Cutis

To the Editor:

Immune checkpoint inhibitors such as anti–programmed cell death protein 1 (anti–PD-1) and anticytotoxic T lymphocyte–associated protein 4 therapies are a promising class of cancer therapeutics. However, they are associated with a variety of immune-related adverse events (irAEs), including cutaneous toxicity.¹ The PD-1/programmed death ligand 1 (PD-L1) pathway is important for the maintenance of immune tolerance, and a blockade has been shown to lead to development of various autoimmune diseases.² We present the case of a patient who developed new-onset localized scleroderma during treatment with the PD-1 inhibitor nivolumab.

A 65-year-old woman presented with a rash on the left thigh that was associated with pruritus, pain, and a pulling sensation. She had a history of stage IV lung adenocarcinoma, with a mass in the right upper lobe with metastatic foci to the left femur, right humerus, right hilar, and pretracheal lymph nodes. She received palliative radiation to the left femur and was started on carboplatin and pemetrexed. Metastasis to the liver was noted after completion of 6 cycles of therapy, and the patient’s treatment was changed to nivolumab. After 17 months on nivolumab therapy (2 years after initial diagnosis and 20 months after radiation therapy), she presented to our dermatology clinic with a cutaneous eruption on the buttocks that spread to the left thigh. The rash failed to improve after 1 month of treatment with emollients and triamcinolone cream 0.1%.

At the current presentation, which was 2 months after she initially presented to our clinic, dermatologic examination revealed erythematous and sclerotic plaques on the left lateral thigh (Figure 1A). Betamethasone cream 0.05% was prescribed, and nivolumab was discontinued due to progression of cutaneous symptoms. A punch biopsy from the left thigh demonstrated superficial dermal sclerosis that was suggestive of chronic radiation dermatitis; direct immunofluorescence testing was negative. The patient was started on prednisone 50 mg daily, which resulted in mild improvement in symptoms.

Within 6 months, new sclerotic plaques developed on the patient’s back and right thigh (Figure 1B). Because the lesions were located outside the radiation field of the left femur, a second biopsy was obtained from the right thigh. Histopathology revealed extensive dermal sclerosis and a perivascular lymphoplasmacytic infiltrate (Figure 2). An antinuclear antibody test was weakly positive (1:40, nucleolar pattern) with a negative extractable nuclear antigen panel result. Anti–double-stranded DNA, anti–topoisomerase 1, anti-Smith, antiribonucleoprotein, anti–Sjögren syndrome type A, anti–Sjögren syndrome type B, and anticentromere serology test results were negative. The patient denied decreased oral aperture, difficulty swallowing, or Raynaud phenomenon. Due to the atypical clinical presentation in the setting of PD-1 inhibitor therapy, the etiology of the eruption was potentially attributable to nivolumab. She was started on treatment with methotrexate 20 mg weekly and clobetasol cream 0.05% twice daily; she continued taking prednisone 5 mg daily. The cutaneous manifestations on the patient’s back completely resolved, and the legs continued to gradually improve on this regimen. Immunotherapy continued to be held due to skin toxicity.

Localized scleroderma is an autoimmune disorder characterized by inflammation and skin thickening. Overactive fibroblasts produce excess collagen, leading to the clinical symptoms of skin thickening, hardening, and discoloration.³ Lesions frequently develop on the arms, face, or legs and can present as patches or linear bands. Unlike systemic sclerosis, the internal organs typically are uninvolved; however, sclerotic lesions can be disfiguring and cause notable disability if they impede joint movement.

The PD-1/PD-L1 pathway is a negative regulator of the immune response that inactivates T cells and helps maintain self-tolerance. Modulation of the PD-1/PD-L1 pathway and overexpression of PD-L1 are seen in various cancers as a mechanism to help malignant cells avoid immune destruction.⁴ Conversely, inhibition of this pathway can be used to stimulate an antitumor immune response. This checkpoint inhibition strategy has been highly successful for the treatment of various cancers including melanoma and non–small cell lung carcinoma. There are several checkpoint inhibitors approved in the United States that are used for cancer therapy and target the PD-1/PD-L1 pathway, such as nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab.⁴ A downside of checkpoint inhibitor treatment is that uncontrolled T-cell activation can lead to irAEs, including cutaneous eruptions, pruritus, diarrhea, colitis, hepatitis, endocrinopathies, pneumonitis, and renal insufficiency.⁵ These toxicities are reversible if treated appropriately but can cause notable morbidity and mortality if left unrecognized. Cutaneous eruption is one of the most common irAEs associated with anti–PD-1 and anti–PD-L1 therapies and can limit therapeutic efficacy, as the drug may need to be held or discontinued due to the severity of the eruption.⁶ Mid-potency to high-potency topical corticosteroids and systemic antihistamines are first-line treatments of grades 1 and 2 skin toxicities associated with PD-1 inhibitor therapy. For eruptions classified as grades 3 or 4 or refractory grade 2, discontinuation of the drug and systemic corticosteroids is recommended.⁷

The cutaneous eruption in immunotherapy-mediated dermatitis is thought to be largely mediated by activated T cells infiltrating the dermis.⁸ In localized scleroderma, increased tumor necrosis factor α, IFN-γ, IFN-γ–induced protein 10, and granulocyte macrophage colony stimulating factor activity have been shown to correlate with disease activity.^9,10 Interestingly, increased tumor necrosis factor α and IFN-γ correlate with better response and increased overall survival in PD-1 inhibition therapy, suggesting a correlation between PD-1 inhibition and T helper activation as noted by the etiology of sclerosis in our patient.¹¹ Additionally, history of radiation was a confounding factor in the diagnosis of our patient, as both sclerodermoid reactions and chronic radiation dermatitis can present with dermal sclerosis. However, the progression of disease outside of the radiation field excluded this etiology. Although new-onset sclerodermoid reactions have been reported with PD-1 inhibitors, they have been described secondary to sclerodermoid reactions from treatment with pembrolizumab.^12,13 One case series reported a case of diffuse sclerodermoid reaction and a limited reaction in response to pembrolizumab treatment, while another case report described a relapse of generalized morphea in response to pembrolizumab treatment.^12,13 One case of relapsing morphea in response to nivolumab treatment for stage IV lung adenocarcinoma also has been reported.¹⁴

Cutaneous toxicities are one of the most common irAEs associated with checkpoint inhibitors and are seen in more than one-third of treated patients. Most frequently, these irAEs manifest as spongiotic dermatitis on histopathology, but a broad spectrum of cutaneous reactions have been observed.¹⁵ Although sclerodermoid reactions have been reported with PD-1 inhibitors, most are described secondary to sclerodermoid reactions with pembrolizumab and involve relapse of previously diagnosed morphea rather than new-onset disease.^12-14

Our case highlights new-onset localized scleroderma in the setting of nivolumab therapy that showed clinical improvement with methotrexate and topical and systemic steroids. This reaction pattern should be considered in all patients who develop cutaneous eruptions when treated with a PD-1 inhibitor. There should be a high index of suspicion for the potential occurrence of irAEs to ensure early recognition and treatment to minimize morbidity and maximize adherence to therapy for the underlying malignancy.

To the Editor:

Immune checkpoint inhibitors such as anti–programmed cell death protein 1 (anti–PD-1) and anticytotoxic T lymphocyte–associated protein 4 therapies are a promising class of cancer therapeutics. However, they are associated with a variety of immune-related adverse events (irAEs), including cutaneous toxicity.¹ The PD-1/programmed death ligand 1 (PD-L1) pathway is important for the maintenance of immune tolerance, and a blockade has been shown to lead to development of various autoimmune diseases.² We present the case of a patient who developed new-onset localized scleroderma during treatment with the PD-1 inhibitor nivolumab.

A 65-year-old woman presented with a rash on the left thigh that was associated with pruritus, pain, and a pulling sensation. She had a history of stage IV lung adenocarcinoma, with a mass in the right upper lobe with metastatic foci to the left femur, right humerus, right hilar, and pretracheal lymph nodes. She received palliative radiation to the left femur and was started on carboplatin and pemetrexed. Metastasis to the liver was noted after completion of 6 cycles of therapy, and the patient’s treatment was changed to nivolumab. After 17 months on nivolumab therapy (2 years after initial diagnosis and 20 months after radiation therapy), she presented to our dermatology clinic with a cutaneous eruption on the buttocks that spread to the left thigh. The rash failed to improve after 1 month of treatment with emollients and triamcinolone cream 0.1%.

At the current presentation, which was 2 months after she initially presented to our clinic, dermatologic examination revealed erythematous and sclerotic plaques on the left lateral thigh (Figure 1A). Betamethasone cream 0.05% was prescribed, and nivolumab was discontinued due to progression of cutaneous symptoms. A punch biopsy from the left thigh demonstrated superficial dermal sclerosis that was suggestive of chronic radiation dermatitis; direct immunofluorescence testing was negative. The patient was started on prednisone 50 mg daily, which resulted in mild improvement in symptoms.

Within 6 months, new sclerotic plaques developed on the patient’s back and right thigh (Figure 1B). Because the lesions were located outside the radiation field of the left femur, a second biopsy was obtained from the right thigh. Histopathology revealed extensive dermal sclerosis and a perivascular lymphoplasmacytic infiltrate (Figure 2). An antinuclear antibody test was weakly positive (1:40, nucleolar pattern) with a negative extractable nuclear antigen panel result. Anti–double-stranded DNA, anti–topoisomerase 1, anti-Smith, antiribonucleoprotein, anti–Sjögren syndrome type A, anti–Sjögren syndrome type B, and anticentromere serology test results were negative. The patient denied decreased oral aperture, difficulty swallowing, or Raynaud phenomenon. Due to the atypical clinical presentation in the setting of PD-1 inhibitor therapy, the etiology of the eruption was potentially attributable to nivolumab. She was started on treatment with methotrexate 20 mg weekly and clobetasol cream 0.05% twice daily; she continued taking prednisone 5 mg daily. The cutaneous manifestations on the patient’s back completely resolved, and the legs continued to gradually improve on this regimen. Immunotherapy continued to be held due to skin toxicity.

Localized scleroderma is an autoimmune disorder characterized by inflammation and skin thickening. Overactive fibroblasts produce excess collagen, leading to the clinical symptoms of skin thickening, hardening, and discoloration.³ Lesions frequently develop on the arms, face, or legs and can present as patches or linear bands. Unlike systemic sclerosis, the internal organs typically are uninvolved; however, sclerotic lesions can be disfiguring and cause notable disability if they impede joint movement.

The PD-1/PD-L1 pathway is a negative regulator of the immune response that inactivates T cells and helps maintain self-tolerance. Modulation of the PD-1/PD-L1 pathway and overexpression of PD-L1 are seen in various cancers as a mechanism to help malignant cells avoid immune destruction.⁴ Conversely, inhibition of this pathway can be used to stimulate an antitumor immune response. This checkpoint inhibition strategy has been highly successful for the treatment of various cancers including melanoma and non–small cell lung carcinoma. There are several checkpoint inhibitors approved in the United States that are used for cancer therapy and target the PD-1/PD-L1 pathway, such as nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab.⁴ A downside of checkpoint inhibitor treatment is that uncontrolled T-cell activation can lead to irAEs, including cutaneous eruptions, pruritus, diarrhea, colitis, hepatitis, endocrinopathies, pneumonitis, and renal insufficiency.⁵ These toxicities are reversible if treated appropriately but can cause notable morbidity and mortality if left unrecognized. Cutaneous eruption is one of the most common irAEs associated with anti–PD-1 and anti–PD-L1 therapies and can limit therapeutic efficacy, as the drug may need to be held or discontinued due to the severity of the eruption.⁶ Mid-potency to high-potency topical corticosteroids and systemic antihistamines are first-line treatments of grades 1 and 2 skin toxicities associated with PD-1 inhibitor therapy. For eruptions classified as grades 3 or 4 or refractory grade 2, discontinuation of the drug and systemic corticosteroids is recommended.⁷

The cutaneous eruption in immunotherapy-mediated dermatitis is thought to be largely mediated by activated T cells infiltrating the dermis.⁸ In localized scleroderma, increased tumor necrosis factor α, IFN-γ, IFN-γ–induced protein 10, and granulocyte macrophage colony stimulating factor activity have been shown to correlate with disease activity.^9,10 Interestingly, increased tumor necrosis factor α and IFN-γ correlate with better response and increased overall survival in PD-1 inhibition therapy, suggesting a correlation between PD-1 inhibition and T helper activation as noted by the etiology of sclerosis in our patient.¹¹ Additionally, history of radiation was a confounding factor in the diagnosis of our patient, as both sclerodermoid reactions and chronic radiation dermatitis can present with dermal sclerosis. However, the progression of disease outside of the radiation field excluded this etiology. Although new-onset sclerodermoid reactions have been reported with PD-1 inhibitors, they have been described secondary to sclerodermoid reactions from treatment with pembrolizumab.^12,13 One case series reported a case of diffuse sclerodermoid reaction and a limited reaction in response to pembrolizumab treatment, while another case report described a relapse of generalized morphea in response to pembrolizumab treatment.^12,13 One case of relapsing morphea in response to nivolumab treatment for stage IV lung adenocarcinoma also has been reported.¹⁴

Cutaneous toxicities are one of the most common irAEs associated with checkpoint inhibitors and are seen in more than one-third of treated patients. Most frequently, these irAEs manifest as spongiotic dermatitis on histopathology, but a broad spectrum of cutaneous reactions have been observed.¹⁵ Although sclerodermoid reactions have been reported with PD-1 inhibitors, most are described secondary to sclerodermoid reactions with pembrolizumab and involve relapse of previously diagnosed morphea rather than new-onset disease.^12-14

Our case highlights new-onset localized scleroderma in the setting of nivolumab therapy that showed clinical improvement with methotrexate and topical and systemic steroids. This reaction pattern should be considered in all patients who develop cutaneous eruptions when treated with a PD-1 inhibitor. There should be a high index of suspicion for the potential occurrence of irAEs to ensure early recognition and treatment to minimize morbidity and maximize adherence to therapy for the underlying malignancy.

To the Editor:

Immune checkpoint inhibitors such as anti–programmed cell death protein 1 (anti–PD-1) and anticytotoxic T lymphocyte–associated protein 4 therapies are a promising class of cancer therapeutics. However, they are associated with a variety of immune-related adverse events (irAEs), including cutaneous toxicity.¹ The PD-1/programmed death ligand 1 (PD-L1) pathway is important for the maintenance of immune tolerance, and a blockade has been shown to lead to development of various autoimmune diseases.² We present the case of a patient who developed new-onset localized scleroderma during treatment with the PD-1 inhibitor nivolumab.

A 65-year-old woman presented with a rash on the left thigh that was associated with pruritus, pain, and a pulling sensation. She had a history of stage IV lung adenocarcinoma, with a mass in the right upper lobe with metastatic foci to the left femur, right humerus, right hilar, and pretracheal lymph nodes. She received palliative radiation to the left femur and was started on carboplatin and pemetrexed. Metastasis to the liver was noted after completion of 6 cycles of therapy, and the patient’s treatment was changed to nivolumab. After 17 months on nivolumab therapy (2 years after initial diagnosis and 20 months after radiation therapy), she presented to our dermatology clinic with a cutaneous eruption on the buttocks that spread to the left thigh. The rash failed to improve after 1 month of treatment with emollients and triamcinolone cream 0.1%.

At the current presentation, which was 2 months after she initially presented to our clinic, dermatologic examination revealed erythematous and sclerotic plaques on the left lateral thigh (Figure 1A). Betamethasone cream 0.05% was prescribed, and nivolumab was discontinued due to progression of cutaneous symptoms. A punch biopsy from the left thigh demonstrated superficial dermal sclerosis that was suggestive of chronic radiation dermatitis; direct immunofluorescence testing was negative. The patient was started on prednisone 50 mg daily, which resulted in mild improvement in symptoms.

Within 6 months, new sclerotic plaques developed on the patient’s back and right thigh (Figure 1B). Because the lesions were located outside the radiation field of the left femur, a second biopsy was obtained from the right thigh. Histopathology revealed extensive dermal sclerosis and a perivascular lymphoplasmacytic infiltrate (Figure 2). An antinuclear antibody test was weakly positive (1:40, nucleolar pattern) with a negative extractable nuclear antigen panel result. Anti–double-stranded DNA, anti–topoisomerase 1, anti-Smith, antiribonucleoprotein, anti–Sjögren syndrome type A, anti–Sjögren syndrome type B, and anticentromere serology test results were negative. The patient denied decreased oral aperture, difficulty swallowing, or Raynaud phenomenon. Due to the atypical clinical presentation in the setting of PD-1 inhibitor therapy, the etiology of the eruption was potentially attributable to nivolumab. She was started on treatment with methotrexate 20 mg weekly and clobetasol cream 0.05% twice daily; she continued taking prednisone 5 mg daily. The cutaneous manifestations on the patient’s back completely resolved, and the legs continued to gradually improve on this regimen. Immunotherapy continued to be held due to skin toxicity.

