Nonmelanoma Skin Cancer

PORTLAND – A standard course of topical 5-fluorouracil (5-FU) does not noticeably improve visual signs of facial photoaging, such as forehead lines and crow’s feet, according to the results of a blinded, controlled study of 281 elderly white men.

Four validated photonumeric measures revealed no statistically significant differences between the intervention and vehicle control arms at 6, 12, or 18 months’ follow-up, Kaveri Korgavkar, MD, said at the annual meeting of the Society for Investigative Dermatology. “This might be a true lack of impact, or current scales may not be sensitive enough to capture aspects of aging that are improved by 5-fluorouracil,” commented Dr. Korgavkar, who presented the findings on behalf of the VAKCCT (the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial) work group.

PORTLAND – A standard course of topical 5-fluorouracil (5-FU) does not noticeably improve visual signs of facial photoaging, such as forehead lines and crow’s feet, according to the results of a blinded, controlled study of 281 elderly white men.

Four validated photonumeric measures revealed no statistically significant differences between the intervention and vehicle control arms at 6, 12, or 18 months’ follow-up, Kaveri Korgavkar, MD, said at the annual meeting of the Society for Investigative Dermatology. “This might be a true lack of impact, or current scales may not be sensitive enough to capture aspects of aging that are improved by 5-fluorouracil,” commented Dr. Korgavkar, who presented the findings on behalf of the VAKCCT (the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial) work group.

PORTLAND – A standard course of topical 5-fluorouracil (5-FU) does not noticeably improve visual signs of facial photoaging, such as forehead lines and crow’s feet, according to the results of a blinded, controlled study of 281 elderly white men.

Four validated photonumeric measures revealed no statistically significant differences between the intervention and vehicle control arms at 6, 12, or 18 months’ follow-up, Kaveri Korgavkar, MD, said at the annual meeting of the Society for Investigative Dermatology. “This might be a true lack of impact, or current scales may not be sensitive enough to capture aspects of aging that are improved by 5-fluorouracil,” commented Dr. Korgavkar, who presented the findings on behalf of the VAKCCT (the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial) work group.

For selected patients with basal cell carcinoma, one-stop shopping – diagnosing, subtyping, and excising the lesion all in one visit – using reflectance confocal microscopy was found noninferior to the standard approach of obtaining a punch biopsy to diagnose and subtype the lesion in one visit and performing surgical excision in a separate visit.

Those were the findings of an open-label, randomized, noninferiority trial in the Netherlands comparing the two approaches in 95 adults with suspected basal cell carcinoma (BCC), investigators reported.

In addition to reducing the number of visits and the total time required for treatment, this new approach uses noninvasive reflectance confocal microscopy in the place of punch biopsy, which patients will likely prefer, said Daniel J. Kadouch, MD, of the department of dermatology, Academic Medical Center, Amsterdam, and his associates (British J Derm. 2017 Apr 9. doi: 10.1111/bjd.15559).

The study excluded patients who had lesions in a high-risk location of the face, lesions larger than 20 mm, recurrent lesions, and macroscopic ulcerating lesions, as well as patients who had basal cell nevus syndrome. Another 22 patients who were found to have non-BCC lesions (1 melanoma, 2 squamous cell carcinomas, 5 cases of Bowen’s disease, and 11 nonmalignant lesions) also were excluded, leaving 40 patients with BCC in the one-stop shopping group and 33 in the standard of care (control) group.

The primary outcome – the proportion of patients with tumor-free margins on the final pathology report after surgical excision – was 100% (40 of 40) in the one-stop shopping group and 94% (31 of 33) in the control group, which demonstrates the noninferiority of the new, less invasive approach, Dr. Kadouch and his associates said.

The mean total treatment time was 2 hours and 23 minutes for the one-stop shopping group. The total treatment time could not be determined for the control group because their surgical times weren’t recorded.

Adverse events included four postoperative wound infections in the one-stop shopping group, all of which were successfully treated with oral antibiotics, and one case of excessive postoperative bleeding in the control group, which required 3 days of hospitalization.

This study was limited in that it excluded patients with large lesions and those with BCC on high-risk areas of the face, which reduces the generalizability of the findings. In addition, a follow-up time of at least 1 year would be needed to detect signs of BCC recurrence in the study participants, the investigators said.

For selected patients with basal cell carcinoma, one-stop shopping – diagnosing, subtyping, and excising the lesion all in one visit – using reflectance confocal microscopy was found noninferior to the standard approach of obtaining a punch biopsy to diagnose and subtype the lesion in one visit and performing surgical excision in a separate visit.

Those were the findings of an open-label, randomized, noninferiority trial in the Netherlands comparing the two approaches in 95 adults with suspected basal cell carcinoma (BCC), investigators reported.

In addition to reducing the number of visits and the total time required for treatment, this new approach uses noninvasive reflectance confocal microscopy in the place of punch biopsy, which patients will likely prefer, said Daniel J. Kadouch, MD, of the department of dermatology, Academic Medical Center, Amsterdam, and his associates (British J Derm. 2017 Apr 9. doi: 10.1111/bjd.15559).

The study excluded patients who had lesions in a high-risk location of the face, lesions larger than 20 mm, recurrent lesions, and macroscopic ulcerating lesions, as well as patients who had basal cell nevus syndrome. Another 22 patients who were found to have non-BCC lesions (1 melanoma, 2 squamous cell carcinomas, 5 cases of Bowen’s disease, and 11 nonmalignant lesions) also were excluded, leaving 40 patients with BCC in the one-stop shopping group and 33 in the standard of care (control) group.

The primary outcome – the proportion of patients with tumor-free margins on the final pathology report after surgical excision – was 100% (40 of 40) in the one-stop shopping group and 94% (31 of 33) in the control group, which demonstrates the noninferiority of the new, less invasive approach, Dr. Kadouch and his associates said.

The mean total treatment time was 2 hours and 23 minutes for the one-stop shopping group. The total treatment time could not be determined for the control group because their surgical times weren’t recorded.

Adverse events included four postoperative wound infections in the one-stop shopping group, all of which were successfully treated with oral antibiotics, and one case of excessive postoperative bleeding in the control group, which required 3 days of hospitalization.

This study was limited in that it excluded patients with large lesions and those with BCC on high-risk areas of the face, which reduces the generalizability of the findings. In addition, a follow-up time of at least 1 year would be needed to detect signs of BCC recurrence in the study participants, the investigators said.

For selected patients with basal cell carcinoma, one-stop shopping – diagnosing, subtyping, and excising the lesion all in one visit – using reflectance confocal microscopy was found noninferior to the standard approach of obtaining a punch biopsy to diagnose and subtype the lesion in one visit and performing surgical excision in a separate visit.

Those were the findings of an open-label, randomized, noninferiority trial in the Netherlands comparing the two approaches in 95 adults with suspected basal cell carcinoma (BCC), investigators reported.

In addition to reducing the number of visits and the total time required for treatment, this new approach uses noninvasive reflectance confocal microscopy in the place of punch biopsy, which patients will likely prefer, said Daniel J. Kadouch, MD, of the department of dermatology, Academic Medical Center, Amsterdam, and his associates (British J Derm. 2017 Apr 9. doi: 10.1111/bjd.15559).

The study excluded patients who had lesions in a high-risk location of the face, lesions larger than 20 mm, recurrent lesions, and macroscopic ulcerating lesions, as well as patients who had basal cell nevus syndrome. Another 22 patients who were found to have non-BCC lesions (1 melanoma, 2 squamous cell carcinomas, 5 cases of Bowen’s disease, and 11 nonmalignant lesions) also were excluded, leaving 40 patients with BCC in the one-stop shopping group and 33 in the standard of care (control) group.

The primary outcome – the proportion of patients with tumor-free margins on the final pathology report after surgical excision – was 100% (40 of 40) in the one-stop shopping group and 94% (31 of 33) in the control group, which demonstrates the noninferiority of the new, less invasive approach, Dr. Kadouch and his associates said.

The mean total treatment time was 2 hours and 23 minutes for the one-stop shopping group. The total treatment time could not be determined for the control group because their surgical times weren’t recorded.

Adverse events included four postoperative wound infections in the one-stop shopping group, all of which were successfully treated with oral antibiotics, and one case of excessive postoperative bleeding in the control group, which required 3 days of hospitalization.

This study was limited in that it excluded patients with large lesions and those with BCC on high-risk areas of the face, which reduces the generalizability of the findings. In addition, a follow-up time of at least 1 year would be needed to detect signs of BCC recurrence in the study participants, the investigators said.

The Diagnosis: Collision Tumor

Excisional biopsy and histopathological examination demonstrated a collision tumor composed of a benign intradermal melanocytic nevus, tumor of follicular infundibulum, and an underlying sclerosing epithelial neoplasm, with a differential diagnosis of desmoplastic trichoepithelioma, morpheaform basal cell carcinoma, and microcystic adnexal carcinoma (Figure).

Common acquired melanocytic nevus presents clinically as a macule, papule, or nodule with smooth regular borders. The pigmented variant displays an evenly distributed pigment on the lesion. Intradermal melanocytic nevus often presents as a flesh-colored nodule, as in our case. Histopathologically, benign intradermal nevus typically is composed of a proliferation of melanocytes that exhibit dispersion as they go deeper in the dermis and maturation that manifests as melanocytes becoming smaller and more spindled in the deeper portions of the lesion.¹ These 2 characteristics plus the bland cytology seen in the present case confirm the benign characteristic of this lesion (Figure, B).

