Consensus-Based Recommendations on the Prevention of Squamous Cell Carcinoma in Solid Organ Transplant Recipients: A Delphi Consensus Statement.

IMPORTANCE: There is a paucity of evidence to guide physicians regarding prevention strategies for cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients (SOTRs). OBJECTIVE: To examine the development and results of a Delphi process initiated to identify consensus-based medical management recommendations for prevention of CSCC in SOTRs. EVIDENCE REVIEW: Dermatologists with more than 5 years' experience treating SOTRs were invited to participate. A novel actinic damage and skin cancer index (AD-SCI), consisting of 6 ordinal stages corresponding to an increasing burden of actinic damage and CSCC, was used to guide survey design. Three sequential web-based surveys were administered from January 1, 2019, to December 31, 2020. Pursuant to Delphi principles, respondents thoroughly reviewed all peer responses between rounds. Supplemental questions were also asked to better understand panelists' rationale for their responses. FINDINGS: The Delphi panel comprised 48 dermatologists. Respondents represented 13 countries, with 27 (56%) from the US. Twenty-nine respondents (60%) were Mohs surgeons. Consensus was reached with 80% or higher concordance among respondents when presented with a statement, question, or management strategy pertaining to prevention of CSCC in SOTRs. A near-consensus category of 70% to less than 80% concordance was also defined. The AD-SCI stage-based recommendations were established if consensus or near-consensus was achieved. The panel was able to make recommendations for 5 of 6 AD-SCI stages. Key recommendations include the following: cryotherapy for scattered actinic keratosis (AK); field therapy for AK when grouped in 1 anatomical area, unless AKs are thick in which case field therapy and cryotherapy were recommended; combination lesion directed and field therapy with fluorouracil for field cancerized skin; and initiation of acitretin therapy and discussion of immunosuppression reduction or modification for patients who develop multiple skin cancers at a high rate (10 CSCCs per year) or develop high-risk CSCC (defined by a tumor with approximately ≥20% risk of nodal metastasis). No consensus recommendation was achieved for SOTRs with a first low risk CSCC. CONCLUSIONS AND RELEVANCE: Physicians may consider implementation of panel recommendations for prevention of CSCC in SOTRs while awaiting high-level-of-evidence data. Additional clinical trials are needed in areas where consensus was not reached.

Topical Therapy Primer for Nondermatologists.

A representative assortment of topical therapies is discussed here with the goal of emphasizing the most commonly encountered diagnoses and treatments for nondermatologists. When using topical therapies, carefully consider the proper active ingredient, potency, vehicle, and quantity of medication. If topical therapy is ineffective, question whether the medication is being used properly, whether the diagnosis is correct, and whether the topical may be contributing to the problem. Examples of the topical contributing to the problem include tinea incognito exacerbated by topical steroid use and allergic contact dermatitis to topical steroid excipients. For some patients, even maximum topical therapy is insufficient and systemic treatment is required. At this point, consultation with a dermatologist may be helpful.

A prospective clinical and pathological examination of injection site reactions with the HIV-1 fusion inhibitor enfuvirtide.

OBJECTIVE: Antiretroviral regimens containing the fusion inhibitor enfuvirtide (ENF) are associated with sustained viral suppression and immunological benefit. However, local injection site reactions (ISR) occur in the majority of patients. The aim of this study was to determine the pathogenesis of ISRs. METHODS: Injection sites were evaluated prospectively from 30 min up to 15-30 days post-injection in ENF-experienced (Cohort I) and ENF-naive patients (Cohort II) during the first 2 weeks of therapy. Four to five injections were given in rotating abdominal sites by a nurse using a standardized technique and were rigorously evaluated. RESULTS: Reactions were observed in 80-100% of patients; the majority of the reactions were mild to moderate, generally appeared within 24-48 h post-injection, and pain, induration and erythema were the most common clinical signs. Whereas most patients experienced ISRs, the overall prevalence in Cohort II was low (35% maximum). Punch biopsies of injection sites in Cohort I consisted primarily of mixed lymphocytic infiltrates with eosinophils and neutrophils. Injection vehicle (ENF buffer minus ENF) and reduced volume (2 x 0.5 ml ENF [45 mg] versus 1.0 ml [90 mg] ENF) were investigated in Cohort II. Fewer reactions appeared with vehicle and pain was absent with the smaller injection volume. Pathology was indistinguishable between ENF, vehicle and normal tissue in Cohort II patients. CONCLUSION: These results suggest that injection technique, injection volume and peptide may influence ISR to ENF.