Localized scleroderma is an autoimmune disorder characterized by inflammation and skin thickening. Overactive fibroblasts produce excess collagen, leading to the clinical symptoms of skin thickening, hardening, and discoloration.³ Lesions frequently develop on the arms, face, or legs and can present as patches or linear bands. Unlike systemic sclerosis, the internal organs typically are uninvolved; however, sclerotic lesions can be disfiguring and cause notable disability if they impede joint movement.

The PD-1/PD-L1 pathway is a negative regulator of the immune response that inactivates T cells and helps maintain self-tolerance. Modulation of the PD-1/PD-L1 pathway and overexpression of PD-L1 are seen in various cancers as a mechanism to help malignant cells avoid immune destruction.⁴ Conversely, inhibition of this pathway can be used to stimulate an antitumor immune response. This checkpoint inhibition strategy has been highly successful for the treatment of various cancers including melanoma and non–small cell lung carcinoma. There are several checkpoint inhibitors approved in the United States that are used for cancer therapy and target the PD-1/PD-L1 pathway, such as nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab.⁴ A downside of checkpoint inhibitor treatment is that uncontrolled T-cell activation can lead to irAEs, including cutaneous eruptions, pruritus, diarrhea, colitis, hepatitis, endocrinopathies, pneumonitis, and renal insufficiency.⁵ These toxicities are reversible if treated appropriately but can cause notable morbidity and mortality if left unrecognized. Cutaneous eruption is one of the most common irAEs associated with anti–PD-1 and anti–PD-L1 therapies and can limit therapeutic efficacy, as the drug may need to be held or discontinued due to the severity of the eruption.⁶ Mid-potency to high-potency topical corticosteroids and systemic antihistamines are first-line treatments of grades 1 and 2 skin toxicities associated with PD-1 inhibitor therapy. For eruptions classified as grades 3 or 4 or refractory grade 2, discontinuation of the drug and systemic corticosteroids is recommended.⁷

The cutaneous eruption in immunotherapy-mediated dermatitis is thought to be largely mediated by activated T cells infiltrating the dermis.⁸ In localized scleroderma, increased tumor necrosis factor α, IFN-γ, IFN-γ–induced protein 10, and granulocyte macrophage colony stimulating factor activity have been shown to correlate with disease activity.^9,10 Interestingly, increased tumor necrosis factor α and IFN-γ correlate with better response and increased overall survival in PD-1 inhibition therapy, suggesting a correlation between PD-1 inhibition and T helper activation as noted by the etiology of sclerosis in our patient.¹¹ Additionally, history of radiation was a confounding factor in the diagnosis of our patient, as both sclerodermoid reactions and chronic radiation dermatitis can present with dermal sclerosis. However, the progression of disease outside of the radiation field excluded this etiology. Although new-onset sclerodermoid reactions have been reported with PD-1 inhibitors, they have been described secondary to sclerodermoid reactions from treatment with pembrolizumab.^12,13 One case series reported a case of diffuse sclerodermoid reaction and a limited reaction in response to pembrolizumab treatment, while another case report described a relapse of generalized morphea in response to pembrolizumab treatment.^12,13 One case of relapsing morphea in response to nivolumab treatment for stage IV lung adenocarcinoma also has been reported.¹⁴

Cutaneous toxicities are one of the most common irAEs associated with checkpoint inhibitors and are seen in more than one-third of treated patients. Most frequently, these irAEs manifest as spongiotic dermatitis on histopathology, but a broad spectrum of cutaneous reactions have been observed.¹⁵ Although sclerodermoid reactions have been reported with PD-1 inhibitors, most are described secondary to sclerodermoid reactions with pembrolizumab and involve relapse of previously diagnosed morphea rather than new-onset disease.^12-14

Our case highlights new-onset localized scleroderma in the setting of nivolumab therapy that showed clinical improvement with methotrexate and topical and systemic steroids. This reaction pattern should be considered in all patients who develop cutaneous eruptions when treated with a PD-1 inhibitor. There should be a high index of suspicion for the potential occurrence of irAEs to ensure early recognition and treatment to minimize morbidity and maximize adherence to therapy for the underlying malignancy.

The transition from medical school to residency is a rewarding milestone but involves a steep learning curve wrought with new responsibilities, new colleagues, and a new schedule, often all within a new setting. This transition period has been a longstanding focus of graduate medical education research, and a recent study identified 6 key areas that residency programs need to address to better facilitate this transition: (1) a sense of community within the residency program, (2) relocation resources, (3) residency preparation courses in medical school, (4) readiness to address racism and bias, (5) connecting with peers, and (6) open communication with program leadership.¹ There is considerable interest in ensuring that this transition is smooth for all graduates, as nearly all US medical schools feature some variety of a residency preparation course during the fourth year of medical school, which, alongside the subinternships, serves to better prepare their graduates for the healthcare workforce.²

What about the transition from intern to dermatology resident? Near the end of intern year, my categorical medicine colleagues experienced a crescendo of responsibilities, all in preparation for junior year. The senior medicine residents, themselves having previously experienced the graduated responsibilities, knew to ease their grip on the reins and provide the late spring interns an opportunity to lead rounds or run a code. This was not the case for the preliminary interns for whom there was no preview available for what was to come; little guidance exists on how to best transform from a preliminary or transitional postgraduate year (PGY) 1 to a dermatology PGY-2. A survey of 44 dermatology residents and 33 dermatology program directors found electives such as rheumatology, infectious diseases, and allergy and immunology to be helpful for this transition, and residents most often cited friendly and supportive senior and fellow residents as the factor that eased their transition to PGY-2.³ Notably, less than half of the residents (40%) surveyed stated that team-building exercises and dedicated time to meet colleagues were helpful for this transition. They identified studying principles of dermatologic disease, learning new clinical duties, and adjusting to new coworkers and supervisors as the greatest work-related stressors during entry to PGY-2.³

My transition from intern year to dermatology was shrouded in uncertainty, and I was fortunate to have supportive seniors and co-residents to ease the process. There is much about starting dermatology residency that cannot be prepared for by reading a book, and a natural metamorphosis into the new role is hard to articulate. Still, the following are pieces of information I wish I knew as a graduating intern, which I hope will prove useful for those graduating to their PGY-2 dermatology year.

The Pace of Outpatient Dermatology

If the preliminary or transitional year did not have an ambulatory component, the switch from wards to clinic can be jarring. An outpatient encounter can be as short as 10 to 15 minutes, necessitating an efficient interview and examination to avoid a backup of patients. Unlike a hospital admission where the history of present illness can expound on multiple concerns and organ systems, the general dermatology visit must focus on the chief concern, with priority given to the clinical examination of the skin. For total-body skin examinations, a formulaic approach to assessing all areas of the body, with fluent transitions and minimal repositioning of the patient, is critical for patient comfort and to save time. Of course, accuracy and thoroughness are paramount, but the constant mindfulness of time and efficiency is uniquely emphasized in the outpatient setting.

Continuity of Care

On the wards, patients are admitted with an acute problem and discharged with the aim to prevent re-admission. However, in the dermatology clinic, the conditions encountered often are chronic, requiring repeated follow-ups that involve dosage tapers, laboratory monitoring, and trial and error. Unlike the rigid algorithm-based treatments utilized in the inpatient setting, the management of the same chronic disease can vary, as it is tailored to the patient based on their comorbidities and response. This longitudinal relationship with patients, whereby many disorders are managed rather than treated, stands in stark contrast to inpatient medicine, and learning to value symptom management rather than focusing on a cure is critical in a largely outpatient specialty such as dermatology.

Consulter to Consultant

Calling a consultation as an intern is challenging and requires succinct delivery of pertinent information while fearing pushback from the consultant. In a survey of 50 hospitalist attendings, only 11% responded that interns could be entrusted to call an effective consultation without supervision.⁴ When undertaking the role of a consultant, the goals should be to identify the team’s main question and to obtain key information necessary to formulate a differential diagnosis. The quality of the consultation will inevitably fluctuate; try to remember what it was like for you as a member of the primary team and remain patient and courteous during the exchange.⁵ In 1983, Goldman et al⁶ published a guideline on effective consultations that often is cited to this day, dubbed the “Ten Commandments for Effective Consultations,” which consists of the following: (1) determine the question that is being asked, (2) establish the urgency of the consultation, (3) gather primary data, (4) communicate as briefly as appropriate, (5) make specific recommendations, (6) provide contingency plans, (7) understand your own role in the process, (8) offer educational information, (9) communicate recommendations directly to the requesting physician, and (10) provide appropriate follow-up.

Consider Your Future

Frequently reflect on what you most enjoy about your job. Although it can be easy to passively engage with intern year as a mere stepping-stone to dermatology residency, the years in PGY-2 and onward require active introspection to find a future niche. What made you gravitate to the specialty of dermatology? Try to identify your predilections for dermatopathology, pediatric dermatology, dermatologic surgery, cosmetic dermatology, and academia. Be consistently cognizant of your life after residency, as some fellowships such as dermatopathology require applications to be submitted at the conclusion of the PGY-2 year. Seek out faculty mentors or alumni who are walking a path similar to the one you want to embark on, as the next stop after graduation may be your forever job.

Depth, Not Breadth

The practice of medicine changes when narrowing the focus to one organ system. In both medical school and intern year, my study habits and history-taking of patients cast a wide net across multiple organ systems, aiming to know just enough about any one specialty to address all chief concerns and to know when it was appropriate to consult a specialist. This paradigm inevitably shifts in dermatology residency, as residents are tasked with memorizing the endless number of diagnoses of the skin alone, comprehending the many shades of “erythematous,” including pink, salmon, red, and purple. Both on the wards and in clinics, I had to grow comfortable with telling patients that I did not have an answer for many of their nondermatologic concerns and directing them to the right specialist. As medicine continues trending to specialization, subspecialization, and sub-subspecialization, the scope of any given physician likely will continue to narrow,⁷ as evidenced by specialty clinics within dermatology such as those focusing on hair loss or immunobullous disease. In this health care system, it is imperative to remember that you are only one physician within a team of care providers—understand your own role in the process and become comfortable with not having the answer to all the questions.

Final Thoughts

In a study of 44 dermatology residents, 35 (83%) indicated zero to less than 1 hour per week of independent preparation for dermatology residency during PGY-1.³ Although the usefulness of preparing is debatable, this figure likely reflects the absence of any insight on how to best prepare for the transition. Recognizing the many contrasts between internal medicine and dermatology and embracing the changes will enable a seamless promotion from a medicine PGY-1 to a dermatology PGY-2.

The transition from medical school to residency is a rewarding milestone but involves a steep learning curve wrought with new responsibilities, new colleagues, and a new schedule, often all within a new setting. This transition period has been a longstanding focus of graduate medical education research, and a recent study identified 6 key areas that residency programs need to address to better facilitate this transition: (1) a sense of community within the residency program, (2) relocation resources, (3) residency preparation courses in medical school, (4) readiness to address racism and bias, (5) connecting with peers, and (6) open communication with program leadership.¹ There is considerable interest in ensuring that this transition is smooth for all graduates, as nearly all US medical schools feature some variety of a residency preparation course during the fourth year of medical school, which, alongside the subinternships, serves to better prepare their graduates for the healthcare workforce.²

What about the transition from intern to dermatology resident? Near the end of intern year, my categorical medicine colleagues experienced a crescendo of responsibilities, all in preparation for junior year. The senior medicine residents, themselves having previously experienced the graduated responsibilities, knew to ease their grip on the reins and provide the late spring interns an opportunity to lead rounds or run a code. This was not the case for the preliminary interns for whom there was no preview available for what was to come; little guidance exists on how to best transform from a preliminary or transitional postgraduate year (PGY) 1 to a dermatology PGY-2. A survey of 44 dermatology residents and 33 dermatology program directors found electives such as rheumatology, infectious diseases, and allergy and immunology to be helpful for this transition, and residents most often cited friendly and supportive senior and fellow residents as the factor that eased their transition to PGY-2.³ Notably, less than half of the residents (40%) surveyed stated that team-building exercises and dedicated time to meet colleagues were helpful for this transition. They identified studying principles of dermatologic disease, learning new clinical duties, and adjusting to new coworkers and supervisors as the greatest work-related stressors during entry to PGY-2.³

My transition from intern year to dermatology was shrouded in uncertainty, and I was fortunate to have supportive seniors and co-residents to ease the process. There is much about starting dermatology residency that cannot be prepared for by reading a book, and a natural metamorphosis into the new role is hard to articulate. Still, the following are pieces of information I wish I knew as a graduating intern, which I hope will prove useful for those graduating to their PGY-2 dermatology year.

The Pace of Outpatient Dermatology

If the preliminary or transitional year did not have an ambulatory component, the switch from wards to clinic can be jarring. An outpatient encounter can be as short as 10 to 15 minutes, necessitating an efficient interview and examination to avoid a backup of patients. Unlike a hospital admission where the history of present illness can expound on multiple concerns and organ systems, the general dermatology visit must focus on the chief concern, with priority given to the clinical examination of the skin. For total-body skin examinations, a formulaic approach to assessing all areas of the body, with fluent transitions and minimal repositioning of the patient, is critical for patient comfort and to save time. Of course, accuracy and thoroughness are paramount, but the constant mindfulness of time and efficiency is uniquely emphasized in the outpatient setting.

Continuity of Care

On the wards, patients are admitted with an acute problem and discharged with the aim to prevent re-admission. However, in the dermatology clinic, the conditions encountered often are chronic, requiring repeated follow-ups that involve dosage tapers, laboratory monitoring, and trial and error. Unlike the rigid algorithm-based treatments utilized in the inpatient setting, the management of the same chronic disease can vary, as it is tailored to the patient based on their comorbidities and response. This longitudinal relationship with patients, whereby many disorders are managed rather than treated, stands in stark contrast to inpatient medicine, and learning to value symptom management rather than focusing on a cure is critical in a largely outpatient specialty such as dermatology.

Consulter to Consultant

Calling a consultation as an intern is challenging and requires succinct delivery of pertinent information while fearing pushback from the consultant. In a survey of 50 hospitalist attendings, only 11% responded that interns could be entrusted to call an effective consultation without supervision.⁴ When undertaking the role of a consultant, the goals should be to identify the team’s main question and to obtain key information necessary to formulate a differential diagnosis. The quality of the consultation will inevitably fluctuate; try to remember what it was like for you as a member of the primary team and remain patient and courteous during the exchange.⁵ In 1983, Goldman et al⁶ published a guideline on effective consultations that often is cited to this day, dubbed the “Ten Commandments for Effective Consultations,” which consists of the following: (1) determine the question that is being asked, (2) establish the urgency of the consultation, (3) gather primary data, (4) communicate as briefly as appropriate, (5) make specific recommendations, (6) provide contingency plans, (7) understand your own role in the process, (8) offer educational information, (9) communicate recommendations directly to the requesting physician, and (10) provide appropriate follow-up.

Consider Your Future

Frequently reflect on what you most enjoy about your job. Although it can be easy to passively engage with intern year as a mere stepping-stone to dermatology residency, the years in PGY-2 and onward require active introspection to find a future niche. What made you gravitate to the specialty of dermatology? Try to identify your predilections for dermatopathology, pediatric dermatology, dermatologic surgery, cosmetic dermatology, and academia. Be consistently cognizant of your life after residency, as some fellowships such as dermatopathology require applications to be submitted at the conclusion of the PGY-2 year. Seek out faculty mentors or alumni who are walking a path similar to the one you want to embark on, as the next stop after graduation may be your forever job.

Depth, Not Breadth

The practice of medicine changes when narrowing the focus to one organ system. In both medical school and intern year, my study habits and history-taking of patients cast a wide net across multiple organ systems, aiming to know just enough about any one specialty to address all chief concerns and to know when it was appropriate to consult a specialist. This paradigm inevitably shifts in dermatology residency, as residents are tasked with memorizing the endless number of diagnoses of the skin alone, comprehending the many shades of “erythematous,” including pink, salmon, red, and purple. Both on the wards and in clinics, I had to grow comfortable with telling patients that I did not have an answer for many of their nondermatologic concerns and directing them to the right specialist. As medicine continues trending to specialization, subspecialization, and sub-subspecialization, the scope of any given physician likely will continue to narrow,⁷ as evidenced by specialty clinics within dermatology such as those focusing on hair loss or immunobullous disease. In this health care system, it is imperative to remember that you are only one physician within a team of care providers—understand your own role in the process and become comfortable with not having the answer to all the questions.

Final Thoughts

In a study of 44 dermatology residents, 35 (83%) indicated zero to less than 1 hour per week of independent preparation for dermatology residency during PGY-1.³ Although the usefulness of preparing is debatable, this figure likely reflects the absence of any insight on how to best prepare for the transition. Recognizing the many contrasts between internal medicine and dermatology and embracing the changes will enable a seamless promotion from a medicine PGY-1 to a dermatology PGY-2.

