Multiple Eruptive Keratoacanthomas Secondary to Nivolumab Immunotherapy.

Immune checkpoint inhibitors are increasingly being utilized for the treatment of advanced neoplastic disease and have been associated with wide-ranging cutaneous adverse effects. Though exceedingly rare, eruptive keratoacanthomas have been associated with the use of immune checkpoint inhibitors such as pembrolizumab and nivolumab, whose molecular target is the programmed cell death protein 1. Herein, we detail a case of numerous eruptive keratoacanthomas arising in a patient one month after initiation of nivolumab for recurrent metastatic oropharyngeal squamous cell carcinoma. Treatment with multiple rounds of intralesional corticosteroids and a several-month course of oral acitretin resulted in partial improvement. Subsequent treatment with intralesional 5-fluorouracil demonstrated near-complete resolution of the keratoacanthomas without discontinuation of nivolumab. Although eruptive keratoacanthomas secondary to immune checkpoint inhibitors are exceptionally rare, physicians should be aware of this cutaneous adverse effect as their use becomes more widespread.

Delayed Onset of Bullous Pemphigoid Secondary to Nivolumab.

The increasing use of immune checkpoint inhibitors, such as nivolumab, a programmed cell death protein 1 (PD-1) inhibitor, for advanced neoplastic disease has revealed significant cutaneous immune-related adverse effects. Herein, we report a case of bullous pemphigoid (BP) secondary to nivolumab therapy for recurrent metastatic oropharyngeal squamous cell carcinoma. In this patient, the time to development of BP was three years, which represents the most delayed onset of BP secondary to a PD-1 inhibitor that has been reported in the literature. Symptoms were initially controlled on low-dose oral prednisone but recurred after two years. The patient was subsequently treated with a several-month taper of high-dose oral prednisone, during which he was able to resume nivolumab without recurrence of skin lesions. Although immune checkpoint inhibitor-induced BP remains rare, physicians should be aware of this serious cutaneous immune-related adverse event as the use of this drug class continues to expand.

Systemic Targeted Treatments for Basal Cell Carcinoma.

The sonic hedgehog (SHH) inhibitors vismodegib and sonidegib are the only 2 first-line systemic medications approved for the treatment of locally aggressive basal cell carcinoma (BCC). Vismodegib is the only SHH inhibitor approved for metastatic BCC. Cemiplimab, an immune checkpoint inhibitor (ICI), is now an approved second-line therapy for locally advanced or metastatic BCC. Efficacy and adverse effect profiles of vismodegib and sonidegib appear comparable, although head-to-head clinical trials have not been conducted. Despite the remarkable efficacy demonstrated by the 2 SHH inhibitors, adverse effects are common and often lead to treatment discontinuation. Alternative dosing schedules may help to manage these side effects, with recent approval of dose interruptions of up to 8 weeks. Given the high rate of recurrence and emerging concern regarding drug resistance, maintenance dosing regimens and potential synergism with other treatment modalities, such as radiotherapy or antifungal therapy, should be further explored. The use of SHH inhibitors in the neoadjuvant setting also is warranted, as it may allow for surgical management of previously inoperable cases of BCC.

Teaching dermatology to the millennial learner.

Millennial learners have educational needs and preferences that differ from those of prior generations. They prefer learning from online resources, appreciate interactive didactic sessions, and desire frequent feedback and guidance. Understanding and adapting to these learner attributes may allow for optimization of the educational environment for members of this generation. The following recommendations were developed to advance a dermatology residency program's curriculum to accommodate the modern learner. Although the efficacy of these teaching tips has yet to be fully established, they are grounded by theory and are evidence-informed. Medical educators who are able to employ these strategies are likely to be successful in teaching and engaging the millennial learner.

Reexamining the Role of Diet in Dermatology.

Dermatologists often are asked by patients to provide dietary recommendations. It was previously thought that many skin conditions were unaffected by diet; however, increasing associations between specific nutritional practices and dermatologic conditions are being recognized. The role of diet in acne has been well studied, but rigorous studies on dietary interventions for other common skin conditions are lacking. Understanding the current nutritional strategies employed by patients as well as the existing literature behind these practices is crucial for dermatologists to provide recommendations for patients regarding diet and skin disease.

Squamoid Eccrine Ductal Carcinoma.