In addition to the benign intradermal melanocytic nevus, an adjacent tumor of follicular infundibulum was noted. Tumor of follicular infundibulum is a rare adnexal tumor. It occurs frequently on the head and neck and shows some female predominance.^2,3 Multiple lesions and eruptive lesions are rare forms that also have been reported.⁴ Histopathologically, the tumor demonstrates an epithelial plate that is present in the papillary dermis and is connected to the epidermis at multiple points with attachment to the follicular outer root sheath. Peripheral palisading is characteristically present above an eosinophilic basement membrane (Figure, A). Rare reports have documented sebaceous and eccrine differentiation.^5,6

Tumor of follicular infundibulum has been reported to be associated with other tumors. Organoid nevus (nevus sebaceous), trichilemmal tumor, and fibroma have been reported to occur as a collision tumor with tumor of follicular infundibulum. An association with Cowden disease also has been described.⁷ Biopsies that represent partial samples should be interpreted cautiously, as step sections can reveal basal cell carcinoma.

The term sclerosing epithelial neoplasm describes tumors that share a paisley tielike epithelial pattern and sclerotic stroma. Small specimens often require clinicopathologic correlation (Figure, C). The differential diagnosis includes morpheaform basal cell carcinoma, desmoplastic trichoepithelioma, and microcystic adnexal carcinoma. A panel of stains using Ber-EP4, PHLDA1, cytokeratin 15, and cytokeratin 19 has been proposed to help differentiate these entities.⁸ CD34 and cytokeratin 20 also have been used with varying success in small specimens.^9,10

The Diagnosis: Collision Tumor

Excisional biopsy and histopathological examination demonstrated a collision tumor composed of a benign intradermal melanocytic nevus, tumor of follicular infundibulum, and an underlying sclerosing epithelial neoplasm, with a differential diagnosis of desmoplastic trichoepithelioma, morpheaform basal cell carcinoma, and microcystic adnexal carcinoma (Figure).

Common acquired melanocytic nevus presents clinically as a macule, papule, or nodule with smooth regular borders. The pigmented variant displays an evenly distributed pigment on the lesion. Intradermal melanocytic nevus often presents as a flesh-colored nodule, as in our case. Histopathologically, benign intradermal nevus typically is composed of a proliferation of melanocytes that exhibit dispersion as they go deeper in the dermis and maturation that manifests as melanocytes becoming smaller and more spindled in the deeper portions of the lesion.¹ These 2 characteristics plus the bland cytology seen in the present case confirm the benign characteristic of this lesion (Figure, B).

In addition to the benign intradermal melanocytic nevus, an adjacent tumor of follicular infundibulum was noted. Tumor of follicular infundibulum is a rare adnexal tumor. It occurs frequently on the head and neck and shows some female predominance.^2,3 Multiple lesions and eruptive lesions are rare forms that also have been reported.⁴ Histopathologically, the tumor demonstrates an epithelial plate that is present in the papillary dermis and is connected to the epidermis at multiple points with attachment to the follicular outer root sheath. Peripheral palisading is characteristically present above an eosinophilic basement membrane (Figure, A). Rare reports have documented sebaceous and eccrine differentiation.^5,6

Tumor of follicular infundibulum has been reported to be associated with other tumors. Organoid nevus (nevus sebaceous), trichilemmal tumor, and fibroma have been reported to occur as a collision tumor with tumor of follicular infundibulum. An association with Cowden disease also has been described.⁷ Biopsies that represent partial samples should be interpreted cautiously, as step sections can reveal basal cell carcinoma.

The term sclerosing epithelial neoplasm describes tumors that share a paisley tielike epithelial pattern and sclerotic stroma. Small specimens often require clinicopathologic correlation (Figure, C). The differential diagnosis includes morpheaform basal cell carcinoma, desmoplastic trichoepithelioma, and microcystic adnexal carcinoma. A panel of stains using Ber-EP4, PHLDA1, cytokeratin 15, and cytokeratin 19 has been proposed to help differentiate these entities.⁸ CD34 and cytokeratin 20 also have been used with varying success in small specimens.^9,10

The Diagnosis: Collision Tumor

Excisional biopsy and histopathological examination demonstrated a collision tumor composed of a benign intradermal melanocytic nevus, tumor of follicular infundibulum, and an underlying sclerosing epithelial neoplasm, with a differential diagnosis of desmoplastic trichoepithelioma, morpheaform basal cell carcinoma, and microcystic adnexal carcinoma (Figure).

Common acquired melanocytic nevus presents clinically as a macule, papule, or nodule with smooth regular borders. The pigmented variant displays an evenly distributed pigment on the lesion. Intradermal melanocytic nevus often presents as a flesh-colored nodule, as in our case. Histopathologically, benign intradermal nevus typically is composed of a proliferation of melanocytes that exhibit dispersion as they go deeper in the dermis and maturation that manifests as melanocytes becoming smaller and more spindled in the deeper portions of the lesion.¹ These 2 characteristics plus the bland cytology seen in the present case confirm the benign characteristic of this lesion (Figure, B).

In addition to the benign intradermal melanocytic nevus, an adjacent tumor of follicular infundibulum was noted. Tumor of follicular infundibulum is a rare adnexal tumor. It occurs frequently on the head and neck and shows some female predominance.^2,3 Multiple lesions and eruptive lesions are rare forms that also have been reported.⁴ Histopathologically, the tumor demonstrates an epithelial plate that is present in the papillary dermis and is connected to the epidermis at multiple points with attachment to the follicular outer root sheath. Peripheral palisading is characteristically present above an eosinophilic basement membrane (Figure, A). Rare reports have documented sebaceous and eccrine differentiation.^5,6

Tumor of follicular infundibulum has been reported to be associated with other tumors. Organoid nevus (nevus sebaceous), trichilemmal tumor, and fibroma have been reported to occur as a collision tumor with tumor of follicular infundibulum. An association with Cowden disease also has been described.⁷ Biopsies that represent partial samples should be interpreted cautiously, as step sections can reveal basal cell carcinoma.

The term sclerosing epithelial neoplasm describes tumors that share a paisley tielike epithelial pattern and sclerotic stroma. Small specimens often require clinicopathologic correlation (Figure, C). The differential diagnosis includes morpheaform basal cell carcinoma, desmoplastic trichoepithelioma, and microcystic adnexal carcinoma. A panel of stains using Ber-EP4, PHLDA1, cytokeratin 15, and cytokeratin 19 has been proposed to help differentiate these entities.⁸ CD34 and cytokeratin 20 also have been used with varying success in small specimens.^9,10

Avelumab (Bavencio) is the first drug to receive approval from the Food and Drug Administration for Merkel cell carcinoma, and new findings show that it elicited durable responses in this hard-to-treat population.

The majority of responses were durable beyond 1 year, with an objective response rate of 33%.

“Merkel cell carcinoma is rare, aggressive skin cancer with a poor prognosis,” said lead author Howard L. Kaufman, MD, a surgical oncologist at the Rutgers Cancer Institute of New Jersey in New Brunswick, who discussed the findings during a presscast held at the annual meeting of the American Association for Cancer Research.

Even though Merkel cell carcinoma is a chemosensitive disease, long-term survival beyond 6 months has not been reported with chemotherapy, explained Dr. Kaufman.

In this phase II trial, Dr. Kaufman and his colleagues assessed the use of avelumab, a fully human anti–PD-L1 monoclonal antibody, in 88 patients with metastatic Merkel cell carcinoma that had progressed after treatment with chemotherapy.

All patients received 10 mg/kg avelumab as an intravenous infusion over one hour every 2 weeks. The primary endpoint was the best objective response and secondary endpoints included progression-free and overall survival.

At a median follow-up of 10.4 months, the response rate was 31.8% (28 responses), and this included 8 complete responses and 20 partial responses.

The estimated proportion of patients with duration of response of 6 months or longer was 92%, and the 6-month progression-free survival rate was 40%.

“The purpose of the presentation now is to report on longer 1-year follow-up data,” said Dr. Kaufman.

In the updated results, the objective response rate was 33.0% (95% confidence interval, 23.3%-43.8%) as two more patients moved into a total response. There were now a total of 10 (11.4%) complete responses and 19 (21.6%) partial responses.

The 6-month durable response rate was 30.6% (95% CI, 20.9%-40.3%), and the median duration of response has not yet been reached (range, 2.8–23.3-plus months; 95% CI, 18.0–not estimable). Responses were ongoing in 21 patients at the time of this analysis.

The estimated proportion of patients with a duration of response lasting 1 year or longer was 74% (95% CI, 53%-87%), and estimated 1-year progression-free survival was 30% (95% CI, 21%-41%). The 1-year overall survival rate was 52% (95% CI, 41%-62%) and median overall survival was 12.9 months (95% CI, 7.5–not estimable).

The maturing survival data suggest that there may be a long-term benefit for a proportion of patients.

“The findings of long-term responses and well-tolerated safety profile suggest that avelumab could be an important new agent for patients with Merkel cell carcinoma who have failed prior chemotherapy,” said Dr. Kaufman. “Given these results, it will be interesting to determine whether response rates could be increased by giving avelumab prior to chemotherapy or in combination with other treatments.”

op@frontlinemedcom.com

Avelumab (Bavencio) is the first drug to receive approval from the Food and Drug Administration for Merkel cell carcinoma, and new findings show that it elicited durable responses in this hard-to-treat population.

The majority of responses were durable beyond 1 year, with an objective response rate of 33%.

“Merkel cell carcinoma is rare, aggressive skin cancer with a poor prognosis,” said lead author Howard L. Kaufman, MD, a surgical oncologist at the Rutgers Cancer Institute of New Jersey in New Brunswick, who discussed the findings during a presscast held at the annual meeting of the American Association for Cancer Research.

Even though Merkel cell carcinoma is a chemosensitive disease, long-term survival beyond 6 months has not been reported with chemotherapy, explained Dr. Kaufman.