The transition from medical school to residency is a rewarding milestone but involves a steep learning curve wrought with new responsibilities, new colleagues, and a new schedule, often all within a new setting. This transition period has been a longstanding focus of graduate medical education research, and a recent study identified 6 key areas that residency programs need to address to better facilitate this transition: (1) a sense of community within the residency program, (2) relocation resources, (3) residency preparation courses in medical school, (4) readiness to address racism and bias, (5) connecting with peers, and (6) open communication with program leadership.¹ There is considerable interest in ensuring that this transition is smooth for all graduates, as nearly all US medical schools feature some variety of a residency preparation course during the fourth year of medical school, which, alongside the subinternships, serves to better prepare their graduates for the healthcare workforce.²

What about the transition from intern to dermatology resident? Near the end of intern year, my categorical medicine colleagues experienced a crescendo of responsibilities, all in preparation for junior year. The senior medicine residents, themselves having previously experienced the graduated responsibilities, knew to ease their grip on the reins and provide the late spring interns an opportunity to lead rounds or run a code. This was not the case for the preliminary interns for whom there was no preview available for what was to come; little guidance exists on how to best transform from a preliminary or transitional postgraduate year (PGY) 1 to a dermatology PGY-2. A survey of 44 dermatology residents and 33 dermatology program directors found electives such as rheumatology, infectious diseases, and allergy and immunology to be helpful for this transition, and residents most often cited friendly and supportive senior and fellow residents as the factor that eased their transition to PGY-2.³ Notably, less than half of the residents (40%) surveyed stated that team-building exercises and dedicated time to meet colleagues were helpful for this transition. They identified studying principles of dermatologic disease, learning new clinical duties, and adjusting to new coworkers and supervisors as the greatest work-related stressors during entry to PGY-2.³

My transition from intern year to dermatology was shrouded in uncertainty, and I was fortunate to have supportive seniors and co-residents to ease the process. There is much about starting dermatology residency that cannot be prepared for by reading a book, and a natural metamorphosis into the new role is hard to articulate. Still, the following are pieces of information I wish I knew as a graduating intern, which I hope will prove useful for those graduating to their PGY-2 dermatology year.

The Pace of Outpatient Dermatology

If the preliminary or transitional year did not have an ambulatory component, the switch from wards to clinic can be jarring. An outpatient encounter can be as short as 10 to 15 minutes, necessitating an efficient interview and examination to avoid a backup of patients. Unlike a hospital admission where the history of present illness can expound on multiple concerns and organ systems, the general dermatology visit must focus on the chief concern, with priority given to the clinical examination of the skin. For total-body skin examinations, a formulaic approach to assessing all areas of the body, with fluent transitions and minimal repositioning of the patient, is critical for patient comfort and to save time. Of course, accuracy and thoroughness are paramount, but the constant mindfulness of time and efficiency is uniquely emphasized in the outpatient setting.

Continuity of Care

On the wards, patients are admitted with an acute problem and discharged with the aim to prevent re-admission. However, in the dermatology clinic, the conditions encountered often are chronic, requiring repeated follow-ups that involve dosage tapers, laboratory monitoring, and trial and error. Unlike the rigid algorithm-based treatments utilized in the inpatient setting, the management of the same chronic disease can vary, as it is tailored to the patient based on their comorbidities and response. This longitudinal relationship with patients, whereby many disorders are managed rather than treated, stands in stark contrast to inpatient medicine, and learning to value symptom management rather than focusing on a cure is critical in a largely outpatient specialty such as dermatology.

Consulter to Consultant

Calling a consultation as an intern is challenging and requires succinct delivery of pertinent information while fearing pushback from the consultant. In a survey of 50 hospitalist attendings, only 11% responded that interns could be entrusted to call an effective consultation without supervision.⁴ When undertaking the role of a consultant, the goals should be to identify the team’s main question and to obtain key information necessary to formulate a differential diagnosis. The quality of the consultation will inevitably fluctuate; try to remember what it was like for you as a member of the primary team and remain patient and courteous during the exchange.⁵ In 1983, Goldman et al⁶ published a guideline on effective consultations that often is cited to this day, dubbed the “Ten Commandments for Effective Consultations,” which consists of the following: (1) determine the question that is being asked, (2) establish the urgency of the consultation, (3) gather primary data, (4) communicate as briefly as appropriate, (5) make specific recommendations, (6) provide contingency plans, (7) understand your own role in the process, (8) offer educational information, (9) communicate recommendations directly to the requesting physician, and (10) provide appropriate follow-up.

Consider Your Future

Frequently reflect on what you most enjoy about your job. Although it can be easy to passively engage with intern year as a mere stepping-stone to dermatology residency, the years in PGY-2 and onward require active introspection to find a future niche. What made you gravitate to the specialty of dermatology? Try to identify your predilections for dermatopathology, pediatric dermatology, dermatologic surgery, cosmetic dermatology, and academia. Be consistently cognizant of your life after residency, as some fellowships such as dermatopathology require applications to be submitted at the conclusion of the PGY-2 year. Seek out faculty mentors or alumni who are walking a path similar to the one you want to embark on, as the next stop after graduation may be your forever job.

Depth, Not Breadth

The practice of medicine changes when narrowing the focus to one organ system. In both medical school and intern year, my study habits and history-taking of patients cast a wide net across multiple organ systems, aiming to know just enough about any one specialty to address all chief concerns and to know when it was appropriate to consult a specialist. This paradigm inevitably shifts in dermatology residency, as residents are tasked with memorizing the endless number of diagnoses of the skin alone, comprehending the many shades of “erythematous,” including pink, salmon, red, and purple. Both on the wards and in clinics, I had to grow comfortable with telling patients that I did not have an answer for many of their nondermatologic concerns and directing them to the right specialist. As medicine continues trending to specialization, subspecialization, and sub-subspecialization, the scope of any given physician likely will continue to narrow,⁷ as evidenced by specialty clinics within dermatology such as those focusing on hair loss or immunobullous disease. In this health care system, it is imperative to remember that you are only one physician within a team of care providers—understand your own role in the process and become comfortable with not having the answer to all the questions.

Final Thoughts

In a study of 44 dermatology residents, 35 (83%) indicated zero to less than 1 hour per week of independent preparation for dermatology residency during PGY-1.³ Although the usefulness of preparing is debatable, this figure likely reflects the absence of any insight on how to best prepare for the transition. Recognizing the many contrasts between internal medicine and dermatology and embracing the changes will enable a seamless promotion from a medicine PGY-1 to a dermatology PGY-2.

To the Editor:

Calcium hydroxylapatite is an injectable filler approved by the US Food and Drug Administration for moderate to severe rhytides of the face and the treatment of facial lipodystrophy in patients with HIV.¹ This long-lasting filler generally is well tolerated with minimal side effects; however, there have been reports of nodules or granulomatous formation following injection.² We present a case of a migrating nodule following injection of a calcium hydroxylapatite filler that appeared ossified on radiographic imaging. We highlight this rarely reported phenomenon to increase awareness of this complication.

A 72-year-old woman presented to our clinic with a mass on the left cheek. The patient had a history of treatment with facial fillers but no notable medical conditions. She initially received hyaluronic acid injectable gel dermal filler twice—3 years apart—before switching to calcium hydroxylapatite injections twice—4 months apart—from an outside provider. One month after the second treatment, she noticed a mass on the left cheek and promptly returned to the provider who performed the calcium hydroxylapatite injections. The provider, who had originally injected in the infraorbital area, stated it was unlikely that the filler would have migrated to the mid cheek and referred the patient to a general dentist who suspected salivary gland pathology. The patient was referred to an oral and maxillofacial surgeon who suspected the mass was related to the parotid gland. Maxillofacial computed tomography (CT) revealed heterotopic ossification vs myositis ossificans, possibly related to the recent injection. The patient was eventually referred to the Division of Plastic Surgery, Department of Surgery, at the University of Texas Medical Branch (Galveston, Texas) for further evaluation. Physical examination revealed a 2×1-cm firm, mobile, nontender mass in the left cheek in the area of the buccinator muscles. The mass did not express any fluid and was most easily palpable from the oral cavity. Radiography findings showed that the calcium hydroxylapatite filler had migrated to this location and formed a nodule (Figure). Because calcium hydroxylapatite fillers generally last 12 to 18 months, we opted to observe the lesion for spontaneous resolution. Four months later, the patient presented to our clinic for follow-up and the mass had reduced in size and appeared to be spontaneously resolving.

We present a unique case of a migrating nodule that occurred after injection with calcium hydroxylapatite, which led to concern for neoplastic tumor formation. This complication is rare, and it is important for practitioners who inject calcium hydroxylapatite as well as those who these patients may be referred to for evaluation to be aware that migrating nodules can occur. This awareness can help reduce unnecessary referrals, medical procedures, and anxiety.

Calcium hydroxylapatite filler is composed of 30% calcium hydroxylapatite microspheres suspended in a 70% sodium carboxymethylcellulose gel. The water-soluble gel rapidly becomes absorbed upon injection; however, the microspheres form a scaffold for the production of newly synthesized collagen. The filling effect generally lasts 12 to 18 months.¹

Calcium hydroxylapatite, similar to most fillers, generally is well tolerated with a low complication rate of 3%.¹ Although nodule formation with calcium hydroxylapatite is rare, it is the most common adverse event and encompasses 96% of complications. The remaining 4% of complications include persistent inflammation, swelling, erythema, and technical mistakes leading to overcorrection.¹ Migrating nodules are rare; however, Beer³ reported a similar case.

Treatment of calcium hydroxylapatite nodules depends on differentiating a cause based on the time of onset. Early nodules that occur within 1 to 2 weeks of the injection usually represent incorrect positioning of the filler and can be treated by massaging the nodule. Other more invasive techniques involve aspiration or injection of sterile water. Late-onset nodules have shown response to corticosteroid injections. For inflammatory nodules of infectious origin, antibiotics can be useful. Surgical excision of the nodule rarely is required, as most nodules will resolve spontaneously, even without intervention.^1,2

Radiologic findings of calcium hydroxylapatite appear as high-attenuation linear streaks or masses on CT (280–700 HU) and as low to intermediate signal intensity on T1- or T2-weighted sequences on magnetic resonance imaging. Oftentimes, calcium hydroxylapatite has a similar radiographic appearance to bone and can persist for 2 years or more on radiographic imaging, longer than they are clinically visible.⁴ The nodule formation from injection with calcium hydroxylapatite can mimic pathologic conditions such as miliary osteomas, myositis ossificans, heterotrophic/dystrophic calcifications, and foreign bodies on CT. Our patient’s CT findings of high attenuation linear streaks and nodules of similar signal intensity to bone were consistent with those previously described in the radiographic literature.

Calcium hydroxylapatite fillers have a good safety profile, but it is important to recognize that nodule formation is a common adverse event and that migration of nodules can occur. Practitioners should recognize this possibility in patients presenting with new masses after filler injection before advocating for potentially invasive and costly procedures and diagnostic modalities.

To the Editor:

Calcium hydroxylapatite is an injectable filler approved by the US Food and Drug Administration for moderate to severe rhytides of the face and the treatment of facial lipodystrophy in patients with HIV.¹ This long-lasting filler generally is well tolerated with minimal side effects; however, there have been reports of nodules or granulomatous formation following injection.² We present a case of a migrating nodule following injection of a calcium hydroxylapatite filler that appeared ossified on radiographic imaging. We highlight this rarely reported phenomenon to increase awareness of this complication.

A 72-year-old woman presented to our clinic with a mass on the left cheek. The patient had a history of treatment with facial fillers but no notable medical conditions. She initially received hyaluronic acid injectable gel dermal filler twice—3 years apart—before switching to calcium hydroxylapatite injections twice—4 months apart—from an outside provider. One month after the second treatment, she noticed a mass on the left cheek and promptly returned to the provider who performed the calcium hydroxylapatite injections. The provider, who had originally injected in the infraorbital area, stated it was unlikely that the filler would have migrated to the mid cheek and referred the patient to a general dentist who suspected salivary gland pathology. The patient was referred to an oral and maxillofacial surgeon who suspected the mass was related to the parotid gland. Maxillofacial computed tomography (CT) revealed heterotopic ossification vs myositis ossificans, possibly related to the recent injection. The patient was eventually referred to the Division of Plastic Surgery, Department of Surgery, at the University of Texas Medical Branch (Galveston, Texas) for further evaluation. Physical examination revealed a 2×1-cm firm, mobile, nontender mass in the left cheek in the area of the buccinator muscles. The mass did not express any fluid and was most easily palpable from the oral cavity. Radiography findings showed that the calcium hydroxylapatite filler had migrated to this location and formed a nodule (Figure). Because calcium hydroxylapatite fillers generally last 12 to 18 months, we opted to observe the lesion for spontaneous resolution. Four months later, the patient presented to our clinic for follow-up and the mass had reduced in size and appeared to be spontaneously resolving.

We present a unique case of a migrating nodule that occurred after injection with calcium hydroxylapatite, which led to concern for neoplastic tumor formation. This complication is rare, and it is important for practitioners who inject calcium hydroxylapatite as well as those who these patients may be referred to for evaluation to be aware that migrating nodules can occur. This awareness can help reduce unnecessary referrals, medical procedures, and anxiety.

Calcium hydroxylapatite filler is composed of 30% calcium hydroxylapatite microspheres suspended in a 70% sodium carboxymethylcellulose gel. The water-soluble gel rapidly becomes absorbed upon injection; however, the microspheres form a scaffold for the production of newly synthesized collagen. The filling effect generally lasts 12 to 18 months.¹

Calcium hydroxylapatite, similar to most fillers, generally is well tolerated with a low complication rate of 3%.¹ Although nodule formation with calcium hydroxylapatite is rare, it is the most common adverse event and encompasses 96% of complications. The remaining 4% of complications include persistent inflammation, swelling, erythema, and technical mistakes leading to overcorrection.¹ Migrating nodules are rare; however, Beer³ reported a similar case.

Treatment of calcium hydroxylapatite nodules depends on differentiating a cause based on the time of onset. Early nodules that occur within 1 to 2 weeks of the injection usually represent incorrect positioning of the filler and can be treated by massaging the nodule. Other more invasive techniques involve aspiration or injection of sterile water. Late-onset nodules have shown response to corticosteroid injections. For inflammatory nodules of infectious origin, antibiotics can be useful. Surgical excision of the nodule rarely is required, as most nodules will resolve spontaneously, even without intervention.^1,2

Radiologic findings of calcium hydroxylapatite appear as high-attenuation linear streaks or masses on CT (280–700 HU) and as low to intermediate signal intensity on T1- or T2-weighted sequences on magnetic resonance imaging. Oftentimes, calcium hydroxylapatite has a similar radiographic appearance to bone and can persist for 2 years or more on radiographic imaging, longer than they are clinically visible.⁴ The nodule formation from injection with calcium hydroxylapatite can mimic pathologic conditions such as miliary osteomas, myositis ossificans, heterotrophic/dystrophic calcifications, and foreign bodies on CT. Our patient’s CT findings of high attenuation linear streaks and nodules of similar signal intensity to bone were consistent with those previously described in the radiographic literature.

Calcium hydroxylapatite fillers have a good safety profile, but it is important to recognize that nodule formation is a common adverse event and that migration of nodules can occur. Practitioners should recognize this possibility in patients presenting with new masses after filler injection before advocating for potentially invasive and costly procedures and diagnostic modalities.

To the Editor:

Calcium hydroxylapatite is an injectable filler approved by the US Food and Drug Administration for moderate to severe rhytides of the face and the treatment of facial lipodystrophy in patients with HIV.¹ This long-lasting filler generally is well tolerated with minimal side effects; however, there have been reports of nodules or granulomatous formation following injection.² We present a case of a migrating nodule following injection of a calcium hydroxylapatite filler that appeared ossified on radiographic imaging. We highlight this rarely reported phenomenon to increase awareness of this complication.

A 72-year-old woman presented to our clinic with a mass on the left cheek. The patient had a history of treatment with facial fillers but no notable medical conditions. She initially received hyaluronic acid injectable gel dermal filler twice—3 years apart—before switching to calcium hydroxylapatite injections twice—4 months apart—from an outside provider. One month after the second treatment, she noticed a mass on the left cheek and promptly returned to the provider who performed the calcium hydroxylapatite injections. The provider, who had originally injected in the infraorbital area, stated it was unlikely that the filler would have migrated to the mid cheek and referred the patient to a general dentist who suspected salivary gland pathology. The patient was referred to an oral and maxillofacial surgeon who suspected the mass was related to the parotid gland. Maxillofacial computed tomography (CT) revealed heterotopic ossification vs myositis ossificans, possibly related to the recent injection. The patient was eventually referred to the Division of Plastic Surgery, Department of Surgery, at the University of Texas Medical Branch (Galveston, Texas) for further evaluation. Physical examination revealed a 2×1-cm firm, mobile, nontender mass in the left cheek in the area of the buccinator muscles. The mass did not express any fluid and was most easily palpable from the oral cavity. Radiography findings showed that the calcium hydroxylapatite filler had migrated to this location and formed a nodule (Figure). Because calcium hydroxylapatite fillers generally last 12 to 18 months, we opted to observe the lesion for spontaneous resolution. Four months later, the patient presented to our clinic for follow-up and the mass had reduced in size and appeared to be spontaneously resolving.

We present a unique case of a migrating nodule that occurred after injection with calcium hydroxylapatite, which led to concern for neoplastic tumor formation. This complication is rare, and it is important for practitioners who inject calcium hydroxylapatite as well as those who these patients may be referred to for evaluation to be aware that migrating nodules can occur. This awareness can help reduce unnecessary referrals, medical procedures, and anxiety.

