Bernice Y. Kwong

Immunohistochemical analysis of lichenoid reactions in patients treated with anti-PD-L1 and anti-PD-1 therapy.

Recent advances in the immunotherapeutic treatment of cancer have led to the development of multiple new directed therapies including monoclonal antibodies that block the immune checkpoint T‐cell receptor programmed death 1 (PD‐1) and the PD‐1 ligand, programmed death ligand 1 (PD‐L1). Various immune‐related toxicities have been associated with these drugs including, most commonly, skin rashes.

ETV3-NCOA2 in indeterminate cell histiocytosis: clonal translocation supports sui generis

To the editor: Indeterminate cell histiocytosis (ICH) is a rare and controversial disorder first described by Wood et al[1][1] in 1985. ICH is characterized by a nonepidermotropic histiocytic infiltrate with immunohistochemical features that overlap with Langerhans cells (LCs) and non-LCs of

Cutaneous Complications of Targeted Melanoma Therapy

Opinion statementThe landscape of advanced and metastatic melanoma therapy has shifted dramatically in recent years. Since 2011, eight drugs (ipilimumab, vemurafenib, dabrafenib, trametinib, cometinib, pembrolizumab, nivolumab, and talimogene laherparepvec) have received FDA approval for the treatment of advanced or metastatic melanoma, including combination regimens of both small molecule kinase and immune checkpoint inhibitors. These therapies have revolutionized the management of unresectable regional nodal and distant melanoma, providing hope of extended survival to patients. As the use of novel agents has increased, so have the cutaneous toxicities associated with these medications. While most skin reactions are low-grade and can be managed conservatively with topical therapies, malignant lesions and more serious or life-threatening drug reactions can arise during therapy, requiring prompt dermatologic recognition and treatment in order to improve patient outcome. Given the survival benefit attributed to these new agents, treating skin toxicity and maintaining patient quality of life is of paramount importance. Oncologists should be aware of the common cutaneous toxicities associated with these medications and should be encouraged to involve dermatologists in the collaborative care of advanced melanoma patients. Close communication between oncologists and dermatologists can help to avoid unnecessary dose reduction or treatment discontinuation and identify situations when treatment cessation is truly warranted.

Eruptive Keratoacanthomas Associated With Pembrolizumab Therapy

Importance To our knowledge, there have been no previous reports of eruptive keratoacanthomas (KAs) in patients receiving pembrolizumab. Objective To report the cases of 3 consecutive patients with pembrolizumab-induced eruptive KAs and their management. Design, Setting, and Participants Case report study of 3 patients from 2 centers with pembrolizumab-treated cancer who all developed eruptive KAs. Interventions All 3 patients had AK treatment with clobetasol ointment and intralesional triamcinolone; 2 patients also underwent open superficial cryosurgery. Results Three consecutive patients with cancer, 2 men and 1 woman (median age, 83 years; range 77-91 years), experienced pembrolizumab-associated eruptive KAs. All patients presented with a sudden onset of multiple lesions on sun-exposed areas of their extremities after a median of 13 months (range, 4-18 months) of pembrolizumab therapy. On lesional biopsy, a lichenoid infiltrate was observed in the underlying dermis, predominantly composed of CD3+ T cells, scattered CD20+ B cells, and relatively few PD-1+ (programmed cell death 1–positive) T cells, an immunophenotypic pattern also observed in other cases of anti–PD-1–induced lichenoid dermatitis. Patients were treated with clobetasol ointment and intralesional triamcinolone, alone or in combination with open superficial cryosurgery. All KAs resolved in all patients, and no new lesions occurred during close follow-up. Pembrolizumab treatment was continued without disruption in all 3 cases, and all patients had complete responses of their primary cancers. Conclusions and Relevance Pembrolizumab is used in advanced melanoma, advanced non–small-cell lung cancer, and in head and neck cancer. A variety of dermatologic immune-related adverse events including maculopapular eruption, lichenoid reactions, pruritus, and vitiligo have been described. This case series demonstrates that pembrolizumab therapy may also be associated with eruptive KAs with characteristic dermal inflammation, which improved with corticosteroid treatment (topical and intralesional) alone or in combination with cryosurgery, allowing patients to continue therapy with pembrolizumab.