In this phase II trial, Dr. Kaufman and his colleagues assessed the use of avelumab, a fully human anti–PD-L1 monoclonal antibody, in 88 patients with metastatic Merkel cell carcinoma that had progressed after treatment with chemotherapy.

All patients received 10 mg/kg avelumab as an intravenous infusion over one hour every 2 weeks. The primary endpoint was the best objective response and secondary endpoints included progression-free and overall survival.

At a median follow-up of 10.4 months, the response rate was 31.8% (28 responses), and this included 8 complete responses and 20 partial responses.

The estimated proportion of patients with duration of response of 6 months or longer was 92%, and the 6-month progression-free survival rate was 40%.

“The purpose of the presentation now is to report on longer 1-year follow-up data,” said Dr. Kaufman.

In the updated results, the objective response rate was 33.0% (95% confidence interval, 23.3%-43.8%) as two more patients moved into a total response. There were now a total of 10 (11.4%) complete responses and 19 (21.6%) partial responses.

The 6-month durable response rate was 30.6% (95% CI, 20.9%-40.3%), and the median duration of response has not yet been reached (range, 2.8–23.3-plus months; 95% CI, 18.0–not estimable). Responses were ongoing in 21 patients at the time of this analysis.

The estimated proportion of patients with a duration of response lasting 1 year or longer was 74% (95% CI, 53%-87%), and estimated 1-year progression-free survival was 30% (95% CI, 21%-41%). The 1-year overall survival rate was 52% (95% CI, 41%-62%) and median overall survival was 12.9 months (95% CI, 7.5–not estimable).

The maturing survival data suggest that there may be a long-term benefit for a proportion of patients.

“The findings of long-term responses and well-tolerated safety profile suggest that avelumab could be an important new agent for patients with Merkel cell carcinoma who have failed prior chemotherapy,” said Dr. Kaufman. “Given these results, it will be interesting to determine whether response rates could be increased by giving avelumab prior to chemotherapy or in combination with other treatments.”

op@frontlinemedcom.com

Avelumab (Bavencio) is the first drug to receive approval from the Food and Drug Administration for Merkel cell carcinoma, and new findings show that it elicited durable responses in this hard-to-treat population.

The majority of responses were durable beyond 1 year, with an objective response rate of 33%.

“Merkel cell carcinoma is rare, aggressive skin cancer with a poor prognosis,” said lead author Howard L. Kaufman, MD, a surgical oncologist at the Rutgers Cancer Institute of New Jersey in New Brunswick, who discussed the findings during a presscast held at the annual meeting of the American Association for Cancer Research.

Even though Merkel cell carcinoma is a chemosensitive disease, long-term survival beyond 6 months has not been reported with chemotherapy, explained Dr. Kaufman.

In this phase II trial, Dr. Kaufman and his colleagues assessed the use of avelumab, a fully human anti–PD-L1 monoclonal antibody, in 88 patients with metastatic Merkel cell carcinoma that had progressed after treatment with chemotherapy.

All patients received 10 mg/kg avelumab as an intravenous infusion over one hour every 2 weeks. The primary endpoint was the best objective response and secondary endpoints included progression-free and overall survival.

At a median follow-up of 10.4 months, the response rate was 31.8% (28 responses), and this included 8 complete responses and 20 partial responses.

The estimated proportion of patients with duration of response of 6 months or longer was 92%, and the 6-month progression-free survival rate was 40%.

“The purpose of the presentation now is to report on longer 1-year follow-up data,” said Dr. Kaufman.

In the updated results, the objective response rate was 33.0% (95% confidence interval, 23.3%-43.8%) as two more patients moved into a total response. There were now a total of 10 (11.4%) complete responses and 19 (21.6%) partial responses.

The 6-month durable response rate was 30.6% (95% CI, 20.9%-40.3%), and the median duration of response has not yet been reached (range, 2.8–23.3-plus months; 95% CI, 18.0–not estimable). Responses were ongoing in 21 patients at the time of this analysis.

The estimated proportion of patients with a duration of response lasting 1 year or longer was 74% (95% CI, 53%-87%), and estimated 1-year progression-free survival was 30% (95% CI, 21%-41%). The 1-year overall survival rate was 52% (95% CI, 41%-62%) and median overall survival was 12.9 months (95% CI, 7.5–not estimable).

The maturing survival data suggest that there may be a long-term benefit for a proportion of patients.

“The findings of long-term responses and well-tolerated safety profile suggest that avelumab could be an important new agent for patients with Merkel cell carcinoma who have failed prior chemotherapy,” said Dr. Kaufman. “Given these results, it will be interesting to determine whether response rates could be increased by giving avelumab prior to chemotherapy or in combination with other treatments.”

op@frontlinemedcom.com

Case Report

A 50-year-old man with a history of antisynthetase syndrome (positive for anti–Jo-1 polymyositis with interstitial lung disease) and sarcoidosis presented for evaluation of numerous new moles. The lesions had developed on the trunk, arms, legs, hands, and feet approximately 3 weeks after starting azathioprine 100 mg once daily for pulmonary and muscular involvement of antisynthetase syndrome. He denied any preceding cutaneous inflammation or sunburns. He had no personal or family history of skin cancer, and no family members had multiple nevi. Physical examination revealed 30 to 40 benign-appearing, 2- to 5-mm, hyperpigmented macules scattered on the medial aspect of the right foot (Figure 1A), left palm (Figure 1B), back, abdomen, chest, arms, and legs. A larger, somewhat asymmetric, irregularly bordered, and irregularly pigmented macule was noted on the left side of the upper back. A punch biopsy of the lesion revealed a benign, mildly atypical lentiginous compound nevus (Figure 2). Pathology confirmed that the lesions represented eruptive melanocytic nevi (EMN). The patient continued azathioprine therapy and was followed with regular full-body skin examinations. Mycophenolate mofetil was suggested as an alternative therapy, if clinically appropriate, though this change has not been made by the patient’s rheumatologists.

Comment

A PubMed search of articles indexed for MEDLINE using the search terms eruptive melanocytic nevi and azathioprine revealed 14 cases of EMN in the setting of azathioprine therapy, either during azathioprine monotherapy or in combination with other immunosuppressants, including systemic corticosteroids, biologics, and cyclosporine (Table).^1-5 The majority of these cases occurred in renal transplant patients,¹ with 3 additional cases reported in the setting of Crohn disease,^2,3,5 and another in a patient with myasthenia gravis.⁴ Patients ranged in age from 8 to 42 years (mean age, 22 years), with lesions developing a few months to up to 7 years after starting therapy. When specified, the reported lesions typically were small, ranging from 1 to 3 mm in size, and developed rapidly over a couple of months with a predilection for the palms, soles, and trunk. Although dysplastic nevi were described in only 2 patients, melanomas were not detected.

Various hypotheses have sought to explain the largely unknown etiology of EMN. Bovenschen et al³ suggested that immunocompromised patients have diminished immune surveillance in the skin, which allows for unchecked proliferation of melanocytes. Specifically, immune suppression may induce melanocyte-stimulating hormone or melanoma growth stimulatory activity, with composition-specific growth in skin at the palms and soles.^3,4 The preferential growth on the palms and soles suggests that those regions may have special sensitivity to melanocyte-stimulating hormone.⁴ Woodhouse and Maytin⁶ postulated that the increased density of eccrine sweat glands in the palms and soles as well as the absence of pilosebaceous units and apocrine glands and plentiful Pacinian and Meissner corpuscles may allow for a unique response to circulating melanocytic growth factors. Another hypothesis suggests the presence of genetic factors that allow subclinical nests of nevus cells to form, which become clinical eruptions following chemotherapy or immunosuppressive therapy.³ Azathioprine also has been suggested to induce various transcription factors that play a critical role in differentiation and proliferation of melanocytic stem cells, which leads to the formation of nevi.⁴ Our case and others similar to it implore that further studies be done to determine the molecular mechanism driving this phenomenon and whether a specific genetic predisposition exists that lowers the threshold for rapid proliferation of melanocytes given an immunosuppressed status.²

The risk for melanoma development in cases of EMN is unknown. Although our review of the literature did not reveal any melanomas reported in cases attributed to azathioprine, a theoretical risk exists given the established associations between melanoma and immunosuppression as well as increased numbers of nevi.⁶ Accordingly, these patients should be followed with regular skin examinations and biopsies of atypical-appearing lesions as indicated.^2,3,5 Braun et al⁴ also suggested the discontinuance of azathioprine and switch to mycophenolic acid, which has not been noted to cause such eruptions; this drug was recommended in our case.

Case Report

A 50-year-old man with a history of antisynthetase syndrome (positive for anti–Jo-1 polymyositis with interstitial lung disease) and sarcoidosis presented for evaluation of numerous new moles. The lesions had developed on the trunk, arms, legs, hands, and feet approximately 3 weeks after starting azathioprine 100 mg once daily for pulmonary and muscular involvement of antisynthetase syndrome. He denied any preceding cutaneous inflammation or sunburns. He had no personal or family history of skin cancer, and no family members had multiple nevi. Physical examination revealed 30 to 40 benign-appearing, 2- to 5-mm, hyperpigmented macules scattered on the medial aspect of the right foot (Figure 1A), left palm (Figure 1B), back, abdomen, chest, arms, and legs. A larger, somewhat asymmetric, irregularly bordered, and irregularly pigmented macule was noted on the left side of the upper back. A punch biopsy of the lesion revealed a benign, mildly atypical lentiginous compound nevus (Figure 2). Pathology confirmed that the lesions represented eruptive melanocytic nevi (EMN). The patient continued azathioprine therapy and was followed with regular full-body skin examinations. Mycophenolate mofetil was suggested as an alternative therapy, if clinically appropriate, though this change has not been made by the patient’s rheumatologists.