Calcium hydroxylapatite filler is composed of 30% calcium hydroxylapatite microspheres suspended in a 70% sodium carboxymethylcellulose gel. The water-soluble gel rapidly becomes absorbed upon injection; however, the microspheres form a scaffold for the production of newly synthesized collagen. The filling effect generally lasts 12 to 18 months.¹

Calcium hydroxylapatite, similar to most fillers, generally is well tolerated with a low complication rate of 3%.¹ Although nodule formation with calcium hydroxylapatite is rare, it is the most common adverse event and encompasses 96% of complications. The remaining 4% of complications include persistent inflammation, swelling, erythema, and technical mistakes leading to overcorrection.¹ Migrating nodules are rare; however, Beer³ reported a similar case.

Treatment of calcium hydroxylapatite nodules depends on differentiating a cause based on the time of onset. Early nodules that occur within 1 to 2 weeks of the injection usually represent incorrect positioning of the filler and can be treated by massaging the nodule. Other more invasive techniques involve aspiration or injection of sterile water. Late-onset nodules have shown response to corticosteroid injections. For inflammatory nodules of infectious origin, antibiotics can be useful. Surgical excision of the nodule rarely is required, as most nodules will resolve spontaneously, even without intervention.^1,2

Radiologic findings of calcium hydroxylapatite appear as high-attenuation linear streaks or masses on CT (280–700 HU) and as low to intermediate signal intensity on T1- or T2-weighted sequences on magnetic resonance imaging. Oftentimes, calcium hydroxylapatite has a similar radiographic appearance to bone and can persist for 2 years or more on radiographic imaging, longer than they are clinically visible.⁴ The nodule formation from injection with calcium hydroxylapatite can mimic pathologic conditions such as miliary osteomas, myositis ossificans, heterotrophic/dystrophic calcifications, and foreign bodies on CT. Our patient’s CT findings of high attenuation linear streaks and nodules of similar signal intensity to bone were consistent with those previously described in the radiographic literature.

Calcium hydroxylapatite fillers have a good safety profile, but it is important to recognize that nodule formation is a common adverse event and that migration of nodules can occur. Practitioners should recognize this possibility in patients presenting with new masses after filler injection before advocating for potentially invasive and costly procedures and diagnostic modalities.

The Diagnosis: Leukemia Cutis

Hematoxylin and eosin staining revealed an infiltration of monomorphic atypical myeloid cells with cleaved nuclei within the dermis, with a relatively uninvolved epidermis (Figure, A). The cells formed aggregates in single-file lines along dermal collagen bundles. Occasional Auer rods, which are crystal aggregates of the enzyme myeloperoxidase, a marker unique to cells of the myeloid lineage (Figure, B) were appreciated.

Immunohistochemical staining for myeloperoxidase was weakly positive; however, flow cytometric evaluation of the bone marrow aspirate revealed that approximately 20% of all CD45+ cells were myeloid blasts. These findings confirmed the diagnosis of recurrent acute myeloid leukemia (AML). The diagnosis of AML can be confirmed with a bone marrow biopsy demonstrating more than 20% of the total cells in blast form as well as evidence that the cells are of myeloid origin, which can be inferred by the presence of Auer rods, positive myeloperoxidase staining, or immunophenotyping. In our patient, the Auer rods, myeloperoxidase staining, and atypical myeloid cells on skin biopsy, in conjunction with the bone marrow biopsy results, confirmed leukemia cutis.

Leukemia cutis is the infiltration of neoplastic proliferating leukocytes in the epidermis, dermis, or subcutis from a primary or more commonly metastatic malignancy. Leukemic cutaneous involvement is seen in up to 13% of leukemia patients and most commonly is seen in monocytic or myelomonocytic forms of AML.¹ It may present anywhere on the body but mostly is found on the back, trunk, and head. It also may have a predilection for areas with a history of trauma or inflammation. The lesions most often are firm, erythematous to violaceous papules and nodules, though leukemia cutis can present with hemorrhagic ulcers, purpura, or other cutaneous manifestations of concomitant thrombocytopenia such as petechiae and ecchymoses.² Involvement of the lower extremities mimicking venous stasis dermatitis has been described.^3,4

Treatment of leukemia cutis requires targeting the underlying leukemia² under the guidance of hematology and oncology as well as the use of chemotherapeutic agents.⁵ The presence of leukemia cutis is a poor prognostic sign, and a discussion regarding goals of care often is appropriate. Our patient initially responded to FLAG (fludarabine, cytarabine, filgrastim) chemotherapy induction and consolidation, which was followed by midostaurin maintenance. However, she ultimately regressed, requiring decitabine and gilteritinib treatment, and died 9 months later from the course of the disease.

Although typically asymptomatic and presenting on the lower limbs, capillaritis (also known as the pigmented purpuric dermatoses) consists of a set of cutaneous conditions that often are chronic and relapsing in nature, as opposed to our patient’s subacute presentation. These benign conditions have several distinct morphologies; some are characterized by pigmented macules or pinpoint red-brown petechiae that most often are found on the legs but also are seen on the trunk and upper extremities.⁶ Of the various clinical presentations of capillaritis, our patient’s skin findings may be most consistent with pigmented purpuric lichenoid dermatitis of Gougerot and Blum, in which purpuric red-brown papules coalesce into plaques, though her lesions were not raised. The other pigmented purpuric dermatoses can present with cayenne pepper–colored petechiae, golden-brown macules, pruritic purpuric patches, or red-brown annular patches,6 which were not seen in our patient.

Venous stasis dermatitis also favors the lower extremities⁷; however, it classically includes the medial malleolus and often presents with scaling and hyperpigmentation from hemosiderin deposition.⁸ It often is associated with pruritus, as opposed to the nonpruritic nonpainful lesions in leukemia cutis. Other signs of venous insufficiency also may be appreciated, including edema or varicose veins,⁷ which were not evident in our patient.

Leukocytoclastic vasculitis, a small vessel vasculitis, also appears as palpable or macular purpura, which classically is asymptomatic and erupts on the shins approximately 1 week after an inciting exposure,⁹ such as medications, pathogens, or autoimmune diseases. One of the least distinctive vasculitides is polyarteritis nodosa, a form of medium vessel vasculitis, which presents most often with palpable purpura or painful nodules on the lower extremities and may be accompanied by livedo reticularis or digital necrosis.⁹ Acute leukemia may be accompanied by inflammatory paraneoplastic conditions including vasculitis, which is thought to be due to leukemic cells infiltrating and damaging blood vessels.¹⁰

Pretibial myxedema is closely associated with Graves disease and shares some features seen in the presentation of our patient’s leukemia cutis. It is asymptomatic, classically affects the pretibial regions, and most commonly affects older adults and women.^11,12 Pretibial myxedema presents with thick indurated plaques rather than patches. Our patient did not demonstrate ophthalmopathy, which nearly always precedes pretibial myxedema.¹² The most common form of pretibial myxedema is nonpitting, though nodular, plaquelike, polypoid, and elephantiasic forms also exist.¹¹ Pretibial myxedema classically favors the shins; however, it also can affect the ankles, dorsal aspects of the feet, and toes. The characteristic induration of the skin is believed to be the result of excess fibroblast production of glycosaminoglycans in the dermis and subcutis likely triggered by stimulation of fibroblast thyroid stimulating hormone receptors.¹¹

The Diagnosis: Leukemia Cutis

Hematoxylin and eosin staining revealed an infiltration of monomorphic atypical myeloid cells with cleaved nuclei within the dermis, with a relatively uninvolved epidermis (Figure, A). The cells formed aggregates in single-file lines along dermal collagen bundles. Occasional Auer rods, which are crystal aggregates of the enzyme myeloperoxidase, a marker unique to cells of the myeloid lineage (Figure, B) were appreciated.

Immunohistochemical staining for myeloperoxidase was weakly positive; however, flow cytometric evaluation of the bone marrow aspirate revealed that approximately 20% of all CD45+ cells were myeloid blasts. These findings confirmed the diagnosis of recurrent acute myeloid leukemia (AML). The diagnosis of AML can be confirmed with a bone marrow biopsy demonstrating more than 20% of the total cells in blast form as well as evidence that the cells are of myeloid origin, which can be inferred by the presence of Auer rods, positive myeloperoxidase staining, or immunophenotyping. In our patient, the Auer rods, myeloperoxidase staining, and atypical myeloid cells on skin biopsy, in conjunction with the bone marrow biopsy results, confirmed leukemia cutis.

Leukemia cutis is the infiltration of neoplastic proliferating leukocytes in the epidermis, dermis, or subcutis from a primary or more commonly metastatic malignancy. Leukemic cutaneous involvement is seen in up to 13% of leukemia patients and most commonly is seen in monocytic or myelomonocytic forms of AML.¹ It may present anywhere on the body but mostly is found on the back, trunk, and head. It also may have a predilection for areas with a history of trauma or inflammation. The lesions most often are firm, erythematous to violaceous papules and nodules, though leukemia cutis can present with hemorrhagic ulcers, purpura, or other cutaneous manifestations of concomitant thrombocytopenia such as petechiae and ecchymoses.² Involvement of the lower extremities mimicking venous stasis dermatitis has been described.^3,4

Treatment of leukemia cutis requires targeting the underlying leukemia² under the guidance of hematology and oncology as well as the use of chemotherapeutic agents.⁵ The presence of leukemia cutis is a poor prognostic sign, and a discussion regarding goals of care often is appropriate. Our patient initially responded to FLAG (fludarabine, cytarabine, filgrastim) chemotherapy induction and consolidation, which was followed by midostaurin maintenance. However, she ultimately regressed, requiring decitabine and gilteritinib treatment, and died 9 months later from the course of the disease.

Although typically asymptomatic and presenting on the lower limbs, capillaritis (also known as the pigmented purpuric dermatoses) consists of a set of cutaneous conditions that often are chronic and relapsing in nature, as opposed to our patient’s subacute presentation. These benign conditions have several distinct morphologies; some are characterized by pigmented macules or pinpoint red-brown petechiae that most often are found on the legs but also are seen on the trunk and upper extremities.⁶ Of the various clinical presentations of capillaritis, our patient’s skin findings may be most consistent with pigmented purpuric lichenoid dermatitis of Gougerot and Blum, in which purpuric red-brown papules coalesce into plaques, though her lesions were not raised. The other pigmented purpuric dermatoses can present with cayenne pepper–colored petechiae, golden-brown macules, pruritic purpuric patches, or red-brown annular patches,6 which were not seen in our patient.

Venous stasis dermatitis also favors the lower extremities⁷; however, it classically includes the medial malleolus and often presents with scaling and hyperpigmentation from hemosiderin deposition.⁸ It often is associated with pruritus, as opposed to the nonpruritic nonpainful lesions in leukemia cutis. Other signs of venous insufficiency also may be appreciated, including edema or varicose veins,⁷ which were not evident in our patient.

Leukocytoclastic vasculitis, a small vessel vasculitis, also appears as palpable or macular purpura, which classically is asymptomatic and erupts on the shins approximately 1 week after an inciting exposure,⁹ such as medications, pathogens, or autoimmune diseases. One of the least distinctive vasculitides is polyarteritis nodosa, a form of medium vessel vasculitis, which presents most often with palpable purpura or painful nodules on the lower extremities and may be accompanied by livedo reticularis or digital necrosis.⁹ Acute leukemia may be accompanied by inflammatory paraneoplastic conditions including vasculitis, which is thought to be due to leukemic cells infiltrating and damaging blood vessels.¹⁰

Pretibial myxedema is closely associated with Graves disease and shares some features seen in the presentation of our patient’s leukemia cutis. It is asymptomatic, classically affects the pretibial regions, and most commonly affects older adults and women.^11,12 Pretibial myxedema presents with thick indurated plaques rather than patches. Our patient did not demonstrate ophthalmopathy, which nearly always precedes pretibial myxedema.¹² The most common form of pretibial myxedema is nonpitting, though nodular, plaquelike, polypoid, and elephantiasic forms also exist.¹¹ Pretibial myxedema classically favors the shins; however, it also can affect the ankles, dorsal aspects of the feet, and toes. The characteristic induration of the skin is believed to be the result of excess fibroblast production of glycosaminoglycans in the dermis and subcutis likely triggered by stimulation of fibroblast thyroid stimulating hormone receptors.¹¹

The Diagnosis: Leukemia Cutis

Hematoxylin and eosin staining revealed an infiltration of monomorphic atypical myeloid cells with cleaved nuclei within the dermis, with a relatively uninvolved epidermis (Figure, A). The cells formed aggregates in single-file lines along dermal collagen bundles. Occasional Auer rods, which are crystal aggregates of the enzyme myeloperoxidase, a marker unique to cells of the myeloid lineage (Figure, B) were appreciated.

Immunohistochemical staining for myeloperoxidase was weakly positive; however, flow cytometric evaluation of the bone marrow aspirate revealed that approximately 20% of all CD45+ cells were myeloid blasts. These findings confirmed the diagnosis of recurrent acute myeloid leukemia (AML). The diagnosis of AML can be confirmed with a bone marrow biopsy demonstrating more than 20% of the total cells in blast form as well as evidence that the cells are of myeloid origin, which can be inferred by the presence of Auer rods, positive myeloperoxidase staining, or immunophenotyping. In our patient, the Auer rods, myeloperoxidase staining, and atypical myeloid cells on skin biopsy, in conjunction with the bone marrow biopsy results, confirmed leukemia cutis.

Leukemia cutis is the infiltration of neoplastic proliferating leukocytes in the epidermis, dermis, or subcutis from a primary or more commonly metastatic malignancy. Leukemic cutaneous involvement is seen in up to 13% of leukemia patients and most commonly is seen in monocytic or myelomonocytic forms of AML.¹ It may present anywhere on the body but mostly is found on the back, trunk, and head. It also may have a predilection for areas with a history of trauma or inflammation. The lesions most often are firm, erythematous to violaceous papules and nodules, though leukemia cutis can present with hemorrhagic ulcers, purpura, or other cutaneous manifestations of concomitant thrombocytopenia such as petechiae and ecchymoses.² Involvement of the lower extremities mimicking venous stasis dermatitis has been described.^3,4

Treatment of leukemia cutis requires targeting the underlying leukemia² under the guidance of hematology and oncology as well as the use of chemotherapeutic agents.⁵ The presence of leukemia cutis is a poor prognostic sign, and a discussion regarding goals of care often is appropriate. Our patient initially responded to FLAG (fludarabine, cytarabine, filgrastim) chemotherapy induction and consolidation, which was followed by midostaurin maintenance. However, she ultimately regressed, requiring decitabine and gilteritinib treatment, and died 9 months later from the course of the disease.

Although typically asymptomatic and presenting on the lower limbs, capillaritis (also known as the pigmented purpuric dermatoses) consists of a set of cutaneous conditions that often are chronic and relapsing in nature, as opposed to our patient’s subacute presentation. These benign conditions have several distinct morphologies; some are characterized by pigmented macules or pinpoint red-brown petechiae that most often are found on the legs but also are seen on the trunk and upper extremities.⁶ Of the various clinical presentations of capillaritis, our patient’s skin findings may be most consistent with pigmented purpuric lichenoid dermatitis of Gougerot and Blum, in which purpuric red-brown papules coalesce into plaques, though her lesions were not raised. The other pigmented purpuric dermatoses can present with cayenne pepper–colored petechiae, golden-brown macules, pruritic purpuric patches, or red-brown annular patches,6 which were not seen in our patient.

Venous stasis dermatitis also favors the lower extremities⁷; however, it classically includes the medial malleolus and often presents with scaling and hyperpigmentation from hemosiderin deposition.⁸ It often is associated with pruritus, as opposed to the nonpruritic nonpainful lesions in leukemia cutis. Other signs of venous insufficiency also may be appreciated, including edema or varicose veins,⁷ which were not evident in our patient.

Leukocytoclastic vasculitis, a small vessel vasculitis, also appears as palpable or macular purpura, which classically is asymptomatic and erupts on the shins approximately 1 week after an inciting exposure,⁹ such as medications, pathogens, or autoimmune diseases. One of the least distinctive vasculitides is polyarteritis nodosa, a form of medium vessel vasculitis, which presents most often with palpable purpura or painful nodules on the lower extremities and may be accompanied by livedo reticularis or digital necrosis.⁹ Acute leukemia may be accompanied by inflammatory paraneoplastic conditions including vasculitis, which is thought to be due to leukemic cells infiltrating and damaging blood vessels.¹⁰

Pretibial myxedema is closely associated with Graves disease and shares some features seen in the presentation of our patient’s leukemia cutis. It is asymptomatic, classically affects the pretibial regions, and most commonly affects older adults and women.^11,12 Pretibial myxedema presents with thick indurated plaques rather than patches. Our patient did not demonstrate ophthalmopathy, which nearly always precedes pretibial myxedema.¹² The most common form of pretibial myxedema is nonpitting, though nodular, plaquelike, polypoid, and elephantiasic forms also exist.¹¹ Pretibial myxedema classically favors the shins; however, it also can affect the ankles, dorsal aspects of the feet, and toes. The characteristic induration of the skin is believed to be the result of excess fibroblast production of glycosaminoglycans in the dermis and subcutis likely triggered by stimulation of fibroblast thyroid stimulating hormone receptors.¹¹

THE COMPARISON

A Areas of alopecia with erythema and scale in a young Black boy with tinea capitis. He also had an enlarged posterior cervical lymph node (arrow) from this fungal infection.

