Cutis

THE DIAGNOSIS: Atypical Fibroxanthoma

Given the appearance of the nodule and the absence of features of a keloid scar, a soft-tissue or adnexal tumor was suspected. Histology revealed a thin epidermis with loss of rete ridges and a Grenz zone. There was a nodular uncircumscribed dermal proliferation of spindle cells forming interweaving fascicles with elongated ovoid nuclei and prominent nucleoli (Figure). There was moderate cellular and nuclear atypia, and no necrosis was observed. The spindle cells stained positive for CD10 and negative for AE1/AE3, cytokeratin 5/6, S100, melanoma triple marker, Factor XIII 1, ERG, CD31, CD34, desmin, and smooth muscle actin; ERG, CD31, CD34, and SMA highlighted small vessels within the tumor. The histologic diagnosis was an atypical spindle cell tumor favoring atypical fibroxanthoma (AFX). The excisional biopsy margins were clear.

The patient was referred to surgical oncology to consider re-excision of margins after the diagnosis was made. A chest radiograph was clear, and magnetic resonance imaging showed mild skin thickening and image enhancement at the left shoulder—possibly a postsurgical change—with no nodularity suggesting a residual or recurrent tumor. Surgical oncology determined that the patient did not require further excision and placed him on regular follow-up every 2 to 3 months for the next 2 years.

uncertain origin that is considered to be on a spectrum with the more aggressive pleomorphic dermal sarcoma (PDS); it can be distinguished from PDS by histologic features such as nerve or vessel invasion.¹ Both entities share oncogenes (eg, tumor protein 53 gene mutations) and are histologically and immunohistochemically similar. Atypical fibroxanthoma largely is viewed as an intermediate-risk tumor that is locally aggressive but rarely metastasizes, with a reported local recurrence rate of 5% to 11% and metastasis risk of 1% to 2%. Conversely, PDS is a more aggressive diagnosis with a high risk for local recurrence and metastasis (7%-69% and 4%-20%, respectively).¹

Atypical fibroxanthomas may mimic other entities, both clinically and histologically. It commonly manifests as a flesh-colored to erythematous, sometimes ulcerated nodule on sun-exposed skin in elderly patients, leading to a broad range of clinical differential diagnoses, including other primary cutaneous malignancies (eg, squamous cell carcinoma, amelanotic melanoma), cutaneous sarcomas (eg, dermatofibrosarcoma protuberans), adnexal and other tumors (eg, pleomorphic fibroma, pilomatricoma), cutaneous metastases, and even keloid scars. As the differentials can look clinically similar, a skin biopsy may be necessary to confirm the diagnosis.

Histologically, AFX tends to show an undifferentiated pleomorphic spindle cell morphology. Notably, histology can be highly variable, with other reported histologic patterns including keloidlike, pleomorphic, epithelioid, rhabdoid, clear-cell, foamy cell, granular cell, bizarre cell, pseudoangiomatous, inflammatory, and osteoclast-rich patterns.² Thus, the histologic differential diagnosis also is broad, and AFX primarily is a diagnosis of exclusion without specific immunohistochemical markers that serve to exclude other diagnoses. For example, AFX tends to stain positive for CD10 and CD68, though these are not specific markers for AFX. Furthermore, although certain histologic markers may commonly be more positive in AFX than PDS (eg, CD74 stains positive in 20% of AFXs and only 1% of PDSs), this is not reliable enough to be diagnostic.³ As such, AFX is distinguished from PDS primarily by histologic features such as subcutaneous tissue invasion, vascular or perineural invasion, necrosis, or local invasion/ metastases.¹ Given the rarity of both tumors, no established management guidelines exist, although excision (wide local excision or Mohs micrographic surgery) usually is recommended, with some authors suggesting margins of 1 cm for AFX and 2 cm to 3 cm for PDS.¹

This atypical case of AFX arising in non–sun-exposed skin in a young man raises questions about whether unknown genetic factors or possibly prior immunosuppression could have contributed to the development of the tumor. A thorough history and physical examination can provide valuable clues for biopsy, including ongoing growth, absence of known prior trauma or acne at the site, and clinical appearance, such as the reddish, solitary, dome-shaped lesion in our patient.

THE DIAGNOSIS: Atypical Fibroxanthoma

Given the appearance of the nodule and the absence of features of a keloid scar, a soft-tissue or adnexal tumor was suspected. Histology revealed a thin epidermis with loss of rete ridges and a Grenz zone. There was a nodular uncircumscribed dermal proliferation of spindle cells forming interweaving fascicles with elongated ovoid nuclei and prominent nucleoli (Figure). There was moderate cellular and nuclear atypia, and no necrosis was observed. The spindle cells stained positive for CD10 and negative for AE1/AE3, cytokeratin 5/6, S100, melanoma triple marker, Factor XIII 1, ERG, CD31, CD34, desmin, and smooth muscle actin; ERG, CD31, CD34, and SMA highlighted small vessels within the tumor. The histologic diagnosis was an atypical spindle cell tumor favoring atypical fibroxanthoma (AFX). The excisional biopsy margins were clear.

The patient was referred to surgical oncology to consider re-excision of margins after the diagnosis was made. A chest radiograph was clear, and magnetic resonance imaging showed mild skin thickening and image enhancement at the left shoulder—possibly a postsurgical change—with no nodularity suggesting a residual or recurrent tumor. Surgical oncology determined that the patient did not require further excision and placed him on regular follow-up every 2 to 3 months for the next 2 years.

uncertain origin that is considered to be on a spectrum with the more aggressive pleomorphic dermal sarcoma (PDS); it can be distinguished from PDS by histologic features such as nerve or vessel invasion.¹ Both entities share oncogenes (eg, tumor protein 53 gene mutations) and are histologically and immunohistochemically similar. Atypical fibroxanthoma largely is viewed as an intermediate-risk tumor that is locally aggressive but rarely metastasizes, with a reported local recurrence rate of 5% to 11% and metastasis risk of 1% to 2%. Conversely, PDS is a more aggressive diagnosis with a high risk for local recurrence and metastasis (7%-69% and 4%-20%, respectively).¹

Atypical fibroxanthomas may mimic other entities, both clinically and histologically. It commonly manifests as a flesh-colored to erythematous, sometimes ulcerated nodule on sun-exposed skin in elderly patients, leading to a broad range of clinical differential diagnoses, including other primary cutaneous malignancies (eg, squamous cell carcinoma, amelanotic melanoma), cutaneous sarcomas (eg, dermatofibrosarcoma protuberans), adnexal and other tumors (eg, pleomorphic fibroma, pilomatricoma), cutaneous metastases, and even keloid scars. As the differentials can look clinically similar, a skin biopsy may be necessary to confirm the diagnosis.

Histologically, AFX tends to show an undifferentiated pleomorphic spindle cell morphology. Notably, histology can be highly variable, with other reported histologic patterns including keloidlike, pleomorphic, epithelioid, rhabdoid, clear-cell, foamy cell, granular cell, bizarre cell, pseudoangiomatous, inflammatory, and osteoclast-rich patterns.² Thus, the histologic differential diagnosis also is broad, and AFX primarily is a diagnosis of exclusion without specific immunohistochemical markers that serve to exclude other diagnoses. For example, AFX tends to stain positive for CD10 and CD68, though these are not specific markers for AFX. Furthermore, although certain histologic markers may commonly be more positive in AFX than PDS (eg, CD74 stains positive in 20% of AFXs and only 1% of PDSs), this is not reliable enough to be diagnostic.³ As such, AFX is distinguished from PDS primarily by histologic features such as subcutaneous tissue invasion, vascular or perineural invasion, necrosis, or local invasion/ metastases.¹ Given the rarity of both tumors, no established management guidelines exist, although excision (wide local excision or Mohs micrographic surgery) usually is recommended, with some authors suggesting margins of 1 cm for AFX and 2 cm to 3 cm for PDS.¹

This atypical case of AFX arising in non–sun-exposed skin in a young man raises questions about whether unknown genetic factors or possibly prior immunosuppression could have contributed to the development of the tumor. A thorough history and physical examination can provide valuable clues for biopsy, including ongoing growth, absence of known prior trauma or acne at the site, and clinical appearance, such as the reddish, solitary, dome-shaped lesion in our patient.

THE DIAGNOSIS: Atypical Fibroxanthoma

Given the appearance of the nodule and the absence of features of a keloid scar, a soft-tissue or adnexal tumor was suspected. Histology revealed a thin epidermis with loss of rete ridges and a Grenz zone. There was a nodular uncircumscribed dermal proliferation of spindle cells forming interweaving fascicles with elongated ovoid nuclei and prominent nucleoli (Figure). There was moderate cellular and nuclear atypia, and no necrosis was observed. The spindle cells stained positive for CD10 and negative for AE1/AE3, cytokeratin 5/6, S100, melanoma triple marker, Factor XIII 1, ERG, CD31, CD34, desmin, and smooth muscle actin; ERG, CD31, CD34, and SMA highlighted small vessels within the tumor. The histologic diagnosis was an atypical spindle cell tumor favoring atypical fibroxanthoma (AFX). The excisional biopsy margins were clear.

The patient was referred to surgical oncology to consider re-excision of margins after the diagnosis was made. A chest radiograph was clear, and magnetic resonance imaging showed mild skin thickening and image enhancement at the left shoulder—possibly a postsurgical change—with no nodularity suggesting a residual or recurrent tumor. Surgical oncology determined that the patient did not require further excision and placed him on regular follow-up every 2 to 3 months for the next 2 years.

uncertain origin that is considered to be on a spectrum with the more aggressive pleomorphic dermal sarcoma (PDS); it can be distinguished from PDS by histologic features such as nerve or vessel invasion.¹ Both entities share oncogenes (eg, tumor protein 53 gene mutations) and are histologically and immunohistochemically similar. Atypical fibroxanthoma largely is viewed as an intermediate-risk tumor that is locally aggressive but rarely metastasizes, with a reported local recurrence rate of 5% to 11% and metastasis risk of 1% to 2%. Conversely, PDS is a more aggressive diagnosis with a high risk for local recurrence and metastasis (7%-69% and 4%-20%, respectively).¹

Atypical fibroxanthomas may mimic other entities, both clinically and histologically. It commonly manifests as a flesh-colored to erythematous, sometimes ulcerated nodule on sun-exposed skin in elderly patients, leading to a broad range of clinical differential diagnoses, including other primary cutaneous malignancies (eg, squamous cell carcinoma, amelanotic melanoma), cutaneous sarcomas (eg, dermatofibrosarcoma protuberans), adnexal and other tumors (eg, pleomorphic fibroma, pilomatricoma), cutaneous metastases, and even keloid scars. As the differentials can look clinically similar, a skin biopsy may be necessary to confirm the diagnosis.

Histologically, AFX tends to show an undifferentiated pleomorphic spindle cell morphology. Notably, histology can be highly variable, with other reported histologic patterns including keloidlike, pleomorphic, epithelioid, rhabdoid, clear-cell, foamy cell, granular cell, bizarre cell, pseudoangiomatous, inflammatory, and osteoclast-rich patterns.² Thus, the histologic differential diagnosis also is broad, and AFX primarily is a diagnosis of exclusion without specific immunohistochemical markers that serve to exclude other diagnoses. For example, AFX tends to stain positive for CD10 and CD68, though these are not specific markers for AFX. Furthermore, although certain histologic markers may commonly be more positive in AFX than PDS (eg, CD74 stains positive in 20% of AFXs and only 1% of PDSs), this is not reliable enough to be diagnostic.³ As such, AFX is distinguished from PDS primarily by histologic features such as subcutaneous tissue invasion, vascular or perineural invasion, necrosis, or local invasion/ metastases.¹ Given the rarity of both tumors, no established management guidelines exist, although excision (wide local excision or Mohs micrographic surgery) usually is recommended, with some authors suggesting margins of 1 cm for AFX and 2 cm to 3 cm for PDS.¹

This atypical case of AFX arising in non–sun-exposed skin in a young man raises questions about whether unknown genetic factors or possibly prior immunosuppression could have contributed to the development of the tumor. A thorough history and physical examination can provide valuable clues for biopsy, including ongoing growth, absence of known prior trauma or acne at the site, and clinical appearance, such as the reddish, solitary, dome-shaped lesion in our patient.

To the Editor:

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases and is characterized by age-related morphology and distribution of lesions. Although AD can manifest at any age, it often develops during childhood, with an estimated worldwide prevalence of 15% to 25% in children and 1% to 10% in adults.¹ Clinical manifestation includes chronic or recurrent xerosis, pruritic eczematous lesions involving the flexural and extensor areas, and cutaneous infections. Immediate skin test reactivity and elevated total IgE levels can be found in up to 80% of patients.²

Although the pathogenesis of AD is complex, multifactorial, and not completely understood, some studies have highlighted the central role of a type 2 immune response, resulting in skin barrier dysfunction, cutaneous inflammation, and neuroimmune dysregulation.^3,4 The primary goals of treatment are to mitigate these factors through improvement of symptoms and long-term disease control. Topical emollients are used to repair the epidermal barrier, and topical anti-inflammatory therapy with corticosteroids or calcineurin inhibitors might be applied during flares; however, systemic treatment is essential for patients with moderate to severe AD that is not controlled with topical treatment or phototherapy.⁵

Until recently, systemic immunosuppressant agents such as corticosteroids, cyclosporine, and methotrexate were the only systemic treatment options for severe AD; however, their effectiveness is limited and they may cause serious long-term adverse events, limiting their regular usage, especially in children.⁶

Therapies that target type 2 immune responses include anti–IL-4/IL-13, anti–IL-13, and anti–IL-31 biologics. Dupilumab is a fully human monoclonal antibody targeting the type 2 immune response. This biologic directly binds to IL-4Rα,which prevents signaling by both the IL-4 and IL-13 pathways. Dupilumab was the first biologic approved by the US Food and Drug Administration (FDA) for the treatment of moderate to severe AD, with demonstrated efficacy and a favorable safety profile.⁵

In addition to biologics, Janus kinase (JAK) inhibitors belong to the small-molecule class. These drugs block the JAK/STAT intracellular signaling pathway, leading to inhibition of downstream effects triggered by several cytokines related to AD pathogenesis. Upadacitinib is an oral JAK inhibitor that was approved by the FDA in 2022 for treatment of severe AD in adults and children aged 12 years and older. This drug promotes a selective and reversible JAK-1 inhibition and has demonstrated rapid onset of action and a sustained reduction in the signs and symptoms of AD.⁷ We report the case of a child with recalcitrant severe AD that showed significant clinical improvement following off-label treatment with upadacitinib after showing a poor clinical response to dupilumab.

A 9-year-old girl presented to our pediatrics department with progressive worsening of severe AD over the previous 2 years. The patient had been diagnosed with AD at 6 months old, at which time she was treated with several prescribed moisturizers, topical and systemic corticosteroids, and calcineurin inhibitors with no clinical improvement.

The patient initially presented to us for evaluation of severe pruritus and associated sleep loss at age 7 years; physical examination revealed severe xerosis and disseminated pruritic eczematous lesions. Her SCORAD (SCORing Atopic Dermatitis) score was 70 (range, 0-103), and laboratory testing showed a high eosinophil count (1.5×10³/μL [range, 0-0.6×10³], 13%) and IgE level (1686 κU/L [range, 0-90]); a skin prick test on the forearm was positive for Blomia tropicalis.

Following her presentation with severe AD at 7 years old, the patient was prescribed systemic treatments including methotrexate and cyclosporine. During treatment with these agents, she presented to our department with several bacterial skin infections that required oral and intravenous antibiotics for treatment. These agents ultimately were discontinued after 12 months due to the adverse effects and poor clinical improvement. At age 8 years, the patient received an initial 600-mg dose of dupilumab followed by 300 mg subcutaneously every 4 weeks for 6 months along with topical corticosteroids and emollients. During treatment with dupilumab, the patient showed no clinical improvement (SCORAD score, 62). Therefore, we decided to change the dose to 200 mg every 2 weeks. The patient still showed no improvement and presented at age 9 years with moderate conjunctivitis and oculocutaneous infection caused by herpes simplex virus, which required treatment with oral acyclovir (Figure 1).

Considering the severe and refractory clinical course and the poor response to the recommended treatments for the patient’s age, oral upadacitinib was administered off label at a dose of 15 mg once daily after informed consent was obtained from her parents. She returned for follow-up once weekly for 1 month. Three days after starting treatment with upadacitinib, she showed considerable improvement in itch, and her SCORAD score decreased from 62 to 31 after 15 days. After 2 months of treatment, she reported no pruritus or sleep loss, and her SCORAD score was 4.5 (Figure 2). The results of a complete blood count, coagulation function test, and liver and kidney function tests were normal at 6-month and 12-month follow-up during upadacitinib therapy. No adverse effects were observed. The patient currently has completed 18 months of treatment, and the disease remains in complete remission.

Atopic dermatitis is highly prevalent in children. According to the International Study of Asthma and Allergies in Childhood, the prevalence of eczema in 2009 was 8.2% among children aged 6 to 7 years and 5% among adolescents aged between 13 and 14 years in Brazil; severe AD was present in 1.5% of children in both age groups.⁸

The main systemic therapies currently available for patients with severe AD are immunosuppressants, biologics, and small-molecule drugs. The considerable adverse effects of immunosuppressants limit their application. Dupilumab is considered the first-line treatment for children with severe AD. Clinical trials and case reports have demonstrated that dupilumab is effective in patients with AD, promoting notable improvement of pruritic eczematous lesions and quality-of-life scores.⁹ Dupilumab has been approved by the FDA for children older than 6 months, and some studies have shown up to a 49% reduction of pruritus in this age group.⁹ The main reported adverse effects were mild conjunctivitis and oral herpes simplex virus infection.^9,10

Upadacitinib is a reversible and selective JAK-1 inhibitor approved by the FDA for treatment of severe AD in patients aged 12 years and older. A multicenter, randomized, double-blind, placebo-controlled trial evaluated adolescents (12-17 years) and adults (18-75 years) with moderate to severe AD who were randomly assigned (1:1:1) to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily for 16 weeks.¹¹ A higher proportion of patients achieved an Eczema Area and Severity Index score of 75 at week 16 with both upadacitinib 15 mg daily (70%) and 30 mg daily (80%) compared to placebo. Improvements also were observed in both SCORAD and pruritus scores. The most commonly reported adverse events were acne, lipid profile abnormalities, and herpes zoster infection.¹¹

Our patient was a child with severe refractory AD that demonstrated a poor treatment response to dupilumab. When switched to off-label upadacitinib, her disease was effectively controlled; the treatment also was well tolerated with no adverse effects. Reports of upadacitinib used to treat AD in patients younger than 12 years are limited in the literature. One case report described a 9-year-old child with concurrent alopecia areata and severe AD who was successfully treated off label with upadacitinib.¹² A clinical trial also has evaluated the pharmacokinetics, safety, and tolerability of upadacitinib in children aged 2 to 12 years with severe AD (ClinicalTrials.gov Identifier: NCT03646604); although the trial was completed in 2024, at the time of this review (July 2025), the results have not been published.

Interestingly, there have been a few reports of adults with severe AD that failed to respond to treatment with immunosuppressants and dupilumab but showed notable clinical improvement when therapy was switched to upadacitinib,^13,14 as we noticed with our patient. These findings suggest that the JAK-STAT intracellular signaling pathway plays an important role in the pathogenesis of AD.

Continued development of safe and efficient targeted treatment for children with severe AD is critical. Upadacitinib was a safe and effective option for treatment of refractory and severe AD in our patient; however, further studies are needed to confirm both the efficacy and safety of JAK inhibitors in this age group.

To the Editor:

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases and is characterized by age-related morphology and distribution of lesions. Although AD can manifest at any age, it often develops during childhood, with an estimated worldwide prevalence of 15% to 25% in children and 1% to 10% in adults.¹ Clinical manifestation includes chronic or recurrent xerosis, pruritic eczematous lesions involving the flexural and extensor areas, and cutaneous infections. Immediate skin test reactivity and elevated total IgE levels can be found in up to 80% of patients.²

Although the pathogenesis of AD is complex, multifactorial, and not completely understood, some studies have highlighted the central role of a type 2 immune response, resulting in skin barrier dysfunction, cutaneous inflammation, and neuroimmune dysregulation.^3,4 The primary goals of treatment are to mitigate these factors through improvement of symptoms and long-term disease control. Topical emollients are used to repair the epidermal barrier, and topical anti-inflammatory therapy with corticosteroids or calcineurin inhibitors might be applied during flares; however, systemic treatment is essential for patients with moderate to severe AD that is not controlled with topical treatment or phototherapy.⁵

Until recently, systemic immunosuppressant agents such as corticosteroids, cyclosporine, and methotrexate were the only systemic treatment options for severe AD; however, their effectiveness is limited and they may cause serious long-term adverse events, limiting their regular usage, especially in children.⁶

Therapies that target type 2 immune responses include anti–IL-4/IL-13, anti–IL-13, and anti–IL-31 biologics. Dupilumab is a fully human monoclonal antibody targeting the type 2 immune response. This biologic directly binds to IL-4Rα,which prevents signaling by both the IL-4 and IL-13 pathways. Dupilumab was the first biologic approved by the US Food and Drug Administration (FDA) for the treatment of moderate to severe AD, with demonstrated efficacy and a favorable safety profile.⁵

In addition to biologics, Janus kinase (JAK) inhibitors belong to the small-molecule class. These drugs block the JAK/STAT intracellular signaling pathway, leading to inhibition of downstream effects triggered by several cytokines related to AD pathogenesis. Upadacitinib is an oral JAK inhibitor that was approved by the FDA in 2022 for treatment of severe AD in adults and children aged 12 years and older. This drug promotes a selective and reversible JAK-1 inhibition and has demonstrated rapid onset of action and a sustained reduction in the signs and symptoms of AD.⁷ We report the case of a child with recalcitrant severe AD that showed significant clinical improvement following off-label treatment with upadacitinib after showing a poor clinical response to dupilumab.