Comment

A PubMed search of articles indexed for MEDLINE using the search terms eruptive melanocytic nevi and azathioprine revealed 14 cases of EMN in the setting of azathioprine therapy, either during azathioprine monotherapy or in combination with other immunosuppressants, including systemic corticosteroids, biologics, and cyclosporine (Table).^1-5 The majority of these cases occurred in renal transplant patients,¹ with 3 additional cases reported in the setting of Crohn disease,^2,3,5 and another in a patient with myasthenia gravis.⁴ Patients ranged in age from 8 to 42 years (mean age, 22 years), with lesions developing a few months to up to 7 years after starting therapy. When specified, the reported lesions typically were small, ranging from 1 to 3 mm in size, and developed rapidly over a couple of months with a predilection for the palms, soles, and trunk. Although dysplastic nevi were described in only 2 patients, melanomas were not detected.

Various hypotheses have sought to explain the largely unknown etiology of EMN. Bovenschen et al³ suggested that immunocompromised patients have diminished immune surveillance in the skin, which allows for unchecked proliferation of melanocytes. Specifically, immune suppression may induce melanocyte-stimulating hormone or melanoma growth stimulatory activity, with composition-specific growth in skin at the palms and soles.^3,4 The preferential growth on the palms and soles suggests that those regions may have special sensitivity to melanocyte-stimulating hormone.⁴ Woodhouse and Maytin⁶ postulated that the increased density of eccrine sweat glands in the palms and soles as well as the absence of pilosebaceous units and apocrine glands and plentiful Pacinian and Meissner corpuscles may allow for a unique response to circulating melanocytic growth factors. Another hypothesis suggests the presence of genetic factors that allow subclinical nests of nevus cells to form, which become clinical eruptions following chemotherapy or immunosuppressive therapy.³ Azathioprine also has been suggested to induce various transcription factors that play a critical role in differentiation and proliferation of melanocytic stem cells, which leads to the formation of nevi.⁴ Our case and others similar to it implore that further studies be done to determine the molecular mechanism driving this phenomenon and whether a specific genetic predisposition exists that lowers the threshold for rapid proliferation of melanocytes given an immunosuppressed status.²

The risk for melanoma development in cases of EMN is unknown. Although our review of the literature did not reveal any melanomas reported in cases attributed to azathioprine, a theoretical risk exists given the established associations between melanoma and immunosuppression as well as increased numbers of nevi.⁶ Accordingly, these patients should be followed with regular skin examinations and biopsies of atypical-appearing lesions as indicated.^2,3,5 Braun et al⁴ also suggested the discontinuance of azathioprine and switch to mycophenolic acid, which has not been noted to cause such eruptions; this drug was recommended in our case.

Case Report

A 50-year-old man with a history of antisynthetase syndrome (positive for anti–Jo-1 polymyositis with interstitial lung disease) and sarcoidosis presented for evaluation of numerous new moles. The lesions had developed on the trunk, arms, legs, hands, and feet approximately 3 weeks after starting azathioprine 100 mg once daily for pulmonary and muscular involvement of antisynthetase syndrome. He denied any preceding cutaneous inflammation or sunburns. He had no personal or family history of skin cancer, and no family members had multiple nevi. Physical examination revealed 30 to 40 benign-appearing, 2- to 5-mm, hyperpigmented macules scattered on the medial aspect of the right foot (Figure 1A), left palm (Figure 1B), back, abdomen, chest, arms, and legs. A larger, somewhat asymmetric, irregularly bordered, and irregularly pigmented macule was noted on the left side of the upper back. A punch biopsy of the lesion revealed a benign, mildly atypical lentiginous compound nevus (Figure 2). Pathology confirmed that the lesions represented eruptive melanocytic nevi (EMN). The patient continued azathioprine therapy and was followed with regular full-body skin examinations. Mycophenolate mofetil was suggested as an alternative therapy, if clinically appropriate, though this change has not been made by the patient’s rheumatologists.

Comment

A PubMed search of articles indexed for MEDLINE using the search terms eruptive melanocytic nevi and azathioprine revealed 14 cases of EMN in the setting of azathioprine therapy, either during azathioprine monotherapy or in combination with other immunosuppressants, including systemic corticosteroids, biologics, and cyclosporine (Table).^1-5 The majority of these cases occurred in renal transplant patients,¹ with 3 additional cases reported in the setting of Crohn disease,^2,3,5 and another in a patient with myasthenia gravis.⁴ Patients ranged in age from 8 to 42 years (mean age, 22 years), with lesions developing a few months to up to 7 years after starting therapy. When specified, the reported lesions typically were small, ranging from 1 to 3 mm in size, and developed rapidly over a couple of months with a predilection for the palms, soles, and trunk. Although dysplastic nevi were described in only 2 patients, melanomas were not detected.

Various hypotheses have sought to explain the largely unknown etiology of EMN. Bovenschen et al³ suggested that immunocompromised patients have diminished immune surveillance in the skin, which allows for unchecked proliferation of melanocytes. Specifically, immune suppression may induce melanocyte-stimulating hormone or melanoma growth stimulatory activity, with composition-specific growth in skin at the palms and soles.^3,4 The preferential growth on the palms and soles suggests that those regions may have special sensitivity to melanocyte-stimulating hormone.⁴ Woodhouse and Maytin⁶ postulated that the increased density of eccrine sweat glands in the palms and soles as well as the absence of pilosebaceous units and apocrine glands and plentiful Pacinian and Meissner corpuscles may allow for a unique response to circulating melanocytic growth factors. Another hypothesis suggests the presence of genetic factors that allow subclinical nests of nevus cells to form, which become clinical eruptions following chemotherapy or immunosuppressive therapy.³ Azathioprine also has been suggested to induce various transcription factors that play a critical role in differentiation and proliferation of melanocytic stem cells, which leads to the formation of nevi.⁴ Our case and others similar to it implore that further studies be done to determine the molecular mechanism driving this phenomenon and whether a specific genetic predisposition exists that lowers the threshold for rapid proliferation of melanocytes given an immunosuppressed status.²

The risk for melanoma development in cases of EMN is unknown. Although our review of the literature did not reveal any melanomas reported in cases attributed to azathioprine, a theoretical risk exists given the established associations between melanoma and immunosuppression as well as increased numbers of nevi.⁶ Accordingly, these patients should be followed with regular skin examinations and biopsies of atypical-appearing lesions as indicated.^2,3,5 Braun et al⁴ also suggested the discontinuance of azathioprine and switch to mycophenolic acid, which has not been noted to cause such eruptions; this drug was recommended in our case.

The Food and Drug Administration has granted accelerated approval to avelumab for the treatment of metastatic Merkel cell carcinoma (MCC) in adult and pediatric patients aged 12 years and older.

Avelumab, a programmed death-ligand 1 (PD-L1)–blocking human IgG1 lambda monoclonal antibody, is the first FDA-approved treatment for metastatic MCC.

Approval was based on a 33% overall response rate in a single arm trial (JAVELIN Merkel 200 trial) of 88 patients with metastatic MCC who had been previously treated with at least one prior chemotherapy regimen, the FDA said in a written statement.

The response duration among that 33% ranged from 2.8 to 23.3+ months, and 86% of responses were durable for 6 months or more. “Responses were observed in patients regardless of PD-L1 tumor expression or presence of Merkel cell polyomavirus,” the FDA said.

There were safety data in 1,738 patients, who received 10 mg/kg of avelumab every 2 weeks. Immune-mediated adverse reactions (pneumonitis, colitis, hepatitis, adrenal insufficiency, hypo- and hyperthyroidism, diabetes mellitus, and nephritis) and life-threatening infusion reactions were the most common, serious adverse events associated with avelumab. Of the 88 patients in the JAVELIN Merkel 200 trial, the most common adverse reactions were fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, rash, decreased appetite, and peripheral edema. Serious adverse reactions that occurred in more than one patient in the trial were acute kidney injury, anemia, abdominal pain, ileus, asthenia, and cellulitis, the FDA said.

The recommended dose of avelumab is 10 mg/kg administered in an intravenous infusion over 60 minutes every 2 weeks. Labeling includes the recommendation that all patients should be premedicated with an antihistamine and acetaminophen before each of the first four infusions.

“As a condition of accelerated approval, an additional study is required to confirm the clinical benefit of avelumab for this indication,” according to the FDA.

The drug is being marketed as Bavencio by EMD Serono.

lnikolaides@frontlinemedcom.com
 

The Food and Drug Administration has granted accelerated approval to avelumab for the treatment of metastatic Merkel cell carcinoma (MCC) in adult and pediatric patients aged 12 years and older.

Avelumab, a programmed death-ligand 1 (PD-L1)–blocking human IgG1 lambda monoclonal antibody, is the first FDA-approved treatment for metastatic MCC.

Approval was based on a 33% overall response rate in a single arm trial (JAVELIN Merkel 200 trial) of 88 patients with metastatic MCC who had been previously treated with at least one prior chemotherapy regimen, the FDA said in a written statement.

The response duration among that 33% ranged from 2.8 to 23.3+ months, and 86% of responses were durable for 6 months or more. “Responses were observed in patients regardless of PD-L1 tumor expression or presence of Merkel cell polyomavirus,” the FDA said.

