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OBJECTIVE The aim of this study was to investigate the relation between timing of subspeciality consult and hemophagocytic lymphohistiocytosis (HLH) consideration, immunosuppression initiation, and in-hospital mortality in patients with HLH. METHODS We conducted a medical records review study of patients 18 years or older with definite or probable HLH at Montefiore Medical Center between 2006 and 2019. Earlier subspeciality consultation (rheumatology, hematology, and infectious disease) was defined as consultation in less than or equal to 18 hours from time of admission. Demographic, clinical characteristics, and outcomes were compared between patients with early and later subspecialty consultation. RESULTS A total of 28 patients were included. The median age was 40 years, and 61% of patients were male. Infection was identified as a cause of HLH in 13 patients (46%). Fifteen patients (54%) were classified as having an earlier subspeciality consultation with a median time (interquartile range) to HLH consideration of 1.0 day (0.3-4.2 days) compared with 7.9 days (3.1-9.9 days) for the later consultation group (p = 0.002). The median time (interquartile range) to immunosuppression initiation was 4.6 days (1.7-7.8 days) versus 10.9 days (5.1-13.4 days) (p = 0.01), respectively. Five patients (33%) had in-hospital deaths in the early consultation group compared with 7 patients (54%) in later consultation group (p = 0.27). Among the subset of patients who survived to discharge, the 90-day readmission rate was higher in the later consultation group (83% vs 30%, p = 0.12). CONCLUSIONS In patients with HLH, earlier subspeciality consultation may play a role in earlier HLH consideration and treatment initiation.

Background/objective Herpes simplex virus (HSV) infection acquired in utero may present with non-vesicular dermatologic findings in affected newborns, which may pose a diagnostic dilemma. We aimed to describe and assess the range of non-vesiculobullous skin lesions that neonates with intrauterine HSV infection may manifest at birth. Methods We collected a multicenter case series and conducted a literature review of neonates with intrauterine HSV infection presenting with non-vesiculobullous cutaneous lesions. Results Twenty-two cases were reviewed, including six managed clinically by members of our team and 16 identified in the literature. Four (18%) were associated with twin pregnancies, and thirteen (59%) cases occurred in premature infants. Only four (18%) mothers had a documented history of HSV infection. Twelve (55%) cases resulted in poor outcomes, including long-term neurologic sequelae or death. Cutaneous manifestations included erosions, ulcerations, crusted papules or plaques, calcinosis cutis, excoriations, macules (erythematous, hypopigmented, or hyperpigmented), cutaneous atrophy, contractures, and bruising. About one-third of neonates developed new-onset vesicular lesions within a week of birth; in each of these cases, accurate diagnosis and therapy were delayed until appearance of vesicles. Conclusions The range of dermatologic findings associated with intrauterine HSV is extremely broad, and the various morphologies present at birth likely reflect different stages of the ongoing evolution of an HSV infection that began in utero. Clinicians should have a low threshold for HSV testing in premature neonates born with atypical cutaneous lesions, since early detection and treatment of HSV may reduce morbidity and mortality from systemic complications.

Background Patient outcomes are improved when dermatologists provide inpatient consultations. Inpatient access to dermatologists is limited, illustrating an opportunity to use teledermatology. Little is known about the ability of dermatologists to accurately diagnose disease and manage inpatients with teledermatology, particularly when using nondermatologist-generated clinical data. Methods This prospective study assessed the ability of teledermatology to diagnose disease and manage 41 dermatology consultations from a large urban tertiary care center, using internal medicine referral documentation and photographs. Twenty-seven dermatology hospitalists were surveyed. Interrater agreement was assessed by the κ statistic. Results There was substantial agreement between in-person and teledermatology assessment of the diagnosis with differential diagnosis (median κ = 0.83), substantial agreement in laboratory evaluation decisions (median κ = 0.67), almost perfect agreement in imaging decisions (median κ = 1.0), and moderate agreement in biopsy decisions (median κ = 0.43). There was almost perfect agreement in treatment (median κ = 1.0), but no agreement in follow-up planning (median κ = 0.0). There was no association between raw photograph quality and the primary plus differential diagnosis or primary diagnosis alone. Limitations Selection bias and single-center nature. Conclusions Teledermatology may be effective in the inpatient setting, with concordant diagnosis, evaluation, and management decisions.

