Dysplastic nevus part II: Dysplastic nevi: Molecular/genetic profiles and management.

Dermatologists frequently see patients with clinically atypical nevi and dermatopathologists interpret histologically dysplastic nevi on a near-daily basis, but there is great variability in the definition and management of such lesions. This part of the CME review focuses on information published since the previous comprehensive review (2012), with emphasis on molecular and genetic attributes of histologically dysplastic nevi and clinical management.

Dysplastic nevus part I: Historical perspective, classification, and epidemiology.

Since the late 1970s, the diagnosis and management of dysplastic nevi have been areas fraught with controversy in the fields of dermatology and dermatopathology. Diagnostic uncertainty and lack of standardized nomenclature continue to propagate confusion among clinicians, dermatopathologists, and patients. In part I of this CME review article, we summarize the historical context that gave rise to the debate surrounding dysplastic nevi and review key features for diagnosis, classification, and management, as well as epidemiology. We discuss essentials of clinical criteria, dermoscopic features, histopathologic features, and the diagnostic utility of total body photography and reflectance confocal microscopy in evaluating dysplastic nevi, with emphasis on information available since the last comprehensive review a decade ago.

The epidemiology, impact, and diagnosis of micronutrient nutritional dermatoses. Part 2: B-complex vitamins.

Nutritional dermatoses are traditionally taught in the context of developing countries, famine, population displacement, and limited access to health care. In the United States, nutritional dermatoses may be underdiagnosed, leading to increased morbidity and utilization of hospital resources. These findings underscore the need for providers in developed nations to be able to identify these deficiencies. Dermatologists play a critical role in the diagnosis and management of patients with nutritional deficiencies, as they often present with cutaneous findings. Part 2 of this review series will focus on the epidemiology, impact, manifestations, and diagnosis of B-complex vitamins, which can present with cutaneous findings, including thiamine, riboflavin, niacin, pyridoxine, and biotin.

The evaluation and management of macronutrient deficiency dermatoses.

In industrialized countries, nutritional dermatoses are likely underdiagnosed and result in increased disease morbidity and utilization of hospital resources. These findings underscore the need for physicians to be able to correctly identify these deficiencies. Nutritional dermatoses may be split into micronutrient deficiencies and macronutrient deficiencies. This article is intended to serve as a supplement to a 2-part review of micronutrient deficiency dermatoses and highlights cutaneous findings in patients with protein-energy malnutrition and essential fatty acid deficiency. This article reviews the evaluation, cutaneous manifestations, and management of macronutrient deficiencies.

The epidemiology, impact, and diagnosis of micronutrient nutritional dermatoses part 1: Zinc, selenium, copper, vitamin A, and vitamin C.

Dermatologists play a critical role in diagnosing and managing nutritional deficiencies as they often present with cutaneous findings. Traditionally, nutritional dermatoses are taught in the context of developing countries, famine, population displacement, and poor health care access; however, in the United States, common risk factors include chronic liver disease, alcoholism, psychiatric disease, bariatric surgery, inflammatory bowel disease, and hemodialysis. Additionally, nutritional dermatoses may be underdiagnosed in the United States and result in increased morbidity and utilization of hospital resources. There is a need for providers in developed nations to identify these deficiencies, and this review aims to meet that practice gap and provide relevant context to these diseases for dermatologists. This 2-part review series will focus on the epidemiology, impact, appearance, and diagnostic modalities for micronutrient deficiencies, including zinc, selenium, copper, and vitamins A and C in part 1. The companion review will focus on the B-complex vitamins.

Management of relapsed cutaneous T-Cell lymphoma following allogeneic hematopoietic stem cell transplantation: Review with representative patient case.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for patients with refractory cutaneous T-cell lymphoma (CTCL) through replacement of the bone marrow responsible for lymphoma cells and possibly induction of a graft-versus-lymphoma effect. However, allo-HSCT is not always curative; relapse of CTCL occurs in about half of patients post-transplant. Treatment of relapsed CTCL after allo-HSCT is challenging because post-transplant patients are at high risk of graft-versus-host disease, and this condition may be precipitated or exacerbated by standard CTCL therapies. The benefit of each potential therapy must therefore be weighed against its risk of graft versus host disease (GVHD). In this article, we review the management of relapsed CTCL after allo-HSCT. We begin with an exemplative patient whose relapsed Sezary syndrome was successfully treated without development of GVHD. We also report high-throughput T-cell receptor sequencing data obtained during the patient's disease relapse and remission. We then review general guidelines for management of relapsed CTCL and summarize all reported cases and outcomes of relapsed CTCL after transplant. We conclude by reviewing the current CTCL therapies and their risk of GVHD.