Squamoid eccrine ductal carcinoma (SEDC) is a rare and under-recognized primary cutaneous tumor with a high risk for local recurrence and metastasis. The tumor has a biphasic histologic appearance consisting of a superficial portion indistinguishable from squamous cell carcinoma (SCC) and a deeper component demonstrating eccrine ductal differentiation. Because of superficial sampling, SEDC often is misdiagnosed as SCC during the initial biopsy. The diagnosis usually is made during complete excision when deeper tissue is sampled. Confirmation of the diagnosis can be achieved by immunohistochemical positivity for carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), cytokeratin (CK) 5/6, and p63. In this article, we review the clinical and histologic details of 5 patients with SEDC who underwent successful treatment with Mohs micrographic surgery (MMS) at a single institution between November 2018 and May 2020. We also review the histologic patterns that helped distinguish SEDC from SCC upon complete excision. Our findings support the use of MMS as the treatment of choice for SEDC, given that all of the patients we reviewed required more than 1 Mohs stage for complete tumor clearance, and none demonstrated evidence of recurrence or metastasis after a mean follow-up period of 11 months.

Inspired by COVID-19 isolation: Evolving educational techniques in dermatology residency programs.

The coronavirus disease 2019 (COVID-19) global pandemic has required dermatology residency programs to convert their learning environment largely to a virtual setting. The impromptu reliance on online lectures, videoconference didactics, and other digital educational resources during this time is welcomed by today's millennial generation of medical trainees and coincides with their learning preferences. Although hands-on direct patient care experiences are currently limited due to reservation of in-office visits for urgent care only, resident participation in teledermatology has permitted them to continue gaining valuable clinical training and may allow for enhanced evaluation of their performance in the future. Given the shown benefits of telemedicine and student preferences for online learning, incorporating these virtual technologies into the curriculum will be essential to advancing dermatology residency education.

A case report of disseminated verrucosis secondary to ustekinumab in a patient with Crohn's disease.

Ustekinumab is a biologic agent with Food and Drug Administration approval for the treatment of moderate-to-severe plaque psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn's disease. It functions to inhibit the p40 subunit common to both interleukin-12 and interleukin-23. These pro-inflammatory cytokines are implicated in autoinflammatory and autoimmune disorders, but they also play an important role in cell-mediated immunity against viral, bacterial, and fungal pathogens. Therefore, antagonism of interleukin-12 and interleukin-23 by ustekinumab may increase the risk of human papillomavirus infection or reactivation which can lead to the development of verrucae. To the best of our knowledge, there is only one published report of disseminated verrucosis secondary to ustekinumab treatment for psoriasis. Here, we present the first case report of ustekinumab-induced disseminated verrucosis occurring in the setting of treatment for Crohn's disease.

Cutaneous Manifestations of Nutritional Excess: Pathophysiologic Effects of Hyperglycemia and Hyperinsulinemia on the Skin.

Hyperglycemia is defined by excess blood glucose and, when persistent, may lead to prediabetic and diabetic states. Insulin is a hormone produced by the beta cells of the pancreas in response to elevated blood glucose. Dysregulated insulin secretion or clearance results in hyperinsulinemia, which also is closely associated with type 2 diabetes mellitus (T2DM) and metabolic disturbances. Hyperglycemia and hyperinsulinemia are endemic within the United States and impart considerable morbidity and mortality. Cutaneous manifestations of chronic hyperglycemia and hyperinsulinemia include acanthosis nigricans (AN), diabetic dermopathy (DD), scleredema diabeticorum (SD), ichthyosiform skin changes, acrochordons, and keratosis pilaris (KP). Necrobiosis lipoidica (NL), bullosis diabeticorum (BD), and generalized granuloma annulare (GA) are more rarely reported in association with hyperglycemia and hyperinsulinemia; however, the strength of these associations remains unclear. It is crucial for dermatologists to recognize these cutaneous manifestations, as they may be the first signs of metabolic syndrome and insulin resistance. Early identification and management of these conditions is key to improving patient health outcomes and reducing health care costs. Herein, we review the clinical presentations of these conditions and their underlying pathophysiologic mechanisms.

Paraneoplastic pemphigus: Revised diagnostic criteria based on literature analysis.