Drug-induced vasculitis and anticoagulant-related skin reactions are commonly encountered in the inpatient and outpatient settings. The spectrum of clinical presentation is broad and ranges from focal, skin-limited disease, to more extensive cutaneous and soft tissue necrosis, to potentially fatal systemic involvement. The prompt recognition of these adverse events can have a significant impact on patient morbidity and mortality. We highlight the key features of the clinical presentation with an emphasis on primary lesion morphology, distribution, and epidemiology of purpuric drug reactions. The proposed pathophysiology, histologic findings, and therapeutic interventions of these potentially life-threatening diseases are discussed.

Recent advancements in anticancer therapy have produced an array of highly specialized therapeutics that prolong disease-free survival, improve tolerability of treatment, and individualize care. With improved treatments and longer survival, treatment-related toxicities are gaining importance. Dermatologic toxicities are common, with therapy-induced secondary cutaneous malignancies of the most frequent and serious for targeted therapies, immunotherapy, and radiotherapy. Often, these eruptive malignant lesions can be treatment limiting and detrimental to quality of life. As such, dermatologists play an important role in multidisciplinary oncologic care teams for surveillance and management of secondary cutaneous malignancies. Proactive dermatologic supervision yields early diagnosis and treatment of secondary cutaneous malignancies, which limits therapy discontinuation and thus optimizes treatment through both therapeutic achievement and overall well-being.

Background Scholarly productivity is an assessment metric for dermatology residents and faculty. How the bibliometric h-index, a publicly available metric that incorporates the quantity and quality of publications, relates to early career choices of dermatologists has not been investigated. Objective We determined the h-indices of the 2017 diplomates of the American Board of Dermatology to ascertain its association with career choice. Methods A cross-sectional analysis was performed using the published list of the 2017 diplomates. Gender and PhD status were compiled. The Scopus database was queried for publications and h-indices. The primary outcome was the pursuit of an academic position, nonacademic position, or fellowship after board certification. Results Among 475 (96%) diplomates, the median (range) h-index was 2 (0–14). Those with MD and PhD degrees had greater h-indices (6.4 ± 3.1 vs. 2.3 ± 2.3, P < .05). There was a difference (P < .05) in h-index between diplomates pursuing an academic position (3.6 ± 3.1), non-procedural fellowship (3.3 ± 3.1), procedural fellowship (2.5 ± 2.0), and non-academic position (2.1 ± 2.1). Conclusions The h-index quantifies academic productivity and may predict early career choices in dermatology.

Stevens-Johnson syndrome and toxic epidermal necrolysis are severe mucocutaneous drug reactions associated with a potentially high mortality rate. They are characterized by epidermal necrosis and extensive detachment. For these reasons, wound care is a fundamental component of patient management. However, there is a lack of evidence-based data, and treatment approaches can vary drastically between institutions. Our aim was to analyze the available studies on this topic as an attempt to review various management strategies. Considering the rarity, variable presentations, and difficulty to prospectively study patients with SJS/TEN, there is a lack of evidence-based data on the topic of wound management. We reviewed the most recently published guidelines, expert opinions, and other studies from different countries and hospital centers. There is a great variability in the utilization of antiseptic agents, wound dressing types, and implementation of surgical debridement across the globe and different institutions. There is a lack of randomized controlled trials. However, the general principle is to protect the underlying viable exposed dermis, minimize the risk of infection, reduce the risk of pigmentary changes and scarring, and optimize the conditions for re-epithelization. Large-scale randomized clinical trials are needed for the optimization of wound care in these conditions.

Programmed cell death 1 (PD-1) and programmed death-ligand 1 (PD-L1) have emerged as popular targets for immune checkpoint inhibitors given the numerous malignancies that have been found to upregul...