A 9-year-old girl presented to our pediatrics department with progressive worsening of severe AD over the previous 2 years. The patient had been diagnosed with AD at 6 months old, at which time she was treated with several prescribed moisturizers, topical and systemic corticosteroids, and calcineurin inhibitors with no clinical improvement.

The patient initially presented to us for evaluation of severe pruritus and associated sleep loss at age 7 years; physical examination revealed severe xerosis and disseminated pruritic eczematous lesions. Her SCORAD (SCORing Atopic Dermatitis) score was 70 (range, 0-103), and laboratory testing showed a high eosinophil count (1.5×10³/μL [range, 0-0.6×10³], 13%) and IgE level (1686 κU/L [range, 0-90]); a skin prick test on the forearm was positive for Blomia tropicalis.

Following her presentation with severe AD at 7 years old, the patient was prescribed systemic treatments including methotrexate and cyclosporine. During treatment with these agents, she presented to our department with several bacterial skin infections that required oral and intravenous antibiotics for treatment. These agents ultimately were discontinued after 12 months due to the adverse effects and poor clinical improvement. At age 8 years, the patient received an initial 600-mg dose of dupilumab followed by 300 mg subcutaneously every 4 weeks for 6 months along with topical corticosteroids and emollients. During treatment with dupilumab, the patient showed no clinical improvement (SCORAD score, 62). Therefore, we decided to change the dose to 200 mg every 2 weeks. The patient still showed no improvement and presented at age 9 years with moderate conjunctivitis and oculocutaneous infection caused by herpes simplex virus, which required treatment with oral acyclovir (Figure 1).

Considering the severe and refractory clinical course and the poor response to the recommended treatments for the patient’s age, oral upadacitinib was administered off label at a dose of 15 mg once daily after informed consent was obtained from her parents. She returned for follow-up once weekly for 1 month. Three days after starting treatment with upadacitinib, she showed considerable improvement in itch, and her SCORAD score decreased from 62 to 31 after 15 days. After 2 months of treatment, she reported no pruritus or sleep loss, and her SCORAD score was 4.5 (Figure 2). The results of a complete blood count, coagulation function test, and liver and kidney function tests were normal at 6-month and 12-month follow-up during upadacitinib therapy. No adverse effects were observed. The patient currently has completed 18 months of treatment, and the disease remains in complete remission.

Atopic dermatitis is highly prevalent in children. According to the International Study of Asthma and Allergies in Childhood, the prevalence of eczema in 2009 was 8.2% among children aged 6 to 7 years and 5% among adolescents aged between 13 and 14 years in Brazil; severe AD was present in 1.5% of children in both age groups.⁸

The main systemic therapies currently available for patients with severe AD are immunosuppressants, biologics, and small-molecule drugs. The considerable adverse effects of immunosuppressants limit their application. Dupilumab is considered the first-line treatment for children with severe AD. Clinical trials and case reports have demonstrated that dupilumab is effective in patients with AD, promoting notable improvement of pruritic eczematous lesions and quality-of-life scores.⁹ Dupilumab has been approved by the FDA for children older than 6 months, and some studies have shown up to a 49% reduction of pruritus in this age group.⁹ The main reported adverse effects were mild conjunctivitis and oral herpes simplex virus infection.^9,10

Upadacitinib is a reversible and selective JAK-1 inhibitor approved by the FDA for treatment of severe AD in patients aged 12 years and older. A multicenter, randomized, double-blind, placebo-controlled trial evaluated adolescents (12-17 years) and adults (18-75 years) with moderate to severe AD who were randomly assigned (1:1:1) to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily for 16 weeks.¹¹ A higher proportion of patients achieved an Eczema Area and Severity Index score of 75 at week 16 with both upadacitinib 15 mg daily (70%) and 30 mg daily (80%) compared to placebo. Improvements also were observed in both SCORAD and pruritus scores. The most commonly reported adverse events were acne, lipid profile abnormalities, and herpes zoster infection.¹¹

Our patient was a child with severe refractory AD that demonstrated a poor treatment response to dupilumab. When switched to off-label upadacitinib, her disease was effectively controlled; the treatment also was well tolerated with no adverse effects. Reports of upadacitinib used to treat AD in patients younger than 12 years are limited in the literature. One case report described a 9-year-old child with concurrent alopecia areata and severe AD who was successfully treated off label with upadacitinib.¹² A clinical trial also has evaluated the pharmacokinetics, safety, and tolerability of upadacitinib in children aged 2 to 12 years with severe AD (ClinicalTrials.gov Identifier: NCT03646604); although the trial was completed in 2024, at the time of this review (July 2025), the results have not been published.

Interestingly, there have been a few reports of adults with severe AD that failed to respond to treatment with immunosuppressants and dupilumab but showed notable clinical improvement when therapy was switched to upadacitinib,^13,14 as we noticed with our patient. These findings suggest that the JAK-STAT intracellular signaling pathway plays an important role in the pathogenesis of AD.

Continued development of safe and efficient targeted treatment for children with severe AD is critical. Upadacitinib was a safe and effective option for treatment of refractory and severe AD in our patient; however, further studies are needed to confirm both the efficacy and safety of JAK inhibitors in this age group.

To the Editor:

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases and is characterized by age-related morphology and distribution of lesions. Although AD can manifest at any age, it often develops during childhood, with an estimated worldwide prevalence of 15% to 25% in children and 1% to 10% in adults.¹ Clinical manifestation includes chronic or recurrent xerosis, pruritic eczematous lesions involving the flexural and extensor areas, and cutaneous infections. Immediate skin test reactivity and elevated total IgE levels can be found in up to 80% of patients.²

Although the pathogenesis of AD is complex, multifactorial, and not completely understood, some studies have highlighted the central role of a type 2 immune response, resulting in skin barrier dysfunction, cutaneous inflammation, and neuroimmune dysregulation.^3,4 The primary goals of treatment are to mitigate these factors through improvement of symptoms and long-term disease control. Topical emollients are used to repair the epidermal barrier, and topical anti-inflammatory therapy with corticosteroids or calcineurin inhibitors might be applied during flares; however, systemic treatment is essential for patients with moderate to severe AD that is not controlled with topical treatment or phototherapy.⁵

Until recently, systemic immunosuppressant agents such as corticosteroids, cyclosporine, and methotrexate were the only systemic treatment options for severe AD; however, their effectiveness is limited and they may cause serious long-term adverse events, limiting their regular usage, especially in children.⁶

Therapies that target type 2 immune responses include anti–IL-4/IL-13, anti–IL-13, and anti–IL-31 biologics. Dupilumab is a fully human monoclonal antibody targeting the type 2 immune response. This biologic directly binds to IL-4Rα,which prevents signaling by both the IL-4 and IL-13 pathways. Dupilumab was the first biologic approved by the US Food and Drug Administration (FDA) for the treatment of moderate to severe AD, with demonstrated efficacy and a favorable safety profile.⁵

In addition to biologics, Janus kinase (JAK) inhibitors belong to the small-molecule class. These drugs block the JAK/STAT intracellular signaling pathway, leading to inhibition of downstream effects triggered by several cytokines related to AD pathogenesis. Upadacitinib is an oral JAK inhibitor that was approved by the FDA in 2022 for treatment of severe AD in adults and children aged 12 years and older. This drug promotes a selective and reversible JAK-1 inhibition and has demonstrated rapid onset of action and a sustained reduction in the signs and symptoms of AD.⁷ We report the case of a child with recalcitrant severe AD that showed significant clinical improvement following off-label treatment with upadacitinib after showing a poor clinical response to dupilumab.

A 9-year-old girl presented to our pediatrics department with progressive worsening of severe AD over the previous 2 years. The patient had been diagnosed with AD at 6 months old, at which time she was treated with several prescribed moisturizers, topical and systemic corticosteroids, and calcineurin inhibitors with no clinical improvement.

The patient initially presented to us for evaluation of severe pruritus and associated sleep loss at age 7 years; physical examination revealed severe xerosis and disseminated pruritic eczematous lesions. Her SCORAD (SCORing Atopic Dermatitis) score was 70 (range, 0-103), and laboratory testing showed a high eosinophil count (1.5×10³/μL [range, 0-0.6×10³], 13%) and IgE level (1686 κU/L [range, 0-90]); a skin prick test on the forearm was positive for Blomia tropicalis.

Following her presentation with severe AD at 7 years old, the patient was prescribed systemic treatments including methotrexate and cyclosporine. During treatment with these agents, she presented to our department with several bacterial skin infections that required oral and intravenous antibiotics for treatment. These agents ultimately were discontinued after 12 months due to the adverse effects and poor clinical improvement. At age 8 years, the patient received an initial 600-mg dose of dupilumab followed by 300 mg subcutaneously every 4 weeks for 6 months along with topical corticosteroids and emollients. During treatment with dupilumab, the patient showed no clinical improvement (SCORAD score, 62). Therefore, we decided to change the dose to 200 mg every 2 weeks. The patient still showed no improvement and presented at age 9 years with moderate conjunctivitis and oculocutaneous infection caused by herpes simplex virus, which required treatment with oral acyclovir (Figure 1).

Considering the severe and refractory clinical course and the poor response to the recommended treatments for the patient’s age, oral upadacitinib was administered off label at a dose of 15 mg once daily after informed consent was obtained from her parents. She returned for follow-up once weekly for 1 month. Three days after starting treatment with upadacitinib, she showed considerable improvement in itch, and her SCORAD score decreased from 62 to 31 after 15 days. After 2 months of treatment, she reported no pruritus or sleep loss, and her SCORAD score was 4.5 (Figure 2). The results of a complete blood count, coagulation function test, and liver and kidney function tests were normal at 6-month and 12-month follow-up during upadacitinib therapy. No adverse effects were observed. The patient currently has completed 18 months of treatment, and the disease remains in complete remission.

Atopic dermatitis is highly prevalent in children. According to the International Study of Asthma and Allergies in Childhood, the prevalence of eczema in 2009 was 8.2% among children aged 6 to 7 years and 5% among adolescents aged between 13 and 14 years in Brazil; severe AD was present in 1.5% of children in both age groups.⁸

The main systemic therapies currently available for patients with severe AD are immunosuppressants, biologics, and small-molecule drugs. The considerable adverse effects of immunosuppressants limit their application. Dupilumab is considered the first-line treatment for children with severe AD. Clinical trials and case reports have demonstrated that dupilumab is effective in patients with AD, promoting notable improvement of pruritic eczematous lesions and quality-of-life scores.⁹ Dupilumab has been approved by the FDA for children older than 6 months, and some studies have shown up to a 49% reduction of pruritus in this age group.⁹ The main reported adverse effects were mild conjunctivitis and oral herpes simplex virus infection.^9,10

Upadacitinib is a reversible and selective JAK-1 inhibitor approved by the FDA for treatment of severe AD in patients aged 12 years and older. A multicenter, randomized, double-blind, placebo-controlled trial evaluated adolescents (12-17 years) and adults (18-75 years) with moderate to severe AD who were randomly assigned (1:1:1) to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily for 16 weeks.¹¹ A higher proportion of patients achieved an Eczema Area and Severity Index score of 75 at week 16 with both upadacitinib 15 mg daily (70%) and 30 mg daily (80%) compared to placebo. Improvements also were observed in both SCORAD and pruritus scores. The most commonly reported adverse events were acne, lipid profile abnormalities, and herpes zoster infection.¹¹

Our patient was a child with severe refractory AD that demonstrated a poor treatment response to dupilumab. When switched to off-label upadacitinib, her disease was effectively controlled; the treatment also was well tolerated with no adverse effects. Reports of upadacitinib used to treat AD in patients younger than 12 years are limited in the literature. One case report described a 9-year-old child with concurrent alopecia areata and severe AD who was successfully treated off label with upadacitinib.¹² A clinical trial also has evaluated the pharmacokinetics, safety, and tolerability of upadacitinib in children aged 2 to 12 years with severe AD (ClinicalTrials.gov Identifier: NCT03646604); although the trial was completed in 2024, at the time of this review (July 2025), the results have not been published.

Interestingly, there have been a few reports of adults with severe AD that failed to respond to treatment with immunosuppressants and dupilumab but showed notable clinical improvement when therapy was switched to upadacitinib,^13,14 as we noticed with our patient. These findings suggest that the JAK-STAT intracellular signaling pathway plays an important role in the pathogenesis of AD.

Continued development of safe and efficient targeted treatment for children with severe AD is critical. Upadacitinib was a safe and effective option for treatment of refractory and severe AD in our patient; however, further studies are needed to confirm both the efficacy and safety of JAK inhibitors in this age group.

THE DIAGNOSIS: Pedunculated Lipofibroma

Histopathology confirmed a pedunculated/polypoid lesion with intradermal lobules of adipocytes/mature adipose tissue admixed with connective tissue bundles and vascular ectasias. Overlying epidermal acanthosis with slight papillomatosis and hyperkeratosis was present (Figure 1). Masson trichrome staining highlighted admixed collagen bundles (Figure 2). Verhoeff–van Gieson staining showed marked reduction in elastic fibers (Figure 3). Immunostaining was negative for smooth muscle actin and desmin. A diagnosis of pedunculated lipofibroma on the nose was made based on both clinical and histopathologic findings.

Pedunculated lipofibroma (or solitary lipofibroma) is the solitary form of nevus lipomatosus cutaneous superficialis (NLCS).⁷ First described by Hoffmann and Zurhelle¹ in 1921, NLCS is an uncommon benign hamartomatous cutaneous lesion/connective tissue nevus that also has a classic multiple form.^1-13 The etiology of NLCS remains unclear, but several theories have been proposed to explain its pathogenesis, including deposition of adipocytes secondary to degenerative changes in dermal connective tissue, focal/local heterotopic development of adipose tissue, and derivation from differentiating lipoblasts (preadipose tissue) originating from precursor vascular or perivascular cells.^2-13

Pedunculated lipofibroma usually develops during the third to sixth decades of life and manifests as a single cutaneous lesion with a smooth surface, often on a non–pelvic girdle location.^7-13 No particular predilection sites are noted, with lesions reported on the arm, axilla, back, upper thigh, knee, and sole.^5,12 There are rare reports of this type of NLCS on the ear, scalp, forehead, or eyelid.^7-11

In the classic form of NLCS, multiple cutaneous lesions are present at birth or develop within the first 2 to 3 decades of life.^2-6 Lesions consist of soft, nontender, pedunculated, flesh-colored or yellowish papules and nodules with a verrucoid or cerebriform surface that may later coalesce to form plaques.^2-6 Predilection sites include the pelvic girdle, buttocks, sacral and coccygeal regions, and upper posterior thighs, with a linear or zosteriform pattern of distribution.^2-6 Rarely, the classic form can arise in elderly patients and/or at an atypical anatomic location (eg, clitoris,³ shoulder,⁵ thorax,⁵ abdomen⁵) and can demonstrate extension of lesions across the midline.⁴ Rare cases of classic NLCS on the scalp² and face^3-6 have been reported, including lesions localized to the nose³ and chin⁴ and others extending from the right mandible to the neck⁵ and right lower lip to the submandibular/posteriorateral cervical region.⁶ In some cases, lesions clinically resemble plane xanthoma⁴ and localized scleroderma.⁶

Adotama et al¹³ proposed a set of clinical features to differentiate classic NLCS, pedunculated lipofibroma (solitary NLCS), and fibroepithelial polyp with adipocytes (distinguished by their furrowed surface, hyperpigmentation, and anatomic predilection for the neck and axilla). Lesions are asymptomatic in both forms of NLCS.^2-13 Family history or predominant sex involvement have not been reported in either clinical type.^2-13 Reported associations with NLCS include a number of endocrinologic conditions including diabetes.⁷ Other coexisting skin findings can include café-au-lait macules, leukodermic (white) spots, overlying hypertrichosis, comedolike alterations, angiokeratoma, hemangioma, and folliculosebaceous cystic hamartoma.⁴ None of these were evident in our patient.

Lesions from both types of NLCS are indistinguishable on histopathology, characterized by the presence of a central core of ectopic mature adipocytes in the papillary/reticular dermis.^2-13 Additional light microscopic features (some seen in our case) have been described, including thickened collagen bundles, reduction of elastic fibers, increased numbers of fibroblasts and/or mast cells, increased (small-vessel) vascularity, focal mucin deposition/myxoid degeneration, a mild perivascular lymphocytic infiltrate, attenuation of adnexal structures, and abnormalities of the epidermis (eg, surface ulceration).^2-13

Prior to biopsy, the differential diagnosis in our patient included angiofibroma, pyogenic granuloma, and basal cell carcinoma given the exophytic, pink, papular appearance of the lesion; however, the histopathologic differential diagnosis included angiofibroma, angiomyolipoma, lymphangioma, nevus sebaceus, and spindle cell lipoma (SCL). In angiofibroma, a dermal proliferation of stellate fibroblasts, dilated blood vessels, and collagenous stroma are seen. Cutaneous angiomyolipoma demonstrates smooth muscle bundles in addition to thickened blood vessels and variable proportions of mature adipocytes. Lymphangioma is characterized by dilated lymph channels lined by flat endothelial cells. Nevus sebaceus shows superficial immature and abnormally formed pilosebaceous units, with epidermal papillomatosis.

Rare cases of SCL on the nose have been described.¹⁴ Similar to pedunculated lipofibroma, reported examples demonstrate mature univacuolar adipocytes with thick collagen fibers and bland uniform spindle cells. Unlike the lesion seen in our patient, nasal SCL may be clinically mobile and typically is localized to the subcutaneous tissue, although dermal tumors also occur.¹⁴ Variably reported histopathologic findings in nasal SCL include circumscription/encapsulation, spindle cells arranged in short fascicles with nuclear palisading, a myxoid/mucinous interstitial matrix, and/or multinucleated giant cells—all light microscopic features that were not identified in our case; however, variable proportions of adipocytic, fibrous, and myxoid components among reported examples of SCL on the nose¹⁴ can make distinction from pedunculated lipofibroma difficult, as both are benign lipomatous tumor variants.

Clinically, pedunculated lipofibroma may be confused with more common benign cutaneous lesions and must be distinguished from other fibrolipomatous lesions on the nose. Specifically, the differential diagnosis includes benign cutaneous papillomas such as acrochordon, angiofibroma, melanocytic nevi, neurofibroma, nevus sebaceus, lymphangioma, and eccrine poroma.^7-13 These all can be readily excluded on histopathology. Pedunculated lipofibroma on the nose, as in our patient, must be distinguished from fibrolipoma¹⁵ and dendritic myxofibrolipoma.¹⁶ Fibrolipoma is a subcutaneous proliferation of mature adipose tissue and fibrous tissue and comprises 1.6% of all facial lipomas reported worldwide.¹⁵ Dendritic myxofibrolipoma is a recently described benign soft-tissue tumor characterized by an admixture of mature adipose tissue, spindle and stellate cells, and an abundant myxoid stroma with prominent collagenization.¹⁶

Treatment of pedunculated lipofibroma on the nose is not indicated except for cosmetic reasons, in which case simple surgical excision would be considered satisfactory. Following biopsy, no further treatment was pursued in our patient.

THE DIAGNOSIS: Pedunculated Lipofibroma

Histopathology confirmed a pedunculated/polypoid lesion with intradermal lobules of adipocytes/mature adipose tissue admixed with connective tissue bundles and vascular ectasias. Overlying epidermal acanthosis with slight papillomatosis and hyperkeratosis was present (Figure 1). Masson trichrome staining highlighted admixed collagen bundles (Figure 2). Verhoeff–van Gieson staining showed marked reduction in elastic fibers (Figure 3). Immunostaining was negative for smooth muscle actin and desmin. A diagnosis of pedunculated lipofibroma on the nose was made based on both clinical and histopathologic findings.

Pedunculated lipofibroma (or solitary lipofibroma) is the solitary form of nevus lipomatosus cutaneous superficialis (NLCS).⁷ First described by Hoffmann and Zurhelle¹ in 1921, NLCS is an uncommon benign hamartomatous cutaneous lesion/connective tissue nevus that also has a classic multiple form.^1-13 The etiology of NLCS remains unclear, but several theories have been proposed to explain its pathogenesis, including deposition of adipocytes secondary to degenerative changes in dermal connective tissue, focal/local heterotopic development of adipose tissue, and derivation from differentiating lipoblasts (preadipose tissue) originating from precursor vascular or perivascular cells.^2-13

Pedunculated lipofibroma usually develops during the third to sixth decades of life and manifests as a single cutaneous lesion with a smooth surface, often on a non–pelvic girdle location.^7-13 No particular predilection sites are noted, with lesions reported on the arm, axilla, back, upper thigh, knee, and sole.^5,12 There are rare reports of this type of NLCS on the ear, scalp, forehead, or eyelid.^7-11

In the classic form of NLCS, multiple cutaneous lesions are present at birth or develop within the first 2 to 3 decades of life.^2-6 Lesions consist of soft, nontender, pedunculated, flesh-colored or yellowish papules and nodules with a verrucoid or cerebriform surface that may later coalesce to form plaques.^2-6 Predilection sites include the pelvic girdle, buttocks, sacral and coccygeal regions, and upper posterior thighs, with a linear or zosteriform pattern of distribution.^2-6 Rarely, the classic form can arise in elderly patients and/or at an atypical anatomic location (eg, clitoris,³ shoulder,⁵ thorax,⁵ abdomen⁵) and can demonstrate extension of lesions across the midline.⁴ Rare cases of classic NLCS on the scalp² and face^3-6 have been reported, including lesions localized to the nose³ and chin⁴ and others extending from the right mandible to the neck⁵ and right lower lip to the submandibular/posteriorateral cervical region.⁶ In some cases, lesions clinically resemble plane xanthoma⁴ and localized scleroderma.⁶

Adotama et al¹³ proposed a set of clinical features to differentiate classic NLCS, pedunculated lipofibroma (solitary NLCS), and fibroepithelial polyp with adipocytes (distinguished by their furrowed surface, hyperpigmentation, and anatomic predilection for the neck and axilla). Lesions are asymptomatic in both forms of NLCS.^2-13 Family history or predominant sex involvement have not been reported in either clinical type.^2-13 Reported associations with NLCS include a number of endocrinologic conditions including diabetes.⁷ Other coexisting skin findings can include café-au-lait macules, leukodermic (white) spots, overlying hypertrichosis, comedolike alterations, angiokeratoma, hemangioma, and folliculosebaceous cystic hamartoma.⁴ None of these were evident in our patient.

