ATOH1, TFAP2B, and CEACAM6 as Immunohistochemical Markers to Distinguish Merkel Cell Carcinoma and Small Cell Lung Cancer.

Merkel cell carcinoma (MCC) and small cell lung cancer (SCLC) can be histologically similar. Immunohistochemistry (IHC) for cytokeratin 20 (CK20) and thyroid transcription factor 1 (TTF-1) are commonly used to differentiate MCC from SCLC; however, these markers have limited sensitivity and specificity. To identify new diagnostic markers, we performed differential gene expression analysis on transcriptome data from MCC and SCLC tumors. Candidate markers included atonal BHLH transcription factor 1 (ATOH1) and transcription factor AP-2ß (TFAP2B) for MCC, as well as carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) for SCLC. Immunostaining for CK20, TTF-1, and new candidate markers was performed on 43 MCC and 59 SCLC samples. All three MCC markers were sensitive and specific, with CK20 and ATOH1 staining 43/43 (100%) MCC and 0/59 (0%) SCLC cases and TFAP2B staining 40/43 (93%) MCC and 0/59 (0%) SCLC cases. TTF-1 stained 47/59 (80%) SCLC and 1/43 (2%) MCC cases. CEACAM6 stained 49/59 (83%) SCLC and 0/43 (0%) MCC cases. Combining CEACAM6 and TTF-1 increased SCLC detection sensitivity to 93% and specificity to 98%. These data suggest that ATOH1, TFAP2B, and CEACAM6 should be explored as markers to differentiate MCC and SCLC.

Cutaneous manifestations of COVID-19.

The severe acute respiratory syndrome coronavirus two (SARS-CoV-2), which causes the 2019 coronavirus disease (COVID-19), has infected patients worldwide. Physicians have increasingly identified cutaneous findings as a significant clinical manifestation of COVID-19. In this review, we describe the clinical presentation, onset, duration, associated symptoms, treatment, and outcome of cutaneous manifestations thus far reported to be related to COVID-19. We have included data from 63 studies and subdivided reported cutaneous manifestations into the categories of viral exanthem, urticarial, vesicular, chilblains/chilblains-like, non-chilblains vasculopathy-related, pityriasis rosea-like, erythema multiforme-like, Kawasaki/Kawasaki-like disease, and others. Physicians should be aware of the known common cutaneous manifestations of COVID-19 and future research is required to better understand the pathophysiology and prognosis of each COVID-19-related skin manifestation.

BRAF Inhibitors for the Treatment of Papulopustular Eruptions from MAPK Pathway Inhibitors.

Inhibitors of the mitogen-activated protein kinase (MAPK) pathway are commonly used in clinical oncology. However, with the exception of BRAF inhibitors (BRAFi), MAPK pathway inhibitors such as epidermal growth factor receptor inhibitors (EGFRi) or MEK inhibitors (MEKi) are associated with dose-limiting papulopustular eruptions. Interestingly, patients treated with a combination of systemic BRAFi and MEKi experience less skin toxicities than patients on monotherapy BRAFi or MEKi. The reduction in cutaneous adverse events with combination therapy is thought to be due to a paradoxical activation of the MAPK pathway by BRAFi in keratinocytes carrying wildtype BRAF. Although treatment options for EGFRi- or MEKi-induced papulopustular eruptions exist, many patients still experience dose reduction, interruption, or discontinuation of EGFRi or MEKi. With the goal of activating MAPK signaling in the skin via BRAFi while minimizing systemic risks, we propose topical BRAFi therapy for the treatment and prevention of papulopustular eruptions due to MAPK pathway inhibitors. If effective, patients will be able to tolerate higher doses of MAPK pathway inhibitors, stay on treatment longer, and achieve better therapeutic outcomes overall.

Nodular secondary syphilis in three HIV-positive patients: a case series.