B White patches of scale from tinea capitis in a young Black boy with no obvious hair loss; however, a potassium hydroxide preparation from the scale was positive for fungus.

C A subtle area of tinea capitis on the scalp of a Latina girl showed comma hairs.

Photographs courtesy of Richard P. Usatine, MD.

Tinea capitis is a common dermatophyte infection of the scalp in school-aged children. The infection is spread by close contact with infected people or with their personal items, including combs, brushes, pillowcases, and hats, as well as animals. It is uncommon in adults.

Epidemiology

Tinea capitis is the most common fungal infection among school-aged children worldwide.¹ In a US-based study of more than 10,000 school-aged children, the prevalence of tinea capitis ranged from 0% to 19.4%, with Black children having the highest rates of infection at 12.9%.² However, people of all races and ages may develop tinea capitis.³

Tinea capitis most commonly is caused by Trichophyton tonsurans and Microsporum canis. Dermatophyte scalp infections caused by T tonsurans produce fungal spores that may occur within the hair shaft (endothrix) or with fungal elements external to the hair shaft (exothrix) such as M canis. Microsporum canis usually fluoresces an apple green color on Wood lamp examination because of the location of the spores.

Key clinical features

Tinea capitis has a variety of clinical presentations: • broken hairs that appear as black dots on the scalp • diffuse scale mimicking seborrheic dermatitis • well-demarcated annular plaques • exudate and tenderness caused by inflammation • scalp pruritus • occipital scalp lymphadenopathy. Worth noting Tinea capitis impacts all patient groups, not just Black patients. In the United States, Black and Hispanic children are most commonly affected.4 Due to a tendency to have dry hair and hair breakage, those with more tightly coiled, textured hair may routinely apply oil and/or grease to the scalp; however, the application of heavy emollients, oils, and grease to camouflage scale contributes to falsenegative fungal cultures of the scalp if applied within 1 week of the fungal culture, which may delay diagnosis. If tinea capitis is suspected, occipital lymphadenopathy on physical examination should prompt treatment for tinea capitis, even without a fungal culture.5 Health disparity highlight A risk factor for tinea capitis is crowded living environments. Some families may live in crowded environments due to economic and housing disparities. This close contact increases the risk for conditions such as tinea capitis.6 Treatment delays may occur due to some cultural practices of applying oils and grease to the hair and scalp, camouflaging the clinical signs of tinea capitis.

THE COMPARISON

A Areas of alopecia with erythema and scale in a young Black boy with tinea capitis. He also had an enlarged posterior cervical lymph node (arrow) from this fungal infection.

B White patches of scale from tinea capitis in a young Black boy with no obvious hair loss; however, a potassium hydroxide preparation from the scale was positive for fungus.

C A subtle area of tinea capitis on the scalp of a Latina girl showed comma hairs.

Photographs courtesy of Richard P. Usatine, MD.

Tinea capitis is a common dermatophyte infection of the scalp in school-aged children. The infection is spread by close contact with infected people or with their personal items, including combs, brushes, pillowcases, and hats, as well as animals. It is uncommon in adults.

Epidemiology

Tinea capitis is the most common fungal infection among school-aged children worldwide.¹ In a US-based study of more than 10,000 school-aged children, the prevalence of tinea capitis ranged from 0% to 19.4%, with Black children having the highest rates of infection at 12.9%.² However, people of all races and ages may develop tinea capitis.³

Tinea capitis most commonly is caused by Trichophyton tonsurans and Microsporum canis. Dermatophyte scalp infections caused by T tonsurans produce fungal spores that may occur within the hair shaft (endothrix) or with fungal elements external to the hair shaft (exothrix) such as M canis. Microsporum canis usually fluoresces an apple green color on Wood lamp examination because of the location of the spores.

Key clinical features

Tinea capitis has a variety of clinical presentations: • broken hairs that appear as black dots on the scalp • diffuse scale mimicking seborrheic dermatitis • well-demarcated annular plaques • exudate and tenderness caused by inflammation • scalp pruritus • occipital scalp lymphadenopathy. Worth noting Tinea capitis impacts all patient groups, not just Black patients. In the United States, Black and Hispanic children are most commonly affected.4 Due to a tendency to have dry hair and hair breakage, those with more tightly coiled, textured hair may routinely apply oil and/or grease to the scalp; however, the application of heavy emollients, oils, and grease to camouflage scale contributes to falsenegative fungal cultures of the scalp if applied within 1 week of the fungal culture, which may delay diagnosis. If tinea capitis is suspected, occipital lymphadenopathy on physical examination should prompt treatment for tinea capitis, even without a fungal culture.5 Health disparity highlight A risk factor for tinea capitis is crowded living environments. Some families may live in crowded environments due to economic and housing disparities. This close contact increases the risk for conditions such as tinea capitis.6 Treatment delays may occur due to some cultural practices of applying oils and grease to the hair and scalp, camouflaging the clinical signs of tinea capitis.

THE COMPARISON

A Areas of alopecia with erythema and scale in a young Black boy with tinea capitis. He also had an enlarged posterior cervical lymph node (arrow) from this fungal infection.

B White patches of scale from tinea capitis in a young Black boy with no obvious hair loss; however, a potassium hydroxide preparation from the scale was positive for fungus.

C A subtle area of tinea capitis on the scalp of a Latina girl showed comma hairs.

Photographs courtesy of Richard P. Usatine, MD.

Tinea capitis is a common dermatophyte infection of the scalp in school-aged children. The infection is spread by close contact with infected people or with their personal items, including combs, brushes, pillowcases, and hats, as well as animals. It is uncommon in adults.

Epidemiology

Tinea capitis is the most common fungal infection among school-aged children worldwide.¹ In a US-based study of more than 10,000 school-aged children, the prevalence of tinea capitis ranged from 0% to 19.4%, with Black children having the highest rates of infection at 12.9%.² However, people of all races and ages may develop tinea capitis.³

Tinea capitis most commonly is caused by Trichophyton tonsurans and Microsporum canis. Dermatophyte scalp infections caused by T tonsurans produce fungal spores that may occur within the hair shaft (endothrix) or with fungal elements external to the hair shaft (exothrix) such as M canis. Microsporum canis usually fluoresces an apple green color on Wood lamp examination because of the location of the spores.

Key clinical features

Tinea capitis has a variety of clinical presentations: • broken hairs that appear as black dots on the scalp • diffuse scale mimicking seborrheic dermatitis • well-demarcated annular plaques • exudate and tenderness caused by inflammation • scalp pruritus • occipital scalp lymphadenopathy. Worth noting Tinea capitis impacts all patient groups, not just Black patients. In the United States, Black and Hispanic children are most commonly affected.4 Due to a tendency to have dry hair and hair breakage, those with more tightly coiled, textured hair may routinely apply oil and/or grease to the scalp; however, the application of heavy emollients, oils, and grease to camouflage scale contributes to falsenegative fungal cultures of the scalp if applied within 1 week of the fungal culture, which may delay diagnosis. If tinea capitis is suspected, occipital lymphadenopathy on physical examination should prompt treatment for tinea capitis, even without a fungal culture.5 Health disparity highlight A risk factor for tinea capitis is crowded living environments. Some families may live in crowded environments due to economic and housing disparities. This close contact increases the risk for conditions such as tinea capitis.6 Treatment delays may occur due to some cultural practices of applying oils and grease to the hair and scalp, camouflaging the clinical signs of tinea capitis.

The Diagnosis: Metastatic Carcinoid Tumor

Carcinoid tumors are derived from neuroendocrine cell compartments and generally arise in the gastrointestinal tract, with a quarter of carcinoids arising in the small bowel.¹ Carcinoid tumors have an incidence of approximately 2 to 5 per 100,000 patients.² Metastasis of carcinoids is approximately 31.2% to 46.7%.¹ Metastasis to the skin is uncommon; we present a rare case of a carcinoid tumor of the terminal ileum with metastasis to the scalp.

Unlike our patient, most patients with carcinoid tumors have an indolent clinical course. The most common cutaneous symptom is flushing, which occurs in 75% of patients.³ Secreted vasoactive peptides such as serotonin may cause other symptoms such as tachycardia, diarrhea, and bronchospasm; together, these symptoms comprise carcinoid syndrome. Carcinoid syndrome requires metastasis of the tumor to the liver or a site outside of the gastrointestinal tract because the liver will metabolize the secreted serotonin. However, even in patients with liver metastasis, carcinoid syndrome only occurs in approximately 10% of patients.⁴ Common skin findings of carcinoid syndrome include pellagralike dermatitis, flushing, and sclerodermalike changes.⁵ Our patient experienced several episodes of presyncope with symptoms of dyspnea, lightheadedness, and flushing but did not have bronchospasm or recurrent diarrhea. Intramuscular octreotide improved some symptoms.

The scalp accounts for approximately 15% of cutaneous metastases, the most common being from the lung, renal, and breast cancers.⁶ Cutaneous metastases of carcinoid tumors are rare. A PubMed search of articles indexed for MEDLINE using the terms metastatic AND [carcinoid OR neuroendocrine] tumors AND [skin OR cutaneous] revealed 47 cases.^7-11 Similar to other skin metastases, cutaneous metastases of carcinoid tumors commonly present as firm erythematous nodules of varying sizes that may be asymptomatic, tender, or pruritic (Figure 1). Cases of carcinoid tumors with cutaneous metastasis as the initial and only presenting sign are exceedingly rare.¹²

Histology of carcinoid tumors reveals a dermal neoplasm composed of loosely cohesive, mildly atypical, polygonal cells with salt-and-pepper chromatin and eosinophilic cytoplasm, which are similar findings to the primary tumor. The cells may grow in the typical trabecular or organoid neuroendocrine pattern or exhibit a pseudoglandular growth pattern with prominent vessels (quiz image, top).¹² Positive chromogranin and synaptophysin immunostaining are the most common and reliable markers used for the diagnosis of carcinoid tumors.

An important histopathologic differential diagnosis is the aggressive Merkel cell carcinoma, which also demonstrates homogenous salt-and-pepper chromatin but exhibits a higher mitotic rate and positive cytokeratin 20 staining (Figure 2).¹³ Basal cell carcinoma (BCC) also may display similar features, including a blue tumor at scanning magnification and nodular or infiltrative growth patterns. The cell morphology of BCC is characterized by islands of basaloid cells with minimal cytoplasm and frequent apoptosis, connecting to the epidermis with peripheral palisading, retraction artifact, and a myxoid stroma; BCC lacks the salt-and-pepper chromatin commonly seen in carcinoid tumors (Figure 3). Basal cell carcinoma is characterized by positive BerEP4 (epithelial cell adhesion molecule immunostain), cytokeratin 5/6, and cytokeratin 14 uptake. Cytokeratin 20, often used to diagnose Merkel cell carcinoma, is negative in BCC. Chromogranin and synaptophysin occasionally may be positive in BCC.¹⁴

The superficial Ewing sarcoma family of tumors also may be included in the differential diagnosis of small round cell tumors of the skin, but they are very rare. These tumors possess strong positive membranous staining of cytokeratin 99 and also can stain positively for synaptophysin and chromogranin.¹⁵ Epithelial membrane antigen, which is negative in Ewing sarcomas, is positive in carcinoid tumors.¹⁶ Neuroendocrine tumors of all sites share similar basic morphologic patterns, and multiple primary tumors should be considered, including small cell lung carcinoma (Figure 4).^17,18 Red granulations and true glandular lumina typically are not seen in the lungs but are common in gastrointestinal carcinoids.¹⁸ Regarding immunohistochemistry, TTF-1 is negative and CDX2 is positive in gastroenteropancreatic carcinoids, suggesting that these 2 markers can help distinguish carcinoids of unknown primary origin.¹⁹

Metastases in carcinoid tumors are common, with one study noting that the highest frequency of small intestinal metastases was from the ileal subset.²⁰ At the time of diagnosis, 58% to 64% of patients with small intestine carcinoid tumors already had nonlocalized disease, with frequent sites being the lymph nodes (89.8%), liver (44.1%), lungs (13.6%), and peritoneum (13.6%). Regional and distant metastases are associated with substantially worse prognoses, with survival rates of 71.7% and 38.5%, respectively.¹ Treatment of symptomatic unresectable disease focuses on symptomatic management with somatostatin analogs that also control tumor growth.²¹

We present a rare case of scalp metastasis of a carcinoid tumor of the terminal ileum. Distant metastasis is associated with poorer prognosis and should be considered in patients with a known history of a carcinoid tumor.

Acknowledgment—We would like to acknowledge the Research Histology and Tissue Imaging Core at University of Illinois Chicago Research Resources Center for the immunohistochemistry studies.

The Diagnosis: Metastatic Carcinoid Tumor

Carcinoid tumors are derived from neuroendocrine cell compartments and generally arise in the gastrointestinal tract, with a quarter of carcinoids arising in the small bowel.¹ Carcinoid tumors have an incidence of approximately 2 to 5 per 100,000 patients.² Metastasis of carcinoids is approximately 31.2% to 46.7%.¹ Metastasis to the skin is uncommon; we present a rare case of a carcinoid tumor of the terminal ileum with metastasis to the scalp.

Unlike our patient, most patients with carcinoid tumors have an indolent clinical course. The most common cutaneous symptom is flushing, which occurs in 75% of patients.³ Secreted vasoactive peptides such as serotonin may cause other symptoms such as tachycardia, diarrhea, and bronchospasm; together, these symptoms comprise carcinoid syndrome. Carcinoid syndrome requires metastasis of the tumor to the liver or a site outside of the gastrointestinal tract because the liver will metabolize the secreted serotonin. However, even in patients with liver metastasis, carcinoid syndrome only occurs in approximately 10% of patients.⁴ Common skin findings of carcinoid syndrome include pellagralike dermatitis, flushing, and sclerodermalike changes.⁵ Our patient experienced several episodes of presyncope with symptoms of dyspnea, lightheadedness, and flushing but did not have bronchospasm or recurrent diarrhea. Intramuscular octreotide improved some symptoms.

The scalp accounts for approximately 15% of cutaneous metastases, the most common being from the lung, renal, and breast cancers.⁶ Cutaneous metastases of carcinoid tumors are rare. A PubMed search of articles indexed for MEDLINE using the terms metastatic AND [carcinoid OR neuroendocrine] tumors AND [skin OR cutaneous] revealed 47 cases.^7-11 Similar to other skin metastases, cutaneous metastases of carcinoid tumors commonly present as firm erythematous nodules of varying sizes that may be asymptomatic, tender, or pruritic (Figure 1). Cases of carcinoid tumors with cutaneous metastasis as the initial and only presenting sign are exceedingly rare.¹²

Histology of carcinoid tumors reveals a dermal neoplasm composed of loosely cohesive, mildly atypical, polygonal cells with salt-and-pepper chromatin and eosinophilic cytoplasm, which are similar findings to the primary tumor. The cells may grow in the typical trabecular or organoid neuroendocrine pattern or exhibit a pseudoglandular growth pattern with prominent vessels (quiz image, top).¹² Positive chromogranin and synaptophysin immunostaining are the most common and reliable markers used for the diagnosis of carcinoid tumors.

An important histopathologic differential diagnosis is the aggressive Merkel cell carcinoma, which also demonstrates homogenous salt-and-pepper chromatin but exhibits a higher mitotic rate and positive cytokeratin 20 staining (Figure 2).¹³ Basal cell carcinoma (BCC) also may display similar features, including a blue tumor at scanning magnification and nodular or infiltrative growth patterns. The cell morphology of BCC is characterized by islands of basaloid cells with minimal cytoplasm and frequent apoptosis, connecting to the epidermis with peripheral palisading, retraction artifact, and a myxoid stroma; BCC lacks the salt-and-pepper chromatin commonly seen in carcinoid tumors (Figure 3). Basal cell carcinoma is characterized by positive BerEP4 (epithelial cell adhesion molecule immunostain), cytokeratin 5/6, and cytokeratin 14 uptake. Cytokeratin 20, often used to diagnose Merkel cell carcinoma, is negative in BCC. Chromogranin and synaptophysin occasionally may be positive in BCC.¹⁴

The superficial Ewing sarcoma family of tumors also may be included in the differential diagnosis of small round cell tumors of the skin, but they are very rare. These tumors possess strong positive membranous staining of cytokeratin 99 and also can stain positively for synaptophysin and chromogranin.¹⁵ Epithelial membrane antigen, which is negative in Ewing sarcomas, is positive in carcinoid tumors.¹⁶ Neuroendocrine tumors of all sites share similar basic morphologic patterns, and multiple primary tumors should be considered, including small cell lung carcinoma (Figure 4).^17,18 Red granulations and true glandular lumina typically are not seen in the lungs but are common in gastrointestinal carcinoids.¹⁸ Regarding immunohistochemistry, TTF-1 is negative and CDX2 is positive in gastroenteropancreatic carcinoids, suggesting that these 2 markers can help distinguish carcinoids of unknown primary origin.¹⁹

Metastases in carcinoid tumors are common, with one study noting that the highest frequency of small intestinal metastases was from the ileal subset.²⁰ At the time of diagnosis, 58% to 64% of patients with small intestine carcinoid tumors already had nonlocalized disease, with frequent sites being the lymph nodes (89.8%), liver (44.1%), lungs (13.6%), and peritoneum (13.6%). Regional and distant metastases are associated with substantially worse prognoses, with survival rates of 71.7% and 38.5%, respectively.¹ Treatment of symptomatic unresectable disease focuses on symptomatic management with somatostatin analogs that also control tumor growth.²¹

We present a rare case of scalp metastasis of a carcinoid tumor of the terminal ileum. Distant metastasis is associated with poorer prognosis and should be considered in patients with a known history of a carcinoid tumor.