Cutaneous vasculitis has many underlying causes, and the clinical and histological findings often overlap. Inflammatory vasculitis can mimic infection; however, distinction is critical for the timely institution of appropriate therapy. We present two patients who had generalized polymorphous eruptions whose cutaneous pathology showed vasculitis with unusual haloed yeast-like cells within the inflammatory infiltrate, mimicking Cryptococcus. The unusual cells stained negatively with Gomori methenamine silver and periodic acid-Schiff fungal stains, but positively for CD68 and had cytoplasmic reactivity with antibody to myeloperoxidase (MPO). Both patients had positive serum anti-MPO antibodies. The first patient experienced a rapidly fatal course, whereas the second patient improved with prompt initiation of systemic corticosteroids. Interestingly, the second case had prior biopsy showing Sweet syndrome with crypotoccoid-appearing cells. Cryptococcoid cells have been described previously in association with neutrophilic dermatoses, but not in the setting of vasculitis as was seen in our patients. Our cases add to the existing literature on crypotoccoid mimickers, and are the first to be reported in association with vasculitis.

Demodex spp. mites are a common colonizer of sebaceous adult skin. Though usually clinically insignificant, demodicosis may be associated with a wide spectrum of skin diseases in immunocompetent hosts, such as erythematotelangiectatic and papulopustular rosacea, Demodex folliculorum, and blepharitis. We present a case of a healthy 9-year-old boy with an exuberant, inflammatory, Demodex-associated pustular eruption of the face, induced by the use of a high-potency topical steroid and successfully treated with oral ivermectin.

In addition to being recognized as a chronic inflammatory disease that manifests in the skin, psoriasis is increasingly understood to be a systemic disease that causes immune dysregulation throughout the body. The systemic nature of psoriasis is evidenced by the higher burden of comorbidities and shorter life expectancies of patients with psoriasis, particularly those with early-onset and severe disease. Notably, psoriasis is associated with an increased risk for cardiovascular disease, which is the most common cause of morbidity and mortality in patients with psoriasis. In this review, we examine the association between psoriasis and cardiovascular disease and specifically focus on the role of interleukin 17–mediated inflammation as a potential mechanistic link between psoriasis and cardiovascular disease. Moreover, we describe potential treatment approaches to reduce the burden of cardiovascular disease in patients with psoriasis and discuss the clinical importance of the association of these 2 diseases with respect to patient management and education.

Syphilis is a well-known sexually transmitted infection infamous for its protean cutaneous manifestations. Over the last decade, the rate of infection in the USA has risen, particularly among human immunodeficiency virus (HIV)-infected individuals and certain ethnic groups. Although the primary chancre developing at the site of inoculation usually has typical and well-characterized features, cutaneous manifestations of secondary syphilis span a wide spectrum and mimic those of other dermatoses. This may be particularly evident in patients with HIV. Such deviations from the expected typical papulosquamous eruption may present a diagnostic challenge and delay diagnosis and therapy. Given the increasing incidence of syphilis among the immunosuppressed patient population, recognition of atypical cutaneous manifestations is critical for adequate management. We review a range of cutaneous manifestations of secondary syphilis and the skin diseases it may mimic.

Nonmelanoma skin cancers (NMSCs) are the most common malignancies in the United States in immunocompetent patients. Among the solid-organ transplant recipients, NMSCs represent a significant disease burden, and they tend to be multiple and more aggressive. While the precise mechanisms responsible for the higher risk of developing cutaneous squamous cell carcinomas (SCCs) have not been completely elucidated, ultraviolet (UV) light has been established to be critical in initiation and promotion of tumor development. More recently, significant emphasis has been placed on the role of the mammalian target of rapamycin (mTOR) pathway in SCC pathogenesis. Furthermore, some studies have demonstrated the ability of mTOR inhibitors to decrease the incidence of new SCCs in the immunosuppressed transplanted patient population. In this review, we will highlight and examine the most recent available data on the role of UV radiation and its interaction with mTOR pathway signaling in SCC pathogenesis.