Lesions from both types of NLCS are indistinguishable on histopathology, characterized by the presence of a central core of ectopic mature adipocytes in the papillary/reticular dermis.^2-13 Additional light microscopic features (some seen in our case) have been described, including thickened collagen bundles, reduction of elastic fibers, increased numbers of fibroblasts and/or mast cells, increased (small-vessel) vascularity, focal mucin deposition/myxoid degeneration, a mild perivascular lymphocytic infiltrate, attenuation of adnexal structures, and abnormalities of the epidermis (eg, surface ulceration).^2-13

Prior to biopsy, the differential diagnosis in our patient included angiofibroma, pyogenic granuloma, and basal cell carcinoma given the exophytic, pink, papular appearance of the lesion; however, the histopathologic differential diagnosis included angiofibroma, angiomyolipoma, lymphangioma, nevus sebaceus, and spindle cell lipoma (SCL). In angiofibroma, a dermal proliferation of stellate fibroblasts, dilated blood vessels, and collagenous stroma are seen. Cutaneous angiomyolipoma demonstrates smooth muscle bundles in addition to thickened blood vessels and variable proportions of mature adipocytes. Lymphangioma is characterized by dilated lymph channels lined by flat endothelial cells. Nevus sebaceus shows superficial immature and abnormally formed pilosebaceous units, with epidermal papillomatosis.

Rare cases of SCL on the nose have been described.¹⁴ Similar to pedunculated lipofibroma, reported examples demonstrate mature univacuolar adipocytes with thick collagen fibers and bland uniform spindle cells. Unlike the lesion seen in our patient, nasal SCL may be clinically mobile and typically is localized to the subcutaneous tissue, although dermal tumors also occur.¹⁴ Variably reported histopathologic findings in nasal SCL include circumscription/encapsulation, spindle cells arranged in short fascicles with nuclear palisading, a myxoid/mucinous interstitial matrix, and/or multinucleated giant cells—all light microscopic features that were not identified in our case; however, variable proportions of adipocytic, fibrous, and myxoid components among reported examples of SCL on the nose¹⁴ can make distinction from pedunculated lipofibroma difficult, as both are benign lipomatous tumor variants.

Clinically, pedunculated lipofibroma may be confused with more common benign cutaneous lesions and must be distinguished from other fibrolipomatous lesions on the nose. Specifically, the differential diagnosis includes benign cutaneous papillomas such as acrochordon, angiofibroma, melanocytic nevi, neurofibroma, nevus sebaceus, lymphangioma, and eccrine poroma.^7-13 These all can be readily excluded on histopathology. Pedunculated lipofibroma on the nose, as in our patient, must be distinguished from fibrolipoma¹⁵ and dendritic myxofibrolipoma.¹⁶ Fibrolipoma is a subcutaneous proliferation of mature adipose tissue and fibrous tissue and comprises 1.6% of all facial lipomas reported worldwide.¹⁵ Dendritic myxofibrolipoma is a recently described benign soft-tissue tumor characterized by an admixture of mature adipose tissue, spindle and stellate cells, and an abundant myxoid stroma with prominent collagenization.¹⁶

Treatment of pedunculated lipofibroma on the nose is not indicated except for cosmetic reasons, in which case simple surgical excision would be considered satisfactory. Following biopsy, no further treatment was pursued in our patient.

THE DIAGNOSIS: Pedunculated Lipofibroma

Histopathology confirmed a pedunculated/polypoid lesion with intradermal lobules of adipocytes/mature adipose tissue admixed with connective tissue bundles and vascular ectasias. Overlying epidermal acanthosis with slight papillomatosis and hyperkeratosis was present (Figure 1). Masson trichrome staining highlighted admixed collagen bundles (Figure 2). Verhoeff–van Gieson staining showed marked reduction in elastic fibers (Figure 3). Immunostaining was negative for smooth muscle actin and desmin. A diagnosis of pedunculated lipofibroma on the nose was made based on both clinical and histopathologic findings.

Pedunculated lipofibroma (or solitary lipofibroma) is the solitary form of nevus lipomatosus cutaneous superficialis (NLCS).⁷ First described by Hoffmann and Zurhelle¹ in 1921, NLCS is an uncommon benign hamartomatous cutaneous lesion/connective tissue nevus that also has a classic multiple form.^1-13 The etiology of NLCS remains unclear, but several theories have been proposed to explain its pathogenesis, including deposition of adipocytes secondary to degenerative changes in dermal connective tissue, focal/local heterotopic development of adipose tissue, and derivation from differentiating lipoblasts (preadipose tissue) originating from precursor vascular or perivascular cells.^2-13

Pedunculated lipofibroma usually develops during the third to sixth decades of life and manifests as a single cutaneous lesion with a smooth surface, often on a non–pelvic girdle location.^7-13 No particular predilection sites are noted, with lesions reported on the arm, axilla, back, upper thigh, knee, and sole.^5,12 There are rare reports of this type of NLCS on the ear, scalp, forehead, or eyelid.^7-11

In the classic form of NLCS, multiple cutaneous lesions are present at birth or develop within the first 2 to 3 decades of life.^2-6 Lesions consist of soft, nontender, pedunculated, flesh-colored or yellowish papules and nodules with a verrucoid or cerebriform surface that may later coalesce to form plaques.^2-6 Predilection sites include the pelvic girdle, buttocks, sacral and coccygeal regions, and upper posterior thighs, with a linear or zosteriform pattern of distribution.^2-6 Rarely, the classic form can arise in elderly patients and/or at an atypical anatomic location (eg, clitoris,³ shoulder,⁵ thorax,⁵ abdomen⁵) and can demonstrate extension of lesions across the midline.⁴ Rare cases of classic NLCS on the scalp² and face^3-6 have been reported, including lesions localized to the nose³ and chin⁴ and others extending from the right mandible to the neck⁵ and right lower lip to the submandibular/posteriorateral cervical region.⁶ In some cases, lesions clinically resemble plane xanthoma⁴ and localized scleroderma.⁶

Adotama et al¹³ proposed a set of clinical features to differentiate classic NLCS, pedunculated lipofibroma (solitary NLCS), and fibroepithelial polyp with adipocytes (distinguished by their furrowed surface, hyperpigmentation, and anatomic predilection for the neck and axilla). Lesions are asymptomatic in both forms of NLCS.^2-13 Family history or predominant sex involvement have not been reported in either clinical type.^2-13 Reported associations with NLCS include a number of endocrinologic conditions including diabetes.⁷ Other coexisting skin findings can include café-au-lait macules, leukodermic (white) spots, overlying hypertrichosis, comedolike alterations, angiokeratoma, hemangioma, and folliculosebaceous cystic hamartoma.⁴ None of these were evident in our patient.

Lesions from both types of NLCS are indistinguishable on histopathology, characterized by the presence of a central core of ectopic mature adipocytes in the papillary/reticular dermis.^2-13 Additional light microscopic features (some seen in our case) have been described, including thickened collagen bundles, reduction of elastic fibers, increased numbers of fibroblasts and/or mast cells, increased (small-vessel) vascularity, focal mucin deposition/myxoid degeneration, a mild perivascular lymphocytic infiltrate, attenuation of adnexal structures, and abnormalities of the epidermis (eg, surface ulceration).^2-13

Prior to biopsy, the differential diagnosis in our patient included angiofibroma, pyogenic granuloma, and basal cell carcinoma given the exophytic, pink, papular appearance of the lesion; however, the histopathologic differential diagnosis included angiofibroma, angiomyolipoma, lymphangioma, nevus sebaceus, and spindle cell lipoma (SCL). In angiofibroma, a dermal proliferation of stellate fibroblasts, dilated blood vessels, and collagenous stroma are seen. Cutaneous angiomyolipoma demonstrates smooth muscle bundles in addition to thickened blood vessels and variable proportions of mature adipocytes. Lymphangioma is characterized by dilated lymph channels lined by flat endothelial cells. Nevus sebaceus shows superficial immature and abnormally formed pilosebaceous units, with epidermal papillomatosis.

Rare cases of SCL on the nose have been described.¹⁴ Similar to pedunculated lipofibroma, reported examples demonstrate mature univacuolar adipocytes with thick collagen fibers and bland uniform spindle cells. Unlike the lesion seen in our patient, nasal SCL may be clinically mobile and typically is localized to the subcutaneous tissue, although dermal tumors also occur.¹⁴ Variably reported histopathologic findings in nasal SCL include circumscription/encapsulation, spindle cells arranged in short fascicles with nuclear palisading, a myxoid/mucinous interstitial matrix, and/or multinucleated giant cells—all light microscopic features that were not identified in our case; however, variable proportions of adipocytic, fibrous, and myxoid components among reported examples of SCL on the nose¹⁴ can make distinction from pedunculated lipofibroma difficult, as both are benign lipomatous tumor variants.

Clinically, pedunculated lipofibroma may be confused with more common benign cutaneous lesions and must be distinguished from other fibrolipomatous lesions on the nose. Specifically, the differential diagnosis includes benign cutaneous papillomas such as acrochordon, angiofibroma, melanocytic nevi, neurofibroma, nevus sebaceus, lymphangioma, and eccrine poroma.^7-13 These all can be readily excluded on histopathology. Pedunculated lipofibroma on the nose, as in our patient, must be distinguished from fibrolipoma¹⁵ and dendritic myxofibrolipoma.¹⁶ Fibrolipoma is a subcutaneous proliferation of mature adipose tissue and fibrous tissue and comprises 1.6% of all facial lipomas reported worldwide.¹⁵ Dendritic myxofibrolipoma is a recently described benign soft-tissue tumor characterized by an admixture of mature adipose tissue, spindle and stellate cells, and an abundant myxoid stroma with prominent collagenization.¹⁶

Treatment of pedunculated lipofibroma on the nose is not indicated except for cosmetic reasons, in which case simple surgical excision would be considered satisfactory. Following biopsy, no further treatment was pursued in our patient.

To the Editor:

Drug-induced hyperpigmentation is a common cause of an acquired increase in pigmentation. Belumosudil is an oral selective inhibitor of Rho-associated coiled-coil containing protein kinase (ROCK2) that is approved for the treatment of chronic graft-vs-host disease (GVHD). We describe a patient who developed diffuse skin bronzing 3 weeks after initiation of belumosudil treatment.

A 64-year-old fair-skinned woman presented to the dermatology clinic with bronzing of the skin and dystrophic nails 3 weeks after starting belumosudil for treatment of chronic GVHD. Six months prior to presentation, the patient had received a bone marrow transplant for chronic lymphoid leukemia. She presented to dermatology 6 months after the transplant with a new-onset rash that was suspicious for GVHD. Physical examination revealed pruritic pink papules diffusely scattered on the legs and forearms (Figure 1). The patient declined biopsy at that time and later followed up with oncology. The patient’s oncologist supported a diagnosis of GVHD, and the patient began treatment with belumosudil 200 mg/d which was intended to be taken until treatment failure due to progression of chronic GVHD.

Three weeks after starting belumosudil, the patient developed diffuse bronzing of the skin and brown, evenly colored patches scattered on the trunk, back, and upper and lower extremities on a background of the presumed GVHD rash (Figure 2). The hyperpigmentation was abrupt, starting on the chest and spreading to the abdomen, extremities, and back (Figure 3).

Again, the patient was offered biopsy for the new-onset pigmentation but declined. During this time, she had no notable sun exposure and primarily stayed indoors despite living in a region with a sunny semi-arid climate. Her medication and supplement list were reviewed and included acalabrutinib, a multivitamin, lutein, biotin, and a fish oil supplement. A compete blood cell count as well as ferritin, transferrin, cortisol, and adrenocorticotropic hormone levels were unremarkable.

The patient continued to take belumosudil for treatment of GVHD. The hyperpigmentation faded slightly by a 2-month follow-up visit but persisted and was stable. She has not tried other treatments for GVHD to manage the hyperpigmentation.

Conditions known to cause diffuse bronzing of the skin include Addison disease, hemochromatosis, Cushing disease, and medication adverse events. Our patient presented with an absence of systemic symptoms, normal laboratory results, and no clinical indicators suggesting alternate causes. Given that the onset of the hyperpigmentation was 3 weeks after she started a new medication, we hypothesized that the bronzing was an adverse effect of the belumosudil—though this correlation cannot be definitively proven by this case.

The most common offending agents for drug-induced skin hyperpigmentation are nonsteroidal anti- inflammatory drugs, antimalarials, amiodarone, cytotoxic drugs, and tetracyclines.^1,2 Our patient’s medication list included the cytotoxic agent acalabrutinib, a Bruton tyrosine kinase inhibitor used for the treatment of non-Hodgkin lymphoma. It has been associated with dermatologic findings of ecchymosis, bruising, panniculitis, and cellulitis, but there are no known reports of hyperpigmentation.³ Our patient had been taking acalabrutinib for 6 months when the GVHD rash developed. At the time, she also was taking a multivitamin and lutein, biotin, and fish oil supplements, none of which have been associated with hyperpigmentation.

Polypharmacy adds a layer of difficulty in identifying the inciting cause of pigmentary change. In our case, symptoms began 3 weeks after the initiation of belumosudil. There were no cutaneous reactions observed in the ROCKstar study of belumosudil; the most common adverse events were upper respiratory tract infection, diarrhea, fatigue, nausea, increased liver enzymes, and dyspnea.^4,5 Patients on belumosudil have developed aggressive cutaneous squamous cell carcinoma.⁶ However, a search of PubMed articles indexed for MEDLINE using the search terms acalabrutinib or belumosudil with hyperpigmentation or cutaneous reaction returned no reports of these medications causing hyperpigmentation or cutaneous deposits.

Treatment of drug-induced hyperpigmentation is difficult because discontinuation of the offending agent typically confirms diagnosis, but interruption of treatment is not always possible, as in our patient. The skin changes can fade over time, but effects typically are long lasting.

Dermatologists play a key role in the identification of drug-induced skin hyperpigmentation. After endocrine or metabolic causes of skin hyperpigmentation have been ruled out, a thorough review of the patient’s medication list should be done to assess for a drug-induced cause. Treatment is limited to sun avoidance, as interruption of treatment may not be possible, and lesions typically do fade over time. These chronic skin changes can have a psychosocial effect on patients and regular follow-up is recommended.

To the Editor:

Drug-induced hyperpigmentation is a common cause of an acquired increase in pigmentation. Belumosudil is an oral selective inhibitor of Rho-associated coiled-coil containing protein kinase (ROCK2) that is approved for the treatment of chronic graft-vs-host disease (GVHD). We describe a patient who developed diffuse skin bronzing 3 weeks after initiation of belumosudil treatment.

A 64-year-old fair-skinned woman presented to the dermatology clinic with bronzing of the skin and dystrophic nails 3 weeks after starting belumosudil for treatment of chronic GVHD. Six months prior to presentation, the patient had received a bone marrow transplant for chronic lymphoid leukemia. She presented to dermatology 6 months after the transplant with a new-onset rash that was suspicious for GVHD. Physical examination revealed pruritic pink papules diffusely scattered on the legs and forearms (Figure 1). The patient declined biopsy at that time and later followed up with oncology. The patient’s oncologist supported a diagnosis of GVHD, and the patient began treatment with belumosudil 200 mg/d which was intended to be taken until treatment failure due to progression of chronic GVHD.

Three weeks after starting belumosudil, the patient developed diffuse bronzing of the skin and brown, evenly colored patches scattered on the trunk, back, and upper and lower extremities on a background of the presumed GVHD rash (Figure 2). The hyperpigmentation was abrupt, starting on the chest and spreading to the abdomen, extremities, and back (Figure 3).

Again, the patient was offered biopsy for the new-onset pigmentation but declined. During this time, she had no notable sun exposure and primarily stayed indoors despite living in a region with a sunny semi-arid climate. Her medication and supplement list were reviewed and included acalabrutinib, a multivitamin, lutein, biotin, and a fish oil supplement. A compete blood cell count as well as ferritin, transferrin, cortisol, and adrenocorticotropic hormone levels were unremarkable.

The patient continued to take belumosudil for treatment of GVHD. The hyperpigmentation faded slightly by a 2-month follow-up visit but persisted and was stable. She has not tried other treatments for GVHD to manage the hyperpigmentation.

Conditions known to cause diffuse bronzing of the skin include Addison disease, hemochromatosis, Cushing disease, and medication adverse events. Our patient presented with an absence of systemic symptoms, normal laboratory results, and no clinical indicators suggesting alternate causes. Given that the onset of the hyperpigmentation was 3 weeks after she started a new medication, we hypothesized that the bronzing was an adverse effect of the belumosudil—though this correlation cannot be definitively proven by this case.

The most common offending agents for drug-induced skin hyperpigmentation are nonsteroidal anti- inflammatory drugs, antimalarials, amiodarone, cytotoxic drugs, and tetracyclines.^1,2 Our patient’s medication list included the cytotoxic agent acalabrutinib, a Bruton tyrosine kinase inhibitor used for the treatment of non-Hodgkin lymphoma. It has been associated with dermatologic findings of ecchymosis, bruising, panniculitis, and cellulitis, but there are no known reports of hyperpigmentation.³ Our patient had been taking acalabrutinib for 6 months when the GVHD rash developed. At the time, she also was taking a multivitamin and lutein, biotin, and fish oil supplements, none of which have been associated with hyperpigmentation.

Polypharmacy adds a layer of difficulty in identifying the inciting cause of pigmentary change. In our case, symptoms began 3 weeks after the initiation of belumosudil. There were no cutaneous reactions observed in the ROCKstar study of belumosudil; the most common adverse events were upper respiratory tract infection, diarrhea, fatigue, nausea, increased liver enzymes, and dyspnea.^4,5 Patients on belumosudil have developed aggressive cutaneous squamous cell carcinoma.⁶ However, a search of PubMed articles indexed for MEDLINE using the search terms acalabrutinib or belumosudil with hyperpigmentation or cutaneous reaction returned no reports of these medications causing hyperpigmentation or cutaneous deposits.

Treatment of drug-induced hyperpigmentation is difficult because discontinuation of the offending agent typically confirms diagnosis, but interruption of treatment is not always possible, as in our patient. The skin changes can fade over time, but effects typically are long lasting.

Dermatologists play a key role in the identification of drug-induced skin hyperpigmentation. After endocrine or metabolic causes of skin hyperpigmentation have been ruled out, a thorough review of the patient’s medication list should be done to assess for a drug-induced cause. Treatment is limited to sun avoidance, as interruption of treatment may not be possible, and lesions typically do fade over time. These chronic skin changes can have a psychosocial effect on patients and regular follow-up is recommended.

To the Editor:

Drug-induced hyperpigmentation is a common cause of an acquired increase in pigmentation. Belumosudil is an oral selective inhibitor of Rho-associated coiled-coil containing protein kinase (ROCK2) that is approved for the treatment of chronic graft-vs-host disease (GVHD). We describe a patient who developed diffuse skin bronzing 3 weeks after initiation of belumosudil treatment.

A 64-year-old fair-skinned woman presented to the dermatology clinic with bronzing of the skin and dystrophic nails 3 weeks after starting belumosudil for treatment of chronic GVHD. Six months prior to presentation, the patient had received a bone marrow transplant for chronic lymphoid leukemia. She presented to dermatology 6 months after the transplant with a new-onset rash that was suspicious for GVHD. Physical examination revealed pruritic pink papules diffusely scattered on the legs and forearms (Figure 1). The patient declined biopsy at that time and later followed up with oncology. The patient’s oncologist supported a diagnosis of GVHD, and the patient began treatment with belumosudil 200 mg/d which was intended to be taken until treatment failure due to progression of chronic GVHD.

Three weeks after starting belumosudil, the patient developed diffuse bronzing of the skin and brown, evenly colored patches scattered on the trunk, back, and upper and lower extremities on a background of the presumed GVHD rash (Figure 2). The hyperpigmentation was abrupt, starting on the chest and spreading to the abdomen, extremities, and back (Figure 3).

Again, the patient was offered biopsy for the new-onset pigmentation but declined. During this time, she had no notable sun exposure and primarily stayed indoors despite living in a region with a sunny semi-arid climate. Her medication and supplement list were reviewed and included acalabrutinib, a multivitamin, lutein, biotin, and a fish oil supplement. A compete blood cell count as well as ferritin, transferrin, cortisol, and adrenocorticotropic hormone levels were unremarkable.

The patient continued to take belumosudil for treatment of GVHD. The hyperpigmentation faded slightly by a 2-month follow-up visit but persisted and was stable. She has not tried other treatments for GVHD to manage the hyperpigmentation.

Conditions known to cause diffuse bronzing of the skin include Addison disease, hemochromatosis, Cushing disease, and medication adverse events. Our patient presented with an absence of systemic symptoms, normal laboratory results, and no clinical indicators suggesting alternate causes. Given that the onset of the hyperpigmentation was 3 weeks after she started a new medication, we hypothesized that the bronzing was an adverse effect of the belumosudil—though this correlation cannot be definitively proven by this case.

