Dermatologic toxicities to immune checkpoint inhibitor therapy: A review of histopathologic features.

Antineoplastic agents that use the immune system have revolutionized cancer treatment. Specifically, implementation of immune checkpoint inhibitors, monoclonal antibodies that block cytotoxic T-lymphocyte-associated antigen-4, programmed cell death protein 1, or programmed cell death ligand 1 show improved and sustained responses in patients with cancer. However, these agents are associated with a plethora of adverse events, many manifesting in the skin. As the clinical application of cancer immunotherapies expands, understanding the clinical and histopathologic features of associated cutaneous toxicities becomes increasingly important to dermatologists, oncologists, and pathologists to ensure timely diagnosis and appropriate care. This review discusses cutaneous reactions to immune checkpoint inhibitors, focusing on histopathologic features.

Psoriasiform Pemphigus Foliaceus in an African American Female: An Important Clinical Manifestation.

A 50-year-old African-American woman presented to the dermatology clinic with a pruritic eruption of 3 years' duration. On clinical examination, the patient had well-demarcated, pink, atrophic plaques and superficial erosions over the inframammary folds and mid-chest. She also had well-demarcated, hyperpigmented, hyperkeratotic scaly plaques over the abdomen, suprapubic region, elbows, knees, and back with sporadic small superficial blisters. A punch biopsy of the right abdomen was performed and revealed psoriasiform epidermal hyperplasia, focal parakeratosis, and acantholysis throughout the superficial spinous and granular layers. Only a sparse inflammatory infiltrate was present in the underlying dermis. Clinical and histological findings supported the diagnosis of pemphigus foliaceus (PF), but psoriasis was included in the differential diagnosis due to the presence of discrete plaques with an erythematous border. We hypothesize that patients with psoriasiform presentations of PF may be misdiagnosed with plaque psoriasis. It is important to distinguish between PF and psoriasis as there is evidence that ultraviolet light, a common treatment for psoriasis, may exacerbate PF. We document and highlight this atypical psoriasiform presentation of PF in a patient with skin of color to raise awareness and improve diagnosis and outcomes.

J Drugs Dermatol. 2018;17(4):471-473.

Ulcerated Basal Cell Carcinomas Masquerading as Venous Leg Ulcers.

BACKGROUND: Nonmelanoma skin cancers rarely arise from venous leg ulcers (VLUs). Although basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer, its association with lower-extremity ulcers is not as frequently reported as other malignancies. OBJECTIVE: To report a case series of biopsy-proven BCC from lower-extremity ulcers of patients who presented at a multispecialty wound clinic. METHODS: Four male patients (mean age, 82.75 years) with 4 chronic VLUs (duration ranging from 2 months to 10 years) underwent a biopsy of their ulcerative lesions. RESULTS: Histologic examination of the specimens revealed 4 cases of BCC. All of the lesions were surgically excised, followed by split-thickness skin graft (n = 2) or healing by secondary intention (n = 2). All of the patients remained healed at follow-up ranging from 15 to 27 months, except for 1 patient who opted for conservative management and had not completely healed at 14 months' follow-up. CONCLUSIONS: Biopsies are warranted for any VLU with documented stalled healing following 3 months of standard of care. One biopsy is performed at the periphery of the ulcer and another at the base in order to rule out the presence of malignant transformation because of BCC, squamous cell carcinoma, sarcoma, melanoma, lymphoma, or metastases.

Purple patches in an immunocompromised patient: a report of secondary disseminated cutaneous mucormycosis in a man with chronic lymphocytic leukemia.

A 60-year-old man with chronic lymphocytic leukemiadeveloped a deeply violaceous annular patchwith a halo of erythema on the right thigh duringhospitalization for neutropenic fever. Associatedsymptoms included chronic cough and fatigue.Bilateral lung opacities with hilar lymphadenopathywere noted on chest computed tomographyscan. Punch biopsy and tissue culture confirmeda diagnosis of secondary disseminated cutaneousmucormycosis. Although rare, physicians shouldinclude mucormycosis in the differential diagnosisof purpuric patches in immunosuppressed patients.Prompt skin biopsy and tissue culture may optimizethe success of treatment.

Dermatology Medical Education: A Multicenter Survey Study of the Undergraduate Perspective of the Dermatology Clinical Clerkship.