Approaches to limit systemic antibiotic use in acne: Systemic alternatives, emerging topical therapies, dietary modification, and laser and light-based treatments.

Acne is one of the most common diseases worldwide and affects ∼50 million individuals in the United States. Oral antibiotics are the most common systemic agent prescribed for the treatment of acne. However, their use might be associated with a variety of adverse outcomes including bacterial resistance and disruption of the microbiome. As a result, multiple treatment guidelines call for limiting the use of oral antibiotics in the treatment of acne, although actual prescribing often does not follow these guidelines. In this review, the rationale for concerns regarding the use of oral antibiotics for the management of acne is reviewed. In addition, we will discuss our approach to complying with the intent of the guidelines, with a focus on novel topical agents, dietary modification, laser and light-based modalities, and systemic medications, such as spironolactone, combined oral contraceptives, and oral isotretinoin.

Role of (18)F-fluorodeoxyglucose positron emission tomography imaging in the management of primary cutaneous lymphomas.

Primary cutaneous lymphomas (PCLs) include both cutaneous T-cell and B-cell lymphomas and comprise the second most common type of extra-nodal non-Hodgkin's lymphomas. The treatment and prognosis of PCLs typically depend on the extent of disease. In evaluating extent of disease in oncological processes, computed tomography (CT) provides a purely anatomical assessment of disease. In comparison, [(18)F]-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) both visualizes and quantifies the biological processes occurring in the disease at the cellular level. This paper reviews the available literature addressing the clinical role of (18)F-FDG PET both alone and in combination with CT in PCLs and draws several conclusions. While (18)F-FDG PET seems superior to CT in its detection of nodal and cutaneous PCL lesions, (18)F-FDG PET does not seem to adequately detect erythroderma, plaque, or patch cutaneous PCL lesions. In addition, several case series have demonstrated that physicians may be able to use the semi-quantitative measurement of (18)F-FDG uptake provided by (18)F-FDG PET to predict which lesions are most aggressive. Other case series have shown that the integrated (18)F-FDG PET/CT may provide an objective measure of treatment response in patients with PCLs.

Observation of lymphadenopathy, systemic symptoms, and treatment in suspected indolent cutaneous B-cell lymphomas.

BACKGROUND: Following the initial diagnosis of a marginal zone or follicle center lymphoma on skin biopsy, patients undergo staging to determine the extent of disease. OBJECTIVE: We sought to characterize the frequency that these patients were found to have a systemic nodal disease upon work-up as well as the impact of imaging on disease management. METHODS: We conducted a retrospective chart review of patients presenting with a working diagnosis of PCMZL or PCFCL treated at The Ohio State University from 1990 to 2022. Data collected included: patient history, progress notes, virtual encounters, laboratory results, presentation features, imaging, and pathology. Biomarkers included ANA, SSA/SSB, BCL6 and H. Pylori labs, bone marrow biopsies, positive imaging, and need of systemic medication and mortality. RESULTS: 71 patients with suspected PCMZL and PCFCL were identified. 66 of 71 patients underwent imaging. Of this group, 12 patients (9 with suspected PCFCL and 3 with suspected PCMZL) demonstrated lymphadenopathy on imaging. Of these 12 patients, 5 underwent biopsy of suspected lymph nodes, and 3 had biopsy-proven nodal involvement and received systemic therapy. Of the remaining 7 patients with evidence of lymphadenopathy on imaging, 4 were thought to have reactive lymph nodes, and 3 were treated empirically with systemic chemotherapy due to the extent or progression of their disease. Of patients with imaging negative for lymphadenopathy, 3 of 52 (5.8%) patients with received systemic treatment, while 49 of 52 patients (94.2%) received localized treatment. LIMITATIONS: Most of the relationships between this data were correlational and patients selected for this study were limited to a single institution. CONCLUSION: Prospective study of the role of imaging without subsequent lymph biopsy to direct treatment decisions is warranted.