The most common offending agents for drug-induced skin hyperpigmentation are nonsteroidal anti- inflammatory drugs, antimalarials, amiodarone, cytotoxic drugs, and tetracyclines.^1,2 Our patient’s medication list included the cytotoxic agent acalabrutinib, a Bruton tyrosine kinase inhibitor used for the treatment of non-Hodgkin lymphoma. It has been associated with dermatologic findings of ecchymosis, bruising, panniculitis, and cellulitis, but there are no known reports of hyperpigmentation.³ Our patient had been taking acalabrutinib for 6 months when the GVHD rash developed. At the time, she also was taking a multivitamin and lutein, biotin, and fish oil supplements, none of which have been associated with hyperpigmentation.

Polypharmacy adds a layer of difficulty in identifying the inciting cause of pigmentary change. In our case, symptoms began 3 weeks after the initiation of belumosudil. There were no cutaneous reactions observed in the ROCKstar study of belumosudil; the most common adverse events were upper respiratory tract infection, diarrhea, fatigue, nausea, increased liver enzymes, and dyspnea.^4,5 Patients on belumosudil have developed aggressive cutaneous squamous cell carcinoma.⁶ However, a search of PubMed articles indexed for MEDLINE using the search terms acalabrutinib or belumosudil with hyperpigmentation or cutaneous reaction returned no reports of these medications causing hyperpigmentation or cutaneous deposits.

Treatment of drug-induced hyperpigmentation is difficult because discontinuation of the offending agent typically confirms diagnosis, but interruption of treatment is not always possible, as in our patient. The skin changes can fade over time, but effects typically are long lasting.

Dermatologists play a key role in the identification of drug-induced skin hyperpigmentation. After endocrine or metabolic causes of skin hyperpigmentation have been ruled out, a thorough review of the patient’s medication list should be done to assess for a drug-induced cause. Treatment is limited to sun avoidance, as interruption of treatment may not be possible, and lesions typically do fade over time. These chronic skin changes can have a psychosocial effect on patients and regular follow-up is recommended.

Mohs micrographic surgery (MMS)—developed by Dr. Frederic Mohs in the 1930s—is the gold standard for treating various cutaneous malignancies. It provides maximal conservation of uninvolved tissues while producing higher cure rates compared to wide local excision.^1,2

We sought to assess the various characteristics that impact patient satisfaction to help Mohs surgeons incorporate relatively simple yet clinically significant practices into their patient encounters. We conducted a systematic literature search of peer-reviewed PubMed articles indexed for MEDLINE from database inception through November 2023 using the terms Mohs micrographic surgery and patient satisfaction. Among the inclusion criteria were studies involving participants having undergone MMS, with objective assessments on patient-reported satisfaction or preferences related to patient education, communication, anxiety-alleviating measures, or QOL in MMS. Studies were excluded if they failed to meet these criteria, were outdated and no longer clinically relevant, or measured unalterable factors with no significant impact on how Mohs surgeons could change clinical practice. Of the 157 nonreplicated studies identified, 34 met inclusion criteria.

Perioperative Patient Communication and Education Techniques

Perioperative Patient Communication—Many studies have evaluated the impact of perioperative patient-provider communication and education on patient satisfaction in those undergoing MMS. Studies focusing on preoperative and postoperative telephone calls, patient consultation formats, and patient-perceived impact of such communication modalities have been well documented (Table 1).^3-8 The importance of the patient follow-up after MMS was further supported by a retrospective study concluding that 88.7% (86/97) of patients regarded follow-up visits as important, and 80% (77/97) desired additional follow-up 3 months after MMS.⁹ Additional studies have highlighted the importance of thorough and open perioperative patient-provider communication during MMS (Table 2).^10-12

Patient-Education Techniques—Many studies have assessed the use of visual models to aid in patient education on MMS, specifically the preprocedural consent process (Table 3).^13-16 Additionally, 2 randomized controlled trials assessing the use of at-home and same-day in-office preoperative educational videos concluded that these interventions increased patient knowledge and confidence regarding procedural risks and benefits, with no statistically significant differences in patient anxiety or satisfaction.^17,18

Despite the availability of these educational videos, many patients often turn to online resources for self-education, which is problematic if reader literacy is incongruent with online readability. One study assessing readability of online MMS resources concluded that the most accessed articles exceeded the recommended reading level for adequate patient comprehension.¹⁹ A survey studying a wide range of variables related to patient satisfaction (eg, demographics, socioeconomics, health status) in 339 MMS patients found that those who considered themselves more involved in the decision-making process were more satisfied in the short-term, and married patients had even higher long-term satisfaction. Interestingly, this study also concluded that undergoing 3 or more MMS stages was associated with higher short- and long-term satisfaction, likely secondary to perceived effects of increased overall care, medical attention, and time spent with the provider.²⁰

Synthesis of this information with emphasis on the higher evidence-based studies—including systematic reviews, meta-analyses, and randomized controlled trials—yields the following beneficial interventions regarding patient education and communication^13-20:

• Preoperative and same-day postoperative telephone follow-up (TFU) do not show statistically significant impacts on patient satisfaction; however, TFU allows for identification of postoperative concerns and inadequate pain management, which may have downstream effects on long-term perception of the overall patient experience.
• The use of video-assisted consent yields improved patient satisfaction and knowledge, while video content—traditional or didactic—has no impact on satisfaction in new MMS patients.
• The use of at-home or same-day in-office preoperative educational videos can improve procedural knowledge and risk-benefit understanding of MMS while having no impact on satisfaction.
• Bedside manner and effective in-person communication by the provider often takes precedence in the patient experience; however, implementation of additional educational modalities should be considered.

Patient Anxiety and QOL

Reducing Patient Anxiety—The use of perioperative distractors to reduce patient anxiety may play an integral role when patients undergo MMS, as there often are prolonged waiting periods between stages when patients may feel increasingly vulnerable or anxious. Table 4 reviews studies on perioperative distractors that showed a statistically significant reduction in MMS patient anxiety.^21-24

Although not statistically significant, additional studies evaluating the use of intraoperative anxiety-reduction methods in MMS have demonstrated a downtrend in patient anxiety with the following interventions: engaging in small talk with clinic staff, bringing a guest, eating, watching television, communicating surgical expectations with the provider, handholding, use of a stress ball, and use of 3-dimensional educational MMS models.^25-27 Similarly, a survey of 73 patients undergoing MMS found that patients tended to enjoy complimentary beverages preprocedurally in the waiting room, reading, speaking with their guest, watching television, or using their telephone during wait times.²⁸ Table 5 lists additional perioperative factors encompassing specific patient and surgical characteristics that help reduce patient anxiety.^29-32

Patient QOL—Many methods aimed at decreasing MMS-related patient anxiety often show no direct impact on patient satisfaction, likely due to the multifactorial nature of the patient-perceived experience. A prospective observational study of MMS patients noted a statistically significant improvement in patient QOL scores 3 months postsurgery (P=.0007), demonstrating that MMS generally results in positive patient outcomes despite preprocedural anxiety.³³ An additional prospective study in MMS patients with nonmelanoma skin cancer concluded that sex, age, and closure type—factors often shown to affect anxiety levels—did not significantly impact patient satisfaction.³⁴ Similarly, high satisfaction levels can be expected among MMS patients undergoing treatment of melanoma in situ, with more than 90% of patients rating their treatment experience a 4 (agree) or 5 (strongly agree) out of 5 in short- and long-term satisfaction assessments (38/41 and 40/42, respectively).³⁵ This assessment, conducted 3 months postoperatively, asked patients to score the statement, “I am completely satisfied with the treatment of my skin problem,” on a scale ranging from 1 (strongly disagree) to 5 (strongly agree).

Lastly, patient perception of their surgeon’s skill may contribute to levels of patient satisfaction. Although suture spacing has not been shown to affect surgical outcomes, it has been demonstrated to impact the patient’s perception of surgical skill and is further supported by a study concluding that closures with 2-mm spacing were ranked significantly lower by patients compared with closures with either 4- or 6-mm spacing (P=.005 and P=.012, respectively).³⁶

Synthesis of this information with emphasis on the higher evidence-based studies—including systematic reviews, meta-analyses, and randomized controlled trials—yields the following beneficial interventions regarding anxiety-reducing measures and patient-perceived QOL^21-36:

• Factors shown to decrease patient anxiety include patient personalized music, virtual-reality experience, perioperative informational videos, and 3-dimensional–printed MMS models.
• Many methods aimed at decreasing MMS-related patient anxiety show no direct impact on patient satisfaction, likely due to the multifactorial nature of the patient-perceived experience.
• Higher anxiety can be associated with worse QOL scores in MMS patients, and additional factors that may have a negative impact on anxiety include female sex, younger age, and tumor location on the face.

Conclusion

Many factors affect patient satisfaction in MMS. Increased awareness and acknowledgement of these factors can foster improved clinical practice and patient experience, which can have downstream effects on patient compliance and overall psychosocial and medical well-being. With the movement toward value-based health care, patient satisfaction ratings are likely to play an increasingly important role in physician reimbursement. Adapting one’s practice to include high-quality, time-efficient, patient-centered care goes hand in hand with increasing MMS patient satisfaction. Careful evaluation and scrutiny of one’s current practices while remaining cognizant of patient population, resource availability, and clinical limitations often reveal opportunities for small adjustments that can have a great impact on patient satisfaction. This thorough assessment and review of the published literature aims to assist MMS surgeons in understanding the role that certain factors—(1) perioperative patient communication and education techniques and (2) patient anxiety, QOL, and additional considerations—have on overall satisfaction with MMS. Specific consideration should be placed on the fact that patient satisfaction is multifactorial, and many different interventions can have a positive impact on the overall patient experience.

Mohs micrographic surgery (MMS)—developed by Dr. Frederic Mohs in the 1930s—is the gold standard for treating various cutaneous malignancies. It provides maximal conservation of uninvolved tissues while producing higher cure rates compared to wide local excision.^1,2

We sought to assess the various characteristics that impact patient satisfaction to help Mohs surgeons incorporate relatively simple yet clinically significant practices into their patient encounters. We conducted a systematic literature search of peer-reviewed PubMed articles indexed for MEDLINE from database inception through November 2023 using the terms Mohs micrographic surgery and patient satisfaction. Among the inclusion criteria were studies involving participants having undergone MMS, with objective assessments on patient-reported satisfaction or preferences related to patient education, communication, anxiety-alleviating measures, or QOL in MMS. Studies were excluded if they failed to meet these criteria, were outdated and no longer clinically relevant, or measured unalterable factors with no significant impact on how Mohs surgeons could change clinical practice. Of the 157 nonreplicated studies identified, 34 met inclusion criteria.

Perioperative Patient Communication and Education Techniques

Perioperative Patient Communication—Many studies have evaluated the impact of perioperative patient-provider communication and education on patient satisfaction in those undergoing MMS. Studies focusing on preoperative and postoperative telephone calls, patient consultation formats, and patient-perceived impact of such communication modalities have been well documented (Table 1).^3-8 The importance of the patient follow-up after MMS was further supported by a retrospective study concluding that 88.7% (86/97) of patients regarded follow-up visits as important, and 80% (77/97) desired additional follow-up 3 months after MMS.⁹ Additional studies have highlighted the importance of thorough and open perioperative patient-provider communication during MMS (Table 2).^10-12

Patient-Education Techniques—Many studies have assessed the use of visual models to aid in patient education on MMS, specifically the preprocedural consent process (Table 3).^13-16 Additionally, 2 randomized controlled trials assessing the use of at-home and same-day in-office preoperative educational videos concluded that these interventions increased patient knowledge and confidence regarding procedural risks and benefits, with no statistically significant differences in patient anxiety or satisfaction.^17,18

Despite the availability of these educational videos, many patients often turn to online resources for self-education, which is problematic if reader literacy is incongruent with online readability. One study assessing readability of online MMS resources concluded that the most accessed articles exceeded the recommended reading level for adequate patient comprehension.¹⁹ A survey studying a wide range of variables related to patient satisfaction (eg, demographics, socioeconomics, health status) in 339 MMS patients found that those who considered themselves more involved in the decision-making process were more satisfied in the short-term, and married patients had even higher long-term satisfaction. Interestingly, this study also concluded that undergoing 3 or more MMS stages was associated with higher short- and long-term satisfaction, likely secondary to perceived effects of increased overall care, medical attention, and time spent with the provider.²⁰

Synthesis of this information with emphasis on the higher evidence-based studies—including systematic reviews, meta-analyses, and randomized controlled trials—yields the following beneficial interventions regarding patient education and communication^13-20:

• Preoperative and same-day postoperative telephone follow-up (TFU) do not show statistically significant impacts on patient satisfaction; however, TFU allows for identification of postoperative concerns and inadequate pain management, which may have downstream effects on long-term perception of the overall patient experience.
• The use of video-assisted consent yields improved patient satisfaction and knowledge, while video content—traditional or didactic—has no impact on satisfaction in new MMS patients.
• The use of at-home or same-day in-office preoperative educational videos can improve procedural knowledge and risk-benefit understanding of MMS while having no impact on satisfaction.
• Bedside manner and effective in-person communication by the provider often takes precedence in the patient experience; however, implementation of additional educational modalities should be considered.

Patient Anxiety and QOL

Reducing Patient Anxiety—The use of perioperative distractors to reduce patient anxiety may play an integral role when patients undergo MMS, as there often are prolonged waiting periods between stages when patients may feel increasingly vulnerable or anxious. Table 4 reviews studies on perioperative distractors that showed a statistically significant reduction in MMS patient anxiety.^21-24

Although not statistically significant, additional studies evaluating the use of intraoperative anxiety-reduction methods in MMS have demonstrated a downtrend in patient anxiety with the following interventions: engaging in small talk with clinic staff, bringing a guest, eating, watching television, communicating surgical expectations with the provider, handholding, use of a stress ball, and use of 3-dimensional educational MMS models.^25-27 Similarly, a survey of 73 patients undergoing MMS found that patients tended to enjoy complimentary beverages preprocedurally in the waiting room, reading, speaking with their guest, watching television, or using their telephone during wait times.²⁸ Table 5 lists additional perioperative factors encompassing specific patient and surgical characteristics that help reduce patient anxiety.^29-32

Patient QOL—Many methods aimed at decreasing MMS-related patient anxiety often show no direct impact on patient satisfaction, likely due to the multifactorial nature of the patient-perceived experience. A prospective observational study of MMS patients noted a statistically significant improvement in patient QOL scores 3 months postsurgery (P=.0007), demonstrating that MMS generally results in positive patient outcomes despite preprocedural anxiety.³³ An additional prospective study in MMS patients with nonmelanoma skin cancer concluded that sex, age, and closure type—factors often shown to affect anxiety levels—did not significantly impact patient satisfaction.³⁴ Similarly, high satisfaction levels can be expected among MMS patients undergoing treatment of melanoma in situ, with more than 90% of patients rating their treatment experience a 4 (agree) or 5 (strongly agree) out of 5 in short- and long-term satisfaction assessments (38/41 and 40/42, respectively).³⁵ This assessment, conducted 3 months postoperatively, asked patients to score the statement, “I am completely satisfied with the treatment of my skin problem,” on a scale ranging from 1 (strongly disagree) to 5 (strongly agree).

Lastly, patient perception of their surgeon’s skill may contribute to levels of patient satisfaction. Although suture spacing has not been shown to affect surgical outcomes, it has been demonstrated to impact the patient’s perception of surgical skill and is further supported by a study concluding that closures with 2-mm spacing were ranked significantly lower by patients compared with closures with either 4- or 6-mm spacing (P=.005 and P=.012, respectively).³⁶

Synthesis of this information with emphasis on the higher evidence-based studies—including systematic reviews, meta-analyses, and randomized controlled trials—yields the following beneficial interventions regarding anxiety-reducing measures and patient-perceived QOL^21-36:

• Factors shown to decrease patient anxiety include patient personalized music, virtual-reality experience, perioperative informational videos, and 3-dimensional–printed MMS models.
• Many methods aimed at decreasing MMS-related patient anxiety show no direct impact on patient satisfaction, likely due to the multifactorial nature of the patient-perceived experience.
• Higher anxiety can be associated with worse QOL scores in MMS patients, and additional factors that may have a negative impact on anxiety include female sex, younger age, and tumor location on the face.

Conclusion

Many factors affect patient satisfaction in MMS. Increased awareness and acknowledgement of these factors can foster improved clinical practice and patient experience, which can have downstream effects on patient compliance and overall psychosocial and medical well-being. With the movement toward value-based health care, patient satisfaction ratings are likely to play an increasingly important role in physician reimbursement. Adapting one’s practice to include high-quality, time-efficient, patient-centered care goes hand in hand with increasing MMS patient satisfaction. Careful evaluation and scrutiny of one’s current practices while remaining cognizant of patient population, resource availability, and clinical limitations often reveal opportunities for small adjustments that can have a great impact on patient satisfaction. This thorough assessment and review of the published literature aims to assist MMS surgeons in understanding the role that certain factors—(1) perioperative patient communication and education techniques and (2) patient anxiety, QOL, and additional considerations—have on overall satisfaction with MMS. Specific consideration should be placed on the fact that patient satisfaction is multifactorial, and many different interventions can have a positive impact on the overall patient experience.

Mohs micrographic surgery (MMS)—developed by Dr. Frederic Mohs in the 1930s—is the gold standard for treating various cutaneous malignancies. It provides maximal conservation of uninvolved tissues while producing higher cure rates compared to wide local excision.^1,2

We sought to assess the various characteristics that impact patient satisfaction to help Mohs surgeons incorporate relatively simple yet clinically significant practices into their patient encounters. We conducted a systematic literature search of peer-reviewed PubMed articles indexed for MEDLINE from database inception through November 2023 using the terms Mohs micrographic surgery and patient satisfaction. Among the inclusion criteria were studies involving participants having undergone MMS, with objective assessments on patient-reported satisfaction or preferences related to patient education, communication, anxiety-alleviating measures, or QOL in MMS. Studies were excluded if they failed to meet these criteria, were outdated and no longer clinically relevant, or measured unalterable factors with no significant impact on how Mohs surgeons could change clinical practice. Of the 157 nonreplicated studies identified, 34 met inclusion criteria.

Perioperative Patient Communication and Education Techniques

Perioperative Patient Communication—Many studies have evaluated the impact of perioperative patient-provider communication and education on patient satisfaction in those undergoing MMS. Studies focusing on preoperative and postoperative telephone calls, patient consultation formats, and patient-perceived impact of such communication modalities have been well documented (Table 1).^3-8 The importance of the patient follow-up after MMS was further supported by a retrospective study concluding that 88.7% (86/97) of patients regarded follow-up visits as important, and 80% (77/97) desired additional follow-up 3 months after MMS.⁹ Additional studies have highlighted the importance of thorough and open perioperative patient-provider communication during MMS (Table 2).^10-12

Patient-Education Techniques—Many studies have assessed the use of visual models to aid in patient education on MMS, specifically the preprocedural consent process (Table 3).^13-16 Additionally, 2 randomized controlled trials assessing the use of at-home and same-day in-office preoperative educational videos concluded that these interventions increased patient knowledge and confidence regarding procedural risks and benefits, with no statistically significant differences in patient anxiety or satisfaction.^17,18

Despite the availability of these educational videos, many patients often turn to online resources for self-education, which is problematic if reader literacy is incongruent with online readability. One study assessing readability of online MMS resources concluded that the most accessed articles exceeded the recommended reading level for adequate patient comprehension.¹⁹ A survey studying a wide range of variables related to patient satisfaction (eg, demographics, socioeconomics, health status) in 339 MMS patients found that those who considered themselves more involved in the decision-making process were more satisfied in the short-term, and married patients had even higher long-term satisfaction. Interestingly, this study also concluded that undergoing 3 or more MMS stages was associated with higher short- and long-term satisfaction, likely secondary to perceived effects of increased overall care, medical attention, and time spent with the provider.²⁰

Synthesis of this information with emphasis on the higher evidence-based studies—including systematic reviews, meta-analyses, and randomized controlled trials—yields the following beneficial interventions regarding patient education and communication^13-20:

• Preoperative and same-day postoperative telephone follow-up (TFU) do not show statistically significant impacts on patient satisfaction; however, TFU allows for identification of postoperative concerns and inadequate pain management, which may have downstream effects on long-term perception of the overall patient experience.
• The use of video-assisted consent yields improved patient satisfaction and knowledge, while video content—traditional or didactic—has no impact on satisfaction in new MMS patients.
• The use of at-home or same-day in-office preoperative educational videos can improve procedural knowledge and risk-benefit understanding of MMS while having no impact on satisfaction.
• Bedside manner and effective in-person communication by the provider often takes precedence in the patient experience; however, implementation of additional educational modalities should be considered.

Patient Anxiety and QOL

Reducing Patient Anxiety—The use of perioperative distractors to reduce patient anxiety may play an integral role when patients undergo MMS, as there often are prolonged waiting periods between stages when patients may feel increasingly vulnerable or anxious. Table 4 reviews studies on perioperative distractors that showed a statistically significant reduction in MMS patient anxiety.^21-24

Although not statistically significant, additional studies evaluating the use of intraoperative anxiety-reduction methods in MMS have demonstrated a downtrend in patient anxiety with the following interventions: engaging in small talk with clinic staff, bringing a guest, eating, watching television, communicating surgical expectations with the provider, handholding, use of a stress ball, and use of 3-dimensional educational MMS models.^25-27 Similarly, a survey of 73 patients undergoing MMS found that patients tended to enjoy complimentary beverages preprocedurally in the waiting room, reading, speaking with their guest, watching television, or using their telephone during wait times.²⁸ Table 5 lists additional perioperative factors encompassing specific patient and surgical characteristics that help reduce patient anxiety.^29-32

Patient QOL—Many methods aimed at decreasing MMS-related patient anxiety often show no direct impact on patient satisfaction, likely due to the multifactorial nature of the patient-perceived experience. A prospective observational study of MMS patients noted a statistically significant improvement in patient QOL scores 3 months postsurgery (P=.0007), demonstrating that MMS generally results in positive patient outcomes despite preprocedural anxiety.³³ An additional prospective study in MMS patients with nonmelanoma skin cancer concluded that sex, age, and closure type—factors often shown to affect anxiety levels—did not significantly impact patient satisfaction.³⁴ Similarly, high satisfaction levels can be expected among MMS patients undergoing treatment of melanoma in situ, with more than 90% of patients rating their treatment experience a 4 (agree) or 5 (strongly agree) out of 5 in short- and long-term satisfaction assessments (38/41 and 40/42, respectively).³⁵ This assessment, conducted 3 months postoperatively, asked patients to score the statement, “I am completely satisfied with the treatment of my skin problem,” on a scale ranging from 1 (strongly disagree) to 5 (strongly agree).

