
The exact cause is unknown, but possible causes include medications, dental amalgam fillings, or an autoimmune reaction. Drugs implicated in causing LP include beta-blockers, methyldopa, penicillamine, quinidine, and quinine. A meta-analysis of case-control studies show a statistically significant association between hepatitis C infection and LP patients; thus, all patients presenting with LP should be screened for hepatitis.1 Individuals of all age groups and races can be affected by LP, but it is predominantly observed in middle-aged adults. Women are also twice as likely to get oral lichen planus.2
Atrophic lichen planus, the least common form of LP, presents as flat, violaceous papules with an atrophic, pale center. Although these papules can be found anywhere on the body, they most commonly affect the trunk and/or legs on areas of the skin previously affected by classical lichen planus.3 In most cases, LP is diagnosed by observing its clinical features. A biopsy is recommended to confirm the diagnosis for more atypical cases.
Histopathology reveals thinning of the epidermis with flattening of the rete ridges, vacuolar degeneration of the basal layer, and a lichenoid mononuclear infiltrate in the papillary dermis.
If the patient is diagnosed with LP but experiences no symptoms, treatment is not needed as LP may resolve spontaneously within 1-2 years. Recurrences are common, however. Lesions may heal with hyperpigmentation. Possible treatments that can help relieve symptoms of pruritus are high potency topical corticosteroids, calcineurin inhibitors, and antihistamines. In more severe and widespread cases, lesions may respond well to systemic corticosteroids or intralesional steroid injections.4 Phototherapy is reported to be effective as well. Acitretin, isotretinoin, methotrexate, hydroxychloroquine, and mycophenolate mofetil are all described in the literature. It is important to note that LP on mucous membranes may be more persistent and resistant to treatment.1
In this patient, a punch biopsy was performed, confirming the diagnosis. The patient was treated with topical and intralesional steroids, as well as a course of prednisone, and her lesions improved with treatment. Hepatitis serologies were negative.
This case and photo were submitted by Ms. Erras of the University of California, San Diego, and Dr. Sateesh, of San Diego Family Dermatology, and edited by Donna Bilu Martin, MD.
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].
References
1. Usatine R, Tinitigan M. Am Fam Physician. 2011 Jul 1;84(1):53-602.
2. Lichen planus, Johns Hopkins Medicine. [Cited 2022 Mar 13.]
3. Atrophic lichen planus, Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. [Cited 2022 Mar 13.]
4. ”Atrophic lichen planus,” Medscape, 2004 Feb 1. [Cited 2022 Mar 13.]
The exact cause is unknown, but possible causes include medications, dental amalgam fillings, or an autoimmune reaction. Drugs implicated in causing LP include beta-blockers, methyldopa, penicillamine, quinidine, and quinine. A meta-analysis of case-control studies show a statistically significant association between hepatitis C infection and LP patients; thus, all patients presenting with LP should be screened for hepatitis.1 Individuals of all age groups and races can be affected by LP, but it is predominantly observed in middle-aged adults. Women are also twice as likely to get oral lichen planus.2
Atrophic lichen planus, the least common form of LP, presents as flat, violaceous papules with an atrophic, pale center. Although these papules can be found anywhere on the body, they most commonly affect the trunk and/or legs on areas of the skin previously affected by classical lichen planus.3 In most cases, LP is diagnosed by observing its clinical features. A biopsy is recommended to confirm the diagnosis for more atypical cases.
Histopathology reveals thinning of the epidermis with flattening of the rete ridges, vacuolar degeneration of the basal layer, and a lichenoid mononuclear infiltrate in the papillary dermis.
If the patient is diagnosed with LP but experiences no symptoms, treatment is not needed as LP may resolve spontaneously within 1-2 years. Recurrences are common, however. Lesions may heal with hyperpigmentation. Possible treatments that can help relieve symptoms of pruritus are high potency topical corticosteroids, calcineurin inhibitors, and antihistamines. In more severe and widespread cases, lesions may respond well to systemic corticosteroids or intralesional steroid injections.4 Phototherapy is reported to be effective as well. Acitretin, isotretinoin, methotrexate, hydroxychloroquine, and mycophenolate mofetil are all described in the literature. It is important to note that LP on mucous membranes may be more persistent and resistant to treatment.1
In this patient, a punch biopsy was performed, confirming the diagnosis. The patient was treated with topical and intralesional steroids, as well as a course of prednisone, and her lesions improved with treatment. Hepatitis serologies were negative.