BACKGROUND: Paraneoplastic pemphigus (PNP) is a rare autoimmune bullous disease classically associated with an underlying neoplasm. The heterogeneous clinical and histopathologic features of the disease make diagnosis challenging for clinicians. There are no formally accepted diagnostic criteria, and newer techniques for identifying antibodies directed against plakin proteins have largely replaced immunoprecipitation, the historic gold standard. METHODS: An analysis of 265 published cases of PNP was performed. The clinical, histopathologic, and immunologic features of PNP were assessed. RESULTS: Based on this review, we modified previous diagnostic criteria to capture 89.4% of PNP cases compared to 71.2% of cases captured by the most commonly referenced criteria devised by Camisa and Helm (p-value < 0.01, z-test; 95% CI [10.2, 33.6]). CONCLUSION: These revised diagnostic criteria address the variable clinical, histopathologic, and biochemical features of PNP, allowing physicians to have greater confidence in diagnosis of this rare and often fatal disease. The revised criteria include three major criteria and two minor criteria, whereby meeting either all three major criteria or two major and both minor criteria would fulfill a diagnosis of paraneoplastic pemphigus. The major criteria include (a) mucous membrane lesions with or without cutaneous involvement, (b) concomitant internal neoplasm, and (b) serologic evidence of anti-plakin antibodies. The minor criteria include (a) acantholysis and/or lichenoid interface dermatitis on histopathology and (b) direct immunofluorescence staining showing intercellular and/or basement membrane staining.

Primary Cutaneous Nocardiosis in an Adolescent with Crohn Disease.

Nocardia is an aerobic, Gram-positive, partially acid-fast bacterium that often manifests as pulmonary infection since the primary route of entry is via the respiratory tract. As an opportunistic organism, Nocardia primarily affects immunocompromised individuals. Infection with Nocardia is uncommon. Primary cutaneous nocardiosis which is caused by percutaneous inoculation is even more rare. Here, we report a case of primary cutaneous nocardiosis in an adolescent with Crohn disease receiving treatment with adalimumab and azathioprine. Early identification and treatment are important to prevent disease progression and to avoid severe complications. Diagnosis is made principally by culture. Given that culture results may take up to two weeks to return, primary cutaneous nocardiosis should be maintained in the differential for any superficial cutaneous infection that arises in individuals undergoing treatment with immunosuppressive agents.

Dermatologic Applications and Safety Considerations of Janus Kinase Inhibitors.

Janus kinase inhibitors, also known as JAK inhibitors or jakinibs, represent a new class of medication that have broad potential to treat dermatologic disease. Currently, the only FDA-approved dermatologic indication for this class of medications is psoriatic arthritis; however, their utility in treating other immune-mediated skin conditions including atopic dermatitis, vitiligo, alopecia areata, and systemic and cutaneous lupus is actively being investigated. Overall, these drugs appear to be well-tolerated and have a safety profile similar to that of other biologics commonly used in dermatologic practice, although an increased risk of thromboembolism has been associated. While risk of mild infection and herpes zoster appears to be increased regardless of JAK selectivity, risk of thrombosis and malignancy based on the subtype of JAK inhibition remains to be seen. Certainly, safety concerns warrant further investigation; however, early data from ongoing clinical trials offer promise for the broad utility of these medications within future dermatologic practice.

Treatment Goals in Psoriasis: Which Outcomes Matter Most?

Psoriasis is a chronic immune-mediated inflammatory disease that predominantly affects the skin and joints. Its detrimental effects on the physical, psychosocial, and emotional well-being of patients leads to a significant reduction in quality of life (QoL). The goals of treatment focus on decreasing disease severity and improving QoL for patients; accomplishing these goals requires physicians to understand both the full impact of the disease on a patient's life and the outcomes that matter most to patients. The use of outcome measures, both physician- and patient-reported, can assist clinicians in evaluating the disease burden and its effect on QoL and in identifying patient preferences for treatment, ultimately enhancing quality of care. However, current outcome measures have many limitations and do not adequately capture patients' needs and priorities. Nevertheless, physicians treating patients with psoriasis are encouraged to utilize these instruments while remaining cognizant of each of their limitations. As there is no consensus on an outcome measure that fully encompasses the complexities of psoriasis and its impact on patients, instruments that are appropriate and applicable to dermatologists and their patients should be developed.

Pleural lipomatosis: An often-forgotten intrathoracic tumor.

Lipomas are benign mesenchymal neoplasms that arise from adipocytes. Most lipomas are found in the subcutaneous tissue; however, they can be present throughout the body. Lipomas arising from the thoracic pleura are exceptionally rare, with only approximately 20 cases ever reported in the literature. While typically asymptomatic, pleural lipomas may cause compressive symptoms such as nonproductive cough, chest pain, and dyspnea if they reach adequate size. A CT scan is usually sufficient for the diagnosis and typically reveals well-defined nodules with homogenous fat attenuation of approximately -50 to -150 Hounsfield units. Management is dependent on various factors including tumor size and location, associated symptoms, and age of the patient. Pleural lipomatosis, although exceedingly rare, should be maintained in the differential diagnosis for any well-defined, fat-attenuating pleural mass identified on conventional radiologic studies. Here we report a case of pleural lipomatosis associated with bilateral pleural effusions identified in an 83-year-old male presenting with acute onset dyspnea.