Lastly, patient perception of their surgeon’s skill may contribute to levels of patient satisfaction. Although suture spacing has not been shown to affect surgical outcomes, it has been demonstrated to impact the patient’s perception of surgical skill and is further supported by a study concluding that closures with 2-mm spacing were ranked significantly lower by patients compared with closures with either 4- or 6-mm spacing (P=.005 and P=.012, respectively).³⁶

Synthesis of this information with emphasis on the higher evidence-based studies—including systematic reviews, meta-analyses, and randomized controlled trials—yields the following beneficial interventions regarding anxiety-reducing measures and patient-perceived QOL^21-36:

• Factors shown to decrease patient anxiety include patient personalized music, virtual-reality experience, perioperative informational videos, and 3-dimensional–printed MMS models.
• Many methods aimed at decreasing MMS-related patient anxiety show no direct impact on patient satisfaction, likely due to the multifactorial nature of the patient-perceived experience.
• Higher anxiety can be associated with worse QOL scores in MMS patients, and additional factors that may have a negative impact on anxiety include female sex, younger age, and tumor location on the face.

Conclusion

Many factors affect patient satisfaction in MMS. Increased awareness and acknowledgement of these factors can foster improved clinical practice and patient experience, which can have downstream effects on patient compliance and overall psychosocial and medical well-being. With the movement toward value-based health care, patient satisfaction ratings are likely to play an increasingly important role in physician reimbursement. Adapting one’s practice to include high-quality, time-efficient, patient-centered care goes hand in hand with increasing MMS patient satisfaction. Careful evaluation and scrutiny of one’s current practices while remaining cognizant of patient population, resource availability, and clinical limitations often reveal opportunities for small adjustments that can have a great impact on patient satisfaction. This thorough assessment and review of the published literature aims to assist MMS surgeons in understanding the role that certain factors—(1) perioperative patient communication and education techniques and (2) patient anxiety, QOL, and additional considerations—have on overall satisfaction with MMS. Specific consideration should be placed on the fact that patient satisfaction is multifactorial, and many different interventions can have a positive impact on the overall patient experience.

While strong relationships with mentors and advisers are critical to navigating the competitive dermatology match process, the advice medical students receive from different individuals can be contradictory. Unaccredited information online—particularly on social media—as well as data reported by applicants can add to potential confusion.¹ Published research has elicited comments and observations from successfully matched medical students about highly discussed topics such as presentations and publications, letters of recommendation, away rotations, and interviews.^2,3 However, there currently are no published data about advice that dermatology mentors actually offer medical students. In this study, we aimed to investigate this gap in the current literature and examine the advice dermatology faculty, program directors, and other mentors at institutions accredited by the Accreditation Council for Graduate Medical Education across the United States give to medical students applying to dermatology residency.

Methods

A 14-question Johns Hopkins Qualtrics survey was sent via the Association of Professors of Dermatology (APD) listserve in June 2024 soliciting responses from members who consider themselves to be mentors to dermatology applicants across the United States. The survey included multiple-choice questions with the option to select multiple answers and a space for open-ended responses. The questions first gathered information on the respondents, including the capacity in which the mentors advised medical students (eg, program director, department chair, clinical faculty). Mentors were asked for the number of years they had been advising mentees and if they were advising students with a home dermatology program. In addition, mentors were asked what advice they give their mentees about aspects of the application process, including gap years, dual applications, research involvement, couples matching, program signaling, away rotations, internship year, letters of recommendation, geographic signaling, interviewing advice, and volunteering during medical school.

On August 18, 2024, survey results from 115 respondents were aggregated. The responses for each question were quantitatively assessed to determine whether there was consensus on specific advice offered. The open-ended responses also were qualitatively assessed to determine the most common responses.

Results

The respondents included program directors (30% [35/115]), clinical faculty (22% [25/115]), department chairs (18% [21/115]), assistant program directors (15% [17/115]), medical school clerkship directors (8% [9/115]), primary mentors (ie, faculty who did not fall into any of the aforementioned categories but still advised medical students interested in dermatology)(5% [6/115]), division chiefs (1% [1/115]), and deans (1% [1/115]). Respondents had been advising students for a median of 10 years (range, 1-40 years [25th percentile, 5.00 years; 75th percentile, 13.75 years]). The majority (90% [103/115]) of mentors surveyed were advising students with a home dermatology program.

Areas of Consensus

In some areas, there was broad consensus among the advice offered by the mentors that were surveyed (eTable).

Research During Medical School—More than 91% (105/115) of the respondents recommended research to encourage academic growth and indicated that the most important reason for conducting research during medical school is to foster mentor-mentee relationships; however, more than one-third of respondents believed research is overvalued by students and research productivity is not as critical for matching as they perceive it to be. When these responses were categorized by respondent positions, 29% (15/52) of program or assistant directors indicated agreement with the statement that research is overvalued.

Away Rotations—There also was a consensus about the importance of away rotations, with 85% (98/115) of respondents advising students to complete 1 to 2 away rotations at sites of high interest, and 13% (15/115) suggesting that students complete as many away rotations as possible. It is worth noting, however, that the official APD Residency Program Directors Section’s statement on away rotations recommends no more than 2 away rotations (or no more than 3 for students with no home program).⁴

Reapplication Advice—Additionally, in a situation where students do not match into a dermatology residency program, the vast majority (71% [82/115]) of respondents advised students to rank competitive intern years to foster connections and improve the chance of matching on the second attempt.

Volunteering During Medical School—Seventy-seven percent (89/115) of mentors encouraged students to engage in volunteerism and advocacy during medical school to create a well-rounded application, and 69% (79/115) of mentors encouraged students to display leadership in their volunteer efforts.

Areas Without Consensus

Letters of Recommendation—Most respondents recommended submitting letters of recommendation only from dermatology professionals (55% [63/115]), with the remainder recommending students request a letter from anyone who could provide a strong recommendation regardless of specialty mix (42% [48/115]).

Dermatologic Subspecialties—For students interested in dermatologic subspecialties, 73% (84/115) of mentors advised that students be honest during interviews but keep an open mind that interests during residencies may change. Forty-three percent (49/115) of respondents encouraged students to promote a subspecialty interest during their interview only if they can demonstrate effort within that subspecialty on their application.

Couples Matching—Most respondents approach couples matching on a case-by-case basis and assess individual priorities when they do advise on this topic. Respondents often advise applicants to identify a few cities/regions and focus strongly on the programs within those regions to avoid spreading themselves too thin; however, one-third (38/115) of respondents indicated that they do not personally offer advice regarding the couples match.

Areas With Diverse Opinions

Gap Years—Nearly one-quarter (24% [28/115]) of mentors reported that they rarely recommend students take a year off and only support those who are adamant about doing so, or that they never support taking a gap year at all. A slight majority (58% [67/115]) recommend a gap year for students strongly interested in dermatologic research, and 38% (44/115) recommend a gap year for students with weaker applications (Figure 1). We received many open-ended responses to this question, with mentors frequently indicating that they advise students to take a gap year on a case-by-case basis, with 44% (51/115) of commenters recommending that students only take paid gap-year research positions.

Program Signaling—The dermatology residency application process implemented a system of preference signaling tokens (PSTs) starting with the 2021-2022 cycle. Not quite half (46% [53/115]) of respondents recommend students apply only to places that they signaled, while 20% (23/115) advise responding to 10 to 15 additional programs. Very few (8% [9/115]) advise students to signal only in their stated region of interest. Approximately half (49% [56/115]) of mentors recommend students only signal based on the programs they feel would be the best fit for them without regard for perceived competitiveness—which aligns with the APD Residency Program Directors Section’s recommendation⁴—while 37% (43/115) recommend students distribute their signals to a wide range of programs. Sixty-three percent (72/115) of respondents recommend gold signaling to the student’s 3 most desired programs regardless of home and away rotation considerations, while 19% (22/115) recommend students give silver signals to their home and away rotation programs, as a rotation is already a signal of a strong desire to be there (Figure 2).

Dual Application—Fifty-three percent (61/115) of mentors recommended dual applying only for those truly interested in multiple specialties. Eighteen percent (21/115) of respondents advised dual applying for those with less than a 75% chance of matching. Twenty-five percent (29/115) of respondents free-wrote comments about approaching dual applying on a case-by-case basis, with many discussing the downsides of dual application and raising concerns that dual applications can hinder applicants’ success, can seem disingenuous, and seem to be a tool used to improve medical school match rates without benefit for the student.

We also stratified the data to compare overall responses from the total cohort with those from only program and assistant program directors. Across the 14 questions, responses from program and assistant program directors alone were similar to the overall cohort results

Comment

This study evaluated nationwide data on mentorship advising in dermatology, detailing mentors’ advice regarding research, gap years, dual applications, away rotations, intern year, couples matching, program signaling, and volunteering during medical school. Based on our results, most respondents agree on the importance of research during medical school, the utility of away rotations, and the value of volunteering during medical school. Similarly, respondents agreed on the importance of having strong letters of recommendation; while some advised asking only dermatology faculty to write letters, others did not have a specialty preference for the letter writers. Respondents also had varying views about sharing interest in subspecialties during residency interviews. Many of the respondents do not provide recommendations regarding geographic signaling and couples matching, expressing that these are parts of an application that are important to approach on a case-by-case basis. Lastly, respondents had diverse opinions regarding the utility of gap years, whether to encourage or discourage dual applications, and how to advise regarding program signaling.

Our results also showed that one-third of respondents believed that research is not as important as it is perceived to be by dermatology applicants. While engaging in research during medical school was almost unanimously encouraged to foster mentor-mentee relationships, respondents expressed that the number of research experiences and publications was not critical. This is an important topic of discussion, as taking a dedicated year away from medical school to complete a research fellowship is becoming a trend among dermatology applicants.⁵ There has been discussion both on unofficial online platforms as well as in the published literature regarding the pressure for medical students interested in dermatology to publish, which may result in a gap year for research.⁶ The literature on the utility of a gap year in match rates is sparse, with one study showing no difference in match rates among Mayo Clinic dermatology residents who took research years vs those who did not.⁷ However, this contrasts with match rates at top dermatology residency programs where 41% of applicants who took a gap year matched vs 19% who did not.^7,8 These conflicting data are reflected in our study results, with respondents expressing different opinions on the utility of gap years.

There also are important equity concerns regarding the role of research years in the dermatology residency match process. Dermatology is one of the least racially diverse specialties, although there have been efforts to increase representation among residents and attending physicians.^9-11 Research years can be important contributors to this lack of representation, as these often are unpaid and can discourage economically disadvantaged students from applying.^9-11 Additionally, applicants may not have the flexibility to defer future salary for a year to match into dermatology; therefore, mentors should offer multiple options to individual applicants instead of solely encouraging gap years, given the conflicting feelings regarding their productivity.

Another topic of disagreement was dual application. Approximately one-third of respondents said they encourage either all students or those with less than a 75% chance of matching to dual apply, while about half only encourage students who are truly interested in multiple specialties to do so. Additionally, a large subset of respondents said they do not encourage dual applications due to concerns that they make applicants a worse candidate for each specialty and overall have negative effects on matching. Twenty-five percent of respondents opted to leave an open-ended response to this question: some offered the perspective that, if applicants feel a need to dual apply due to a weaker application, they do not advise the applicant to apply to dermatology. Many open ended responses underscored that the respondent does not encourage dual applications because they are inherently more time consuming, could hinder the applicant’s success, can seem disingenuous, and are a tool used to improve medical school match rates without being beneficial for the student. Some respondents also favored reapplying to dermatology the following year instead of dual applying. Finally, a subset of mentors indicated that they approach dual applications on a case-by-case basis, and others reported they do not have much experience advising on this topic. Currently, there are no known data in the literature on the efficacy and utility of dual applications in the dermatology match process; therefore, our study provides valuable insight for applicants interested in the impacts of the dual application. Overall, students should approach this option with mentors on an individual basis but ultimately should be aware of the concerns and mixed perceptions of the dual application process.

With regard to program signaling, previous research has shown that PSTs have a large impact on the chance of being granted an interview.¹² In our study, we provide a comprehensive overview of advising regarding these signals. While mentors often responded that they did not have much experience advising in this domain—and it is too soon to tell the impact of this program signaling—many offered differing opinions. Many said they recommend that students give a gold signal to their 3 most desired programs regardless of home and away rotations and perceived competitiveness, which follows the guidelines issued by the APD; however, 19% recommend only giving silver signals to home and away rotation programs, as participation in those programs is considered a sufficient signal of interest. Additionally, about half of mentors recommended that students only apply where they signal, whereas 20% recommended applying to 10 to 15 programs beyond those signaled. Future studies should investigate the impact of PSTs on interview invitations once sufficient application cycles have occurred.

Study Limitations

This study was conducted via email to the APD listserve. The total number of faculty on this listserve is unknown; therefore, we do not know the total response rate of the survey. Additionally, we surveyed mentors in this listserve, who therefore receive more emails and overall correspondence about the dermatology match and may be more involved in these conversations. The mentors who responded to our survey may have a different approach and response to our various survey questions than a given mentor across the United States who did not respond to this survey. A final limitation of our study is that the survey responses a mentor gives may not fully match the advice that they give their students privately.

Conclusion

Our survey of dermatology mentors across the United States provides valuable insight into how mentors advise for a strong dermatology residency application. Mentors agreed on the importance of research during medical school, away rotations, strong letters of recommendation, and volunteerism and advocacy to promote a strong residency application. Important topics of disagreement include the decision for dermatology applicants to take a dedicated gap year in medical school, how to use tokens/signals effectively, and the dual application process. Our findings also underscore important application components that applicants and mentors should approach on an individual basis. Future studies should investigate the impact of signals/tokens on the match process as well as the utility of gap years and dual applications, working to standardize the advice applicants receive.

While strong relationships with mentors and advisers are critical to navigating the competitive dermatology match process, the advice medical students receive from different individuals can be contradictory. Unaccredited information online—particularly on social media—as well as data reported by applicants can add to potential confusion.¹ Published research has elicited comments and observations from successfully matched medical students about highly discussed topics such as presentations and publications, letters of recommendation, away rotations, and interviews.^2,3 However, there currently are no published data about advice that dermatology mentors actually offer medical students. In this study, we aimed to investigate this gap in the current literature and examine the advice dermatology faculty, program directors, and other mentors at institutions accredited by the Accreditation Council for Graduate Medical Education across the United States give to medical students applying to dermatology residency.

Methods

A 14-question Johns Hopkins Qualtrics survey was sent via the Association of Professors of Dermatology (APD) listserve in June 2024 soliciting responses from members who consider themselves to be mentors to dermatology applicants across the United States. The survey included multiple-choice questions with the option to select multiple answers and a space for open-ended responses. The questions first gathered information on the respondents, including the capacity in which the mentors advised medical students (eg, program director, department chair, clinical faculty). Mentors were asked for the number of years they had been advising mentees and if they were advising students with a home dermatology program. In addition, mentors were asked what advice they give their mentees about aspects of the application process, including gap years, dual applications, research involvement, couples matching, program signaling, away rotations, internship year, letters of recommendation, geographic signaling, interviewing advice, and volunteering during medical school.

On August 18, 2024, survey results from 115 respondents were aggregated. The responses for each question were quantitatively assessed to determine whether there was consensus on specific advice offered. The open-ended responses also were qualitatively assessed to determine the most common responses.

Results

The respondents included program directors (30% [35/115]), clinical faculty (22% [25/115]), department chairs (18% [21/115]), assistant program directors (15% [17/115]), medical school clerkship directors (8% [9/115]), primary mentors (ie, faculty who did not fall into any of the aforementioned categories but still advised medical students interested in dermatology)(5% [6/115]), division chiefs (1% [1/115]), and deans (1% [1/115]). Respondents had been advising students for a median of 10 years (range, 1-40 years [25th percentile, 5.00 years; 75th percentile, 13.75 years]). The majority (90% [103/115]) of mentors surveyed were advising students with a home dermatology program.

Areas of Consensus

In some areas, there was broad consensus among the advice offered by the mentors that were surveyed (eTable).

Research During Medical School—More than 91% (105/115) of the respondents recommended research to encourage academic growth and indicated that the most important reason for conducting research during medical school is to foster mentor-mentee relationships; however, more than one-third of respondents believed research is overvalued by students and research productivity is not as critical for matching as they perceive it to be. When these responses were categorized by respondent positions, 29% (15/52) of program or assistant directors indicated agreement with the statement that research is overvalued.

Away Rotations—There also was a consensus about the importance of away rotations, with 85% (98/115) of respondents advising students to complete 1 to 2 away rotations at sites of high interest, and 13% (15/115) suggesting that students complete as many away rotations as possible. It is worth noting, however, that the official APD Residency Program Directors Section’s statement on away rotations recommends no more than 2 away rotations (or no more than 3 for students with no home program).⁴

Reapplication Advice—Additionally, in a situation where students do not match into a dermatology residency program, the vast majority (71% [82/115]) of respondents advised students to rank competitive intern years to foster connections and improve the chance of matching on the second attempt.

Volunteering During Medical School—Seventy-seven percent (89/115) of mentors encouraged students to engage in volunteerism and advocacy during medical school to create a well-rounded application, and 69% (79/115) of mentors encouraged students to display leadership in their volunteer efforts.

Areas Without Consensus

Letters of Recommendation—Most respondents recommended submitting letters of recommendation only from dermatology professionals (55% [63/115]), with the remainder recommending students request a letter from anyone who could provide a strong recommendation regardless of specialty mix (42% [48/115]).

Dermatologic Subspecialties—For students interested in dermatologic subspecialties, 73% (84/115) of mentors advised that students be honest during interviews but keep an open mind that interests during residencies may change. Forty-three percent (49/115) of respondents encouraged students to promote a subspecialty interest during their interview only if they can demonstrate effort within that subspecialty on their application.

Couples Matching—Most respondents approach couples matching on a case-by-case basis and assess individual priorities when they do advise on this topic. Respondents often advise applicants to identify a few cities/regions and focus strongly on the programs within those regions to avoid spreading themselves too thin; however, one-third (38/115) of respondents indicated that they do not personally offer advice regarding the couples match.

Areas With Diverse Opinions

Gap Years—Nearly one-quarter (24% [28/115]) of mentors reported that they rarely recommend students take a year off and only support those who are adamant about doing so, or that they never support taking a gap year at all. A slight majority (58% [67/115]) recommend a gap year for students strongly interested in dermatologic research, and 38% (44/115) recommend a gap year for students with weaker applications (Figure 1). We received many open-ended responses to this question, with mentors frequently indicating that they advise students to take a gap year on a case-by-case basis, with 44% (51/115) of commenters recommending that students only take paid gap-year research positions.

Program Signaling—The dermatology residency application process implemented a system of preference signaling tokens (PSTs) starting with the 2021-2022 cycle. Not quite half (46% [53/115]) of respondents recommend students apply only to places that they signaled, while 20% (23/115) advise responding to 10 to 15 additional programs. Very few (8% [9/115]) advise students to signal only in their stated region of interest. Approximately half (49% [56/115]) of mentors recommend students only signal based on the programs they feel would be the best fit for them without regard for perceived competitiveness—which aligns with the APD Residency Program Directors Section’s recommendation⁴—while 37% (43/115) recommend students distribute their signals to a wide range of programs. Sixty-three percent (72/115) of respondents recommend gold signaling to the student’s 3 most desired programs regardless of home and away rotation considerations, while 19% (22/115) recommend students give silver signals to their home and away rotation programs, as a rotation is already a signal of a strong desire to be there (Figure 2).

Dual Application—Fifty-three percent (61/115) of mentors recommended dual applying only for those truly interested in multiple specialties. Eighteen percent (21/115) of respondents advised dual applying for those with less than a 75% chance of matching. Twenty-five percent (29/115) of respondents free-wrote comments about approaching dual applying on a case-by-case basis, with many discussing the downsides of dual application and raising concerns that dual applications can hinder applicants’ success, can seem disingenuous, and seem to be a tool used to improve medical school match rates without benefit for the student.

We also stratified the data to compare overall responses from the total cohort with those from only program and assistant program directors. Across the 14 questions, responses from program and assistant program directors alone were similar to the overall cohort results

Comment

This study evaluated nationwide data on mentorship advising in dermatology, detailing mentors’ advice regarding research, gap years, dual applications, away rotations, intern year, couples matching, program signaling, and volunteering during medical school. Based on our results, most respondents agree on the importance of research during medical school, the utility of away rotations, and the value of volunteering during medical school. Similarly, respondents agreed on the importance of having strong letters of recommendation; while some advised asking only dermatology faculty to write letters, others did not have a specialty preference for the letter writers. Respondents also had varying views about sharing interest in subspecialties during residency interviews. Many of the respondents do not provide recommendations regarding geographic signaling and couples matching, expressing that these are parts of an application that are important to approach on a case-by-case basis. Lastly, respondents had diverse opinions regarding the utility of gap years, whether to encourage or discourage dual applications, and how to advise regarding program signaling.