BACKGROUND: Dermatologic adverse events stemming from anticancer therapies have become an increasingly frequent clinical problem. Inhibitors of mammalian target of rapamycin (mTOR), such as temsirolimus and everolimus, have been associated with a high rate of skin eruptions, but their clinical and histopathologic characteristics have not been explored. METHODS: A retrospective analysis of patients who were referred to the Dermatology Service for diagnosis and management of rash in the setting of therapy with the mTOR inhibitors everolimus and temsirolimus was performed. The parameters that were studied included the time to onset, clinical presentation at the time of dermatologic evaluation, associated symptoms, evolution, results of microbiologic studies, concomitant medications, the need for dose reduction and/or treatment interruption because of rash, and routine histopathology. RESULTS: In total, 13 patients were analyzed. Most rashes were mild (grade 1; 31%) and moderate (grade 2; 54%) in severity, and grade 3 rashes were observed only in 2 patients (15%). The trunk was the most frequently affected region (77%), with the scalp (23%), face (38%), neck (54%), and extremities (69%) also commonly involved. Erythematous papules and pustules constituted the predominant primary lesion morphology (62%). No unique or uniform histopathologic reaction pattern was observed. The most common reaction pattern was that of a mixed, spongiotic interface and perivascular dermatitis, which was observed in 7 of 11 patients (63%). CONCLUSIONS: Although mTOR inhibitors may commonly induce erythematous papules and pustules, they are associated with a spectrum of lesion morphologies and a variety of histopathologic findings. Further clinicohistologic correlation studies are needed. Cancer 2012. © 2012 American Cancer Society.

As the number and uses for targeted therapies such as epidermal growth factor receptor inhibitors (EGFRIs) increase, so does the need to recognize and treat the dermatologic side-effects of these agents. Although agents such as gefitinib, erlotinib, cetuximab, lapatinib, and panitumumab have less systemic side-effects than traditional cytotoxic chemotherapy, dermatologic adverse events from EGFRIs are significantly more common. These dermatologic toxicities have previously led to reduction or cessation of therapy and recently have been shown to decrease patients' quality of life.This review provides a symptom-based treatment approach to the common dermatologic adverse effects seen with the epidermal growth factor receptor antagonists: papulopustular rash, xerosis, pruritus as well as hair, nail, and mucosal changes. Each dermatologic toxicity is described; prophylaxis and treatment options, from topical to systemic, are presented based on a review of the current literature with emphasis on new clinical trials results. We also provide specific recommendations based on our practice in a specialty clinic.Although the field continues to evolve, this review presents the most up-to-date information on managing dermatologic adverse effects of EGFRIs. Practitioners should find this article to be a practical resource in approaching patients on EGFRIs with dermatologic toxicities. As we learn how to optimally manage the adverse effects of these agents, we practitioners have the opportunity to increase patients' quality of life and decrease reductions or cessations of life-prolonging therapy.

Summary Background. Epidermal growth factor receptor inhibitors (EGFRIs) are associated with a characteristic papulopustular rash, an adverse event considered to be a class effect of these agents. Erlotinib, a small-molecule EGFRI, causes a papulopustular rash in 68–75% of patients. The limited reported data suggest that deleterious effects of ultraviolet radiation (UVR) may enhance the development of EGFRI-induced rash. Because the level of the biological pigment melanin correlates with increased protection against UVR, we hypothesized that lighter levels of skin pigmentation are associated with greater severity of rash. Aim. To characterize the relationship between skin phototype (SPT) and rash severity. Methods. A retrospective chart review was conducted of 40 patients on erlotinib. Skin sensitivity to UVR was categorized using the Fitzpatrick SPT classification scheme. Grading of rash was performed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 3. Results. There was an inverse relationship between SPT and rash severity. Grade 0 was seen in the majority of patients with SPT V/VI, grade 1/2 in the majority of patients with SPT III/IV, and grade 3/4 rash in the majority of patients with SPT I/II (grade 0: 7% SPT I/II, 32% SPT III/IV and 50% SPT IV/V; grade 1/2: 33%, 63% and 50%, respectively; grade 3/4: 60%, 5% and 0%, respectively) (P