There were safety data in 1,738 patients, who received 10 mg/kg of avelumab every 2 weeks. Immune-mediated adverse reactions (pneumonitis, colitis, hepatitis, adrenal insufficiency, hypo- and hyperthyroidism, diabetes mellitus, and nephritis) and life-threatening infusion reactions were the most common, serious adverse events associated with avelumab. Of the 88 patients in the JAVELIN Merkel 200 trial, the most common adverse reactions were fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, rash, decreased appetite, and peripheral edema. Serious adverse reactions that occurred in more than one patient in the trial were acute kidney injury, anemia, abdominal pain, ileus, asthenia, and cellulitis, the FDA said.

The recommended dose of avelumab is 10 mg/kg administered in an intravenous infusion over 60 minutes every 2 weeks. Labeling includes the recommendation that all patients should be premedicated with an antihistamine and acetaminophen before each of the first four infusions.

“As a condition of accelerated approval, an additional study is required to confirm the clinical benefit of avelumab for this indication,” according to the FDA.

The drug is being marketed as Bavencio by EMD Serono.

lnikolaides@frontlinemedcom.com
 

The Food and Drug Administration has granted accelerated approval to avelumab for the treatment of metastatic Merkel cell carcinoma (MCC) in adult and pediatric patients aged 12 years and older.

Avelumab, a programmed death-ligand 1 (PD-L1)–blocking human IgG1 lambda monoclonal antibody, is the first FDA-approved treatment for metastatic MCC.

Approval was based on a 33% overall response rate in a single arm trial (JAVELIN Merkel 200 trial) of 88 patients with metastatic MCC who had been previously treated with at least one prior chemotherapy regimen, the FDA said in a written statement.

The response duration among that 33% ranged from 2.8 to 23.3+ months, and 86% of responses were durable for 6 months or more. “Responses were observed in patients regardless of PD-L1 tumor expression or presence of Merkel cell polyomavirus,” the FDA said.

There were safety data in 1,738 patients, who received 10 mg/kg of avelumab every 2 weeks. Immune-mediated adverse reactions (pneumonitis, colitis, hepatitis, adrenal insufficiency, hypo- and hyperthyroidism, diabetes mellitus, and nephritis) and life-threatening infusion reactions were the most common, serious adverse events associated with avelumab. Of the 88 patients in the JAVELIN Merkel 200 trial, the most common adverse reactions were fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, rash, decreased appetite, and peripheral edema. Serious adverse reactions that occurred in more than one patient in the trial were acute kidney injury, anemia, abdominal pain, ileus, asthenia, and cellulitis, the FDA said.

The recommended dose of avelumab is 10 mg/kg administered in an intravenous infusion over 60 minutes every 2 weeks. Labeling includes the recommendation that all patients should be premedicated with an antihistamine and acetaminophen before each of the first four infusions.

“As a condition of accelerated approval, an additional study is required to confirm the clinical benefit of avelumab for this indication,” according to the FDA.

The drug is being marketed as Bavencio by EMD Serono.

lnikolaides@frontlinemedcom.com
 

To the Editor:
Vismodegib, a first-in-class inhibitor of the hedgehog signaling pathway, is useful in the treatment of advanced basal cell carcinomas (BCCs).¹ Common side effects of vismodegib include alopecia (58%), muscle spasms (71%), and dysgeusia (71%).² Some of these side effects have been hypothesized to be mechanism related.^3,4 Keratoacanthomas have been reported to occur after vismodegib treatment of BCC.⁵ We report 3 cases illustrating reversible cutaneous side effects of vismodegib: alopecia, follicular dermatitis, and drug hypersensitivity reaction.

A 53-year-old man with a locally advanced BCC of the right medial canthus began experiencing progressive and diffuse hair loss on the beard area, parietal scalp, eyelashes, and eyebrows after 2 months of vismodegib treatment. At 12 months of treatment, he had complete loss of eyelashes and eyebrows (Figure, A). After vismodegib was discontinued due to disease progression, all of his hair began regrowing within several months, with complete hair regrowth observed at 20 months after the last dose (Figure, B).

A 55-year-old man with several locally advanced BCCs developed new-onset mildly pruritic, acneform lesions on the chest and back after 4 months of vismodegib treatment. Biopsy of the lesions showed a folliculocentric mixed dermal infiltrate. The patient did not have a history of follicular dermatitis. The dermatitis resolved several months after onset without treatment, despite continued vismodegib.

A 55-year-old man with locally advanced BCCs developed erythematous dermal plaques on the arms and chest after 2 months of vismodegib treatment. Lesions were asymptomatic. He was not using any other medications and did not have any contact allergen exposures. Punch biopsy showed superficial and deep perivascular dermatitis with occasional eosinophils, consistent with drug hypersensitivity. Although lesions spontaneously resolved without treatment after 1 month, he experienced a couple more bouts of these lesions over the next year. He continued vismodegib for 2 years without return of this eruption.

The average time frame for hair regrowth after vismodegib cessation has not been characterized and awaits future larger studies. The frequency of follicular dermatitis and drug eruption also has not been determined and may require careful observation by dermatologists in larger numbers of treated patients. 

Because the hedgehog pathway is critical for normal hair follicle function, follicle-based toxicities of vismodegib including alopecia and folliculitis could be hypothesized to reflect effective blockade of the pathway.⁶ Currently, there are no data that these changes correlate with tumor response. 

Although alopecia is a recognized side effect of vismodegib, regrowth has not been previously reported.^1,2 Knowledge of the reversibility of alopecia as well as other toxicities has the potential to influence patient decision-making on drug initiation and adherence.

To the Editor:
Vismodegib, a first-in-class inhibitor of the hedgehog signaling pathway, is useful in the treatment of advanced basal cell carcinomas (BCCs).¹ Common side effects of vismodegib include alopecia (58%), muscle spasms (71%), and dysgeusia (71%).² Some of these side effects have been hypothesized to be mechanism related.^3,4 Keratoacanthomas have been reported to occur after vismodegib treatment of BCC.⁵ We report 3 cases illustrating reversible cutaneous side effects of vismodegib: alopecia, follicular dermatitis, and drug hypersensitivity reaction.

A 53-year-old man with a locally advanced BCC of the right medial canthus began experiencing progressive and diffuse hair loss on the beard area, parietal scalp, eyelashes, and eyebrows after 2 months of vismodegib treatment. At 12 months of treatment, he had complete loss of eyelashes and eyebrows (Figure, A). After vismodegib was discontinued due to disease progression, all of his hair began regrowing within several months, with complete hair regrowth observed at 20 months after the last dose (Figure, B).

A 55-year-old man with several locally advanced BCCs developed new-onset mildly pruritic, acneform lesions on the chest and back after 4 months of vismodegib treatment. Biopsy of the lesions showed a folliculocentric mixed dermal infiltrate. The patient did not have a history of follicular dermatitis. The dermatitis resolved several months after onset without treatment, despite continued vismodegib.

A 55-year-old man with locally advanced BCCs developed erythematous dermal plaques on the arms and chest after 2 months of vismodegib treatment. Lesions were asymptomatic. He was not using any other medications and did not have any contact allergen exposures. Punch biopsy showed superficial and deep perivascular dermatitis with occasional eosinophils, consistent with drug hypersensitivity. Although lesions spontaneously resolved without treatment after 1 month, he experienced a couple more bouts of these lesions over the next year. He continued vismodegib for 2 years without return of this eruption.

The average time frame for hair regrowth after vismodegib cessation has not been characterized and awaits future larger studies. The frequency of follicular dermatitis and drug eruption also has not been determined and may require careful observation by dermatologists in larger numbers of treated patients. 

Because the hedgehog pathway is critical for normal hair follicle function, follicle-based toxicities of vismodegib including alopecia and folliculitis could be hypothesized to reflect effective blockade of the pathway.⁶ Currently, there are no data that these changes correlate with tumor response. 

Although alopecia is a recognized side effect of vismodegib, regrowth has not been previously reported.^1,2 Knowledge of the reversibility of alopecia as well as other toxicities has the potential to influence patient decision-making on drug initiation and adherence.

To the Editor:
Vismodegib, a first-in-class inhibitor of the hedgehog signaling pathway, is useful in the treatment of advanced basal cell carcinomas (BCCs).¹ Common side effects of vismodegib include alopecia (58%), muscle spasms (71%), and dysgeusia (71%).² Some of these side effects have been hypothesized to be mechanism related.^3,4 Keratoacanthomas have been reported to occur after vismodegib treatment of BCC.⁵ We report 3 cases illustrating reversible cutaneous side effects of vismodegib: alopecia, follicular dermatitis, and drug hypersensitivity reaction.

A 53-year-old man with a locally advanced BCC of the right medial canthus began experiencing progressive and diffuse hair loss on the beard area, parietal scalp, eyelashes, and eyebrows after 2 months of vismodegib treatment. At 12 months of treatment, he had complete loss of eyelashes and eyebrows (Figure, A). After vismodegib was discontinued due to disease progression, all of his hair began regrowing within several months, with complete hair regrowth observed at 20 months after the last dose (Figure, B).

A 55-year-old man with several locally advanced BCCs developed new-onset mildly pruritic, acneform lesions on the chest and back after 4 months of vismodegib treatment. Biopsy of the lesions showed a folliculocentric mixed dermal infiltrate. The patient did not have a history of follicular dermatitis. The dermatitis resolved several months after onset without treatment, despite continued vismodegib.

A 55-year-old man with locally advanced BCCs developed erythematous dermal plaques on the arms and chest after 2 months of vismodegib treatment. Lesions were asymptomatic. He was not using any other medications and did not have any contact allergen exposures. Punch biopsy showed superficial and deep perivascular dermatitis with occasional eosinophils, consistent with drug hypersensitivity. Although lesions spontaneously resolved without treatment after 1 month, he experienced a couple more bouts of these lesions over the next year. He continued vismodegib for 2 years without return of this eruption.