Our results also showed that one-third of respondents believed that research is not as important as it is perceived to be by dermatology applicants. While engaging in research during medical school was almost unanimously encouraged to foster mentor-mentee relationships, respondents expressed that the number of research experiences and publications was not critical. This is an important topic of discussion, as taking a dedicated year away from medical school to complete a research fellowship is becoming a trend among dermatology applicants.⁵ There has been discussion both on unofficial online platforms as well as in the published literature regarding the pressure for medical students interested in dermatology to publish, which may result in a gap year for research.⁶ The literature on the utility of a gap year in match rates is sparse, with one study showing no difference in match rates among Mayo Clinic dermatology residents who took research years vs those who did not.⁷ However, this contrasts with match rates at top dermatology residency programs where 41% of applicants who took a gap year matched vs 19% who did not.^7,8 These conflicting data are reflected in our study results, with respondents expressing different opinions on the utility of gap years.

There also are important equity concerns regarding the role of research years in the dermatology residency match process. Dermatology is one of the least racially diverse specialties, although there have been efforts to increase representation among residents and attending physicians.^9-11 Research years can be important contributors to this lack of representation, as these often are unpaid and can discourage economically disadvantaged students from applying.^9-11 Additionally, applicants may not have the flexibility to defer future salary for a year to match into dermatology; therefore, mentors should offer multiple options to individual applicants instead of solely encouraging gap years, given the conflicting feelings regarding their productivity.

Another topic of disagreement was dual application. Approximately one-third of respondents said they encourage either all students or those with less than a 75% chance of matching to dual apply, while about half only encourage students who are truly interested in multiple specialties to do so. Additionally, a large subset of respondents said they do not encourage dual applications due to concerns that they make applicants a worse candidate for each specialty and overall have negative effects on matching. Twenty-five percent of respondents opted to leave an open-ended response to this question: some offered the perspective that, if applicants feel a need to dual apply due to a weaker application, they do not advise the applicant to apply to dermatology. Many open ended responses underscored that the respondent does not encourage dual applications because they are inherently more time consuming, could hinder the applicant’s success, can seem disingenuous, and are a tool used to improve medical school match rates without being beneficial for the student. Some respondents also favored reapplying to dermatology the following year instead of dual applying. Finally, a subset of mentors indicated that they approach dual applications on a case-by-case basis, and others reported they do not have much experience advising on this topic. Currently, there are no known data in the literature on the efficacy and utility of dual applications in the dermatology match process; therefore, our study provides valuable insight for applicants interested in the impacts of the dual application. Overall, students should approach this option with mentors on an individual basis but ultimately should be aware of the concerns and mixed perceptions of the dual application process.

With regard to program signaling, previous research has shown that PSTs have a large impact on the chance of being granted an interview.¹² In our study, we provide a comprehensive overview of advising regarding these signals. While mentors often responded that they did not have much experience advising in this domain—and it is too soon to tell the impact of this program signaling—many offered differing opinions. Many said they recommend that students give a gold signal to their 3 most desired programs regardless of home and away rotations and perceived competitiveness, which follows the guidelines issued by the APD; however, 19% recommend only giving silver signals to home and away rotation programs, as participation in those programs is considered a sufficient signal of interest. Additionally, about half of mentors recommended that students only apply where they signal, whereas 20% recommended applying to 10 to 15 programs beyond those signaled. Future studies should investigate the impact of PSTs on interview invitations once sufficient application cycles have occurred.

Study Limitations

This study was conducted via email to the APD listserve. The total number of faculty on this listserve is unknown; therefore, we do not know the total response rate of the survey. Additionally, we surveyed mentors in this listserve, who therefore receive more emails and overall correspondence about the dermatology match and may be more involved in these conversations. The mentors who responded to our survey may have a different approach and response to our various survey questions than a given mentor across the United States who did not respond to this survey. A final limitation of our study is that the survey responses a mentor gives may not fully match the advice that they give their students privately.

Conclusion

Our survey of dermatology mentors across the United States provides valuable insight into how mentors advise for a strong dermatology residency application. Mentors agreed on the importance of research during medical school, away rotations, strong letters of recommendation, and volunteerism and advocacy to promote a strong residency application. Important topics of disagreement include the decision for dermatology applicants to take a dedicated gap year in medical school, how to use tokens/signals effectively, and the dual application process. Our findings also underscore important application components that applicants and mentors should approach on an individual basis. Future studies should investigate the impact of signals/tokens on the match process as well as the utility of gap years and dual applications, working to standardize the advice applicants receive.

While strong relationships with mentors and advisers are critical to navigating the competitive dermatology match process, the advice medical students receive from different individuals can be contradictory. Unaccredited information online—particularly on social media—as well as data reported by applicants can add to potential confusion.¹ Published research has elicited comments and observations from successfully matched medical students about highly discussed topics such as presentations and publications, letters of recommendation, away rotations, and interviews.^2,3 However, there currently are no published data about advice that dermatology mentors actually offer medical students. In this study, we aimed to investigate this gap in the current literature and examine the advice dermatology faculty, program directors, and other mentors at institutions accredited by the Accreditation Council for Graduate Medical Education across the United States give to medical students applying to dermatology residency.

Methods

A 14-question Johns Hopkins Qualtrics survey was sent via the Association of Professors of Dermatology (APD) listserve in June 2024 soliciting responses from members who consider themselves to be mentors to dermatology applicants across the United States. The survey included multiple-choice questions with the option to select multiple answers and a space for open-ended responses. The questions first gathered information on the respondents, including the capacity in which the mentors advised medical students (eg, program director, department chair, clinical faculty). Mentors were asked for the number of years they had been advising mentees and if they were advising students with a home dermatology program. In addition, mentors were asked what advice they give their mentees about aspects of the application process, including gap years, dual applications, research involvement, couples matching, program signaling, away rotations, internship year, letters of recommendation, geographic signaling, interviewing advice, and volunteering during medical school.

On August 18, 2024, survey results from 115 respondents were aggregated. The responses for each question were quantitatively assessed to determine whether there was consensus on specific advice offered. The open-ended responses also were qualitatively assessed to determine the most common responses.

Results

The respondents included program directors (30% [35/115]), clinical faculty (22% [25/115]), department chairs (18% [21/115]), assistant program directors (15% [17/115]), medical school clerkship directors (8% [9/115]), primary mentors (ie, faculty who did not fall into any of the aforementioned categories but still advised medical students interested in dermatology)(5% [6/115]), division chiefs (1% [1/115]), and deans (1% [1/115]). Respondents had been advising students for a median of 10 years (range, 1-40 years [25th percentile, 5.00 years; 75th percentile, 13.75 years]). The majority (90% [103/115]) of mentors surveyed were advising students with a home dermatology program.

Areas of Consensus

In some areas, there was broad consensus among the advice offered by the mentors that were surveyed (eTable).

Research During Medical School—More than 91% (105/115) of the respondents recommended research to encourage academic growth and indicated that the most important reason for conducting research during medical school is to foster mentor-mentee relationships; however, more than one-third of respondents believed research is overvalued by students and research productivity is not as critical for matching as they perceive it to be. When these responses were categorized by respondent positions, 29% (15/52) of program or assistant directors indicated agreement with the statement that research is overvalued.

Away Rotations—There also was a consensus about the importance of away rotations, with 85% (98/115) of respondents advising students to complete 1 to 2 away rotations at sites of high interest, and 13% (15/115) suggesting that students complete as many away rotations as possible. It is worth noting, however, that the official APD Residency Program Directors Section’s statement on away rotations recommends no more than 2 away rotations (or no more than 3 for students with no home program).⁴

Reapplication Advice—Additionally, in a situation where students do not match into a dermatology residency program, the vast majority (71% [82/115]) of respondents advised students to rank competitive intern years to foster connections and improve the chance of matching on the second attempt.

Volunteering During Medical School—Seventy-seven percent (89/115) of mentors encouraged students to engage in volunteerism and advocacy during medical school to create a well-rounded application, and 69% (79/115) of mentors encouraged students to display leadership in their volunteer efforts.

Areas Without Consensus

Letters of Recommendation—Most respondents recommended submitting letters of recommendation only from dermatology professionals (55% [63/115]), with the remainder recommending students request a letter from anyone who could provide a strong recommendation regardless of specialty mix (42% [48/115]).

Dermatologic Subspecialties—For students interested in dermatologic subspecialties, 73% (84/115) of mentors advised that students be honest during interviews but keep an open mind that interests during residencies may change. Forty-three percent (49/115) of respondents encouraged students to promote a subspecialty interest during their interview only if they can demonstrate effort within that subspecialty on their application.

Couples Matching—Most respondents approach couples matching on a case-by-case basis and assess individual priorities when they do advise on this topic. Respondents often advise applicants to identify a few cities/regions and focus strongly on the programs within those regions to avoid spreading themselves too thin; however, one-third (38/115) of respondents indicated that they do not personally offer advice regarding the couples match.

Areas With Diverse Opinions

Gap Years—Nearly one-quarter (24% [28/115]) of mentors reported that they rarely recommend students take a year off and only support those who are adamant about doing so, or that they never support taking a gap year at all. A slight majority (58% [67/115]) recommend a gap year for students strongly interested in dermatologic research, and 38% (44/115) recommend a gap year for students with weaker applications (Figure 1). We received many open-ended responses to this question, with mentors frequently indicating that they advise students to take a gap year on a case-by-case basis, with 44% (51/115) of commenters recommending that students only take paid gap-year research positions.

Program Signaling—The dermatology residency application process implemented a system of preference signaling tokens (PSTs) starting with the 2021-2022 cycle. Not quite half (46% [53/115]) of respondents recommend students apply only to places that they signaled, while 20% (23/115) advise responding to 10 to 15 additional programs. Very few (8% [9/115]) advise students to signal only in their stated region of interest. Approximately half (49% [56/115]) of mentors recommend students only signal based on the programs they feel would be the best fit for them without regard for perceived competitiveness—which aligns with the APD Residency Program Directors Section’s recommendation⁴—while 37% (43/115) recommend students distribute their signals to a wide range of programs. Sixty-three percent (72/115) of respondents recommend gold signaling to the student’s 3 most desired programs regardless of home and away rotation considerations, while 19% (22/115) recommend students give silver signals to their home and away rotation programs, as a rotation is already a signal of a strong desire to be there (Figure 2).

Dual Application—Fifty-three percent (61/115) of mentors recommended dual applying only for those truly interested in multiple specialties. Eighteen percent (21/115) of respondents advised dual applying for those with less than a 75% chance of matching. Twenty-five percent (29/115) of respondents free-wrote comments about approaching dual applying on a case-by-case basis, with many discussing the downsides of dual application and raising concerns that dual applications can hinder applicants’ success, can seem disingenuous, and seem to be a tool used to improve medical school match rates without benefit for the student.

We also stratified the data to compare overall responses from the total cohort with those from only program and assistant program directors. Across the 14 questions, responses from program and assistant program directors alone were similar to the overall cohort results

Comment

This study evaluated nationwide data on mentorship advising in dermatology, detailing mentors’ advice regarding research, gap years, dual applications, away rotations, intern year, couples matching, program signaling, and volunteering during medical school. Based on our results, most respondents agree on the importance of research during medical school, the utility of away rotations, and the value of volunteering during medical school. Similarly, respondents agreed on the importance of having strong letters of recommendation; while some advised asking only dermatology faculty to write letters, others did not have a specialty preference for the letter writers. Respondents also had varying views about sharing interest in subspecialties during residency interviews. Many of the respondents do not provide recommendations regarding geographic signaling and couples matching, expressing that these are parts of an application that are important to approach on a case-by-case basis. Lastly, respondents had diverse opinions regarding the utility of gap years, whether to encourage or discourage dual applications, and how to advise regarding program signaling.

Our results also showed that one-third of respondents believed that research is not as important as it is perceived to be by dermatology applicants. While engaging in research during medical school was almost unanimously encouraged to foster mentor-mentee relationships, respondents expressed that the number of research experiences and publications was not critical. This is an important topic of discussion, as taking a dedicated year away from medical school to complete a research fellowship is becoming a trend among dermatology applicants.⁵ There has been discussion both on unofficial online platforms as well as in the published literature regarding the pressure for medical students interested in dermatology to publish, which may result in a gap year for research.⁶ The literature on the utility of a gap year in match rates is sparse, with one study showing no difference in match rates among Mayo Clinic dermatology residents who took research years vs those who did not.⁷ However, this contrasts with match rates at top dermatology residency programs where 41% of applicants who took a gap year matched vs 19% who did not.^7,8 These conflicting data are reflected in our study results, with respondents expressing different opinions on the utility of gap years.

There also are important equity concerns regarding the role of research years in the dermatology residency match process. Dermatology is one of the least racially diverse specialties, although there have been efforts to increase representation among residents and attending physicians.^9-11 Research years can be important contributors to this lack of representation, as these often are unpaid and can discourage economically disadvantaged students from applying.^9-11 Additionally, applicants may not have the flexibility to defer future salary for a year to match into dermatology; therefore, mentors should offer multiple options to individual applicants instead of solely encouraging gap years, given the conflicting feelings regarding their productivity.

Another topic of disagreement was dual application. Approximately one-third of respondents said they encourage either all students or those with less than a 75% chance of matching to dual apply, while about half only encourage students who are truly interested in multiple specialties to do so. Additionally, a large subset of respondents said they do not encourage dual applications due to concerns that they make applicants a worse candidate for each specialty and overall have negative effects on matching. Twenty-five percent of respondents opted to leave an open-ended response to this question: some offered the perspective that, if applicants feel a need to dual apply due to a weaker application, they do not advise the applicant to apply to dermatology. Many open ended responses underscored that the respondent does not encourage dual applications because they are inherently more time consuming, could hinder the applicant’s success, can seem disingenuous, and are a tool used to improve medical school match rates without being beneficial for the student. Some respondents also favored reapplying to dermatology the following year instead of dual applying. Finally, a subset of mentors indicated that they approach dual applications on a case-by-case basis, and others reported they do not have much experience advising on this topic. Currently, there are no known data in the literature on the efficacy and utility of dual applications in the dermatology match process; therefore, our study provides valuable insight for applicants interested in the impacts of the dual application. Overall, students should approach this option with mentors on an individual basis but ultimately should be aware of the concerns and mixed perceptions of the dual application process.

With regard to program signaling, previous research has shown that PSTs have a large impact on the chance of being granted an interview.¹² In our study, we provide a comprehensive overview of advising regarding these signals. While mentors often responded that they did not have much experience advising in this domain—and it is too soon to tell the impact of this program signaling—many offered differing opinions. Many said they recommend that students give a gold signal to their 3 most desired programs regardless of home and away rotations and perceived competitiveness, which follows the guidelines issued by the APD; however, 19% recommend only giving silver signals to home and away rotation programs, as participation in those programs is considered a sufficient signal of interest. Additionally, about half of mentors recommended that students only apply where they signal, whereas 20% recommended applying to 10 to 15 programs beyond those signaled. Future studies should investigate the impact of PSTs on interview invitations once sufficient application cycles have occurred.

Study Limitations

This study was conducted via email to the APD listserve. The total number of faculty on this listserve is unknown; therefore, we do not know the total response rate of the survey. Additionally, we surveyed mentors in this listserve, who therefore receive more emails and overall correspondence about the dermatology match and may be more involved in these conversations. The mentors who responded to our survey may have a different approach and response to our various survey questions than a given mentor across the United States who did not respond to this survey. A final limitation of our study is that the survey responses a mentor gives may not fully match the advice that they give their students privately.

Conclusion

Our survey of dermatology mentors across the United States provides valuable insight into how mentors advise for a strong dermatology residency application. Mentors agreed on the importance of research during medical school, away rotations, strong letters of recommendation, and volunteerism and advocacy to promote a strong residency application. Important topics of disagreement include the decision for dermatology applicants to take a dedicated gap year in medical school, how to use tokens/signals effectively, and the dual application process. Our findings also underscore important application components that applicants and mentors should approach on an individual basis. Future studies should investigate the impact of signals/tokens on the match process as well as the utility of gap years and dual applications, working to standardize the advice applicants receive.

THE DIAGNOSIS: Epithelioid Fibrous Histiocytoma

In our patient, immunohistochemical stains for Factor XIIIa, CD68, and anaplastic lymphoma kinase (ALK) 1 confirmed the diagnosis of epithelioid fibrous histiocytoma (EFH). The location and relatively large size of the lesion led to a joint decision by the patient and physician to perform a complete excision, which was done with no complications.

Once considered a rare variant of dermatofibroma, EFH most commonly manifests as a solitary, vascular-appearing or flesh-colored papule or nodule on the legs. It often develops in the fifth decade of life with greater prevalence in men.^1-5 Our patient is one of the few known cases of EFH in children that have been reported in the literature.^3,6 Although EFH is benign, complete excision typically is performed due to the rarity of the lesion.³

The overexpression of ALK distinguishes EFH from other fibrohistiocytic lesions (Figure 1).⁵ The most common fusion partners are sequestosome 1 and vinculin (VCL), which account for more than 70% of cases.^3,5,7 Interestingly, VCL-ALK fusions have been reported to occur in a subset of pediatric renal cell carcinomas and recently in an ovoid spindle cell neoplasm considered to be a low-grade sarcoma.^3,7-9 Further studies have identified less common fusion partners, including the dynactin subunit 1, ETS variant transcription factor 6, protein-tyrosine phosphatase, receptor-type, F polypeptide-interacting protein-binding protein 1, sperm antigen with calponin homology and coiled-coil domains 1, tropomyosin 3, protein kinase cAMP-dependent type II regulatory subunit alpha, melanophilin, and Echinoderm microtubule-associated protein-like 4 genes.^3,8

In contrast to benign fibrous histiocytomas, EFHs primarily consist of epithelioid cells, have well-defined borders, exhibit prominent vascularity, usually are situated close to the epidermis, and lack multinucleated cells or histiocytes laden with lipids or hemosiderin.² The characteristic histopathologic finding is rounded or angulated epithelioid cells, with eosinophilic cytoplasm accounting for more than 50% of the tumor cell population.^1-3,5 The nuclei of the epithelioid cells are rounded and vesicular with small eosinophilic nucleoli and low mitotic activity. Common clinical features include an exophytic nodule with a classic epidermal collarette and an epidermis that exhibits variable degrees of hyperplasia.^1-3,5 Epithelioid fibrous histiocytomas often are confined to the superficial dermis and rarely extend to the subcutaneous layer. The stroma is collagenous with prominent vascularity, although older lesions can become more hyalinized and sclerotic.³ Histopathologically, these tumors can be a diagnostic challenge, as they often are mistaken for other fibrohistiocytic or melanocytic lesions.

Atypical fibroxanthoma (AFX) manifests as a dome-shaped exophytic nodule that can rapidly grow to 1 to 2 cm. Historically, it was thought to be a pseudomalignancy, but most investigators consider it within the spectrum of pleomorphic dermal sarcoma and undifferentiated pleomorphic sarcoma. Atypical fibroxanthoma usually occurs on the head and neck in elderly patients with sun-damaged skin. Histopathologically, the neoplastic cells of AFX range from atypical spindle cells and pleomorphic round to polygonal epithelioid cells to large, irregularly shaped multinucleated cells, some with foamy cytoplasm (Figure 2). The atypical spindle cells stain diffusely positive for CD10 and vimentin, while small subpopulations stain positively for CD68 or CD163 and procollagen 1. Smooth muscle actin inconsistently stains the tumor, and when it does, the staining typically is faint and patchy. Atypical fibroxanthomas usually do not stain positively for melanocytic, skeletal muscle, or keratinocytic markers.

Cellular dermatofibroma typically manifests as small, dome-shaped papules on the arms and legs that normally range from a few millimeters to 1 cm but occasionally measure up to 2 cm. Histopathologically, there are interweaving fascicles of spindle cells with hyperchromatic nuclei and peripheral splaying of the plump spindle cells that wrap around collagen bundles, known as collagen trapping (Figure 3). Unlike EFH, multinucleated cells and histiocytes with abundant lipids and hemosiderin often accompany the spindle cells in cellular dermatofibromas, which stain strongly positive for CD10 and vimentin, similar to AFX and EFH. The smooth muscle actin–staining pattern usually is faint and patchy, and in some cases, cellular dermatofibroma may not stain at all. Factor XIIIa and CD68 highlight the 2 populations of cells—fibroblasts and histiocytes—that make up the lesion.⁴

Epithelioid sarcoma comprises 2 types: distal (or conventional) type occurring on the distal arms and legs, particularly the hands and fingers of young adults, and proximal type occurring on the trunk and proximal extremities, including the upper arms and thighs.¹⁰ Epithelioid sarcoma is a rare aggressive malignancy that usually manifests as a firm nodule, sometimes with ulceration depending on the size. Histopathologically, diffuse dermal proliferation of ovoid to polygonal epithelioid cells arranged in short fascicles and nodular aggregations is observed (Figure 4). Spindle cells may be observed at the periphery of the lesion. Areas of necrosis are a frequent finding and a helpful diagnostic clue. Nearly all cases stain positively for pancytokeratin, CAM5.2, epithelial membrane antigen, and vimentin, and approximately half stain positively for CD34; there are variable expressions of ERG and smooth muscle actin.¹⁰ In most cases, epithelioid sarcoma does not stain positively for S100 or CD68. The majority (90%) of cases harbor a mutation in the SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 gene, resulting in the loss of INI1 protein expression, which can be demonstrated by immunohistochemistry. ¹⁰ As the cytologic atypia usually is minimal, epithelioid sarcoma may be misdiagnosed as a necrotizing granuloma and benign fibrous lesions, particularly when superficial or small partial biopsies are performed.