Hedgehog pathway inhibitors for locally advanced and metastatic basal cell carcinoma: A real-world single-center retrospective review.

Basal cell carcinoma (BCC) is highly curable by surgical excision or radiation. In rare cases, BCC can be locally destructive or difficult to surgically remove. Hedgehog inhibition (HHI) with vismodegib or sonidegib induces a 50-60% response rate. Long-term toxicity includes muscle spasms and weight loss leading to dose decreases. This retrospective chart review also investigates the impact of CoQ10 and calcium supplementation in patients treated with HHI drugs at a single academic medical center from 2012 to 2022. We reviewed the charts of adult patients diagnosed with locally advanced or metastatic BCC treated with vismodegib or sonidegib primarily for progression-free survival (PFS). Secondary objectives included overall survival, BCC-specific survival, time to and reasons for discontinuation, overall response rate, safety and tolerability, use of CoQ10 and calcium supplements, and insurance coverage. Of 55 patients assessable for outcome, 34 (61.8%) had an overall clinical benefit, with 25 (45.4%) having a complete response and 9 (16.3%) a partial response. Stable disease was seen in 14 (25.4%) and 7 (12.7%) progressed. Of the 34 patients who responded to treatment, 9 recurred. Patients who were rechallenged with HHI could respond again. The median overall BCC-specific survival rate at 5 years is 89%. Dose reductions or discontinuations for vismodegib and sonidegib occurred in 59% versus 24% of cases, or 30% versus 9% of cases, respectively. With CoQ10 and calcium supplementation, only 17% required a dose reduction versus 42% without. HHI is highly effective for treating advanced BCC but may require dosing decreases. Sonidegib was better tolerated than vismodegib. CoQ10 and calcium supplementation can effectively prevent muscle spasms.

Hypopigmented onychocytic matricoma as a clinical mimic of onychomatricoma: clinical, intraoperative and histopathologic correlations.

Onychocytic matricoma is a newly described matrical tumor of the nail unit that clinically presents with localized thickening of the nail plate and melanonychia and represents a benign acanthoma of onychocytes. Onychocytic matricoma can be classified according to its histopathologic type (acanthotic, papillomatous or keratogenous with retarded maturation) and pigmentation (pigmented, melanocytic or non-pigmented). However, there are no published reports of non-pigmented onychocytic matricoma. We report a case of hypopigmented onychocytic matricoma that presented with a thickened nail plate, xanthonychia and histopathologic features of acanthosis, prekeratogenous zone and keratogenous zone cells forming pseudosquamous eddies, and minimal pigmentation with Fontana staining. We also provide detailed clinical, intraoperative and histopathologic correlations of this rare tumor. Both clinicians and dermatopathologists should be aware that onychocytic matricoma can present with xanthonychia, thickening of the nail plate and mimic an onychomatricoma.

Patient Care Outcomes in Hospitalized Patients with Acute Generalized Exanthematous Pustulosis: A Cross-Sectional Database Study.

BACKGROUND: Current understanding of the etiology, natural history, and outcomes of acute generalized exanthematous pustulosis (AGEP) has been limited, with most available studies consisting of small or heterogenous cohorts. OBJECTIVES: The aim of this study was to further characterize associated factors and disease outcomes of AGEP. METHODS: A cross-sectional study design was employed with formal inclusion and causality criteria. Patients were identified from an inpatient database at an academic medical center, including 65 patients with AGEP and a control group of 61 patients with non-severe cutaneous adverse reactions. RESULTS: Increased age and body mass index (BMI) were associated with higher risk of AGEP (p < 0.001). Length of stay was longer for both the overall AGEP cohort (13.1 days) and a subcohort with a primary discharge diagnosis of AGEP (9.7 days) compared with the control group (3.6 days) [p < 0.001]. Patients with AGEP were more likely to be discharged to a long-term care facility compared with control patients (p < 0.001). CONCLUSIONS: AGEP was associated with longer length of hospitalization, higher rates of discharge to long-term care facilities, and higher mortality compared with non-severe cutaneous adverse drug reaction (SCAR) medication reactions. Future research should examine the association between morbid obesity and this particular drug reaction, and the possibility of decreasing hospitalization length given the relatively low risk of mortality among patients with AGEP.