Acknowledgment—We would like to acknowledge the Research Histology and Tissue Imaging Core at University of Illinois Chicago Research Resources Center for the immunohistochemistry studies.

The Diagnosis: Metastatic Carcinoid Tumor

Carcinoid tumors are derived from neuroendocrine cell compartments and generally arise in the gastrointestinal tract, with a quarter of carcinoids arising in the small bowel.¹ Carcinoid tumors have an incidence of approximately 2 to 5 per 100,000 patients.² Metastasis of carcinoids is approximately 31.2% to 46.7%.¹ Metastasis to the skin is uncommon; we present a rare case of a carcinoid tumor of the terminal ileum with metastasis to the scalp.

Unlike our patient, most patients with carcinoid tumors have an indolent clinical course. The most common cutaneous symptom is flushing, which occurs in 75% of patients.³ Secreted vasoactive peptides such as serotonin may cause other symptoms such as tachycardia, diarrhea, and bronchospasm; together, these symptoms comprise carcinoid syndrome. Carcinoid syndrome requires metastasis of the tumor to the liver or a site outside of the gastrointestinal tract because the liver will metabolize the secreted serotonin. However, even in patients with liver metastasis, carcinoid syndrome only occurs in approximately 10% of patients.⁴ Common skin findings of carcinoid syndrome include pellagralike dermatitis, flushing, and sclerodermalike changes.⁵ Our patient experienced several episodes of presyncope with symptoms of dyspnea, lightheadedness, and flushing but did not have bronchospasm or recurrent diarrhea. Intramuscular octreotide improved some symptoms.

The scalp accounts for approximately 15% of cutaneous metastases, the most common being from the lung, renal, and breast cancers.⁶ Cutaneous metastases of carcinoid tumors are rare. A PubMed search of articles indexed for MEDLINE using the terms metastatic AND [carcinoid OR neuroendocrine] tumors AND [skin OR cutaneous] revealed 47 cases.^7-11 Similar to other skin metastases, cutaneous metastases of carcinoid tumors commonly present as firm erythematous nodules of varying sizes that may be asymptomatic, tender, or pruritic (Figure 1). Cases of carcinoid tumors with cutaneous metastasis as the initial and only presenting sign are exceedingly rare.¹²

Histology of carcinoid tumors reveals a dermal neoplasm composed of loosely cohesive, mildly atypical, polygonal cells with salt-and-pepper chromatin and eosinophilic cytoplasm, which are similar findings to the primary tumor. The cells may grow in the typical trabecular or organoid neuroendocrine pattern or exhibit a pseudoglandular growth pattern with prominent vessels (quiz image, top).¹² Positive chromogranin and synaptophysin immunostaining are the most common and reliable markers used for the diagnosis of carcinoid tumors.

An important histopathologic differential diagnosis is the aggressive Merkel cell carcinoma, which also demonstrates homogenous salt-and-pepper chromatin but exhibits a higher mitotic rate and positive cytokeratin 20 staining (Figure 2).¹³ Basal cell carcinoma (BCC) also may display similar features, including a blue tumor at scanning magnification and nodular or infiltrative growth patterns. The cell morphology of BCC is characterized by islands of basaloid cells with minimal cytoplasm and frequent apoptosis, connecting to the epidermis with peripheral palisading, retraction artifact, and a myxoid stroma; BCC lacks the salt-and-pepper chromatin commonly seen in carcinoid tumors (Figure 3). Basal cell carcinoma is characterized by positive BerEP4 (epithelial cell adhesion molecule immunostain), cytokeratin 5/6, and cytokeratin 14 uptake. Cytokeratin 20, often used to diagnose Merkel cell carcinoma, is negative in BCC. Chromogranin and synaptophysin occasionally may be positive in BCC.¹⁴

The superficial Ewing sarcoma family of tumors also may be included in the differential diagnosis of small round cell tumors of the skin, but they are very rare. These tumors possess strong positive membranous staining of cytokeratin 99 and also can stain positively for synaptophysin and chromogranin.¹⁵ Epithelial membrane antigen, which is negative in Ewing sarcomas, is positive in carcinoid tumors.¹⁶ Neuroendocrine tumors of all sites share similar basic morphologic patterns, and multiple primary tumors should be considered, including small cell lung carcinoma (Figure 4).^17,18 Red granulations and true glandular lumina typically are not seen in the lungs but are common in gastrointestinal carcinoids.¹⁸ Regarding immunohistochemistry, TTF-1 is negative and CDX2 is positive in gastroenteropancreatic carcinoids, suggesting that these 2 markers can help distinguish carcinoids of unknown primary origin.¹⁹

Metastases in carcinoid tumors are common, with one study noting that the highest frequency of small intestinal metastases was from the ileal subset.²⁰ At the time of diagnosis, 58% to 64% of patients with small intestine carcinoid tumors already had nonlocalized disease, with frequent sites being the lymph nodes (89.8%), liver (44.1%), lungs (13.6%), and peritoneum (13.6%). Regional and distant metastases are associated with substantially worse prognoses, with survival rates of 71.7% and 38.5%, respectively.¹ Treatment of symptomatic unresectable disease focuses on symptomatic management with somatostatin analogs that also control tumor growth.²¹

We present a rare case of scalp metastasis of a carcinoid tumor of the terminal ileum. Distant metastasis is associated with poorer prognosis and should be considered in patients with a known history of a carcinoid tumor.

Acknowledgment—We would like to acknowledge the Research Histology and Tissue Imaging Core at University of Illinois Chicago Research Resources Center for the immunohistochemistry studies.

Mohs micrographic surgery (MMS) is most commonly used for the surgical management of squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs) in high-risk locations. The ability for 100% margin evaluation with MMS also has shown lower recurrence rates compared with wide local excision for less common and/or more aggressive tumors. However, there is a lack of standardization on initial and subsequent margin size when treating these less common skin tumors, such as dermatofibrosarcoma protuberans (DFSP), atypical fibroxanthoma (AFX), and sebaceous carcinoma.

Because Mohs surgeons must balance normal tissue preservation with the importance of tumor clearance in the context of comprehensive margin control, we aimed to assess the practice patterns of Mohs surgeons regarding margin size for these unique tumors. The average margin size for each Mohs layer has been reported to be 1 to 3 mm for BCC compared with 3 to 6 mm or larger for other skin cancers, such as melanoma in situ (MIS).^1-3 We hypothesized that the initial margin size would vary among surgeons and likely be greater for more aggressive and rarer malignancies as well as for lesions on the trunk and extremities.

Methods

A descriptive survey was created using SurveyMonkey and distributed to members of the American College of Mohs Surgery (ACMS). Survey participants and their responses were anonymous. Demographic information on survey participants was collected in addition to initial and subsequent MMS margin size for DFSP, AFX, MIS, invasive melanoma, sebaceous carcinoma, microcystic adnexal carcinoma (MAC), poorly differentiated SCC, Merkel cell carcinoma, extramammary Paget disease, leiomyosarcoma, and endocrine mucin-producing sweat gland carcinoma. Survey participants were asked to choose from a range of margin sizes: 1 to 3 mm, 4 to 6 mm, 7 to 9 mm, and greater than 9 mm. This study was approved by the University of Texas Southwest Medical Center (Dallas, Texas) institutional review board.

Results

Eighty-seven respondents from the ACMS listserve completed the survey (response rate <10%). Of these, 58 respondents (66.7%) reported practicing for more than 5 years, and 58 (66.7%) were male. Practice setting was primarily private/community (71.3% [62/87]), and survey respondents were located across the United States. More than 50% of survey respondents treated the following tumors on the head and neck in their respective practices: DFSP (80.9% [55/68]), AFX (95.6% [65/68]), MIS (67.7% [46/68]), sebaceous carcinoma (92.7% [63/68]), MAC (83.8% [57/68]), poorly differentiated SCC (97.1% [66/68]), and endocrine mucin-producing sweat gland carcinoma (51.5% [35/68]). More than 50% of survey respondents treated the following tumors on the trunk and extremities: DFSP (90.3% [47/52]), AFX (86.4% [45/52]), MIS (55.8% [29/52]), sebaceous carcinoma (80.8% [42/52]), MAC (73.1% [38/52]), poorly differentiated SCC (94.2% [49/52]), and extramammary Paget disease (53.9% [28/52]). Invasive melanoma, Merkel cell carcinoma, and leiomyosarcoma were overall less commonly treated.

In general, respondent Mohs surgeons were more likely to take larger initial and subsequent margins for tumors treated on the trunk and extremities compared with the head and neck (Table). In addition, initial margin size often was larger than the 1- to 3-mm margin commonly used in Mohs surgery for BCCs and less aggressive SCCs (Table). A larger initial margin size (>9 mm) and subsequent margin size (4–6 mm) was more commonly reported for certain tumors known to be more aggressive and/or have extensive subclinical extension, such as DFSP and invasive melanoma. Of note, most respondents performed 4- to 6-mm margins (37/67 [55.2%]) for poorly differentiated SCC. Overall, there was a high range of margin size variability among Mohs surgeons for these unique and/or more aggressive skin tumors.

Comment

Given that no guidelines exist on margins with MMS for less commonly treated skin tumors, this study helps give Mohs surgeons perspective on current practice patterns for both initial and subsequent Mohs margin sizes. High margin-size variability among Mohs surgeons is expected, as surgeons also need to account for high-risk features of the tumor or specific locations where tissue sparing is critical. Overall, Mohs surgeons are more likely to take larger initial margins for these less common skin tumors compared with BCCs or SCCs. Initial margin size was consistently larger on the trunk and extremities where tissue sparing often is less critical.

Our survey was limited by a small sample size and incomplete response of the ACMS membership. In addition, most respondents practiced in a private/community setting, which may have led to bias, as academic centers may manage rare malignancies more commonly and/or have increased access to immunostains and multispecialty care. Future registries for rare skin malignancies will hopefully be developed that will allow for further consensus on standardized margins. Additional studies on the average number of stages required to clear these less common tumors also are warranted.

Mohs micrographic surgery (MMS) is most commonly used for the surgical management of squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs) in high-risk locations. The ability for 100% margin evaluation with MMS also has shown lower recurrence rates compared with wide local excision for less common and/or more aggressive tumors. However, there is a lack of standardization on initial and subsequent margin size when treating these less common skin tumors, such as dermatofibrosarcoma protuberans (DFSP), atypical fibroxanthoma (AFX), and sebaceous carcinoma.

Because Mohs surgeons must balance normal tissue preservation with the importance of tumor clearance in the context of comprehensive margin control, we aimed to assess the practice patterns of Mohs surgeons regarding margin size for these unique tumors. The average margin size for each Mohs layer has been reported to be 1 to 3 mm for BCC compared with 3 to 6 mm or larger for other skin cancers, such as melanoma in situ (MIS).^1-3 We hypothesized that the initial margin size would vary among surgeons and likely be greater for more aggressive and rarer malignancies as well as for lesions on the trunk and extremities.

Methods

A descriptive survey was created using SurveyMonkey and distributed to members of the American College of Mohs Surgery (ACMS). Survey participants and their responses were anonymous. Demographic information on survey participants was collected in addition to initial and subsequent MMS margin size for DFSP, AFX, MIS, invasive melanoma, sebaceous carcinoma, microcystic adnexal carcinoma (MAC), poorly differentiated SCC, Merkel cell carcinoma, extramammary Paget disease, leiomyosarcoma, and endocrine mucin-producing sweat gland carcinoma. Survey participants were asked to choose from a range of margin sizes: 1 to 3 mm, 4 to 6 mm, 7 to 9 mm, and greater than 9 mm. This study was approved by the University of Texas Southwest Medical Center (Dallas, Texas) institutional review board.

Results

Eighty-seven respondents from the ACMS listserve completed the survey (response rate <10%). Of these, 58 respondents (66.7%) reported practicing for more than 5 years, and 58 (66.7%) were male. Practice setting was primarily private/community (71.3% [62/87]), and survey respondents were located across the United States. More than 50% of survey respondents treated the following tumors on the head and neck in their respective practices: DFSP (80.9% [55/68]), AFX (95.6% [65/68]), MIS (67.7% [46/68]), sebaceous carcinoma (92.7% [63/68]), MAC (83.8% [57/68]), poorly differentiated SCC (97.1% [66/68]), and endocrine mucin-producing sweat gland carcinoma (51.5% [35/68]). More than 50% of survey respondents treated the following tumors on the trunk and extremities: DFSP (90.3% [47/52]), AFX (86.4% [45/52]), MIS (55.8% [29/52]), sebaceous carcinoma (80.8% [42/52]), MAC (73.1% [38/52]), poorly differentiated SCC (94.2% [49/52]), and extramammary Paget disease (53.9% [28/52]). Invasive melanoma, Merkel cell carcinoma, and leiomyosarcoma were overall less commonly treated.

In general, respondent Mohs surgeons were more likely to take larger initial and subsequent margins for tumors treated on the trunk and extremities compared with the head and neck (Table). In addition, initial margin size often was larger than the 1- to 3-mm margin commonly used in Mohs surgery for BCCs and less aggressive SCCs (Table). A larger initial margin size (>9 mm) and subsequent margin size (4–6 mm) was more commonly reported for certain tumors known to be more aggressive and/or have extensive subclinical extension, such as DFSP and invasive melanoma. Of note, most respondents performed 4- to 6-mm margins (37/67 [55.2%]) for poorly differentiated SCC. Overall, there was a high range of margin size variability among Mohs surgeons for these unique and/or more aggressive skin tumors.

Comment

Given that no guidelines exist on margins with MMS for less commonly treated skin tumors, this study helps give Mohs surgeons perspective on current practice patterns for both initial and subsequent Mohs margin sizes. High margin-size variability among Mohs surgeons is expected, as surgeons also need to account for high-risk features of the tumor or specific locations where tissue sparing is critical. Overall, Mohs surgeons are more likely to take larger initial margins for these less common skin tumors compared with BCCs or SCCs. Initial margin size was consistently larger on the trunk and extremities where tissue sparing often is less critical.

Our survey was limited by a small sample size and incomplete response of the ACMS membership. In addition, most respondents practiced in a private/community setting, which may have led to bias, as academic centers may manage rare malignancies more commonly and/or have increased access to immunostains and multispecialty care. Future registries for rare skin malignancies will hopefully be developed that will allow for further consensus on standardized margins. Additional studies on the average number of stages required to clear these less common tumors also are warranted.

Mohs micrographic surgery (MMS) is most commonly used for the surgical management of squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs) in high-risk locations. The ability for 100% margin evaluation with MMS also has shown lower recurrence rates compared with wide local excision for less common and/or more aggressive tumors. However, there is a lack of standardization on initial and subsequent margin size when treating these less common skin tumors, such as dermatofibrosarcoma protuberans (DFSP), atypical fibroxanthoma (AFX), and sebaceous carcinoma.

Because Mohs surgeons must balance normal tissue preservation with the importance of tumor clearance in the context of comprehensive margin control, we aimed to assess the practice patterns of Mohs surgeons regarding margin size for these unique tumors. The average margin size for each Mohs layer has been reported to be 1 to 3 mm for BCC compared with 3 to 6 mm or larger for other skin cancers, such as melanoma in situ (MIS).^1-3 We hypothesized that the initial margin size would vary among surgeons and likely be greater for more aggressive and rarer malignancies as well as for lesions on the trunk and extremities.

Methods

A descriptive survey was created using SurveyMonkey and distributed to members of the American College of Mohs Surgery (ACMS). Survey participants and their responses were anonymous. Demographic information on survey participants was collected in addition to initial and subsequent MMS margin size for DFSP, AFX, MIS, invasive melanoma, sebaceous carcinoma, microcystic adnexal carcinoma (MAC), poorly differentiated SCC, Merkel cell carcinoma, extramammary Paget disease, leiomyosarcoma, and endocrine mucin-producing sweat gland carcinoma. Survey participants were asked to choose from a range of margin sizes: 1 to 3 mm, 4 to 6 mm, 7 to 9 mm, and greater than 9 mm. This study was approved by the University of Texas Southwest Medical Center (Dallas, Texas) institutional review board.