Intradermal Spitz nevi can measure from a few millimeters to more than 2 cm and can range from pink to brown to black. The most common locations are the lower extremities as well as the head and neck. Histopathologically, intradermal Spitz nevi have nests of large epithelioid melanocytes with large nuclei and abundant cytoplasm (eFigure). Nuclear pseudo-inclusions, which are cytoplasmic invaginations into the nucleus, are frequent. Unlike the other conditions in the differential, these entities stain positively for melanocytic markers—S100, SOX10, and Melan-A—but not CD68 or CD163.11 A variety of kinase fusions are observed in Spitz nevi, including the ALK gene, neurotrophic tyrosine receptor kinase, ROS proto-oncogene 1, megakaryocyte-erythroid progenitor, and v-raf murine sarcoma viral oncogene homolog B1 genes.¹²

THE DIAGNOSIS: Epithelioid Fibrous Histiocytoma

In our patient, immunohistochemical stains for Factor XIIIa, CD68, and anaplastic lymphoma kinase (ALK) 1 confirmed the diagnosis of epithelioid fibrous histiocytoma (EFH). The location and relatively large size of the lesion led to a joint decision by the patient and physician to perform a complete excision, which was done with no complications.

Once considered a rare variant of dermatofibroma, EFH most commonly manifests as a solitary, vascular-appearing or flesh-colored papule or nodule on the legs. It often develops in the fifth decade of life with greater prevalence in men.^1-5 Our patient is one of the few known cases of EFH in children that have been reported in the literature.^3,6 Although EFH is benign, complete excision typically is performed due to the rarity of the lesion.³

The overexpression of ALK distinguishes EFH from other fibrohistiocytic lesions (Figure 1).⁵ The most common fusion partners are sequestosome 1 and vinculin (VCL), which account for more than 70% of cases.^3,5,7 Interestingly, VCL-ALK fusions have been reported to occur in a subset of pediatric renal cell carcinomas and recently in an ovoid spindle cell neoplasm considered to be a low-grade sarcoma.^3,7-9 Further studies have identified less common fusion partners, including the dynactin subunit 1, ETS variant transcription factor 6, protein-tyrosine phosphatase, receptor-type, F polypeptide-interacting protein-binding protein 1, sperm antigen with calponin homology and coiled-coil domains 1, tropomyosin 3, protein kinase cAMP-dependent type II regulatory subunit alpha, melanophilin, and Echinoderm microtubule-associated protein-like 4 genes.^3,8

In contrast to benign fibrous histiocytomas, EFHs primarily consist of epithelioid cells, have well-defined borders, exhibit prominent vascularity, usually are situated close to the epidermis, and lack multinucleated cells or histiocytes laden with lipids or hemosiderin.² The characteristic histopathologic finding is rounded or angulated epithelioid cells, with eosinophilic cytoplasm accounting for more than 50% of the tumor cell population.^1-3,5 The nuclei of the epithelioid cells are rounded and vesicular with small eosinophilic nucleoli and low mitotic activity. Common clinical features include an exophytic nodule with a classic epidermal collarette and an epidermis that exhibits variable degrees of hyperplasia.^1-3,5 Epithelioid fibrous histiocytomas often are confined to the superficial dermis and rarely extend to the subcutaneous layer. The stroma is collagenous with prominent vascularity, although older lesions can become more hyalinized and sclerotic.³ Histopathologically, these tumors can be a diagnostic challenge, as they often are mistaken for other fibrohistiocytic or melanocytic lesions.

Atypical fibroxanthoma (AFX) manifests as a dome-shaped exophytic nodule that can rapidly grow to 1 to 2 cm. Historically, it was thought to be a pseudomalignancy, but most investigators consider it within the spectrum of pleomorphic dermal sarcoma and undifferentiated pleomorphic sarcoma. Atypical fibroxanthoma usually occurs on the head and neck in elderly patients with sun-damaged skin. Histopathologically, the neoplastic cells of AFX range from atypical spindle cells and pleomorphic round to polygonal epithelioid cells to large, irregularly shaped multinucleated cells, some with foamy cytoplasm (Figure 2). The atypical spindle cells stain diffusely positive for CD10 and vimentin, while small subpopulations stain positively for CD68 or CD163 and procollagen 1. Smooth muscle actin inconsistently stains the tumor, and when it does, the staining typically is faint and patchy. Atypical fibroxanthomas usually do not stain positively for melanocytic, skeletal muscle, or keratinocytic markers.

Cellular dermatofibroma typically manifests as small, dome-shaped papules on the arms and legs that normally range from a few millimeters to 1 cm but occasionally measure up to 2 cm. Histopathologically, there are interweaving fascicles of spindle cells with hyperchromatic nuclei and peripheral splaying of the plump spindle cells that wrap around collagen bundles, known as collagen trapping (Figure 3). Unlike EFH, multinucleated cells and histiocytes with abundant lipids and hemosiderin often accompany the spindle cells in cellular dermatofibromas, which stain strongly positive for CD10 and vimentin, similar to AFX and EFH. The smooth muscle actin–staining pattern usually is faint and patchy, and in some cases, cellular dermatofibroma may not stain at all. Factor XIIIa and CD68 highlight the 2 populations of cells—fibroblasts and histiocytes—that make up the lesion.⁴

Epithelioid sarcoma comprises 2 types: distal (or conventional) type occurring on the distal arms and legs, particularly the hands and fingers of young adults, and proximal type occurring on the trunk and proximal extremities, including the upper arms and thighs.¹⁰ Epithelioid sarcoma is a rare aggressive malignancy that usually manifests as a firm nodule, sometimes with ulceration depending on the size. Histopathologically, diffuse dermal proliferation of ovoid to polygonal epithelioid cells arranged in short fascicles and nodular aggregations is observed (Figure 4). Spindle cells may be observed at the periphery of the lesion. Areas of necrosis are a frequent finding and a helpful diagnostic clue. Nearly all cases stain positively for pancytokeratin, CAM5.2, epithelial membrane antigen, and vimentin, and approximately half stain positively for CD34; there are variable expressions of ERG and smooth muscle actin.¹⁰ In most cases, epithelioid sarcoma does not stain positively for S100 or CD68. The majority (90%) of cases harbor a mutation in the SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 gene, resulting in the loss of INI1 protein expression, which can be demonstrated by immunohistochemistry. ¹⁰ As the cytologic atypia usually is minimal, epithelioid sarcoma may be misdiagnosed as a necrotizing granuloma and benign fibrous lesions, particularly when superficial or small partial biopsies are performed.

Intradermal Spitz nevi can measure from a few millimeters to more than 2 cm and can range from pink to brown to black. The most common locations are the lower extremities as well as the head and neck. Histopathologically, intradermal Spitz nevi have nests of large epithelioid melanocytes with large nuclei and abundant cytoplasm (eFigure). Nuclear pseudo-inclusions, which are cytoplasmic invaginations into the nucleus, are frequent. Unlike the other conditions in the differential, these entities stain positively for melanocytic markers—S100, SOX10, and Melan-A—but not CD68 or CD163.11 A variety of kinase fusions are observed in Spitz nevi, including the ALK gene, neurotrophic tyrosine receptor kinase, ROS proto-oncogene 1, megakaryocyte-erythroid progenitor, and v-raf murine sarcoma viral oncogene homolog B1 genes.¹²

THE DIAGNOSIS: Epithelioid Fibrous Histiocytoma

In our patient, immunohistochemical stains for Factor XIIIa, CD68, and anaplastic lymphoma kinase (ALK) 1 confirmed the diagnosis of epithelioid fibrous histiocytoma (EFH). The location and relatively large size of the lesion led to a joint decision by the patient and physician to perform a complete excision, which was done with no complications.

Once considered a rare variant of dermatofibroma, EFH most commonly manifests as a solitary, vascular-appearing or flesh-colored papule or nodule on the legs. It often develops in the fifth decade of life with greater prevalence in men.^1-5 Our patient is one of the few known cases of EFH in children that have been reported in the literature.^3,6 Although EFH is benign, complete excision typically is performed due to the rarity of the lesion.³

The overexpression of ALK distinguishes EFH from other fibrohistiocytic lesions (Figure 1).⁵ The most common fusion partners are sequestosome 1 and vinculin (VCL), which account for more than 70% of cases.^3,5,7 Interestingly, VCL-ALK fusions have been reported to occur in a subset of pediatric renal cell carcinomas and recently in an ovoid spindle cell neoplasm considered to be a low-grade sarcoma.^3,7-9 Further studies have identified less common fusion partners, including the dynactin subunit 1, ETS variant transcription factor 6, protein-tyrosine phosphatase, receptor-type, F polypeptide-interacting protein-binding protein 1, sperm antigen with calponin homology and coiled-coil domains 1, tropomyosin 3, protein kinase cAMP-dependent type II regulatory subunit alpha, melanophilin, and Echinoderm microtubule-associated protein-like 4 genes.^3,8

In contrast to benign fibrous histiocytomas, EFHs primarily consist of epithelioid cells, have well-defined borders, exhibit prominent vascularity, usually are situated close to the epidermis, and lack multinucleated cells or histiocytes laden with lipids or hemosiderin.² The characteristic histopathologic finding is rounded or angulated epithelioid cells, with eosinophilic cytoplasm accounting for more than 50% of the tumor cell population.^1-3,5 The nuclei of the epithelioid cells are rounded and vesicular with small eosinophilic nucleoli and low mitotic activity. Common clinical features include an exophytic nodule with a classic epidermal collarette and an epidermis that exhibits variable degrees of hyperplasia.^1-3,5 Epithelioid fibrous histiocytomas often are confined to the superficial dermis and rarely extend to the subcutaneous layer. The stroma is collagenous with prominent vascularity, although older lesions can become more hyalinized and sclerotic.³ Histopathologically, these tumors can be a diagnostic challenge, as they often are mistaken for other fibrohistiocytic or melanocytic lesions.

Atypical fibroxanthoma (AFX) manifests as a dome-shaped exophytic nodule that can rapidly grow to 1 to 2 cm. Historically, it was thought to be a pseudomalignancy, but most investigators consider it within the spectrum of pleomorphic dermal sarcoma and undifferentiated pleomorphic sarcoma. Atypical fibroxanthoma usually occurs on the head and neck in elderly patients with sun-damaged skin. Histopathologically, the neoplastic cells of AFX range from atypical spindle cells and pleomorphic round to polygonal epithelioid cells to large, irregularly shaped multinucleated cells, some with foamy cytoplasm (Figure 2). The atypical spindle cells stain diffusely positive for CD10 and vimentin, while small subpopulations stain positively for CD68 or CD163 and procollagen 1. Smooth muscle actin inconsistently stains the tumor, and when it does, the staining typically is faint and patchy. Atypical fibroxanthomas usually do not stain positively for melanocytic, skeletal muscle, or keratinocytic markers.

Cellular dermatofibroma typically manifests as small, dome-shaped papules on the arms and legs that normally range from a few millimeters to 1 cm but occasionally measure up to 2 cm. Histopathologically, there are interweaving fascicles of spindle cells with hyperchromatic nuclei and peripheral splaying of the plump spindle cells that wrap around collagen bundles, known as collagen trapping (Figure 3). Unlike EFH, multinucleated cells and histiocytes with abundant lipids and hemosiderin often accompany the spindle cells in cellular dermatofibromas, which stain strongly positive for CD10 and vimentin, similar to AFX and EFH. The smooth muscle actin–staining pattern usually is faint and patchy, and in some cases, cellular dermatofibroma may not stain at all. Factor XIIIa and CD68 highlight the 2 populations of cells—fibroblasts and histiocytes—that make up the lesion.⁴

Epithelioid sarcoma comprises 2 types: distal (or conventional) type occurring on the distal arms and legs, particularly the hands and fingers of young adults, and proximal type occurring on the trunk and proximal extremities, including the upper arms and thighs.¹⁰ Epithelioid sarcoma is a rare aggressive malignancy that usually manifests as a firm nodule, sometimes with ulceration depending on the size. Histopathologically, diffuse dermal proliferation of ovoid to polygonal epithelioid cells arranged in short fascicles and nodular aggregations is observed (Figure 4). Spindle cells may be observed at the periphery of the lesion. Areas of necrosis are a frequent finding and a helpful diagnostic clue. Nearly all cases stain positively for pancytokeratin, CAM5.2, epithelial membrane antigen, and vimentin, and approximately half stain positively for CD34; there are variable expressions of ERG and smooth muscle actin.¹⁰ In most cases, epithelioid sarcoma does not stain positively for S100 or CD68. The majority (90%) of cases harbor a mutation in the SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 gene, resulting in the loss of INI1 protein expression, which can be demonstrated by immunohistochemistry. ¹⁰ As the cytologic atypia usually is minimal, epithelioid sarcoma may be misdiagnosed as a necrotizing granuloma and benign fibrous lesions, particularly when superficial or small partial biopsies are performed.

Intradermal Spitz nevi can measure from a few millimeters to more than 2 cm and can range from pink to brown to black. The most common locations are the lower extremities as well as the head and neck. Histopathologically, intradermal Spitz nevi have nests of large epithelioid melanocytes with large nuclei and abundant cytoplasm (eFigure). Nuclear pseudo-inclusions, which are cytoplasmic invaginations into the nucleus, are frequent. Unlike the other conditions in the differential, these entities stain positively for melanocytic markers—S100, SOX10, and Melan-A—but not CD68 or CD163.11 A variety of kinase fusions are observed in Spitz nevi, including the ALK gene, neurotrophic tyrosine receptor kinase, ROS proto-oncogene 1, megakaryocyte-erythroid progenitor, and v-raf murine sarcoma viral oncogene homolog B1 genes.¹²

Patients who undergo cutaneous surgery and chronic wound care often are exposed to various topical agents that carry allergenic potential, including antiseptic rinses, bandage adhesives, mineral pastes, and antibiotic ointments.¹ Allergic contact dermatitis (ACD) in postoperative or chronic wounds can lead to considerable morbidity, particularly when the diagnosis is unclear. Differentiating between ACD and wound infection is paramount because the treatments for these conditions often are mutually exclusive.² While patch testing for contact allergy could be considered for postoperative patients or those with chronic wounds who exhibit concerning symptoms such as erythema or pruritus, these scenarios require prompt diagnosis and treatment. Herein, we describe a technique that involves secondary application of potentially allergenic topical components to a small area of normal skin during wound management to facilitate early detection of ACD and differentiation from wound infection.

Practice Gap 

Contact allergies are common in patients with postoperative or chronic wounds. When patch tested, approximately 80% of patients with chronic venous ulcers demonstrated at least 1 positive allergic reaction based on a Canadian study.³ Similarly, postoperative ACD in dermatologic surgery occurs in more than 1.6% of cases in North America and Europe, a rate that is similar to or higher than the rate of postoperative infection, approximately 1% to 2%.⁴ Postoperative patients and those with chronic wounds have multiple risk factors for ACD. Firstly, applying topical therapies to inflamed or compromised skin increases the risk for contact sensitization.⁵ Additionally, multiple topical therapies containing known allergenic components may be recommended for wound care, including impregnated or organic dressings, antibiotic ointments, adhesives, antiseptic washes, and topical therapies containing inactive ingredients such as lanolin derivatives.⁶ Contact with numerous compounds at the same time increases the risk for a contact allergy as well as co-sensitization.⁷ Similarly, the longer topical agents are applied, the greater the risk for a contact allergy, with sensitization liable to occur at any point during treatment.

Preventive topical antibiotics have garnered a negative reputation among dermatologists, often due to varying data on their efficacy and the overuse of highly allergenic over-the-counter topical antibiotics such as neomycin.⁸ However, data also have suggested that topical antibiotics can reduce postoperative infections in higher risk surgical cases, specifically certain head and neck surgeries.⁹ Likewise, topical antibiotics are useful for wound colonization with Pseudomonas, which can remain superficial and slow down healing without progressing to a systemic infection.¹⁰ Such cases can be successfully treated or prevented with topical therapies, thereby bypassing the more concerning adverse effects of systemic antibiotics. In particular, systemic fluoroquinolones often are used to treat Pseudomonas and can have many serious adverse effects, including tendon rupture, drug interactions, and arrhythmias.¹¹ Therefore, it is worth implementing topical treatments for wounds colonized with Pseudomonas to spare patients these potential complications.

When a postoperative patient develops a rash at the surgical site, it is critical to differentiate between wound infection and contact allergy, as the treatments for these two conditions may be mutually exclusive and treating the wrong condition may exacerbate the other, such as mistakenly using topical corticosteroids for a wound infection.⁷ Prompt treatment is necessary for wound infections, as time is limited for patch testing when a rash is already present and the diagnosis is questionable. Allergic contact dermatitis typically erupts 48 to 96 hours following exposure to a contact allergen, often manifesting as intensely pruritic erythematous patches or vesicles.⁶ Wound infections are characterized by pain and warmth, with erythema and edema present in both conditions. Postoperative infections manifest usually 4 to 7 days following surgery.¹² Despite these differences, pruritus and pain are common in the wound healing process; thus, differentiating an infection from ACD on a clinical basis alone is not always possible. Furthermore, presentation of a contact allergy may be delayed beyond the typical 96-hour timeframe if a patient is newly sensitized to an allergen, causing the timeline of rash development to appear similar to that of a wound infection. In such cases, systemic antibiotics often are prescribed empirically; hence, clearer and timelier differentiation between contact allergy and wound infection reduces unnecessary antibiotic prescriptions, thereby avoiding systemic adverse effects and promoting responsible antibiotic stewardship.¹²

The Technique

Since potentially allergenic topical therapies often are indicated in wound management, we propose that patients serve as internal controls to test continuously for contact allergy sensitization. We recommend that patients apply a small amount of the topical agent, product, or dressing to the inner forearm each time they apply it to the wound. If the patient is sensitized to the product initially or becomes sensitized during treatment, evidence of ACD will be visible not only at the site of the wound but also in the area of secondary application. The inner forearm is recommended for convenience and reproducibility, but a patient may choose a different site as long as it remains consistent. Although certain contact allergens rarely may react solely at a site of inflamed skin, our team has quickly identified ACD and avoided misdiagnosis of chronic or postsurgical wound infection using this approach.¹³ Subsequent patch testing is indicated when a contact allergy is detected.

Practice Implications

Topical therapies including ointments, washes, and dressing components have the potential to cause sensitization and contact allergy. Despite the concern for development of ACD, topical antibiotics play a useful role in cutaneous surgery.⁷ Synchronous testing for contact allergy when managing wounds with topical therapies could improve diagnostic accuracy when an allergic reaction occurs. This technique provides a means of harnessing the benefits of topical agents while monitoring the risk for ACD in postoperative and chronic wound care settings.

Patients who undergo cutaneous surgery and chronic wound care often are exposed to various topical agents that carry allergenic potential, including antiseptic rinses, bandage adhesives, mineral pastes, and antibiotic ointments.¹ Allergic contact dermatitis (ACD) in postoperative or chronic wounds can lead to considerable morbidity, particularly when the diagnosis is unclear. Differentiating between ACD and wound infection is paramount because the treatments for these conditions often are mutually exclusive.² While patch testing for contact allergy could be considered for postoperative patients or those with chronic wounds who exhibit concerning symptoms such as erythema or pruritus, these scenarios require prompt diagnosis and treatment. Herein, we describe a technique that involves secondary application of potentially allergenic topical components to a small area of normal skin during wound management to facilitate early detection of ACD and differentiation from wound infection.

Practice Gap 

Contact allergies are common in patients with postoperative or chronic wounds. When patch tested, approximately 80% of patients with chronic venous ulcers demonstrated at least 1 positive allergic reaction based on a Canadian study.³ Similarly, postoperative ACD in dermatologic surgery occurs in more than 1.6% of cases in North America and Europe, a rate that is similar to or higher than the rate of postoperative infection, approximately 1% to 2%.⁴ Postoperative patients and those with chronic wounds have multiple risk factors for ACD. Firstly, applying topical therapies to inflamed or compromised skin increases the risk for contact sensitization.⁵ Additionally, multiple topical therapies containing known allergenic components may be recommended for wound care, including impregnated or organic dressings, antibiotic ointments, adhesives, antiseptic washes, and topical therapies containing inactive ingredients such as lanolin derivatives.⁶ Contact with numerous compounds at the same time increases the risk for a contact allergy as well as co-sensitization.⁷ Similarly, the longer topical agents are applied, the greater the risk for a contact allergy, with sensitization liable to occur at any point during treatment.

Preventive topical antibiotics have garnered a negative reputation among dermatologists, often due to varying data on their efficacy and the overuse of highly allergenic over-the-counter topical antibiotics such as neomycin.⁸ However, data also have suggested that topical antibiotics can reduce postoperative infections in higher risk surgical cases, specifically certain head and neck surgeries.⁹ Likewise, topical antibiotics are useful for wound colonization with Pseudomonas, which can remain superficial and slow down healing without progressing to a systemic infection.¹⁰ Such cases can be successfully treated or prevented with topical therapies, thereby bypassing the more concerning adverse effects of systemic antibiotics. In particular, systemic fluoroquinolones often are used to treat Pseudomonas and can have many serious adverse effects, including tendon rupture, drug interactions, and arrhythmias.¹¹ Therefore, it is worth implementing topical treatments for wounds colonized with Pseudomonas to spare patients these potential complications.

When a postoperative patient develops a rash at the surgical site, it is critical to differentiate between wound infection and contact allergy, as the treatments for these two conditions may be mutually exclusive and treating the wrong condition may exacerbate the other, such as mistakenly using topical corticosteroids for a wound infection.⁷ Prompt treatment is necessary for wound infections, as time is limited for patch testing when a rash is already present and the diagnosis is questionable. Allergic contact dermatitis typically erupts 48 to 96 hours following exposure to a contact allergen, often manifesting as intensely pruritic erythematous patches or vesicles.⁶ Wound infections are characterized by pain and warmth, with erythema and edema present in both conditions. Postoperative infections manifest usually 4 to 7 days following surgery.¹² Despite these differences, pruritus and pain are common in the wound healing process; thus, differentiating an infection from ACD on a clinical basis alone is not always possible. Furthermore, presentation of a contact allergy may be delayed beyond the typical 96-hour timeframe if a patient is newly sensitized to an allergen, causing the timeline of rash development to appear similar to that of a wound infection. In such cases, systemic antibiotics often are prescribed empirically; hence, clearer and timelier differentiation between contact allergy and wound infection reduces unnecessary antibiotic prescriptions, thereby avoiding systemic adverse effects and promoting responsible antibiotic stewardship.¹²

The Technique

Since potentially allergenic topical therapies often are indicated in wound management, we propose that patients serve as internal controls to test continuously for contact allergy sensitization. We recommend that patients apply a small amount of the topical agent, product, or dressing to the inner forearm each time they apply it to the wound. If the patient is sensitized to the product initially or becomes sensitized during treatment, evidence of ACD will be visible not only at the site of the wound but also in the area of secondary application. The inner forearm is recommended for convenience and reproducibility, but a patient may choose a different site as long as it remains consistent. Although certain contact allergens rarely may react solely at a site of inflamed skin, our team has quickly identified ACD and avoided misdiagnosis of chronic or postsurgical wound infection using this approach.¹³ Subsequent patch testing is indicated when a contact allergy is detected.