The last decade in oncology has been highlighted by the emergence of novel, highly specific anti-cancer agents, targeting a variety of molecular structures and able to inhibit aberrantly activated oncogenic pathways. Epidermal growth factor receptor inhibitors (EGFRIs) represent one type of such "targeted" agents. Their use made treatment more tolerable and resulted in significant reduction of systemic adverse effects. However, EGFRIs are associated with toxicities affecting the skin and adnexal structures, and mucosal surfaces that affect the majority of treated patients. Significant dermatologic toxicities have changed the role and involvement of dermatologists in their care. It is essential to be familiar with these adverse effects, potential complications, long-term sequelae, and available effective treatment strategies in order to appropriately manage these patients. This review will describe the clinical presentation, histopathology, underlying mechanisms, and management options, emphasizing evidence-based approaches.

Candida krusei (C. krusei) is a multidrug-resistant opportunistic fungal pathogen that may cause disseminated infections in immunocompromised hosts. However, its clinical and histologic features are not well-characterized. We present a unique case to contribute to the growing knowledge base associated with this organism. During hospitalization for neutropenic fever, a 19-year-old man with acute myeloid leukemia, who underwent hematopoietic stem cell transplantation, developed a generalized folliculocentric eruption following initiation of antifungal therapy for newly diagnosed C. krusei fungemia. Despite adequate antifungal coverage and negative blood cultures, the follicular-based erythematous papules persisted. Biopsies demonstrated yeast within ruptured follicles, without angiotropism or involvement of the interfollicular dermis, subcutaneous tissue, or stratum corneum. Concurrent skin tissue cultures confirmed C. krusei. The patient remained febrile despite aggressive antifungal therapy, with relapse of leukemia and subsequent death. Our case is unusual given the development of cutaneous lesions following clearance of fungemia, with yeast limited to ruptured follicular lumina, possibly indicating a primary cutaneous source or early transfollicular/transepidermal elimination. Given the limited available descriptions of cutaneous histopathology for C. krusei, we seek to add to the understanding of its pathophysiology and aid in the diagnosis and treatment of this often fatal infection.

Numerous complications can be observed in the post-transplant period among recipients of hematopoietic stem cells including graft-versus-host disease (GVHD), which is associated with significant morbidity and mortality. On the other hand, graft versus tumor (GVT) effect is a well-described phenomenon in patients with hematologic malignancies and has also been reported in renal cell cancer, ovarian cancer, breast carcinoma, and melanoma. We describe spontaneous regression of a cutaneous invasive squamous cell carcinoma and multifocal atypical intraepidermal proliferations in a patient with chronic graft-versus-host disease following initiation of extracorporeal photopheresis (ECP). This observation raises questions regarding the GVT in cutaneous neoplasms and potential immunomodulatory effects of ECP.

To the Editor,Imatinib mesylate, an orally available inhibitor of constitutively activated BCR-ABL tyrosine kinase, platelet-derived growth factor receptor (PDGFR) alpha and beta, and the c-kit rec...

Numerous complications can be observed in the post-transplant period among recipients of hematopoietic stem cells including graft-versus-host disease (GVHD), which is associated with significant morbidity and mortality. On the other hand, graft versus tumor (GVT) effect is a well-described phenomenon in patients with hematologic malignancies and has also been reported in renal cell cancer, ovarian cancer, breast carcinoma, and melanoma. We describe spontaneous regression of a cutaneous invasive squamous cell carcinoma and multifocal atypical intraepidermal proliferations in a patient with chronic graft-versus-host disease following initiation of extracorporeal photopheresis (ECP). This observation raises questions regarding the GVT in cutaneous neoplasms and potential immunomodulatory effects of ECP.