Results

Eighty-seven respondents from the ACMS listserve completed the survey (response rate <10%). Of these, 58 respondents (66.7%) reported practicing for more than 5 years, and 58 (66.7%) were male. Practice setting was primarily private/community (71.3% [62/87]), and survey respondents were located across the United States. More than 50% of survey respondents treated the following tumors on the head and neck in their respective practices: DFSP (80.9% [55/68]), AFX (95.6% [65/68]), MIS (67.7% [46/68]), sebaceous carcinoma (92.7% [63/68]), MAC (83.8% [57/68]), poorly differentiated SCC (97.1% [66/68]), and endocrine mucin-producing sweat gland carcinoma (51.5% [35/68]). More than 50% of survey respondents treated the following tumors on the trunk and extremities: DFSP (90.3% [47/52]), AFX (86.4% [45/52]), MIS (55.8% [29/52]), sebaceous carcinoma (80.8% [42/52]), MAC (73.1% [38/52]), poorly differentiated SCC (94.2% [49/52]), and extramammary Paget disease (53.9% [28/52]). Invasive melanoma, Merkel cell carcinoma, and leiomyosarcoma were overall less commonly treated.

In general, respondent Mohs surgeons were more likely to take larger initial and subsequent margins for tumors treated on the trunk and extremities compared with the head and neck (Table). In addition, initial margin size often was larger than the 1- to 3-mm margin commonly used in Mohs surgery for BCCs and less aggressive SCCs (Table). A larger initial margin size (>9 mm) and subsequent margin size (4–6 mm) was more commonly reported for certain tumors known to be more aggressive and/or have extensive subclinical extension, such as DFSP and invasive melanoma. Of note, most respondents performed 4- to 6-mm margins (37/67 [55.2%]) for poorly differentiated SCC. Overall, there was a high range of margin size variability among Mohs surgeons for these unique and/or more aggressive skin tumors.

Comment

Given that no guidelines exist on margins with MMS for less commonly treated skin tumors, this study helps give Mohs surgeons perspective on current practice patterns for both initial and subsequent Mohs margin sizes. High margin-size variability among Mohs surgeons is expected, as surgeons also need to account for high-risk features of the tumor or specific locations where tissue sparing is critical. Overall, Mohs surgeons are more likely to take larger initial margins for these less common skin tumors compared with BCCs or SCCs. Initial margin size was consistently larger on the trunk and extremities where tissue sparing often is less critical.

Our survey was limited by a small sample size and incomplete response of the ACMS membership. In addition, most respondents practiced in a private/community setting, which may have led to bias, as academic centers may manage rare malignancies more commonly and/or have increased access to immunostains and multispecialty care. Future registries for rare skin malignancies will hopefully be developed that will allow for further consensus on standardized margins. Additional studies on the average number of stages required to clear these less common tumors also are warranted.

To the Editor:

Segmental neurofibromatosis, or neurofibromatosis type 5 (NF5), is a rare subtype of neurofibromatosis type 1 (NF1)(also known as von Recklinghausen disease). Phenotypic manifestations of NF5 include café-au-lait macules, neurofibromas, or both in 1 or more adjacent dermatomes. In contrast to the systemic features of NF1, the dermatomal distribution of NF5 demonstrates mosaicism due to a spontaneous postzygotic mutation in the neurofibromin 1 gene, NF1. We describe an atypical presentation of NF5 with bilateral features on the upper extremities.

A 74-year-old woman presented with soft pink- to flesh-colored growths on the left dorsal forearm and hand that were observed incidentally during a Mohs procedure for treatment of a basal cell carcinoma on the upper cutaneous lip. The patient reported that the lesions initially appeared on the left dorsal hand at approximately 16 years of age and had since spread proximally up to the mid dorsal forearm over the course of her lifetime. She denied any pain but claimed the affected area could be itchy. The lesions did not interfere with her daily activities, but they negatively impacted her social life due to their cosmetic appearance as well as her fear that they could be contagious. She denied any family history of NF1.

Physical examination revealed innumerable soft, pink- to flesh-colored cutaneous nodules ranging from 3 to 9 mm in diameter clustered uniformly on the left dorsal hand and lower forearm within the C6, C7, and C8 dermatomal regions (Figure, A). A singular brown patch measuring 20 mm in diameter also was observed on the right dorsal hand within the C6 dermatome, which the patient reported had been present since birth (Figure, B). The nodules and pigmented patch were clinically diagnosed as cutaneous neurofibromas on the left arm and a café-au-lait macule on the right arm, each manifesting within the C6 dermatome on separate upper extremities. Lisch nodules, axillary freckling, and acoustic schwannomas were not observed. Because of the dermatomal distribution of the lesions and lack of family history of NF1, a diagnosis of bilateral NF5 was made. The patient stated she had declined treatment of the neurofibromas from her referring general dermatologist due to possible risk for recurrence.

Segmental neurofibromatosis was first described in 1931 by Gammel,¹ and in 1982, segmental neurofibromatosis was classified as NF5 by Riccardi.² After Tinschert et al³ later demonstrated NF5 to be a somatic mutation of NF1,³ Ruggieri and Huson⁴ proposed the term mosaic neurofibromatosis 1 in 2001.

While the prevalence of NF1 is 1 in 3000 individuals,⁵ NF5 is rare with an occurrence of 1 in 40,000.⁶ In NF5, a spontaneous NF1 gene mutation occurs on chromosome 17 in a dividing cell after conception.⁷ Individuals with NF5 are born mosaic with 2 genotypes—one normal and one abnormal—for the NF1 gene.⁸ This contrasts with the autosomal-dominant and systemic characteristics of NF1, which has the NF1 gene mutation in all cells. Patients with NF5 generally are not expected to have affected offspring because the spontaneous mutation usually arises in somatic cells; however, a postzygotic mutation in the gonadal region could potentially affect germline cells, resulting in vertical transmission, with documented cases of offspring with systemic NF1.⁴ Because of the risk for malignancy with systemic neurofibromatosis, early diagnosis with genetic counseling is imperative in patients with both NF1 and NF5.

Neurofibromatosis type 5 is a clinical diagnosis based on the presence of neurofibromas and/or café-au-lait macules in a dermatomal distribution. The clinical presentation depends on when and where the NF1 gene mutation occurs in utero as cells multiply, differentiate, and migrate.⁸ Earlier mutations result in a broader manifestation of NF5 in comparison to late mutations, which have more localized features. An NF1 gene mutation causes a loss of function of neurofibromin, a tumor suppressor protein, in Schwann cells and fibroblasts.⁸ This produces neurofibromas and café-au-lait macules, respectively.⁸

A large literature review on segmental neurofibromatosis by Garcia-Romero et al⁶ identified 320 individuals who did not meet full inclusion criteria for NF1 between 1977 and 2012. Overall, 76% of cases were unilaterally distributed. The investigators identified 157 individual case reports in which the most to least common presentation was pigmentary changes only, neurofibromas only, mixed pigmentary changes with neurofibromas, and plexiform neurofibromas only; however, many of these cases were children who may have later developed both neurofibromas and pigmentary changes during puberty.⁶ Additional features of NF5 may include freckling, Lisch nodules, optic gliomas, malignant peripheral nerve sheath tumors, skeletal abnormalities, precocious puberty, vascular malformations, hypertension, seizures, and/or learning difficulties based on the affected anatomy.

Segmental neurofibromatosis, or NF5, is a rare subtype of NF1. Our case demonstrates an unusual bilateral distribution of NF5 with cutaneous neurofibromas and a café-au-lait macule on the upper extremities. Awareness of variations of neurofibromatosis and their genetic implications is essential in establishing earlier clinical diagnoses in cases with subtle manifestations.

To the Editor:

Segmental neurofibromatosis, or neurofibromatosis type 5 (NF5), is a rare subtype of neurofibromatosis type 1 (NF1)(also known as von Recklinghausen disease). Phenotypic manifestations of NF5 include café-au-lait macules, neurofibromas, or both in 1 or more adjacent dermatomes. In contrast to the systemic features of NF1, the dermatomal distribution of NF5 demonstrates mosaicism due to a spontaneous postzygotic mutation in the neurofibromin 1 gene, NF1. We describe an atypical presentation of NF5 with bilateral features on the upper extremities.

A 74-year-old woman presented with soft pink- to flesh-colored growths on the left dorsal forearm and hand that were observed incidentally during a Mohs procedure for treatment of a basal cell carcinoma on the upper cutaneous lip. The patient reported that the lesions initially appeared on the left dorsal hand at approximately 16 years of age and had since spread proximally up to the mid dorsal forearm over the course of her lifetime. She denied any pain but claimed the affected area could be itchy. The lesions did not interfere with her daily activities, but they negatively impacted her social life due to their cosmetic appearance as well as her fear that they could be contagious. She denied any family history of NF1.

Physical examination revealed innumerable soft, pink- to flesh-colored cutaneous nodules ranging from 3 to 9 mm in diameter clustered uniformly on the left dorsal hand and lower forearm within the C6, C7, and C8 dermatomal regions (Figure, A). A singular brown patch measuring 20 mm in diameter also was observed on the right dorsal hand within the C6 dermatome, which the patient reported had been present since birth (Figure, B). The nodules and pigmented patch were clinically diagnosed as cutaneous neurofibromas on the left arm and a café-au-lait macule on the right arm, each manifesting within the C6 dermatome on separate upper extremities. Lisch nodules, axillary freckling, and acoustic schwannomas were not observed. Because of the dermatomal distribution of the lesions and lack of family history of NF1, a diagnosis of bilateral NF5 was made. The patient stated she had declined treatment of the neurofibromas from her referring general dermatologist due to possible risk for recurrence.

Segmental neurofibromatosis was first described in 1931 by Gammel,¹ and in 1982, segmental neurofibromatosis was classified as NF5 by Riccardi.² After Tinschert et al³ later demonstrated NF5 to be a somatic mutation of NF1,³ Ruggieri and Huson⁴ proposed the term mosaic neurofibromatosis 1 in 2001.

While the prevalence of NF1 is 1 in 3000 individuals,⁵ NF5 is rare with an occurrence of 1 in 40,000.⁶ In NF5, a spontaneous NF1 gene mutation occurs on chromosome 17 in a dividing cell after conception.⁷ Individuals with NF5 are born mosaic with 2 genotypes—one normal and one abnormal—for the NF1 gene.⁸ This contrasts with the autosomal-dominant and systemic characteristics of NF1, which has the NF1 gene mutation in all cells. Patients with NF5 generally are not expected to have affected offspring because the spontaneous mutation usually arises in somatic cells; however, a postzygotic mutation in the gonadal region could potentially affect germline cells, resulting in vertical transmission, with documented cases of offspring with systemic NF1.⁴ Because of the risk for malignancy with systemic neurofibromatosis, early diagnosis with genetic counseling is imperative in patients with both NF1 and NF5.

Neurofibromatosis type 5 is a clinical diagnosis based on the presence of neurofibromas and/or café-au-lait macules in a dermatomal distribution. The clinical presentation depends on when and where the NF1 gene mutation occurs in utero as cells multiply, differentiate, and migrate.⁸ Earlier mutations result in a broader manifestation of NF5 in comparison to late mutations, which have more localized features. An NF1 gene mutation causes a loss of function of neurofibromin, a tumor suppressor protein, in Schwann cells and fibroblasts.⁸ This produces neurofibromas and café-au-lait macules, respectively.⁸

A large literature review on segmental neurofibromatosis by Garcia-Romero et al⁶ identified 320 individuals who did not meet full inclusion criteria for NF1 between 1977 and 2012. Overall, 76% of cases were unilaterally distributed. The investigators identified 157 individual case reports in which the most to least common presentation was pigmentary changes only, neurofibromas only, mixed pigmentary changes with neurofibromas, and plexiform neurofibromas only; however, many of these cases were children who may have later developed both neurofibromas and pigmentary changes during puberty.⁶ Additional features of NF5 may include freckling, Lisch nodules, optic gliomas, malignant peripheral nerve sheath tumors, skeletal abnormalities, precocious puberty, vascular malformations, hypertension, seizures, and/or learning difficulties based on the affected anatomy.

Segmental neurofibromatosis, or NF5, is a rare subtype of NF1. Our case demonstrates an unusual bilateral distribution of NF5 with cutaneous neurofibromas and a café-au-lait macule on the upper extremities. Awareness of variations of neurofibromatosis and their genetic implications is essential in establishing earlier clinical diagnoses in cases with subtle manifestations.

To the Editor:

Segmental neurofibromatosis, or neurofibromatosis type 5 (NF5), is a rare subtype of neurofibromatosis type 1 (NF1)(also known as von Recklinghausen disease). Phenotypic manifestations of NF5 include café-au-lait macules, neurofibromas, or both in 1 or more adjacent dermatomes. In contrast to the systemic features of NF1, the dermatomal distribution of NF5 demonstrates mosaicism due to a spontaneous postzygotic mutation in the neurofibromin 1 gene, NF1. We describe an atypical presentation of NF5 with bilateral features on the upper extremities.

A 74-year-old woman presented with soft pink- to flesh-colored growths on the left dorsal forearm and hand that were observed incidentally during a Mohs procedure for treatment of a basal cell carcinoma on the upper cutaneous lip. The patient reported that the lesions initially appeared on the left dorsal hand at approximately 16 years of age and had since spread proximally up to the mid dorsal forearm over the course of her lifetime. She denied any pain but claimed the affected area could be itchy. The lesions did not interfere with her daily activities, but they negatively impacted her social life due to their cosmetic appearance as well as her fear that they could be contagious. She denied any family history of NF1.

Physical examination revealed innumerable soft, pink- to flesh-colored cutaneous nodules ranging from 3 to 9 mm in diameter clustered uniformly on the left dorsal hand and lower forearm within the C6, C7, and C8 dermatomal regions (Figure, A). A singular brown patch measuring 20 mm in diameter also was observed on the right dorsal hand within the C6 dermatome, which the patient reported had been present since birth (Figure, B). The nodules and pigmented patch were clinically diagnosed as cutaneous neurofibromas on the left arm and a café-au-lait macule on the right arm, each manifesting within the C6 dermatome on separate upper extremities. Lisch nodules, axillary freckling, and acoustic schwannomas were not observed. Because of the dermatomal distribution of the lesions and lack of family history of NF1, a diagnosis of bilateral NF5 was made. The patient stated she had declined treatment of the neurofibromas from her referring general dermatologist due to possible risk for recurrence.

Segmental neurofibromatosis was first described in 1931 by Gammel,¹ and in 1982, segmental neurofibromatosis was classified as NF5 by Riccardi.² After Tinschert et al³ later demonstrated NF5 to be a somatic mutation of NF1,³ Ruggieri and Huson⁴ proposed the term mosaic neurofibromatosis 1 in 2001.

While the prevalence of NF1 is 1 in 3000 individuals,⁵ NF5 is rare with an occurrence of 1 in 40,000.⁶ In NF5, a spontaneous NF1 gene mutation occurs on chromosome 17 in a dividing cell after conception.⁷ Individuals with NF5 are born mosaic with 2 genotypes—one normal and one abnormal—for the NF1 gene.⁸ This contrasts with the autosomal-dominant and systemic characteristics of NF1, which has the NF1 gene mutation in all cells. Patients with NF5 generally are not expected to have affected offspring because the spontaneous mutation usually arises in somatic cells; however, a postzygotic mutation in the gonadal region could potentially affect germline cells, resulting in vertical transmission, with documented cases of offspring with systemic NF1.⁴ Because of the risk for malignancy with systemic neurofibromatosis, early diagnosis with genetic counseling is imperative in patients with both NF1 and NF5.

Neurofibromatosis type 5 is a clinical diagnosis based on the presence of neurofibromas and/or café-au-lait macules in a dermatomal distribution. The clinical presentation depends on when and where the NF1 gene mutation occurs in utero as cells multiply, differentiate, and migrate.⁸ Earlier mutations result in a broader manifestation of NF5 in comparison to late mutations, which have more localized features. An NF1 gene mutation causes a loss of function of neurofibromin, a tumor suppressor protein, in Schwann cells and fibroblasts.⁸ This produces neurofibromas and café-au-lait macules, respectively.⁸

A large literature review on segmental neurofibromatosis by Garcia-Romero et al⁶ identified 320 individuals who did not meet full inclusion criteria for NF1 between 1977 and 2012. Overall, 76% of cases were unilaterally distributed. The investigators identified 157 individual case reports in which the most to least common presentation was pigmentary changes only, neurofibromas only, mixed pigmentary changes with neurofibromas, and plexiform neurofibromas only; however, many of these cases were children who may have later developed both neurofibromas and pigmentary changes during puberty.⁶ Additional features of NF5 may include freckling, Lisch nodules, optic gliomas, malignant peripheral nerve sheath tumors, skeletal abnormalities, precocious puberty, vascular malformations, hypertension, seizures, and/or learning difficulties based on the affected anatomy.

Segmental neurofibromatosis, or NF5, is a rare subtype of NF1. Our case demonstrates an unusual bilateral distribution of NF5 with cutaneous neurofibromas and a café-au-lait macule on the upper extremities. Awareness of variations of neurofibromatosis and their genetic implications is essential in establishing earlier clinical diagnoses in cases with subtle manifestations.