BACKGROUND/AIMS: Limited data are available regarding the undergraduate dermatology clinical clerkship curriculum in the United States. Our primaryaim is to assess medical students' perspectives of the dermatology clinical clerkship. METHODS: A multicenter survey study was conducted, which included four California dermatology academic programs. A 17-item questionnaire was designed to investigate medical student perception with regard tothe overall educational value of the various teaching aspects of the dermatology clinical clerkship. RESULTS: A total of 152 medical student surveys were completed. Over half of the medical students felt proficient in diagnosing the most commondermatologic conditions. Eighty-seven percent of medical students were very satisfied with the dermatology clerkship. Ninety-one percent of students felt the length of the clerkship was appropriate. CONCLUSIONS: The vast majority of medical students reported a high level of proficiency in the treatment and diagnosis of common skin disorders. In contrast, our findings suggest that medical students may not begaining sufficient hands-on experience in conducting certain dermatologic procedures following the dermatology clerkship. Overall, medical studentperception of the dermatology clinical clerkship was mostly positive.

Chemotherapy reaction induced by ixabepilone, a microtubule stabilizing agent, mimicking extramammary Paget's disease in a patient with breast carcinoma.

The histopathologic characteristics of reactions caused by the many novel anticancer agents are under-recognized. We report a case of a 67-year-old female with locally advanced metastatic breast cancer, who initially presented with an extensive reticulated erythematous patch on the trunk caused by intravascular metastases confirmed by a skin biopsy. Owing to disease progression, she was started on ixabepilone, a mitotic inhibitor. While receiving ixabepilone, another skin biopsy was obtained and initially interpreted as extramammary Paget's disease. However, the biopsy showed metaphase arrest of numerous keratinocytes in the basilar and suprabasilar epidermis. Atypical epithelial cells were only present in the intravascular spaces similar to the initial biopsy. Given the temporal association between the initiation of ixabepilone therapy and the epidermal mitotic arrest, a diagnosis of chemotherapy reaction to ixabepilone was rendered. Ixabepilone is an analog of epothilone, a microtubule stabilizer causing mitotic arrest of the cell cycle approved for the treatment of metastatic and locally advanced treatment-resistant breast cancer. The demonstration of epidermal mitotic arrest caused by ixabepilone is without precedent. The case emphasizes the importance of considering a chemotherapy reaction in the histologic differential diagnosis of epidermal mitotic arrest in a cancer patient receiving chemotherapy.

What can U.S. dermatology learn from health care systems abroad? An observation of Taiwan's system of clinical efficiency as a possible model for increased patient access to care and affordability.

BACKGROUND: Difficulty in patient access to care and affordability are major problems faced by our dermatology specialty in the United States. However, Taiwan provides adequate and affordable dermatologic care for all of its citizens. Herein we describe our first-hand observations and findings of the outpatient dermatology experience in Taipei, and contrast it to the experience in the United States. OBSERVATION: In Taipei, Taiwan, we observed patient management, electronic documentation, and billing during outpatient dermatology visits in five settings: one academic hospital outpatient dermatology department, one academic hospital Information Technology department, and three private dermatologists' offices. Through our observations, we found that the dermatology specialty in Taiwan is able to overcome challenges with access to care and affordability through three key system features: (1) short yet frequent patient visits (2) close proximity of ancillary staff, and (3) an integrated and paperless electronic medical record and billing system. CONCLUSIONS: The Taiwan system is attained with some sacrifice, such as shorter time spent with patients and less personalized care. However, because this system can meet the basic dermatological needs of the entire population, possibly better than our current system, it behooves us to study the Taiwan system with respect and care.

Sporotrichoid granuloma annulare-like dermatitis associated with systemic B-cell lymphoma.

IMPORTANCE: Granuloma annulare is typically a benign, self-limited disease. Atypical presentations have been reported in association with systemic disease, including malignancy. Such patients may require additional diagnostic studies to assess for underlying malignancy. We report a patient with extensive sporotrichoid granuloma annulare-like dermatitis in association with systemic B-cell lymphoma. OBSERVATIONS: An 83-year-old man with a three-year history of progressive sporotrichoid annular plaques and nodules on the arm developed ipsilateral retroauricular palpable lymphadenopathy, the latter consistent with B-cell lymphoma. Multiple skin biopsies of the plaques and nodules revealed granuloma annulare-like dermatitis. Lesions were unresponsive to intralesional and intramuscular corticosteroids, antibiotics, and antifungal agents, but rapidly improved following initiation of rituximab to treat his underlying lymphoma. CONCLUSIONS AND RELEVANCE: Atypical presentations of granuloma annulare including granuloma annulare-like dermatitis warrant evaluation for systemic malignancy in a subset of patients.

Diet and psoriasis, part I: Impact of weight loss interventions.