The average time frame for hair regrowth after vismodegib cessation has not been characterized and awaits future larger studies. The frequency of follicular dermatitis and drug eruption also has not been determined and may require careful observation by dermatologists in larger numbers of treated patients. 

Because the hedgehog pathway is critical for normal hair follicle function, follicle-based toxicities of vismodegib including alopecia and folliculitis could be hypothesized to reflect effective blockade of the pathway.⁶ Currently, there are no data that these changes correlate with tumor response. 

Although alopecia is a recognized side effect of vismodegib, regrowth has not been previously reported.^1,2 Knowledge of the reversibility of alopecia as well as other toxicities has the potential to influence patient decision-making on drug initiation and adherence.

Nonwhite organ transplant recipients (OTRs) are more likely to present with inflammatory or infectious conditions after transplantation, while white organ recipients more commonly present with malignant disease, new research suggests.

While the high incidence of skin cancers has been well described in patients who undergo solid organ transplants, little is known about the risk factors, incidence, locations, and types of skin disease that occur in nonwhite OTRs, wrote Christina Lee Chung, MD, from Drexel University, Philadelphia, and her coauthors in JAMA Dermatology.

In a retrospective review, the investigators examined the medical records of 412 organ transplant recipients treated at an academic referral center during 2011-2016, of whom 154 were white, 35 were Asian, 33 were Hispanic, and 190 were black (JAMA Dermatology. 2017 Mar 8. doi: 10.1001/jamadermatol.2017.0045).

Among the white patients, malignant or premalignant disease was the most common diagnostic category (67.8%), followed by inflammatory (20.7%) and infectious processes (11.6%). However, among nonwhite organ transplant recipients, inflammatory processes were present in 48.8% of patients, infectious processes in 37.5% and the remaining 13.7% presented with malignant or premalignant lesions.

Black and Hispanic patients were more likely to present with inflammatory or infectious disease; only 8.6% presented with malignant conditions and 16% presented with premalignant disease.

Among the Asian patient population, one-third presented with malignant or premalignant, one-third presented with infectious, and one-third presented with inflammatory conditions.

“Although early detection and treatment of cancer is vital, nonwhite OTRs would also benefit from addressing nonmalignant processes that are exacerbated by immunosuppression,” the authors wrote.

Overall, 389 skin cancers were diagnosed, with squamous cell carcinoma in situ (SCC) the most common type of skin cancer diagnosed in each racial or ethnic group. The mean time between transplant and first skin cancer lesion was 12.67 years in black patients, 6.5 years in Hispanic patients, 6.13 years among white patients, and 3.75 years in Asian patients.

The vast majority of skin cancers (95.1%) were found in white patients. While the majority of lesions in white and Asian patients were found in sun-exposed areas, the few skin cancers seen in black patients were more likely to be found in sun-protected areas, particularly the genitals.

Four of the six genital SCCs tested positive for high-risk human papillomavirus strains – in one Asian patient and three black patients – while the two SCCs found on lower extremities in Hispanic patients tested negative for HPV.

Researchers also looked at skin cancer awareness among the organ transplant recipients using data from initial visit questionnaires. They found that more than 17 of the 22 (77.3%) white organ transplant recipients surveyed were aware their skin cancer risk was increased, compared with 30 of the 44 (68.2%) nonwhite patients.

Similarly, 72.7% of white patients surveyed were aware that sunscreen decreased the risk of cancer, compared with 59.1% of nonwhite patients; 27.3% of white patients reported using a daily sunscreen, compared with 13.6% of nonwhite patients.

“Based on our findings, we suggest that optimal posttransplant dermatologic care be determined based on the race or ethnicity of the patients; however, regardless of skin type or race or ethnicity, a baseline full-skin assessment should be performed in all patients,” the authors wrote.

They proposed that skin cancer follow-up screenings should be given to Asian and Hispanic patients immediately after transplant, but that black organ transplant recipients could delay yearly screenings.

However, they said routine skin checks should begin earlier after transplantation for all nonwhite transplant recipients with a history of, or clinically evident HPV infection.

No conflicts of interest were declared.

Nonwhite organ transplant recipients (OTRs) are more likely to present with inflammatory or infectious conditions after transplantation, while white organ recipients more commonly present with malignant disease, new research suggests.

While the high incidence of skin cancers has been well described in patients who undergo solid organ transplants, little is known about the risk factors, incidence, locations, and types of skin disease that occur in nonwhite OTRs, wrote Christina Lee Chung, MD, from Drexel University, Philadelphia, and her coauthors in JAMA Dermatology.

In a retrospective review, the investigators examined the medical records of 412 organ transplant recipients treated at an academic referral center during 2011-2016, of whom 154 were white, 35 were Asian, 33 were Hispanic, and 190 were black (JAMA Dermatology. 2017 Mar 8. doi: 10.1001/jamadermatol.2017.0045).

Among the white patients, malignant or premalignant disease was the most common diagnostic category (67.8%), followed by inflammatory (20.7%) and infectious processes (11.6%). However, among nonwhite organ transplant recipients, inflammatory processes were present in 48.8% of patients, infectious processes in 37.5% and the remaining 13.7% presented with malignant or premalignant lesions.

Black and Hispanic patients were more likely to present with inflammatory or infectious disease; only 8.6% presented with malignant conditions and 16% presented with premalignant disease.

Among the Asian patient population, one-third presented with malignant or premalignant, one-third presented with infectious, and one-third presented with inflammatory conditions.

“Although early detection and treatment of cancer is vital, nonwhite OTRs would also benefit from addressing nonmalignant processes that are exacerbated by immunosuppression,” the authors wrote.

Overall, 389 skin cancers were diagnosed, with squamous cell carcinoma in situ (SCC) the most common type of skin cancer diagnosed in each racial or ethnic group. The mean time between transplant and first skin cancer lesion was 12.67 years in black patients, 6.5 years in Hispanic patients, 6.13 years among white patients, and 3.75 years in Asian patients.

The vast majority of skin cancers (95.1%) were found in white patients. While the majority of lesions in white and Asian patients were found in sun-exposed areas, the few skin cancers seen in black patients were more likely to be found in sun-protected areas, particularly the genitals.

Four of the six genital SCCs tested positive for high-risk human papillomavirus strains – in one Asian patient and three black patients – while the two SCCs found on lower extremities in Hispanic patients tested negative for HPV.

Researchers also looked at skin cancer awareness among the organ transplant recipients using data from initial visit questionnaires. They found that more than 17 of the 22 (77.3%) white organ transplant recipients surveyed were aware their skin cancer risk was increased, compared with 30 of the 44 (68.2%) nonwhite patients.

Similarly, 72.7% of white patients surveyed were aware that sunscreen decreased the risk of cancer, compared with 59.1% of nonwhite patients; 27.3% of white patients reported using a daily sunscreen, compared with 13.6% of nonwhite patients.

“Based on our findings, we suggest that optimal posttransplant dermatologic care be determined based on the race or ethnicity of the patients; however, regardless of skin type or race or ethnicity, a baseline full-skin assessment should be performed in all patients,” the authors wrote.

They proposed that skin cancer follow-up screenings should be given to Asian and Hispanic patients immediately after transplant, but that black organ transplant recipients could delay yearly screenings.

However, they said routine skin checks should begin earlier after transplantation for all nonwhite transplant recipients with a history of, or clinically evident HPV infection.

No conflicts of interest were declared.

Nonwhite organ transplant recipients (OTRs) are more likely to present with inflammatory or infectious conditions after transplantation, while white organ recipients more commonly present with malignant disease, new research suggests.

While the high incidence of skin cancers has been well described in patients who undergo solid organ transplants, little is known about the risk factors, incidence, locations, and types of skin disease that occur in nonwhite OTRs, wrote Christina Lee Chung, MD, from Drexel University, Philadelphia, and her coauthors in JAMA Dermatology.

In a retrospective review, the investigators examined the medical records of 412 organ transplant recipients treated at an academic referral center during 2011-2016, of whom 154 were white, 35 were Asian, 33 were Hispanic, and 190 were black (JAMA Dermatology. 2017 Mar 8. doi: 10.1001/jamadermatol.2017.0045).

Among the white patients, malignant or premalignant disease was the most common diagnostic category (67.8%), followed by inflammatory (20.7%) and infectious processes (11.6%). However, among nonwhite organ transplant recipients, inflammatory processes were present in 48.8% of patients, infectious processes in 37.5% and the remaining 13.7% presented with malignant or premalignant lesions.

Black and Hispanic patients were more likely to present with inflammatory or infectious disease; only 8.6% presented with malignant conditions and 16% presented with premalignant disease.

Among the Asian patient population, one-third presented with malignant or premalignant, one-third presented with infectious, and one-third presented with inflammatory conditions.

“Although early detection and treatment of cancer is vital, nonwhite OTRs would also benefit from addressing nonmalignant processes that are exacerbated by immunosuppression,” the authors wrote.

Overall, 389 skin cancers were diagnosed, with squamous cell carcinoma in situ (SCC) the most common type of skin cancer diagnosed in each racial or ethnic group. The mean time between transplant and first skin cancer lesion was 12.67 years in black patients, 6.5 years in Hispanic patients, 6.13 years among white patients, and 3.75 years in Asian patients.

The vast majority of skin cancers (95.1%) were found in white patients. While the majority of lesions in white and Asian patients were found in sun-exposed areas, the few skin cancers seen in black patients were more likely to be found in sun-protected areas, particularly the genitals.

Four of the six genital SCCs tested positive for high-risk human papillomavirus strains – in one Asian patient and three black patients – while the two SCCs found on lower extremities in Hispanic patients tested negative for HPV.