To the Editor:

Vedolizumab is an innovative monoclonal antibody targeted against the α4β7 integrin that is approved for treatment of moderate to severe ulcerative colitis and Crohn disease refractory to standard treatment.¹ Vedolizumab is thought to be gut specific, blocking integrins specific to T lymphocytes destined for the gastrointestinal tract and their interaction with endothelial cells, thereby modulating the adaptive immune system in the gut without systemic immunosuppression.² It generally is well tolerated, and acne rarely has been reported as an adverse event.^3,4 We present a case of acne fulminans without systemic symptoms (AF-WOSS) as a severe side effect of vedolizumab that responded very well to systemic steroids and oral isotretinoin in addition to the discontinuation of treatment.

A 46-year-old obese man presented to our dermatology clinic with a chief complaint of rapidly progressive tender skin lesions. The patient had a long-standing history of severe fistulating and stricturing Crohn disease status post–bowel resection with ileostomy and had recently started treatment with vedolizumab after failing treatment with infliximab, adalimumab, certolizumab pegol, ustekinumab, and methotrexate. Several weeks after beginning infusions of vedolizumab, the patient began to develop many erythematous papules and pustules on the face, chest (Figure 1), and buttocks that rapidly progressed into painful and coalescing nodules and cysts over the next several months. He was prescribed benzoyl peroxide wash 10% as well as several weeks of oral doxycycline 100 mg twice daily with no improvement. The patient denied any other new medications or triggers, fever, chills, bone pain, headache, fatigue, or myalgia. The skin involvement continued to worsen with successive vedolizumab infusions over a period of 8 weeks, which ultimately resulted in cessation of vedolizumab.

Physical examination revealed large, tender, pink, erythematous, and indurated plaques that were heavily studded with pink papules, pustules, and nodules on the cheeks (Figure 2), central chest, and buttocks. A punch biopsy of a pustule on the cheek showed ruptured suppurative folliculitis. The patient subsequently was diagnosed with AF-WOSS.

The patient then completed a 7-day course of sulfamethoxazole-trimethoprim followed by a 10-day course of amoxicillin-clavulanic acid, neither of which led to improvement of the lesions. He then was started on an oral prednisone taper (1 mg/kg starting dose) that ultimately totaled 14 weeks in length due to his frequent flares any time prednisone was decreased below 40 mg daily. After 3 weeks on the oral prednisone, the patient was started on 0.3 mg/kg of concomitant oral isotretinoin every other day, which slowly was increased as tolerated until he reached a goal dose of roughly 150 mg/kg, which resolved the acneform papules and pustules and allowed for successful tapering off the prednisone.

Many studies have been published regarding the safety and side-effect profile of vedolizumab, but most do not report acne as an adverse event.^3-5 A German cohort study by Baumgart et al³ reported acne as a side effect in 15 of 212 (7.1%) patients but did not classify the severity. Another case report noted nodulocystic acne in a patient receiving vedolizumab for treatment of inflammatory bowel disease; however, this patient responded well to the use of a tetracycline antibiotic and was able to continue therapy with vedolizumab.⁵ Our patient demonstrated a severe and uncommon case of acne classified as AF-WOSS following initiation of therapy with vedolizumab, which required treatment with systemic steroids plus oral isotretinoin and resulted in cessation of vedolizumab.

As new therapies emerge, it is important to document new or severe adverse effects so providers can choose an appropriate therapy and adequately counsel patients regarding the side effects. Although vedolizumab was thought to have gut-specific action, there is new evidence to suggest that the principal ligand of the α4β7 integrin, mucosal addressin cell adhesion molecule-1, is not only expressed on gut endothelial cells but also on fibroblasts and melanomas, which may provide insight into the observed extraintestinal side effects of vedolizumab.⁶

To the Editor:

Vedolizumab is an innovative monoclonal antibody targeted against the α4β7 integrin that is approved for treatment of moderate to severe ulcerative colitis and Crohn disease refractory to standard treatment.¹ Vedolizumab is thought to be gut specific, blocking integrins specific to T lymphocytes destined for the gastrointestinal tract and their interaction with endothelial cells, thereby modulating the adaptive immune system in the gut without systemic immunosuppression.² It generally is well tolerated, and acne rarely has been reported as an adverse event.^3,4 We present a case of acne fulminans without systemic symptoms (AF-WOSS) as a severe side effect of vedolizumab that responded very well to systemic steroids and oral isotretinoin in addition to the discontinuation of treatment.

A 46-year-old obese man presented to our dermatology clinic with a chief complaint of rapidly progressive tender skin lesions. The patient had a long-standing history of severe fistulating and stricturing Crohn disease status post–bowel resection with ileostomy and had recently started treatment with vedolizumab after failing treatment with infliximab, adalimumab, certolizumab pegol, ustekinumab, and methotrexate. Several weeks after beginning infusions of vedolizumab, the patient began to develop many erythematous papules and pustules on the face, chest (Figure 1), and buttocks that rapidly progressed into painful and coalescing nodules and cysts over the next several months. He was prescribed benzoyl peroxide wash 10% as well as several weeks of oral doxycycline 100 mg twice daily with no improvement. The patient denied any other new medications or triggers, fever, chills, bone pain, headache, fatigue, or myalgia. The skin involvement continued to worsen with successive vedolizumab infusions over a period of 8 weeks, which ultimately resulted in cessation of vedolizumab.

Physical examination revealed large, tender, pink, erythematous, and indurated plaques that were heavily studded with pink papules, pustules, and nodules on the cheeks (Figure 2), central chest, and buttocks. A punch biopsy of a pustule on the cheek showed ruptured suppurative folliculitis. The patient subsequently was diagnosed with AF-WOSS.

The patient then completed a 7-day course of sulfamethoxazole-trimethoprim followed by a 10-day course of amoxicillin-clavulanic acid, neither of which led to improvement of the lesions. He then was started on an oral prednisone taper (1 mg/kg starting dose) that ultimately totaled 14 weeks in length due to his frequent flares any time prednisone was decreased below 40 mg daily. After 3 weeks on the oral prednisone, the patient was started on 0.3 mg/kg of concomitant oral isotretinoin every other day, which slowly was increased as tolerated until he reached a goal dose of roughly 150 mg/kg, which resolved the acneform papules and pustules and allowed for successful tapering off the prednisone.

Many studies have been published regarding the safety and side-effect profile of vedolizumab, but most do not report acne as an adverse event.^3-5 A German cohort study by Baumgart et al³ reported acne as a side effect in 15 of 212 (7.1%) patients but did not classify the severity. Another case report noted nodulocystic acne in a patient receiving vedolizumab for treatment of inflammatory bowel disease; however, this patient responded well to the use of a tetracycline antibiotic and was able to continue therapy with vedolizumab.⁵ Our patient demonstrated a severe and uncommon case of acne classified as AF-WOSS following initiation of therapy with vedolizumab, which required treatment with systemic steroids plus oral isotretinoin and resulted in cessation of vedolizumab.

As new therapies emerge, it is important to document new or severe adverse effects so providers can choose an appropriate therapy and adequately counsel patients regarding the side effects. Although vedolizumab was thought to have gut-specific action, there is new evidence to suggest that the principal ligand of the α4β7 integrin, mucosal addressin cell adhesion molecule-1, is not only expressed on gut endothelial cells but also on fibroblasts and melanomas, which may provide insight into the observed extraintestinal side effects of vedolizumab.⁶

To the Editor:

Vedolizumab is an innovative monoclonal antibody targeted against the α4β7 integrin that is approved for treatment of moderate to severe ulcerative colitis and Crohn disease refractory to standard treatment.¹ Vedolizumab is thought to be gut specific, blocking integrins specific to T lymphocytes destined for the gastrointestinal tract and their interaction with endothelial cells, thereby modulating the adaptive immune system in the gut without systemic immunosuppression.² It generally is well tolerated, and acne rarely has been reported as an adverse event.^3,4 We present a case of acne fulminans without systemic symptoms (AF-WOSS) as a severe side effect of vedolizumab that responded very well to systemic steroids and oral isotretinoin in addition to the discontinuation of treatment.

A 46-year-old obese man presented to our dermatology clinic with a chief complaint of rapidly progressive tender skin lesions. The patient had a long-standing history of severe fistulating and stricturing Crohn disease status post–bowel resection with ileostomy and had recently started treatment with vedolizumab after failing treatment with infliximab, adalimumab, certolizumab pegol, ustekinumab, and methotrexate. Several weeks after beginning infusions of vedolizumab, the patient began to develop many erythematous papules and pustules on the face, chest (Figure 1), and buttocks that rapidly progressed into painful and coalescing nodules and cysts over the next several months. He was prescribed benzoyl peroxide wash 10% as well as several weeks of oral doxycycline 100 mg twice daily with no improvement. The patient denied any other new medications or triggers, fever, chills, bone pain, headache, fatigue, or myalgia. The skin involvement continued to worsen with successive vedolizumab infusions over a period of 8 weeks, which ultimately resulted in cessation of vedolizumab.

Physical examination revealed large, tender, pink, erythematous, and indurated plaques that were heavily studded with pink papules, pustules, and nodules on the cheeks (Figure 2), central chest, and buttocks. A punch biopsy of a pustule on the cheek showed ruptured suppurative folliculitis. The patient subsequently was diagnosed with AF-WOSS.

The patient then completed a 7-day course of sulfamethoxazole-trimethoprim followed by a 10-day course of amoxicillin-clavulanic acid, neither of which led to improvement of the lesions. He then was started on an oral prednisone taper (1 mg/kg starting dose) that ultimately totaled 14 weeks in length due to his frequent flares any time prednisone was decreased below 40 mg daily. After 3 weeks on the oral prednisone, the patient was started on 0.3 mg/kg of concomitant oral isotretinoin every other day, which slowly was increased as tolerated until he reached a goal dose of roughly 150 mg/kg, which resolved the acneform papules and pustules and allowed for successful tapering off the prednisone.

Many studies have been published regarding the safety and side-effect profile of vedolizumab, but most do not report acne as an adverse event.^3-5 A German cohort study by Baumgart et al³ reported acne as a side effect in 15 of 212 (7.1%) patients but did not classify the severity. Another case report noted nodulocystic acne in a patient receiving vedolizumab for treatment of inflammatory bowel disease; however, this patient responded well to the use of a tetracycline antibiotic and was able to continue therapy with vedolizumab.⁵ Our patient demonstrated a severe and uncommon case of acne classified as AF-WOSS following initiation of therapy with vedolizumab, which required treatment with systemic steroids plus oral isotretinoin and resulted in cessation of vedolizumab.

As new therapies emerge, it is important to document new or severe adverse effects so providers can choose an appropriate therapy and adequately counsel patients regarding the side effects. Although vedolizumab was thought to have gut-specific action, there is new evidence to suggest that the principal ligand of the α4β7 integrin, mucosal addressin cell adhesion molecule-1, is not only expressed on gut endothelial cells but also on fibroblasts and melanomas, which may provide insight into the observed extraintestinal side effects of vedolizumab.⁶

Practice Gap

One of the most important elements of successful reconstruction is effective undermining prior to placement of buried sutures. The main benefit of an evenly undermined plane is that tension is reduced, thus permitting seamless tissue mobilization and wound edge approximation.¹

However, achieving a consistent and appropriate plane can present challenges in certain blind spots within one’s field of work. A right hand–dominant surgeon might find it difficult to undermine tissue between the 3-o’clock and 6-o’clock positions (Figure 1) and often must resort to unnatural positioning to obtain adequate reach.

We propose a technique of reversing the grip on undermining scissors that improves efficiency without sacrificing technique.

Technique

The surgeon simply grasps the ring handles with the ring finger and thumb with the tip pointing to the wrist (Figure 2). Most of the control comes from rotating the wrist while spreading with the thumb (Figure 3).

The main advantage of the reverse-grip technique is that it prevents abduction of the arm at the shoulder joint, which reduces shoulder fatigue and keeps the elbow close to the trunk and away from the sterile surgical field. Achieving optimal ergonomics during surgery has been shown to reduce pain and likely prolong the surgeon’s career.²

A limitation of the reverse-grip technique is that direct visualization of the undermining plane is not achieved; however, direct visualization also is not obtained when undermining in the standard fashion unless the instruments are passed to the surgical assistant or the surgeon moves to the other side of the table.

Undermining can be performed safely without direct visualization as long as several rules are followed:

• The undermining plane is first established under direct visualization on the far side of the wound—at the 6-o’clock to 12-o’clock positions—and then followed to the area where direct visualization is not obtained.

• A blunt-tipped scissor is used to prevent penetrating trauma to neurovascular bundles. Blunt-tipped instruments allow more “feel” through tactile feedback to the surgeon and prevent accidental injury to these critical structures.

• A curved scissor is used with “tips up,” such that the surgeon does not unintentionally make the undermining plane deeper than anticipated.

Practice Implications

With practice, one can perform circumferential undermining independently with few alterations in stance and while maintaining a natural position throughout. Use of skin hooks to elevate the skin can further aid in visualizing the correct depth of undermining. If executed correctly, the reverse-grip technique can expand the surgeon’s work field, thus providing ease of dissection in difficult-to-reach areas.

Practice Gap

One of the most important elements of successful reconstruction is effective undermining prior to placement of buried sutures. The main benefit of an evenly undermined plane is that tension is reduced, thus permitting seamless tissue mobilization and wound edge approximation.¹

However, achieving a consistent and appropriate plane can present challenges in certain blind spots within one’s field of work. A right hand–dominant surgeon might find it difficult to undermine tissue between the 3-o’clock and 6-o’clock positions (Figure 1) and often must resort to unnatural positioning to obtain adequate reach.

We propose a technique of reversing the grip on undermining scissors that improves efficiency without sacrificing technique.

Technique

The surgeon simply grasps the ring handles with the ring finger and thumb with the tip pointing to the wrist (Figure 2). Most of the control comes from rotating the wrist while spreading with the thumb (Figure 3).

The main advantage of the reverse-grip technique is that it prevents abduction of the arm at the shoulder joint, which reduces shoulder fatigue and keeps the elbow close to the trunk and away from the sterile surgical field. Achieving optimal ergonomics during surgery has been shown to reduce pain and likely prolong the surgeon’s career.²

A limitation of the reverse-grip technique is that direct visualization of the undermining plane is not achieved; however, direct visualization also is not obtained when undermining in the standard fashion unless the instruments are passed to the surgical assistant or the surgeon moves to the other side of the table.

Undermining can be performed safely without direct visualization as long as several rules are followed:

• The undermining plane is first established under direct visualization on the far side of the wound—at the 6-o’clock to 12-o’clock positions—and then followed to the area where direct visualization is not obtained.

• A blunt-tipped scissor is used to prevent penetrating trauma to neurovascular bundles. Blunt-tipped instruments allow more “feel” through tactile feedback to the surgeon and prevent accidental injury to these critical structures.

• A curved scissor is used with “tips up,” such that the surgeon does not unintentionally make the undermining plane deeper than anticipated.

Practice Implications

With practice, one can perform circumferential undermining independently with few alterations in stance and while maintaining a natural position throughout. Use of skin hooks to elevate the skin can further aid in visualizing the correct depth of undermining. If executed correctly, the reverse-grip technique can expand the surgeon’s work field, thus providing ease of dissection in difficult-to-reach areas.

Practice Gap

One of the most important elements of successful reconstruction is effective undermining prior to placement of buried sutures. The main benefit of an evenly undermined plane is that tension is reduced, thus permitting seamless tissue mobilization and wound edge approximation.¹

However, achieving a consistent and appropriate plane can present challenges in certain blind spots within one’s field of work. A right hand–dominant surgeon might find it difficult to undermine tissue between the 3-o’clock and 6-o’clock positions (Figure 1) and often must resort to unnatural positioning to obtain adequate reach.

We propose a technique of reversing the grip on undermining scissors that improves efficiency without sacrificing technique.

Technique

The surgeon simply grasps the ring handles with the ring finger and thumb with the tip pointing to the wrist (Figure 2). Most of the control comes from rotating the wrist while spreading with the thumb (Figure 3).

The main advantage of the reverse-grip technique is that it prevents abduction of the arm at the shoulder joint, which reduces shoulder fatigue and keeps the elbow close to the trunk and away from the sterile surgical field. Achieving optimal ergonomics during surgery has been shown to reduce pain and likely prolong the surgeon’s career.²

A limitation of the reverse-grip technique is that direct visualization of the undermining plane is not achieved; however, direct visualization also is not obtained when undermining in the standard fashion unless the instruments are passed to the surgical assistant or the surgeon moves to the other side of the table.

Undermining can be performed safely without direct visualization as long as several rules are followed:

• The undermining plane is first established under direct visualization on the far side of the wound—at the 6-o’clock to 12-o’clock positions—and then followed to the area where direct visualization is not obtained.

• A blunt-tipped scissor is used to prevent penetrating trauma to neurovascular bundles. Blunt-tipped instruments allow more “feel” through tactile feedback to the surgeon and prevent accidental injury to these critical structures.

• A curved scissor is used with “tips up,” such that the surgeon does not unintentionally make the undermining plane deeper than anticipated.

Practice Implications

With practice, one can perform circumferential undermining independently with few alterations in stance and while maintaining a natural position throughout. Use of skin hooks to elevate the skin can further aid in visualizing the correct depth of undermining. If executed correctly, the reverse-grip technique can expand the surgeon’s work field, thus providing ease of dissection in difficult-to-reach areas.