The incidences of life-threatening toxicities such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are inconsistently reported. The potential association of anticancer agents with SJS or TEN has not been systematically investigated. We searched the literature (Ovid: 1950 to June 2013 and PubMed: 1948 to June 2013) using terms for SJS/TEN and anticancer therapies. Primary case reports, case series, and clinical trials were included. In addition, MedWatch, the Food and Drug Administration Adverse Event Reporting System (FAERS), was searched (1968 to August 2012) for SJS/TEN reports associated with anticancer therapies. Proportional reporting ratios (PRR>2, N>3), empirical Bayes geometric mean (EBGM>2, N>3), and lower 95% confidence interval (EBGM0.05>2) were used as thresholds to constitute a signal of association between SJS/TEN and anticancer drugs. There were 46 SJS and 37 TEN cases associated with 18 and 22 anticancer drugs in the literature, respectively. Among cases in the FAERS, significant signals were associated with SJS for bendamustine and with TEN for bendamustine, busulfan, chlorambucil, fludarabine, lomustine, and procarbazine. Several drugs reported in the published literature to be associated with SJS/TEN were not found to have significant signals in FAERS. Proactive pharmacovigilance to detect and define safety signals serves to aid oncology practitioners in the recognition of possible, yet uncommon, serious, and/or life-threatening skin reactions.

Anticancer therapies cause a wide range of dermatologic adverse events (AE). Although the frequency and severity of these events have been described, their effects on health-related quality of life (QoL) remain poorly understood, and the ones having a greater impact have not been ascertained. To assess QoL in patients on conventional versus targeted anti-cancer therapies using a dermatology-specific questionnaire. Patients (n = 283) completed the Skindex-16, a QoL questionnaire measuring the effects on three domains: symptoms, emotions, and function. Patients were grouped into two categories according to the types of oncology treatments received: (1) targeted therapies and (2) non-targeted therapies. Correlations of Skindex-16 scores with type of anti-cancer therapy, number of AEs, and specific dermatologic AEs were investigated. Significant differences between patients treated with targeted versus non-targeted therapy with regards to total Skindex-16 (p = 0.02) and emotion subdomain (p = 0.02) scores were observed. Additionally, patients on targeted therapies experienced a significantly greater number of AEs (p

A fundamental shift in chemotherapeutic approach has occurred over the last several decades. A new class of so-called targeted agents, designed to target aberrant molecular pathways responsible for promoting carcinogenesis, was added to the arsenal of cytotoxic drugs that target rapidly proliferating tumor cells. These advances improved patient care and decreased morbidity and mortality. While systemic adverse events such as bone marrow suppression and gastrointestinal toxicities have diminished with the use of targeted agents, the spectrum of dermatologic toxicities have expanded. Mechanisms underlying the development of such a variety of cutaneous adverse events remain to be elucidated, but a significant amount of data shedding light on potential pathophysiology has accumulated. This chapter will review these data.

Background. Bevacizumab, a monoclonal antibody targeting a vascular endothelial growth factor (VEGF) protein, has been reported to induce mucosal toxicities. However, the clinical characteristics of these particular toxicities have not been well characterized. We aimed at providing a detailed clinical description of signs and symptoms limited to the tongue mucosa in patients treated with bevacizumab. Methods. A retrospective review of medical records and clinical photographs was performed with specific attention to clinical presentation, evolution, associated symptoms, concomitant medications, and treatment methods. Results. In total, four patients presented to the dermatology service with clinical findings characterized by multifocal, erythematous circinate and serpiginous erosions on the dorsal tongue surrounded by white hyperkeratotic rims that were temporally related to bevacizumab therapy. Associated increased sensitivity to spicy foods was frequently observed. Conclusion. These characteristic clinical findings are consistent with geographic tongue. However, large prospective evaluations are necessary to confirm this potential relationship. If bevacizumab is indeed associated with geographic tongue, increased awareness may result in improved reporting and characterization of this particular adverse event.