One of the most frequently asked questions by patients with psoriasis is whether dietary changes can improve their condition. Included in this discussion is whether dietary weight loss can benefit their skin disease. Obesity has been associated with a proinflammatory state and several studies have demonstrated a relationship between body mass index and psoriasis severity. However, the question of whether weight loss interventions can impact psoriasis outcome is less clear. Here, we review the literature to examine the efficacy of weight loss interventions, both dietary and surgical, on psoriasis disease course.

Diet and psoriasis, part III: role of nutritional supplements.

Patients with psoriasis are increasingly turning to the use of alternative and complementary medicine to manage their psoriasis. Patients often inquire about what dietary supplements may be beneficial, including the use of oral vitamin D, vitamin B12, selenium, and omega-3 fatty acids in fish oils. In this review we examine the extent to which each of these common nutritional interventions has been studied for the treatment of psoriasis. We weighed evidence from both controlled and uncontrolled prospective trials. The evidence of benefit was highest for fish oils. For other supplements, there is need for additional large, randomized clinical trials to establish evidence of efficacy.

Diet and psoriasis, part II: celiac disease and role of a gluten-free diet.

Patients with psoriasis have been shown to have a higher prevalence of other autoimmune diseases including celiac disease, a condition marked by sensitivity to dietary gluten. A number of studies suggest that psoriasis and celiac disease share common genetic and inflammatory pathways. Here we review the epidemiologic association between psoriasis and celiac disease and perform a meta-analysis to determine whether patients with psoriasis more frequently harbor serologic markers of celiac disease. We also examine whether a gluten-free diet can improve psoriatic skin disease.

Etiology, evaluation, and management of xerostomia.

Xerostomia is defined as the complaint of oral dryness. It is a condition that primarily affects older adults and can have a significant negative effect on one's quality of life. Patients with xerostomia often do not have objective signs of hyposalivation. The underlying etiology of xerostomia includes a variety of systemic diseases and local factors. Our aim is to provide a comprehensive review of the differential diagnosis, evaluation, and management of xerostomia. Prompt diagnosis and management can alleviate the clinical manifestations of this debilitating condition.

Oral candidiasis.

Oral candidiasis (OC) is a common fungal disease encountered in dermatology, most commonly caused by an overgrowth of Candida albicans in the mouth. Although thrush is a well-recognized presentation of OC, it behooves clinicians to be aware of the many other presentations of this disease and how to accurately diagnose and manage these cases. The clinical presentations of OC can be broadly classified as white or erythematous candidiasis, with various subtypes in each category. The treatments include appropriate oral hygiene, topical agents, and systemic medications. This review focuses on the various clinical presentations of OC and treatment options.

Botanical agents for the treatment of nonmelanoma skin cancer.

Nonmelanoma skin cancers, including basal cell carcinoma and squamous cell carcinoma, are common neoplasms worldwide and are the most common cancers in the United States. Standard therapy for cutaneous neoplasms typically involves surgical removal. However, there is increasing interest in the use of topical alternatives for the prevention and treatment of nonmelanoma skin cancer, particularly superficial variants. Botanicals are compounds derived from herbs, spices, stems, roots, and other substances of plant origin and may be used in the form of dried or fresh plants, extracted plant material, or specific plant-derived chemicals. They possess multiple properties including antioxidant, anti-inflammatory, and immunomodulatory properties and are, therefore, believed to be possible chemopreventive agents or substances that may suppress or reverse the process of carcinogenesis. Here, we provide a review of botanical agents studied for the treatment and prevention of nonmelanoma skin cancers.

The role of 39 psoriasis risk variants on age of psoriasis onset.

Recent genome-wide association studies (GWAS) have identified multiple genetic risk factors for psoriasis, but data on their association with age of onset have been marginally explored. The goal of this study was to evaluate known risk alleles of psoriasis for association with age of psoriasis onset in three well-defined case-only cohorts totaling 1,498 psoriasis patients. We selected 39 genetic variants from psoriasis GWAS and tested these variants for association with age of psoriasis onset in a meta-analysis. We found that rs10484554 and rs12191877 near HLA-C and rs17716942 near IFIH1 were associated with age of psoriasis onset with false discovery rate < 0.05. The association between rs17716942 and age of onset was not replicated in a fourth independent cohort of 489 patients (P = 0.94). The imputed HLA-C∗06:02 allele demonstrated a much stronger association with age of psoriasis onset than rs10484554 and rs12191877. We conclude that despite the discovery of numerous psoriasis risk alleles, HLA-C∗06:02 still plays the most important role in determining the age of onset of psoriasis. Larger studies are needed to evaluate the contribution of other risk alleles, including IFIH1, to age of psoriasis onset.