Management of Dermatologic Complications of Lung Cancer Therapies

Opinion statementIn recent years, oncogene-directed targeted agents and immunotherapies have expanded the treatment armamentarium for advanced lung cancer and, in particular, non-small cell lung cancer (NSCLC). Along with extended survival, these agents are accompanied by a host of cutaneous complications that affect the skin, hair, and nails. These skin complications range from the well-characterized papulopustular (acneiform) eruption of the epidermal growth factor receptor (EGFR) inhibitors to the emerging characterization of lichenoid skin eruptions seen during treatment with antibodies targeting the programmed cell death protein 1 (PD-1) and programmed cell death protein 1 ligand (PD-L1). When promptly recognized and accurately diagnosed, most cutaneous adverse events can be managed with supportive treatments, avoiding the need to interrupt antitumor therapy. Furthermore, preemptive management of skin problems can lead to significantly decreased severity of many cutaneous complications of these therapies. We encourage close collaboration between dermatologists and oncologists to better characterize cutaneous toxicity, select appropriate management, and avoid unnecessary dose reduction or discontinuation while simultaneously improving patient quality of life.

Effect of voriconazole on risk of nonmelanoma skin cancer after hematopoietic cell transplantation

Background: Voriconazole has previously been associated with increased risk for cutaneous squamous cell carcinoma (SCC) in solid organ transplant recipients. Less is known about the risk in patients after hematopoietic cell transplantation (HCT). Objective: We evaluated the effect of voriconazole on the risk for nonmelanoma skin cancer (NMSC), including SCC and basal cell carcionoma, among those who have undergone allogeneic and autologous HCT. Methods: In all, 1220 individuals who had undergone allogeneic HCT and 1418 who had undergone autologous HCT were included in a retrospective cohort study. Multivariate analysis included voriconazole exposure and other known risk factors for NMSC. Results: In multivariate analysis, voriconazole use increased the risk for NMSC (hazard ratio, 1.82; 95% confidence interval, 1.13‐2.91) among those who had undergone allogeneic HCT, particularly for SCC (hazard ratio, 2.25; 95% confidence interval, 1.30‐3.89). Voriconazole use did not appear to confer increased risk for NMSC among those who had undergone autologous HCT. Limitations: This is a retrospective study. Conclusion: Voriconazole use represents an independent factor that may contribute to increased risk specifically for SCC in the allogeneic HCT population.

Ibrutinib‐associated rash: a single‐centre experience of clinicopathological features and management

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Granuloma annulare associated with immune checkpoint inhibitors

absorption of the sunscreen was effective from the moment of application, but did not stabilize until minute 10 (Fig. 1d,e). The blank formulation showed similar stabilization times to the reference sunscreen, but the pixel intensity was lower (i.e. the colours were lighter). Our results demonstrate that the interval of time recommended for the use of sunscreens to be fully functional is far superior to the necessary to obtain optimal results and photostability. The International Agency for Research on Cancer recommendations on the correct use of sunscreen products include the application of 2 mg/cm of sunscreen 30 min before exposure and reapplication every 2 h thereafter. However, using UV photography (technique now used as a tool in skin cancer prevention interventions), we were able to visualize changes in colour that reflected the sunscreen’s absorption capacity in shorter times. In conclusion, the sunscreen tested clearly exerted a protective effect from the moment of application and it is not necessary to wait longer than 10 min before sun exposure. Therefore, in practical terms, a waiting time of 30 min following classical recommendations would not appear to be necessary. The study was supported by the Spanish Foundation CEIMAR (Campus de Excelencia Internacional del Mar). M.V. de G alvez,* J. Aguilera, E. A. Buend ıa, C. S anchez-Rold an, E. Herrera-Ceballos Photobiological Dermatology Laboratory, Medical Research Center, Department of Dermatology and Medicine, Faculty of Medicine, University of M alaga, M alaga, Spain, Dermatology Service, Hospital Cl ınico Universitario Virgen de la Victoria, M alaga, Spain *Correspondence: M.V. de G alvez. E-mail: mga@uma.es

Localized bullous pemphigoid in a melanoma patient with dual exposure to PD-1 checkpoint inhibition and radiation therapy

BP: bullous pemphigoid PD-1: programmed cell-death receptor

Acral verruca-like presentation of chronic graft-vs.-host disease

Chronic graft‐vs.‐host disease (GVHD) is a severe and potentially fatal complication in patients after undergoing allogeneic stem cell transplant. This disease may be hard to diagnose as it has numerous cutaneous presentations.