This case and photo were submitted by Ms. Erras of the University of California, San Diego, and Dr. Sateesh, of San Diego Family Dermatology, and edited by Donna Bilu Martin, MD.
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].
References
1. Usatine R, Tinitigan M. Am Fam Physician. 2011 Jul 1;84(1):53-602.
2. Lichen planus, Johns Hopkins Medicine. [Cited 2022 Mar 13.]
3. Atrophic lichen planus, Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. [Cited 2022 Mar 13.]
4. ”Atrophic lichen planus,” Medscape, 2004 Feb 1. [Cited 2022 Mar 13.]
Betamethasone cream did not alleviate symptoms.
An 11-year-old female presented with skin discoloration on her back
Becker’s nevus
The history and physical exam are most consistent with Becker’s nevus, also known as Becker’s melanosis. This is a benign cutaneous hamartoma, usually found in males, characterized by a large, irregularly shaped brown patch, often with hypertrichosis.1 Becker’s nevus can be congenital but is more commonly noticed in late childhood or early adolescence, with thickening, increased pigmentation, and hair growth. Becker’s nevus is considered an overgrowth of epidermal pigment cells and hair follicles and is thought to be attributable to postzygotic mutations (with ACTB mutations most reported).1 It is often located unilaterally on the upper trunk but is occasionally present elsewhere on the body. Acne may occasionally develop within the nevus, which is believed to be triggered by puberty-associated androgens.1 The lesion tends to persist indefinitely but has no propensity for malignant transformation.
Becker’s nevus is generally an isolated skin lesion without other anomalies. However, in rare instances, it may be associated with ipsilateral breast hypoplasia or hypoplastic defects of the muscle, skin, or skeleton, which is known as Becker’s nevus syndrome.2 Treatment is not medically warranted for an isolated Becker’s nevus but may be pursued for cosmetic reasons. Although treatment is generally discouraged because of variable success, laser hair removal and laser therapy may be pursued to address the hypertrichosis and hyperpigmentation, respectively.
What is on the differential?
A café-au-lait macule (CALM) is a light- to dark-brown, oval lesion that commonly presents at birth or in early childhood. CALMs vary widely in size from less than 1.5 cm to more than 20 cm in diameter. They are asymptomatic and grow in proportion to the individual over time.3 Becker’s nevus can be distinguished from CALMs by the development of hypertrichosis, typical location and course, and other skin changes within the nevus.
Postinflammatory hyperpigmentation (PIH) is characterized by asymptomatic, darkened macules or patches that are brown to blue-gray in color. It is one of the most common causes of hyperpigmentation, particularly in skin of color, and can take months to years to resolve. PIH is caused by increased melanin production in response to a cutaneous inflammatory process, such as a drug reaction, allergy, mechanical or thermal injury, infection, phototoxicity, or an underlying skin condition.3 Our patient’s history with the lack of an inciting inflammatory process is more consistent with Becker’s nevus.
Erythema ab igne is a cutaneous reaction to heat that presents as a hyperpigmented patch with a reticular or mottled configuration and superficial venular telangiectasia. The lesion is initially erythematous and progresses to a pale pink to purplish dark-brown color.4 Causes include long-term use of a heating pad, laptop, electric blanket, or a hot water bottle. The absence of prolonged heat exposure in our patient’s history does not favor erythema ab igne.
Pigmentary mosaicism is characterized by a distinctive pattern of hyperpigmentation that follows the lines of ectodermal embryologic development, known as the lines of Blaschko.5 This condition is also known as linear and whorled nevoid hypermelanosis because of its streaky or swirl-like pattern. Pigmentary mosaicism can be present at birth or appear within the first few weeks of life. It is caused by genetic heterogeneity in neuroectodermal cells, which results in skin with areas of varying colors. Pigmentary mosaicism is unlikely in this case as our patient’s lesion does not follow the lines of Blaschko.