Nodular secondary syphilis is an uncommon variant of secondary syphilis. We identified three cases of nodular secondary syphilis at our institution. The first patient presented with a diffuse nodular rash that included his scrotum and penis. The second patient had disseminated skin-colored nodules with serosanguinous crust on his face, trunk, and extremities. The third patient had a pruritic papular and nodular rash with overlying crust. All three patients had a reactive rapid plasma reagin and tested positive for fluorescent treponemal antibody absorption. All were eventually confirmed to be human immunodeficiency virus-positive. Histopathological examination demonstrated inflammatory infiltrate in the dermis composed of lymphocytes, histiocytes, and plasma cells, and treponemal staining highlighted spirochetes in the dermis. The patients were successfully treated with intramuscular penicillin benzathine G. Physicians should be aware of nodular syphilis as a less common cutaneous manifestation of secondary syphilis. Prompt diagnosis of secondary syphilis can expedite resolution of the infection and avoid progression to tertiary syphilis.

Anti-tumor necrosis factor agents in sarcoidosis: A systematic review of efficacy and safety.

BACKGROUND: Though anti-tumor necrosis factor agents (anti-TNFs) have been recommended as third-line therapy for sarcoidosis, an up-to-date systematic synthesis of their efficacy and safety is lacking. OBJECTIVES: To systematically review the literature to characterize the efficacy and safety of anti-TNFs in sarcoidosis. SETTINGS: All countries and treatment settings were included. METHODS: We searched MEDLINE, EMBASE, CINAHL, Web of Science, ClinicalTrials.gov, Cochrane Library, and Google Scholar from inception to November 27, 2017. Studies of five or more cases of sarcoidosis treated with anti-TNFs were included. Descriptive statistics were performed. RESULTS: Sixty-five studies (including five randomized controlled trials [RCTs]) were identified, comprising 1525 patients. For pulmonary sarcoidosis, one RCT found infliximab (IFX) significantly improved vital capacity vs. placebo; a second detected no difference. In non-randomized studies, IFX improved pulmonary function in 79% of patients. For cutaneous sarcoidosis, compared to placebo, adalimumab (ADA) showed greater Physician Global Assessment response and significantly reduced target lesion area, and IFX significantly decreased Sarcoidosis Area and Severity Index induration and erythema scores. In non-randomized studies of cutaneous, ocular, neurologic, and multisystem sarcoidosis, IFX improved 89%, 69%, 77%, and 71% of cases, respectively. ADA improved 77% of ocular sarcoidosis cases. IFX displayed a steroid-sparing effect. Half of patients relapsed after discontinuation of IFX, ADA, etanercept, or certolizumab pegol. In RCTs, compared to placebo, anti-TNFs had comparable overall and serious adverse events and slightly more serious infections. CONCLUSIONS: Available evidence suggests the efficacy and safety of IFX in pulmonary, cutaneous, ocular, neurologic, and multisystem sarcoidosis, and ADA in cutaneous and ocular sarcoidosis.

Treatment preferences and treatment satisfaction among psoriasis patients: a systematic review.

A critical gap exists in determining treatment preferences and treatment satisfaction from patient perspectives, which is paramount to achieving therapeutic success. The objective of this systematic review is to determine factors influencing treatment preferences and treatment satisfaction among psoriasis patients. PubMed, EMBASE, and Web of Science databases were searched between November 1, 2010, and December 1, 2017. Observational and interventional research studies published in the English language that discussed patient preferences and patient satisfaction in the treatment of psoriasis were reviewed and synthesized. We utilized data on treatment preferences and treatment satisfaction from 35,388 psoriasis patients based on 60 articles from the years 2010 to 2017. Treatment preferences were heterogeneous and changed over time among psoriasis patients. Across all treatment modalities, the most important treatment attributes were treatment location, probability of improvement, and delivery method. For biologics specifically, the most important attributes were risk of adverse events and probability of treatment benefit. Factors that influenced patients' preferences for certain treatments included age, sex, comorbidities, disease duration, and prior treatments. Notably, some psoriasis patients placed higher importance on a treatment's process attributes (e.g., access and delivery) over its outcome attributes (e.g., efficacy). Overall, patient satisfaction with existing therapies remains modest; however, those treated with biologic agents exhibited highest treatment satisfaction over oral therapy, phototherapy, and topical therapy.