Basal cell carcinomas (BCCs) can be diagnosed using different dermoscopic modalities.To evaluate dermoscopic features of BCCs using nonpolarized and polarized dermoscopy to highlight similarities and differences between dermoscopic modalities.Retrospective study of 149 BCCs under nonpolarized dermoscopy (NPD), polarized contact dermoscopy (PCD), and polarized noncontact dermoscopy (PNCD). Images were evaluated for a range of dermoscopic colors, structures, and vessels. Features were compared according to histopathologic subtype.The most common dermoscopic structures in BCCs across all modalities included globules (50.3-51.0%), dots (49.7-50.3%), white structureless areas (63.1-74.5%), structureless gray-brown areas (24.2-24.8%), and ulcerations (28.2%). The most frequently observed vasculature included arborizing vessels (18.8-38.3%), short fine telangiectasias (SFTs) (73.8-82.6%), and vascular blush (41.6-83.2%). Structures with higher levels of agreement across modalities included pigmented structures and ulcerations. Lower levels of agreement existed between contact and noncontact modalities for certain vascular features. White shiny structures, which include shiny white lines (chrysalis and crystalline structures) (0-69.1%), shiny white areas (0-25.5%), and rosettes (0-11.4%), exhibited no agreement between NPD and polarized modalities.This study highlights differences in dermoscopic features of BCCs under three dermoscopic modalities. Shiny white lines (chrysalis and crystalline structures) and shiny white areas may be used as additional criteria to diagnose BCCs.

Imatinib mesylate (STI 571; Gleevec; Novartis Pharmaceuticals, Basel, Switzerland) is an orally available tyrosine kinase inhibitor that targets a constitutively activated BCR-ABL tyrosine kinase with additional inhibitory effects on platelet derived growth factor (PDGF) receptors alpha and beta, and KIT. It has revolutionized the treatment of adult and pediatric patients with Philadelphia chromosome positive chronic myelogenous leukemia (CML) and is also FDA-approved for KIT-positive advanced gastrointestinal tumor (GIST) and dermatofibrosarcoma protuberans. A wide spectrum of dermatologic toxicities has been associated with this agent, among which a maculopapular rash is the most common event. In addition, a variety of pigmentary abnormalities of the skin and mucosal surfaces have been reported. Hypopigmentation is a well-recognized adverse effect. In contrast, paradoxical hyperpigmentation has only rarely been documented. In this case report we describe imatinib-induced cutaneous hyperpigmentation and graying of hair occurring in the same patient with dermatofibrosarcoma protuberans treated with imatinib.

Dermatologic adverse events stemming from anticancer therapies have become an increasingly frequent clinical problem. Inhibitors of mammalian target of rapamycin (mTOR), such as temsirolimus and everolimus, have been associated with a high rate of skin eruptions, but their clinical and histopathologic characteristics have not been explored.A retrospective analysis of patients who were referred to the Dermatology Service for diagnosis and management of rash in the setting of therapy with the mTOR inhibitors everolimus and temsirolimus was performed. The parameters that were studied included the time to onset, clinical presentation at the time of dermatologic evaluation, associated symptoms, evolution, results of microbiologic studies, concomitant medications, the need for dose reduction and/or treatment interruption because of rash, and routine histopathology.In total, 13 patients were analyzed. Most rashes were mild (grade 1; 31%) and moderate (grade 2; 54%) in severity, and grade 3 rashes were observed only in 2 patients (15%). The trunk was the most frequently affected region (77%), with the scalp (23%), face (38%), neck (54%), and extremities (69%) also commonly involved. Erythematous papules and pustules constituted the predominant primary lesion morphology (62%). No unique or uniform histopathologic reaction pattern was observed. The most common reaction pattern was that of a mixed, spongiotic interface and perivascular dermatitis, which was observed in 7 of 11 patients (63%).Although mTOR inhibitors may commonly induce erythematous papules and pustules, they are associated with a spectrum of lesion morphologies and a variety of histopathologic findings. Further clinicohistologic correlation studies are needed.