Ms. Laborada is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is the 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. Ms. Laborada and Dr. Eichenfield have no relevant financial disclosures.
References
1. Atzmony L et al. J Cutan Pathol. 2020;47(8):681-5.
2. Danarti R et al. J Am Acad Dermatol. 2004;51(6):965-9.
3. Paller A and Mancini AJ. “Hurwitz Clinical Pediatric Dermatology: A textbook of skin disorders of childhood and adolescence” 4th ed. Philadelphia: Elsevier Saunders, 2011.
4. Patel DP. JAMA Dermatol. 2017;153(7):685.
5. Kromann AB et al. Orphanet J Rare Dis. 2018;13(1):39.
Becker’s nevus
The history and physical exam are most consistent with Becker’s nevus, also known as Becker’s melanosis. This is a benign cutaneous hamartoma, usually found in males, characterized by a large, irregularly shaped brown patch, often with hypertrichosis.1 Becker’s nevus can be congenital but is more commonly noticed in late childhood or early adolescence, with thickening, increased pigmentation, and hair growth. Becker’s nevus is considered an overgrowth of epidermal pigment cells and hair follicles and is thought to be attributable to postzygotic mutations (with ACTB mutations most reported).1 It is often located unilaterally on the upper trunk but is occasionally present elsewhere on the body. Acne may occasionally develop within the nevus, which is believed to be triggered by puberty-associated androgens.1 The lesion tends to persist indefinitely but has no propensity for malignant transformation.
Becker’s nevus is generally an isolated skin lesion without other anomalies. However, in rare instances, it may be associated with ipsilateral breast hypoplasia or hypoplastic defects of the muscle, skin, or skeleton, which is known as Becker’s nevus syndrome.2 Treatment is not medically warranted for an isolated Becker’s nevus but may be pursued for cosmetic reasons. Although treatment is generally discouraged because of variable success, laser hair removal and laser therapy may be pursued to address the hypertrichosis and hyperpigmentation, respectively.
What is on the differential?
A café-au-lait macule (CALM) is a light- to dark-brown, oval lesion that commonly presents at birth or in early childhood. CALMs vary widely in size from less than 1.5 cm to more than 20 cm in diameter. They are asymptomatic and grow in proportion to the individual over time.3 Becker’s nevus can be distinguished from CALMs by the development of hypertrichosis, typical location and course, and other skin changes within the nevus.
Postinflammatory hyperpigmentation (PIH) is characterized by asymptomatic, darkened macules or patches that are brown to blue-gray in color. It is one of the most common causes of hyperpigmentation, particularly in skin of color, and can take months to years to resolve. PIH is caused by increased melanin production in response to a cutaneous inflammatory process, such as a drug reaction, allergy, mechanical or thermal injury, infection, phototoxicity, or an underlying skin condition.3 Our patient’s history with the lack of an inciting inflammatory process is more consistent with Becker’s nevus.
Erythema ab igne is a cutaneous reaction to heat that presents as a hyperpigmented patch with a reticular or mottled configuration and superficial venular telangiectasia. The lesion is initially erythematous and progresses to a pale pink to purplish dark-brown color.4 Causes include long-term use of a heating pad, laptop, electric blanket, or a hot water bottle. The absence of prolonged heat exposure in our patient’s history does not favor erythema ab igne.
Pigmentary mosaicism is characterized by a distinctive pattern of hyperpigmentation that follows the lines of ectodermal embryologic development, known as the lines of Blaschko.5 This condition is also known as linear and whorled nevoid hypermelanosis because of its streaky or swirl-like pattern. Pigmentary mosaicism can be present at birth or appear within the first few weeks of life. It is caused by genetic heterogeneity in neuroectodermal cells, which results in skin with areas of varying colors. Pigmentary mosaicism is unlikely in this case as our patient’s lesion does not follow the lines of Blaschko.
Ms. Laborada is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is the 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. Ms. Laborada and Dr. Eichenfield have no relevant financial disclosures.
References
1. Atzmony L et al. J Cutan Pathol. 2020;47(8):681-5.
2. Danarti R et al. J Am Acad Dermatol. 2004;51(6):965-9.
3. Paller A and Mancini AJ. “Hurwitz Clinical Pediatric Dermatology: A textbook of skin disorders of childhood and adolescence” 4th ed. Philadelphia: Elsevier Saunders, 2011.
