Considering a Biologic: What's a Clinician to Do? Screening and Laboratory Monitoring for Biologic Therapies in the Treatment of Psoriasis.

Biologic therapies have revolutionized the treatment of psoriasis; however, these immunomodulatory therapies may increase the risk of reactivation of latent and chronic infections. Tumor necrosis factor alpha (TNF-α) inhibitors, in particular, have been associated with the increased risk of reactivation of tuberculosis (TB) in patients with latent TB, as well as hepatitis B virus (HBV), in patients with chronic HBV infections. Currently, baseline TB tests are the only screening tests supported with strong evidence. High-grade evidence for HBV screening tests is lacking; however, these tests are sometimes performed in clinical practice. We describe current recommendations for screening tests prior to the initiation of biologic therapy.

Tumor mutational burden and somatic mutation status to predict disease recurrence in advanced melanoma.

Tumor mutational burden (TMB) has recently been identified as a biomarker of response to immune checkpoint inhibitors in many cancers, including melanoma. Co-assessment of TMB with inflammatory markers and genetic mutations may better predict disease outcomes. The goal of this study was to evaluate the potential for TMB and somatic mutations in combination to predict the recurrence of disease in advanced melanoma. A retrospective review of 85 patients with stage III or IV melanoma whose tumors were analyzed by next-generation sequencing was conducted. Fisher's exact test was used to assess differences in TMB category by somatic mutation status as well as recurrence locations. Kaplan-Meier estimates and Cox-proportional regression model were used for survival analyses. The most frequently detected mutations were TERT (32.9%), CDKN2A (28.2%), KMT2 (25.9%), BRAF V600E (24.7%), and NRAS (24.7%). Patients with TMB-L + BRAFWT status were more likely to have a recurrence [hazard ratio (HR), 3.43; confidence interval (CI), 1.29-9.15; P = 0.01] compared to TMB-H + BRAF WT. Patients with TMB-L + NRASmut were more likely to have a recurrence (HR, 5.29; 95% CI, 1.44-19.45; P = 0.01) compared to TMB-H + NRAS WT. TMB-L tumors were associated with local (P = 0.029) and in-transit (P = 0.004) recurrences. Analysis of TMB alone may be insufficient in understanding the relationship between melanoma's molecular profile and the body's immune system. Classification into BRAFmut, NRASmut, and tumor mutational load groups may aid in identifying patients who are more likely to have disease recurrence in advanced melanoma.

A Retrospective, Observational Analysis of Tumor Infiltrating Lymphocytes and Tumor Regression in Melanoma.

BACKGROUND: Tumor infiltrating lymphocytes (TILs) and regression are thought to be distinct markers of the immune response to melanoma. OBJECTIVE: This study sought to analyze the relationship of TIL grade and presence of regression to each other and to other prognostic histopathologic and clinical values in melanoma. MATERIALS AND METHODS: A retrospective analysis was conducted using patients diagnosed with melanoma between 2013 and 2019 whose complete histopathologic reports were available. RESULTS: Regression was seen in 48.9%, 30.1% and 37.9% of patients with brisk, non-brisk, and absent TILs respectively (P=0.019). Melanoma tumors with brisk TILs were found to have a lower Breslow thickness than those with non-brisk or absent (P= 0.001). Tumors with regression were also found to have lower Breslow thickness (P<0.001). Neither TIL grade nor regression were protective of nodal metastasis or associated with improved survival. CONCLUSION: Brisk TILs have a positive association with thinner tumors and the presence of tumor regression relative to non-brisk or absent TILs. This may suggest a more robust immune response in tumors with brisk TILs. Further exploration of the interplay between TIL grade, lymphocyte cell subtype and lymphocyte density may help explain this finding.

Extreme winter weather: A force to be remembered in dermatopathology.

It is important for the dermatopathologist to be adept in differentiating tissue artifacts from normal tissue variants and pathologies. Numerous tissue artifacts have been described to date; however, once we are familiar with the common artifacts that appear in our practice, we may not immediately recognize other confounders. For example, dermatopathologists in more temperate regions of the country may not be familiar with freezing artifact. In this case series, we present three common diagnoses in dermatopathology that were obscured by the extreme winter weather that severely impacted the Southern United States in February 2021 and discuss methods to prevent these artifacts.

Considering a Biologic: What's a Clinician to Do? Management of Biologics in Surgery, Vaccinations, and Cancer.

In the past two decades, biologic therapy has become ubiquitous in the treatment of psoriasis; however, important considerations should be taken with regard to biologic use in the context of surgery, vaccinations, and cancers. With conflicting evidence on the effects of perioperative biologic use, we recommend withholding tumor necrosis factor alpha (TNF-α) inhibitor therapy for one dose prior to surgical procedures.1 Although no studies have shown a direct link between live vaccines and infection in patients receiving biologics, due to the theoretical risk of live vaccines producing infection in patients with altered immune responses, we recommend withholding biologic therapy for 4 to 5 half-lives prior to the administration of live or live-attenuated vaccines.2,3 Finally, although an increased rate of cancer recurrence has not been demonstrated with biologic use, experts recommend withholding biologic therapy for 2 years after the completion of treatment for invasive cancers and 5 years after the completion of treatment for aggressive malignancies (including melanomas, breast cancers, sarcomas, urinary tract cancers, and myelomas)4; however, exceptions should be considered depending on the patient's circumstances and severity of the psoriasis. (SKINmed. 2021;19:17-0).

Painful Abdominal Outpouching in an Adult Male.

Post-herpetic abdominal pseudohernia is a neurologic complication of herpes zoster resulting from paresis of the abdominal wall muscles ipsilateral to the eruption. This poorly known condition may raise suspicion for true abdominal wall hernia or other concerning etiologies, resulting in extensive work-up and imaging. Post-herpetic abdominal pseudohernia is a relatively benign condition, which resolves spontaneously in the majority of cases. Therefore, it is important for the clinician to be aware of this complication in order to avoid unnecessary imaging or excessive management, which may increase the cost of care and burden to the patient.

Indeterminate Cell Histiocytosis Mimicking Rosacea.

Indeterminate cell histiocytosis (ICH) is a rare proliferative disorder of histiocytes, which display morphologic and immunophenotypic characteristics of both Langerhans cell histiocytosis (LCH) and non-Langerhans cell histiocytosis (NLCH). We describe an unusual clinical presentation of ICH mimicking rosacea and provide a relevant review of the literature.

COVID toes or pernio?

"COVID toes" are a new phenomenon of pernio-like lesions that has been associated with coronavirus disease 2019 (COVID-19) infection. As dermatology practices reopen and increase patient volumes amid the waning of the coronavirus pandemic, it is important to consider the finding of pernio and pernio-like lesions in the context of both COVID-19 and its other possible etiologies. This contribution will discuss possible causes of pernio and pernio-like lesions and offer suggestions for appropriate diagnostic workup and management when indicated.