Researchers also looked at skin cancer awareness among the organ transplant recipients using data from initial visit questionnaires. They found that more than 17 of the 22 (77.3%) white organ transplant recipients surveyed were aware their skin cancer risk was increased, compared with 30 of the 44 (68.2%) nonwhite patients.

Similarly, 72.7% of white patients surveyed were aware that sunscreen decreased the risk of cancer, compared with 59.1% of nonwhite patients; 27.3% of white patients reported using a daily sunscreen, compared with 13.6% of nonwhite patients.

“Based on our findings, we suggest that optimal posttransplant dermatologic care be determined based on the race or ethnicity of the patients; however, regardless of skin type or race or ethnicity, a baseline full-skin assessment should be performed in all patients,” the authors wrote.

They proposed that skin cancer follow-up screenings should be given to Asian and Hispanic patients immediately after transplant, but that black organ transplant recipients could delay yearly screenings.

However, they said routine skin checks should begin earlier after transplantation for all nonwhite transplant recipients with a history of, or clinically evident HPV infection.

No conflicts of interest were declared.

Imatinib mesylate is a tyrosine kinase inhibitor initially approved by the US Food and Drug Administration in 2001 for chronic myeloid leukemia (CML). The indications for imatinib have expanded since its initial approval. It is increasingly important that dermatologists recognize adverse cutaneous manifestations associated with imatinib and are aware of their management and outcomes to avoid unnecessarily discontinuing a potentially lifesaving medication.

Adverse cutaneous manifestations in response to imatinib are not infrequent, accounting for 7% to 21% of all side effects.¹ The most frequent cutaneous manifestations of imatinib are dry skin, alopecia, facial edema, and photosensitivity rash, respectively.¹ Other less common manifestations include exfoliative dermatitis, nail disorders, psoriasis, folliculitis, hypotrichosis, urticaria, petechiae, Stevens-Johnson syndrome, erythema multiforme, Sweet syndrome, and leukocytoclastic vasculitis.

We report a case of imatinib-induced lichenoid drug eruption (LDE), a rare cutaneous side effect of imatinib use, along with a review of the literature.

Case Report

An 86-year-old man with a history of gastrointestinal stromal tumors (GISTs) and myelodysplastic syndrome presented with diffuse hyperpigmented skin lesions on the trunk, arms, legs, and lower lip of 2 weeks’ duration. He had been taking imatinib 400 mg once daily for 5 months for GIST. Although the oncologist stopped the medication 2 weeks prior, the lesions were persistent and gradually expanded to involve the trunk, arms, legs, and lower lip. He denied any pain or pruritus. Physical examination revealed multiple ill-defined, brown to violaceous, slightly scaly macules and patches on the trunk (Figures 1A and 1B), arms, and legs (Figure 1C), as well as violaceous to erythematous patches on the mucosal aspect of the lower lip (Figure 2). Two 4-mm punch biopsies were performed from the chest and back, which revealed an atrophic epidermis, lichenoid infiltration, and multiple melanophages in the upper dermis consistent with LDE (Figure 3). Direct immunofluorescence was negative. Therefore, based on the clinicopathologic correlation, the diagnosis of imatinib-induced LDE was made. He was treated with clobetasol ointment twice daily for 3 weeks with some improvement. His GIST was stable on follow-up computed tomography 3 months after presentation, and imatinib was resumed 1 month later with continued rash that was stable with topical corticosteroid treatment.

Comment

In addition to CML, imatinib has been approved for acute lymphoblastic leukemia, myelodysplastic syndromes, aggressive systemic mastocytosis, hypereosinophilic syndrome, chronic eosinophilic leukemia, dermatofibrosarcoma protuberans, and GIST. Moreover, off-label use of imatinib for various other tyrosine kinase–positive cancers and rheumatologic conditions have been documented.^2,3 With the expanding use of imatinib, there will be more occasions for dermatologists to encounter cutaneous manifestations associated with its use.

According to a PubMed search of articles indexed for MEDLINE using the terms imatinib mesylate lichenoid drug, there have been few case reports of LDE associated with imatinib in the literature (eTable).^4-24 Compared to classic LDE, imatinib-induced LDE has a few characteristic findings. Classic LDE frequently spares the oral mucosa and genitalia, but imatinib-induced LDE with manifestations on the oral mucosa and genitalia as well as cutaneous eruptions have been reported.^4-9 In fact, the first known case of imatinib-induced LDE was an oral eruption in a patient with CML.⁴ In patients with oral involvement, lesions have been described as lacy reticular macules and violaceous papules, erosions, and ulcers.^4,5,12 Interestingly, of those cases manifesting as concomitant oral and cutaneous LDE, the oral eruptions recurred more frequently, with 3 of 12 patients having recurrence of oral lesions after the cutaneous manifestations resolved.^8,16 Genital manifestations of imatinib-induced LDE were much less common.^9,11

To date, subsequent reports of imatinib-induced LDE have documented skin manifestations consistent with classic LDE occurring in a diffuse, bilateral, photodistributed pattern.^10,15,16 One case presented with diffuse hyperpigmentation associated with LDE in a Japanese patient.²⁰ The authors suggested this finding may be more prominent in patients with skin of color,²⁰ which is consistent with the current case. Nail findings such as subungual hyperkeratosis and longitudinal ridging also have been reported.^9,11

The latency period between initiation of imat-inib and onset of LDE generally ranges from 1 to 12 months, with onset most commonly occurring between 2 to 5 months or with dosage increase (eTable). Imatinib-induced LDE primarily has been documented with a 400-mg dose, with 1 case of a 600-mg dose and 1 case of an 800-mg dose, which suggests dose dependency. Furthermore, reports exist of several patients responding well to dose reduction with subsequent recurrence on dose reescalation.^13,15

Historically, LDE resolves with discontinuation of the drug after a few weeks to months. When discontinuation of imatinib is unfavorable or patients report symptoms including severe pruritus or pain, treatment should be considered. Topical or oral corticosteroids can be used to treat imatinib-induced LDE, similar to lichen planus. When oral corticosteroids are contraindicated (eg, due to poor patient tolerance), oral acitretin at 25 to 35 mg once daily for 6 to 12 weeks has been reported as an alternative treatment.²⁵

In the majority of cases of imatinib-induced LDE, it was undesirable to stop imatinib (eTable). Notably, in half the reported cases, imatinib was able to be continued and patients were treated symptomatically with either oral and/or topical steroids and/or acitretin with complete remission or tolerable recurrences. Dalmau et al⁹ reported 3 patients who responded poorly to topical and oral steroids and were subsequently treated with acitretin 25 mg once daily; 2 of 3 patients responded favorably to treatment and imatinib was able to be continued. In the current case imatinib initially helped, but because his rash was relatively asymptomatic, imatinib was restarted with control of rash with topical steroids. He developed some pancytopenia, which required intermittent stoppage of the imatinib.

Conclusion

We present a case of imatinib-induced cutaneous and oral LDE in a patient with GIST. Topical corticosteroids, oral acitretin, and oral steroids all may be reasonable treatment options if discontinuing imatinib is not possible in a symptomatic patient. If these therapies fail and the eruption is extensive or intolerable, dosage adjustment is another option to consider before discontinuation of imatinib.

Imatinib mesylate is a tyrosine kinase inhibitor initially approved by the US Food and Drug Administration in 2001 for chronic myeloid leukemia (CML). The indications for imatinib have expanded since its initial approval. It is increasingly important that dermatologists recognize adverse cutaneous manifestations associated with imatinib and are aware of their management and outcomes to avoid unnecessarily discontinuing a potentially lifesaving medication.

Adverse cutaneous manifestations in response to imatinib are not infrequent, accounting for 7% to 21% of all side effects.¹ The most frequent cutaneous manifestations of imatinib are dry skin, alopecia, facial edema, and photosensitivity rash, respectively.¹ Other less common manifestations include exfoliative dermatitis, nail disorders, psoriasis, folliculitis, hypotrichosis, urticaria, petechiae, Stevens-Johnson syndrome, erythema multiforme, Sweet syndrome, and leukocytoclastic vasculitis.

We report a case of imatinib-induced lichenoid drug eruption (LDE), a rare cutaneous side effect of imatinib use, along with a review of the literature.

Case Report

An 86-year-old man with a history of gastrointestinal stromal tumors (GISTs) and myelodysplastic syndrome presented with diffuse hyperpigmented skin lesions on the trunk, arms, legs, and lower lip of 2 weeks’ duration. He had been taking imatinib 400 mg once daily for 5 months for GIST. Although the oncologist stopped the medication 2 weeks prior, the lesions were persistent and gradually expanded to involve the trunk, arms, legs, and lower lip. He denied any pain or pruritus. Physical examination revealed multiple ill-defined, brown to violaceous, slightly scaly macules and patches on the trunk (Figures 1A and 1B), arms, and legs (Figure 1C), as well as violaceous to erythematous patches on the mucosal aspect of the lower lip (Figure 2). Two 4-mm punch biopsies were performed from the chest and back, which revealed an atrophic epidermis, lichenoid infiltration, and multiple melanophages in the upper dermis consistent with LDE (Figure 3). Direct immunofluorescence was negative. Therefore, based on the clinicopathologic correlation, the diagnosis of imatinib-induced LDE was made. He was treated with clobetasol ointment twice daily for 3 weeks with some improvement. His GIST was stable on follow-up computed tomography 3 months after presentation, and imatinib was resumed 1 month later with continued rash that was stable with topical corticosteroid treatment.

Comment

In addition to CML, imatinib has been approved for acute lymphoblastic leukemia, myelodysplastic syndromes, aggressive systemic mastocytosis, hypereosinophilic syndrome, chronic eosinophilic leukemia, dermatofibrosarcoma protuberans, and GIST. Moreover, off-label use of imatinib for various other tyrosine kinase–positive cancers and rheumatologic conditions have been documented.^2,3 With the expanding use of imatinib, there will be more occasions for dermatologists to encounter cutaneous manifestations associated with its use.