Early Detection and Prognostic Assessment of Cutaneous Melanoma: Consensus on Optimal Practice and the Role of Gene Expression Profile Testing.

Importance: Therapy for advanced melanoma has transformed during the past decade, but early detection and prognostic assessment of cutaneous melanoma (CM) remain paramount goals. Best practices for screening and use of pigmented lesion evaluation tools and gene expression profile (GEP) testing in CM remain to be defined. Objective: To provide consensus recommendations on optimal screening practices and prebiopsy diagnostic, postbiopsy diagnostic, and prognostic assessment of CM. Evidence Review: Case scenarios were interrogated using a modified Delphi consensus method. Melanoma panelists (n = 60) were invited to vote on hypothetical scenarios via an emailed survey (n = 42), which was followed by a consensus conference (n = 51) that reviewed the literature and the rationale for survey answers. Panelists participated in a follow-up survey for final recommendations on the scenarios (n = 45). Findings: The panelists reached consensus (≥70% agreement) in supporting a risk-stratified approach to melanoma screening in clinical settings and public screening events, screening personnel recommendations (self/partner, primary care provider, general dermatologist, and pigmented lesion expert), screening intervals, and acceptable appointment wait times. Participants also reached consensus that visual and dermoscopic examination are sufficient for evaluation and follow-up of melanocytic skin lesions deemed innocuous. The panelists reached consensus on interpreting reflectance confocal microscopy and some but not all results from epidermal tape stripping, but they did not reach consensus on use of certain pigmented lesion evaluation tools, such as electrical impedance spectroscopy. Regarding GEP scores, the panelists reached consensus that a low-risk prognostic GEP score should not outweigh concerning histologic features when selecting patients to undergo sentinel lymph node biopsy but did not reach consensus on imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status. Conclusions and Relevance: For this consensus statement, panelists reached consensus on aspects of a risk-stratified approach to melanoma screening and follow-up as well as use of visual examination and dermoscopy. These findings support a practical approach to diagnosing and evaluating CM. Panelists did not reach consensus on a clearly defined role for GEP testing in clinical decision-making, citing the need for additional studies to establish the clinical use of existing GEP assays.

Refractory dermatitis contributed by pityriasis versicolor: a case report.

BACKGROUND: Dermatologic toxicity is a very common immune-related adverse event (irAE) for patients with melanoma who are receiving immune checkpoint inhibitor therapy (ICI). Concurrent skin infection, such as in the case of pityriasis versicolor reported here, can mimic and/or exacerbate dermatologic toxicity from irAE. CASE PRESENTATION: A 58-year-old Caucasian man with a history of pityriasis versicolor infection and metastatic melanoma received ICI therapy. He developed progressively worsening pruritic maculopapular lesions 22 weeks into his treatment that ultimately covered 40% of his body. He was diagnosed with dermatologic toxicity due to ICI therapy with concurrent pityriasis versicolor. He was initially started on topical steroid and topical antifungal cream but achieved minimum improvement. His treatment was then escalated to oral prednisone, but it only achieved modest control of his dermatitis. All subsequent attempts to wean him from oral prednisone resulted in worsening of his dermatitis. Eventually he was started on oral fluconazole in combination with prednisone, which led to rapid resolution of his dermatitis. CONCLUSION: We report a case of dermatological toxicity due to an irAE with concurrent pityriasis versicolor. The steroid treatment for irAE was likely exacerbating the underlying fungal infection, and the fungal infection was in term mimicking the symptoms of irAE. This patient's severe dermatitis was only brought under control after receiving a more potent antifungal therapy in combination with a steroid. It is vital to look beyond the irAE when managing dermatitis in patients receiving ICI therapy.