Practice Implications

Topical therapies including ointments, washes, and dressing components have the potential to cause sensitization and contact allergy. Despite the concern for development of ACD, topical antibiotics play a useful role in cutaneous surgery.⁷ Synchronous testing for contact allergy when managing wounds with topical therapies could improve diagnostic accuracy when an allergic reaction occurs. This technique provides a means of harnessing the benefits of topical agents while monitoring the risk for ACD in postoperative and chronic wound care settings.

Patients who undergo cutaneous surgery and chronic wound care often are exposed to various topical agents that carry allergenic potential, including antiseptic rinses, bandage adhesives, mineral pastes, and antibiotic ointments.¹ Allergic contact dermatitis (ACD) in postoperative or chronic wounds can lead to considerable morbidity, particularly when the diagnosis is unclear. Differentiating between ACD and wound infection is paramount because the treatments for these conditions often are mutually exclusive.² While patch testing for contact allergy could be considered for postoperative patients or those with chronic wounds who exhibit concerning symptoms such as erythema or pruritus, these scenarios require prompt diagnosis and treatment. Herein, we describe a technique that involves secondary application of potentially allergenic topical components to a small area of normal skin during wound management to facilitate early detection of ACD and differentiation from wound infection.

Practice Gap 

Contact allergies are common in patients with postoperative or chronic wounds. When patch tested, approximately 80% of patients with chronic venous ulcers demonstrated at least 1 positive allergic reaction based on a Canadian study.³ Similarly, postoperative ACD in dermatologic surgery occurs in more than 1.6% of cases in North America and Europe, a rate that is similar to or higher than the rate of postoperative infection, approximately 1% to 2%.⁴ Postoperative patients and those with chronic wounds have multiple risk factors for ACD. Firstly, applying topical therapies to inflamed or compromised skin increases the risk for contact sensitization.⁵ Additionally, multiple topical therapies containing known allergenic components may be recommended for wound care, including impregnated or organic dressings, antibiotic ointments, adhesives, antiseptic washes, and topical therapies containing inactive ingredients such as lanolin derivatives.⁶ Contact with numerous compounds at the same time increases the risk for a contact allergy as well as co-sensitization.⁷ Similarly, the longer topical agents are applied, the greater the risk for a contact allergy, with sensitization liable to occur at any point during treatment.

Preventive topical antibiotics have garnered a negative reputation among dermatologists, often due to varying data on their efficacy and the overuse of highly allergenic over-the-counter topical antibiotics such as neomycin.⁸ However, data also have suggested that topical antibiotics can reduce postoperative infections in higher risk surgical cases, specifically certain head and neck surgeries.⁹ Likewise, topical antibiotics are useful for wound colonization with Pseudomonas, which can remain superficial and slow down healing without progressing to a systemic infection.¹⁰ Such cases can be successfully treated or prevented with topical therapies, thereby bypassing the more concerning adverse effects of systemic antibiotics. In particular, systemic fluoroquinolones often are used to treat Pseudomonas and can have many serious adverse effects, including tendon rupture, drug interactions, and arrhythmias.¹¹ Therefore, it is worth implementing topical treatments for wounds colonized with Pseudomonas to spare patients these potential complications.

When a postoperative patient develops a rash at the surgical site, it is critical to differentiate between wound infection and contact allergy, as the treatments for these two conditions may be mutually exclusive and treating the wrong condition may exacerbate the other, such as mistakenly using topical corticosteroids for a wound infection.⁷ Prompt treatment is necessary for wound infections, as time is limited for patch testing when a rash is already present and the diagnosis is questionable. Allergic contact dermatitis typically erupts 48 to 96 hours following exposure to a contact allergen, often manifesting as intensely pruritic erythematous patches or vesicles.⁶ Wound infections are characterized by pain and warmth, with erythema and edema present in both conditions. Postoperative infections manifest usually 4 to 7 days following surgery.¹² Despite these differences, pruritus and pain are common in the wound healing process; thus, differentiating an infection from ACD on a clinical basis alone is not always possible. Furthermore, presentation of a contact allergy may be delayed beyond the typical 96-hour timeframe if a patient is newly sensitized to an allergen, causing the timeline of rash development to appear similar to that of a wound infection. In such cases, systemic antibiotics often are prescribed empirically; hence, clearer and timelier differentiation between contact allergy and wound infection reduces unnecessary antibiotic prescriptions, thereby avoiding systemic adverse effects and promoting responsible antibiotic stewardship.¹²

The Technique

Since potentially allergenic topical therapies often are indicated in wound management, we propose that patients serve as internal controls to test continuously for contact allergy sensitization. We recommend that patients apply a small amount of the topical agent, product, or dressing to the inner forearm each time they apply it to the wound. If the patient is sensitized to the product initially or becomes sensitized during treatment, evidence of ACD will be visible not only at the site of the wound but also in the area of secondary application. The inner forearm is recommended for convenience and reproducibility, but a patient may choose a different site as long as it remains consistent. Although certain contact allergens rarely may react solely at a site of inflamed skin, our team has quickly identified ACD and avoided misdiagnosis of chronic or postsurgical wound infection using this approach.¹³ Subsequent patch testing is indicated when a contact allergy is detected.

Practice Implications

Topical therapies including ointments, washes, and dressing components have the potential to cause sensitization and contact allergy. Despite the concern for development of ACD, topical antibiotics play a useful role in cutaneous surgery.⁷ Synchronous testing for contact allergy when managing wounds with topical therapies could improve diagnostic accuracy when an allergic reaction occurs. This technique provides a means of harnessing the benefits of topical agents while monitoring the risk for ACD in postoperative and chronic wound care settings.

To the Editor:

Acne vulgaris and irritable bowel syndrome (IBS) are both associated with microbial dysbiosis and chronic inflammation.^1-3 While the prevalence of IBS among patients with acne has been examined previously,^4,5 there has been limited focus on the risk for new-onset IBS following acne diagnosis. Current evidence suggests isotretinoin may be associated with a lower risk for IBS compared to oral antibiotics⁶; however, evidence supporting this association is limited outside these cohorts, highlighting the need for further investigation. In this large-scale study, we sought to investigate the incidence of new-onset IBS among patients with acne compared with healthy controls as well as to evaluate whether oral acne treatments (ie, oral antibiotics or isotretinoin) are associated with new-onset IBS in this population.

A retrospective cohort study was conducted using data from the US Collaborative Network in TriNetX from October 2014 to October 2024. Patients were identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes, Current Procedural Terminology codes, Anatomical Therapeutic Chemical Classification System codes, and RxNorm codes (Table 1). These codes were selected based on prior literature review, clinical relevance, and their ability to capture diagnoses of acne and IBS as well as relevant exclusion criteria. Patients were considered eligible if they were between the ages of 18 and 90 years. Individuals with a history of IBS, inflammatory bowel disease, infectious gastroenteritis, or celiac disease were excluded from our analysis. 

To examine potential associations between acne and IBS, 2 primary cohorts were established: patients with acne who were managed without systemic medications and healthy controls (ie, patients with no history of acne) who had no exposure to systemic acne treatments (Figure). Further, to assess the relationship between oral acne treatments (macrolides, tetracyclines, isotretinoin) and IBS, additional cohorts were created for each therapy and were compared to a cohort of patients with acne who were managed without systemic medications. To control for potential concomitant treatments, patients who had received any systemic treatment other than the specific therapy for their treatment cohort were excluded from our analysis.

To account for potential confounders, all cohorts were 1:1 propensity score matched by demographics, tobacco and alcohol use, type 2 diabetes, obesity, anxiety, and depression (eTable). Each cohort was followed for 2 years after their index of event: the date of acne diagnosis for the acne cohort, the date of systemic treatment initiation for the treatment cohorts, and the date of the general adult encounter without abnormal findings for the control cohort. The primary outcome was the incidence of IBS, assessed by odds ratio (OR) and 95% CIs.

We identified 375,944 patients with acne managed without systemic treatment and 3,148,443 healthy controls who met study criteria. After the 1:1 propensity score match, each cohort included 49,690 patients (eTable). In the 2-year period after acne diagnosis, patients were more likely to develop IBS compared with controls (1421 vs 1285 [OR, 1.10; 95% CI, 1.02-1.19])(Table 2). Patients with acne who were treated with tetracyclines (n=208,971) were 30% more likely to develop IBS than those managed without systemic medications (1114 vs 856 [OR, 1.30; 95% CI, 1.19-1.42]). Within the tetracycline cohort, doxycycline-treated patients were 25% more likely to develop IBS compared with those treated with minocycline (213 vs 170 [OR, 1.25; 95% CI, 1.02-1.53]). Similarly, the use of macrolides (n=136,334) for acne treatment was significantly associated with an increased risk for IBS (1023 vs 595 [OR, 1.73; 95% CI, 1.57-1.92; P<.0001]) compared with controls. No statistically significant association was observed between isotretinoin and the incidence of IBS (Table 2).

In this large-scale cohort study, acne was associated with an increased likelihood of developing IBS within 2 years of an acne diagnosis compared with healthy controls. While a prior study also identified this association, it had a broader follow-up window ranging from 8 to 10 years.² In contrast, our analysis specifically quantified the risk within the first 2 years of diagnosis. This distinction suggested potential for earlier IBS onset in patients with acne than has previously been recognized and may serve as an early clinical indicator for IBS risk in this population. 

Our findings further suggested an association between oral tetracyclines and macrolides and an increased risk for IBS. This aligns with existing literature suggesting that oral antibiotic use can disrupt the gut microbiota and lead to potential gastrointestinal complications⁷ and reinforces the importance of careful antibiotic stewardship in dermatologic practice. 

Although isotretinoin initially was surrounded by substantial controversy regarding its potential impact on gut health—particularly in inflammatory bowel ­disease⁸—our results do not support an increased risk for IBS among patients with acne who use isotretinoin. These findings challenge previous concerns and align with research suggesting that isotretinoin could be a safer alternative to antibiotic use for eligible patients who have a history of gastrointestinal disorders.⁶

This study highlights an important but underrecognized link between acne and IBS risk, emphasizing the need for early monitoring of gastrointestinal symptoms and careful antibiotic stewardship in dermatologic practice. Gastroenterology consultation may be advisable for patients with acne who have persistent gastrointestinal symptoms to facilitate a more integrated, patient-centered approach to care.

Limitations of this study include potential misclassification of International Classification of Diseases, Tenth Revision, Clinical Modification codes, selection bias, and residual confounding from unmeasured factors such as diet, lifestyle, disease severity, and treatment adherence due to the reliance on electronic health record data.

Our findings build upon prior evidence linking acne and IBS and offer important insights into the timing of this association following acne diagnosis. Future research should explore biological mechanisms underlying the gut-skin axis and evaluate targeted interventions to mitigate IBS risk in patients with acne.

To the Editor:

Acne vulgaris and irritable bowel syndrome (IBS) are both associated with microbial dysbiosis and chronic inflammation.^1-3 While the prevalence of IBS among patients with acne has been examined previously,^4,5 there has been limited focus on the risk for new-onset IBS following acne diagnosis. Current evidence suggests isotretinoin may be associated with a lower risk for IBS compared to oral antibiotics⁶; however, evidence supporting this association is limited outside these cohorts, highlighting the need for further investigation. In this large-scale study, we sought to investigate the incidence of new-onset IBS among patients with acne compared with healthy controls as well as to evaluate whether oral acne treatments (ie, oral antibiotics or isotretinoin) are associated with new-onset IBS in this population.

A retrospective cohort study was conducted using data from the US Collaborative Network in TriNetX from October 2014 to October 2024. Patients were identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes, Current Procedural Terminology codes, Anatomical Therapeutic Chemical Classification System codes, and RxNorm codes (Table 1). These codes were selected based on prior literature review, clinical relevance, and their ability to capture diagnoses of acne and IBS as well as relevant exclusion criteria. Patients were considered eligible if they were between the ages of 18 and 90 years. Individuals with a history of IBS, inflammatory bowel disease, infectious gastroenteritis, or celiac disease were excluded from our analysis. 

To examine potential associations between acne and IBS, 2 primary cohorts were established: patients with acne who were managed without systemic medications and healthy controls (ie, patients with no history of acne) who had no exposure to systemic acne treatments (Figure). Further, to assess the relationship between oral acne treatments (macrolides, tetracyclines, isotretinoin) and IBS, additional cohorts were created for each therapy and were compared to a cohort of patients with acne who were managed without systemic medications. To control for potential concomitant treatments, patients who had received any systemic treatment other than the specific therapy for their treatment cohort were excluded from our analysis.

To account for potential confounders, all cohorts were 1:1 propensity score matched by demographics, tobacco and alcohol use, type 2 diabetes, obesity, anxiety, and depression (eTable). Each cohort was followed for 2 years after their index of event: the date of acne diagnosis for the acne cohort, the date of systemic treatment initiation for the treatment cohorts, and the date of the general adult encounter without abnormal findings for the control cohort. The primary outcome was the incidence of IBS, assessed by odds ratio (OR) and 95% CIs.

We identified 375,944 patients with acne managed without systemic treatment and 3,148,443 healthy controls who met study criteria. After the 1:1 propensity score match, each cohort included 49,690 patients (eTable). In the 2-year period after acne diagnosis, patients were more likely to develop IBS compared with controls (1421 vs 1285 [OR, 1.10; 95% CI, 1.02-1.19])(Table 2). Patients with acne who were treated with tetracyclines (n=208,971) were 30% more likely to develop IBS than those managed without systemic medications (1114 vs 856 [OR, 1.30; 95% CI, 1.19-1.42]). Within the tetracycline cohort, doxycycline-treated patients were 25% more likely to develop IBS compared with those treated with minocycline (213 vs 170 [OR, 1.25; 95% CI, 1.02-1.53]). Similarly, the use of macrolides (n=136,334) for acne treatment was significantly associated with an increased risk for IBS (1023 vs 595 [OR, 1.73; 95% CI, 1.57-1.92; P<.0001]) compared with controls. No statistically significant association was observed between isotretinoin and the incidence of IBS (Table 2).

In this large-scale cohort study, acne was associated with an increased likelihood of developing IBS within 2 years of an acne diagnosis compared with healthy controls. While a prior study also identified this association, it had a broader follow-up window ranging from 8 to 10 years.² In contrast, our analysis specifically quantified the risk within the first 2 years of diagnosis. This distinction suggested potential for earlier IBS onset in patients with acne than has previously been recognized and may serve as an early clinical indicator for IBS risk in this population. 

Our findings further suggested an association between oral tetracyclines and macrolides and an increased risk for IBS. This aligns with existing literature suggesting that oral antibiotic use can disrupt the gut microbiota and lead to potential gastrointestinal complications⁷ and reinforces the importance of careful antibiotic stewardship in dermatologic practice. 

Although isotretinoin initially was surrounded by substantial controversy regarding its potential impact on gut health—particularly in inflammatory bowel ­disease⁸—our results do not support an increased risk for IBS among patients with acne who use isotretinoin. These findings challenge previous concerns and align with research suggesting that isotretinoin could be a safer alternative to antibiotic use for eligible patients who have a history of gastrointestinal disorders.⁶

This study highlights an important but underrecognized link between acne and IBS risk, emphasizing the need for early monitoring of gastrointestinal symptoms and careful antibiotic stewardship in dermatologic practice. Gastroenterology consultation may be advisable for patients with acne who have persistent gastrointestinal symptoms to facilitate a more integrated, patient-centered approach to care.

Limitations of this study include potential misclassification of International Classification of Diseases, Tenth Revision, Clinical Modification codes, selection bias, and residual confounding from unmeasured factors such as diet, lifestyle, disease severity, and treatment adherence due to the reliance on electronic health record data.

Our findings build upon prior evidence linking acne and IBS and offer important insights into the timing of this association following acne diagnosis. Future research should explore biological mechanisms underlying the gut-skin axis and evaluate targeted interventions to mitigate IBS risk in patients with acne.

To the Editor:

Acne vulgaris and irritable bowel syndrome (IBS) are both associated with microbial dysbiosis and chronic inflammation.^1-3 While the prevalence of IBS among patients with acne has been examined previously,^4,5 there has been limited focus on the risk for new-onset IBS following acne diagnosis. Current evidence suggests isotretinoin may be associated with a lower risk for IBS compared to oral antibiotics⁶; however, evidence supporting this association is limited outside these cohorts, highlighting the need for further investigation. In this large-scale study, we sought to investigate the incidence of new-onset IBS among patients with acne compared with healthy controls as well as to evaluate whether oral acne treatments (ie, oral antibiotics or isotretinoin) are associated with new-onset IBS in this population.

A retrospective cohort study was conducted using data from the US Collaborative Network in TriNetX from October 2014 to October 2024. Patients were identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes, Current Procedural Terminology codes, Anatomical Therapeutic Chemical Classification System codes, and RxNorm codes (Table 1). These codes were selected based on prior literature review, clinical relevance, and their ability to capture diagnoses of acne and IBS as well as relevant exclusion criteria. Patients were considered eligible if they were between the ages of 18 and 90 years. Individuals with a history of IBS, inflammatory bowel disease, infectious gastroenteritis, or celiac disease were excluded from our analysis. 

To examine potential associations between acne and IBS, 2 primary cohorts were established: patients with acne who were managed without systemic medications and healthy controls (ie, patients with no history of acne) who had no exposure to systemic acne treatments (Figure). Further, to assess the relationship between oral acne treatments (macrolides, tetracyclines, isotretinoin) and IBS, additional cohorts were created for each therapy and were compared to a cohort of patients with acne who were managed without systemic medications. To control for potential concomitant treatments, patients who had received any systemic treatment other than the specific therapy for their treatment cohort were excluded from our analysis.

To account for potential confounders, all cohorts were 1:1 propensity score matched by demographics, tobacco and alcohol use, type 2 diabetes, obesity, anxiety, and depression (eTable). Each cohort was followed for 2 years after their index of event: the date of acne diagnosis for the acne cohort, the date of systemic treatment initiation for the treatment cohorts, and the date of the general adult encounter without abnormal findings for the control cohort. The primary outcome was the incidence of IBS, assessed by odds ratio (OR) and 95% CIs.

We identified 375,944 patients with acne managed without systemic treatment and 3,148,443 healthy controls who met study criteria. After the 1:1 propensity score match, each cohort included 49,690 patients (eTable). In the 2-year period after acne diagnosis, patients were more likely to develop IBS compared with controls (1421 vs 1285 [OR, 1.10; 95% CI, 1.02-1.19])(Table 2). Patients with acne who were treated with tetracyclines (n=208,971) were 30% more likely to develop IBS than those managed without systemic medications (1114 vs 856 [OR, 1.30; 95% CI, 1.19-1.42]). Within the tetracycline cohort, doxycycline-treated patients were 25% more likely to develop IBS compared with those treated with minocycline (213 vs 170 [OR, 1.25; 95% CI, 1.02-1.53]). Similarly, the use of macrolides (n=136,334) for acne treatment was significantly associated with an increased risk for IBS (1023 vs 595 [OR, 1.73; 95% CI, 1.57-1.92; P<.0001]) compared with controls. No statistically significant association was observed between isotretinoin and the incidence of IBS (Table 2).

In this large-scale cohort study, acne was associated with an increased likelihood of developing IBS within 2 years of an acne diagnosis compared with healthy controls. While a prior study also identified this association, it had a broader follow-up window ranging from 8 to 10 years.² In contrast, our analysis specifically quantified the risk within the first 2 years of diagnosis. This distinction suggested potential for earlier IBS onset in patients with acne than has previously been recognized and may serve as an early clinical indicator for IBS risk in this population. 

Our findings further suggested an association between oral tetracyclines and macrolides and an increased risk for IBS. This aligns with existing literature suggesting that oral antibiotic use can disrupt the gut microbiota and lead to potential gastrointestinal complications⁷ and reinforces the importance of careful antibiotic stewardship in dermatologic practice. 

Although isotretinoin initially was surrounded by substantial controversy regarding its potential impact on gut health—particularly in inflammatory bowel ­disease⁸—our results do not support an increased risk for IBS among patients with acne who use isotretinoin. These findings challenge previous concerns and align with research suggesting that isotretinoin could be a safer alternative to antibiotic use for eligible patients who have a history of gastrointestinal disorders.⁶

This study highlights an important but underrecognized link between acne and IBS risk, emphasizing the need for early monitoring of gastrointestinal symptoms and careful antibiotic stewardship in dermatologic practice. Gastroenterology consultation may be advisable for patients with acne who have persistent gastrointestinal symptoms to facilitate a more integrated, patient-centered approach to care.

Limitations of this study include potential misclassification of International Classification of Diseases, Tenth Revision, Clinical Modification codes, selection bias, and residual confounding from unmeasured factors such as diet, lifestyle, disease severity, and treatment adherence due to the reliance on electronic health record data.

Our findings build upon prior evidence linking acne and IBS and offer important insights into the timing of this association following acne diagnosis. Future research should explore biological mechanisms underlying the gut-skin axis and evaluate targeted interventions to mitigate IBS risk in patients with acne.