According to a PubMed search of articles indexed for MEDLINE using the terms imatinib mesylate lichenoid drug, there have been few case reports of LDE associated with imatinib in the literature (eTable).^4-24 Compared to classic LDE, imatinib-induced LDE has a few characteristic findings. Classic LDE frequently spares the oral mucosa and genitalia, but imatinib-induced LDE with manifestations on the oral mucosa and genitalia as well as cutaneous eruptions have been reported.^4-9 In fact, the first known case of imatinib-induced LDE was an oral eruption in a patient with CML.⁴ In patients with oral involvement, lesions have been described as lacy reticular macules and violaceous papules, erosions, and ulcers.^4,5,12 Interestingly, of those cases manifesting as concomitant oral and cutaneous LDE, the oral eruptions recurred more frequently, with 3 of 12 patients having recurrence of oral lesions after the cutaneous manifestations resolved.^8,16 Genital manifestations of imatinib-induced LDE were much less common.^9,11

To date, subsequent reports of imatinib-induced LDE have documented skin manifestations consistent with classic LDE occurring in a diffuse, bilateral, photodistributed pattern.^10,15,16 One case presented with diffuse hyperpigmentation associated with LDE in a Japanese patient.²⁰ The authors suggested this finding may be more prominent in patients with skin of color,²⁰ which is consistent with the current case. Nail findings such as subungual hyperkeratosis and longitudinal ridging also have been reported.^9,11

The latency period between initiation of imat-inib and onset of LDE generally ranges from 1 to 12 months, with onset most commonly occurring between 2 to 5 months or with dosage increase (eTable). Imatinib-induced LDE primarily has been documented with a 400-mg dose, with 1 case of a 600-mg dose and 1 case of an 800-mg dose, which suggests dose dependency. Furthermore, reports exist of several patients responding well to dose reduction with subsequent recurrence on dose reescalation.^13,15

Historically, LDE resolves with discontinuation of the drug after a few weeks to months. When discontinuation of imatinib is unfavorable or patients report symptoms including severe pruritus or pain, treatment should be considered. Topical or oral corticosteroids can be used to treat imatinib-induced LDE, similar to lichen planus. When oral corticosteroids are contraindicated (eg, due to poor patient tolerance), oral acitretin at 25 to 35 mg once daily for 6 to 12 weeks has been reported as an alternative treatment.²⁵

In the majority of cases of imatinib-induced LDE, it was undesirable to stop imatinib (eTable). Notably, in half the reported cases, imatinib was able to be continued and patients were treated symptomatically with either oral and/or topical steroids and/or acitretin with complete remission or tolerable recurrences. Dalmau et al⁹ reported 3 patients who responded poorly to topical and oral steroids and were subsequently treated with acitretin 25 mg once daily; 2 of 3 patients responded favorably to treatment and imatinib was able to be continued. In the current case imatinib initially helped, but because his rash was relatively asymptomatic, imatinib was restarted with control of rash with topical steroids. He developed some pancytopenia, which required intermittent stoppage of the imatinib.

Conclusion

We present a case of imatinib-induced cutaneous and oral LDE in a patient with GIST. Topical corticosteroids, oral acitretin, and oral steroids all may be reasonable treatment options if discontinuing imatinib is not possible in a symptomatic patient. If these therapies fail and the eruption is extensive or intolerable, dosage adjustment is another option to consider before discontinuation of imatinib.

Imatinib mesylate is a tyrosine kinase inhibitor initially approved by the US Food and Drug Administration in 2001 for chronic myeloid leukemia (CML). The indications for imatinib have expanded since its initial approval. It is increasingly important that dermatologists recognize adverse cutaneous manifestations associated with imatinib and are aware of their management and outcomes to avoid unnecessarily discontinuing a potentially lifesaving medication.

Adverse cutaneous manifestations in response to imatinib are not infrequent, accounting for 7% to 21% of all side effects.¹ The most frequent cutaneous manifestations of imatinib are dry skin, alopecia, facial edema, and photosensitivity rash, respectively.¹ Other less common manifestations include exfoliative dermatitis, nail disorders, psoriasis, folliculitis, hypotrichosis, urticaria, petechiae, Stevens-Johnson syndrome, erythema multiforme, Sweet syndrome, and leukocytoclastic vasculitis.

We report a case of imatinib-induced lichenoid drug eruption (LDE), a rare cutaneous side effect of imatinib use, along with a review of the literature.

Case Report

An 86-year-old man with a history of gastrointestinal stromal tumors (GISTs) and myelodysplastic syndrome presented with diffuse hyperpigmented skin lesions on the trunk, arms, legs, and lower lip of 2 weeks’ duration. He had been taking imatinib 400 mg once daily for 5 months for GIST. Although the oncologist stopped the medication 2 weeks prior, the lesions were persistent and gradually expanded to involve the trunk, arms, legs, and lower lip. He denied any pain or pruritus. Physical examination revealed multiple ill-defined, brown to violaceous, slightly scaly macules and patches on the trunk (Figures 1A and 1B), arms, and legs (Figure 1C), as well as violaceous to erythematous patches on the mucosal aspect of the lower lip (Figure 2). Two 4-mm punch biopsies were performed from the chest and back, which revealed an atrophic epidermis, lichenoid infiltration, and multiple melanophages in the upper dermis consistent with LDE (Figure 3). Direct immunofluorescence was negative. Therefore, based on the clinicopathologic correlation, the diagnosis of imatinib-induced LDE was made. He was treated with clobetasol ointment twice daily for 3 weeks with some improvement. His GIST was stable on follow-up computed tomography 3 months after presentation, and imatinib was resumed 1 month later with continued rash that was stable with topical corticosteroid treatment.

Comment

In addition to CML, imatinib has been approved for acute lymphoblastic leukemia, myelodysplastic syndromes, aggressive systemic mastocytosis, hypereosinophilic syndrome, chronic eosinophilic leukemia, dermatofibrosarcoma protuberans, and GIST. Moreover, off-label use of imatinib for various other tyrosine kinase–positive cancers and rheumatologic conditions have been documented.^2,3 With the expanding use of imatinib, there will be more occasions for dermatologists to encounter cutaneous manifestations associated with its use.

According to a PubMed search of articles indexed for MEDLINE using the terms imatinib mesylate lichenoid drug, there have been few case reports of LDE associated with imatinib in the literature (eTable).^4-24 Compared to classic LDE, imatinib-induced LDE has a few characteristic findings. Classic LDE frequently spares the oral mucosa and genitalia, but imatinib-induced LDE with manifestations on the oral mucosa and genitalia as well as cutaneous eruptions have been reported.^4-9 In fact, the first known case of imatinib-induced LDE was an oral eruption in a patient with CML.⁴ In patients with oral involvement, lesions have been described as lacy reticular macules and violaceous papules, erosions, and ulcers.^4,5,12 Interestingly, of those cases manifesting as concomitant oral and cutaneous LDE, the oral eruptions recurred more frequently, with 3 of 12 patients having recurrence of oral lesions after the cutaneous manifestations resolved.^8,16 Genital manifestations of imatinib-induced LDE were much less common.^9,11

To date, subsequent reports of imatinib-induced LDE have documented skin manifestations consistent with classic LDE occurring in a diffuse, bilateral, photodistributed pattern.^10,15,16 One case presented with diffuse hyperpigmentation associated with LDE in a Japanese patient.²⁰ The authors suggested this finding may be more prominent in patients with skin of color,²⁰ which is consistent with the current case. Nail findings such as subungual hyperkeratosis and longitudinal ridging also have been reported.^9,11

The latency period between initiation of imat-inib and onset of LDE generally ranges from 1 to 12 months, with onset most commonly occurring between 2 to 5 months or with dosage increase (eTable). Imatinib-induced LDE primarily has been documented with a 400-mg dose, with 1 case of a 600-mg dose and 1 case of an 800-mg dose, which suggests dose dependency. Furthermore, reports exist of several patients responding well to dose reduction with subsequent recurrence on dose reescalation.^13,15

Historically, LDE resolves with discontinuation of the drug after a few weeks to months. When discontinuation of imatinib is unfavorable or patients report symptoms including severe pruritus or pain, treatment should be considered. Topical or oral corticosteroids can be used to treat imatinib-induced LDE, similar to lichen planus. When oral corticosteroids are contraindicated (eg, due to poor patient tolerance), oral acitretin at 25 to 35 mg once daily for 6 to 12 weeks has been reported as an alternative treatment.²⁵

In the majority of cases of imatinib-induced LDE, it was undesirable to stop imatinib (eTable). Notably, in half the reported cases, imatinib was able to be continued and patients were treated symptomatically with either oral and/or topical steroids and/or acitretin with complete remission or tolerable recurrences. Dalmau et al⁹ reported 3 patients who responded poorly to topical and oral steroids and were subsequently treated with acitretin 25 mg once daily; 2 of 3 patients responded favorably to treatment and imatinib was able to be continued. In the current case imatinib initially helped, but because his rash was relatively asymptomatic, imatinib was restarted with control of rash with topical steroids. He developed some pancytopenia, which required intermittent stoppage of the imatinib.

Conclusion

We present a case of imatinib-induced cutaneous and oral LDE in a patient with GIST. Topical corticosteroids, oral acitretin, and oral steroids all may be reasonable treatment options if discontinuing imatinib is not possible in a symptomatic patient. If these therapies fail and the eruption is extensive or intolerable, dosage adjustment is another option to consider before discontinuation of imatinib.