4. Patel DP. JAMA Dermatol. 2017;153(7):685.
5. Kromann AB et al. Orphanet J Rare Dis. 2018;13(1):39.
Becker’s nevus
The history and physical exam are most consistent with Becker’s nevus, also known as Becker’s melanosis. This is a benign cutaneous hamartoma, usually found in males, characterized by a large, irregularly shaped brown patch, often with hypertrichosis.1 Becker’s nevus can be congenital but is more commonly noticed in late childhood or early adolescence, with thickening, increased pigmentation, and hair growth. Becker’s nevus is considered an overgrowth of epidermal pigment cells and hair follicles and is thought to be attributable to postzygotic mutations (with ACTB mutations most reported).1 It is often located unilaterally on the upper trunk but is occasionally present elsewhere on the body. Acne may occasionally develop within the nevus, which is believed to be triggered by puberty-associated androgens.1 The lesion tends to persist indefinitely but has no propensity for malignant transformation.
Becker’s nevus is generally an isolated skin lesion without other anomalies. However, in rare instances, it may be associated with ipsilateral breast hypoplasia or hypoplastic defects of the muscle, skin, or skeleton, which is known as Becker’s nevus syndrome.2 Treatment is not medically warranted for an isolated Becker’s nevus but may be pursued for cosmetic reasons. Although treatment is generally discouraged because of variable success, laser hair removal and laser therapy may be pursued to address the hypertrichosis and hyperpigmentation, respectively.
What is on the differential?
A café-au-lait macule (CALM) is a light- to dark-brown, oval lesion that commonly presents at birth or in early childhood. CALMs vary widely in size from less than 1.5 cm to more than 20 cm in diameter. They are asymptomatic and grow in proportion to the individual over time.3 Becker’s nevus can be distinguished from CALMs by the development of hypertrichosis, typical location and course, and other skin changes within the nevus.
Postinflammatory hyperpigmentation (PIH) is characterized by asymptomatic, darkened macules or patches that are brown to blue-gray in color. It is one of the most common causes of hyperpigmentation, particularly in skin of color, and can take months to years to resolve. PIH is caused by increased melanin production in response to a cutaneous inflammatory process, such as a drug reaction, allergy, mechanical or thermal injury, infection, phototoxicity, or an underlying skin condition.3 Our patient’s history with the lack of an inciting inflammatory process is more consistent with Becker’s nevus.
Erythema ab igne is a cutaneous reaction to heat that presents as a hyperpigmented patch with a reticular or mottled configuration and superficial venular telangiectasia. The lesion is initially erythematous and progresses to a pale pink to purplish dark-brown color.4 Causes include long-term use of a heating pad, laptop, electric blanket, or a hot water bottle. The absence of prolonged heat exposure in our patient’s history does not favor erythema ab igne.
Pigmentary mosaicism is characterized by a distinctive pattern of hyperpigmentation that follows the lines of ectodermal embryologic development, known as the lines of Blaschko.5 This condition is also known as linear and whorled nevoid hypermelanosis because of its streaky or swirl-like pattern. Pigmentary mosaicism can be present at birth or appear within the first few weeks of life. It is caused by genetic heterogeneity in neuroectodermal cells, which results in skin with areas of varying colors. Pigmentary mosaicism is unlikely in this case as our patient’s lesion does not follow the lines of Blaschko.
Ms. Laborada is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is the 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. Ms. Laborada and Dr. Eichenfield have no relevant financial disclosures.
References
1. Atzmony L et al. J Cutan Pathol. 2020;47(8):681-5.
2. Danarti R et al. J Am Acad Dermatol. 2004;51(6):965-9.
3. Paller A and Mancini AJ. “Hurwitz Clinical Pediatric Dermatology: A textbook of skin disorders of childhood and adolescence” 4th ed. Philadelphia: Elsevier Saunders, 2011.
4. Patel DP. JAMA Dermatol. 2017;153(7):685.
5. Kromann AB et al. Orphanet J Rare Dis. 2018;13(1):39.