Evaluation and management of fungal infections in immunocompromised patients.

As the population of chronically immunosuppressed individuals continues to grow, the prevalence of fungal infections is increasing. Fungal infections in this patient population represent challenges in diagnosis and management. This article will review the common superficial and invasive mycoses that occur in the solid organ transplant and HIV-infected populations. Disease presentations are reviewed, but emphasis is placed on cutaneous manifestations. Recent advances in antifungal therapy and their direct application to specific diseases provide important new approaches to this complex and often seriously ill patient population.

Cutaneous effects of highly active antiretroviral therapy in HIV-infected patients.

Effective highly active antiretroviral therapy (HAART) has increased survival in patients infected with the human immunodeficiency virus (HIV). However, HAART is not without toxicities. Cutaneous adverse reactions from antiretroviral agents have become increasingly important to recognize as the population of patients surviving with HIV infection grows. Dermatologists play an important role in managing these cutaneous effects of HAART therapy in HIV patients. This article reviews cutaneous adverse effects from nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and fusion inhibitors, as well as separately addresses lipodystrophy, and immune reconstitution.

Cutaneous findings in patients with pulmonary arterial hypertension receiving long-term epoprostenol therapy.

Pulmonary arterial hypertension (PAH) is a rare debilitating disease characterized by an increase in pulmonary vascular resistance and progressive right ventricular failure. PAH may be primary or associated with other conditions such as collagen vascular disease, portal hypertension, and HIV. Intravenous epoprostenol improves the survival, exercise tolerance, hemodynamics, and quality of life in patients with PAH and is believed to work through multiple pathways including vasodilation, opposition of smooth-muscle hypertrophy, and inhibition of platelet aggregation. Common dose-limiting side effects are flushing, jaw pain, arthralgias, myalgias, and headache, which are attributed to the vasodilatory effects of epoprostenol. In clinical practice, patients often develop persistent rash that is distinct from the flushing associated with epoprostenol. The specific findings both on physical examination and on dermatopathology have not, however, been well described. This report describes the cutaneous and dermatopathologic findings of 12 patients who developed persistent rash while receiving long-term prostacyclin for PAH.

Hypertrophic herpes simplex virus in HIV patients.

In conclusion, HSV lesions in HIV patients can present as chronic, hyperproliferative plaques as opposed to the classic acute ulcerative lesions. Knowledge of this presentation will motivate the physician to be diligent in the diagnostic workup. This may necessitate repeat biopsies and cultures. Due to the high incidence of resistant isolates, sensitivity testing and knowledge of antiviral mechanisms will facilitate treatment in an HIV patient.

Early melanoma detection: nonuniform dermoscopic features and growth.

BACKGROUND: Dermoscopy alone is not sufficient to detect all early melanomas. Total body photos reveal growth of melanomas but also reveal growth of melanocytic nevi. OBJECTIVE: We set out to determine whether a simplified algorithm on the basis of nonuniform dermoscopic features combined with growth noted from baseline total body photos targeted the early melanocytic neoplasms most likely to be malignant. METHODS: Lesions removed during follow-up of patients with total body photographs were reviewed and 169 melanocytic lesions were identified for which both gross clinical and dermoscopic photos were available. The images were evaluated separately by 3 academic dermatologists, without knowledge of the given pathologic diagnosis, for uniformity (consistent gradient of features from center to edge) and change (specifically, that which could indicate melanoma growth in normal skin or within a nevus). RESULTS: Using a minimum of 2 out of 3 agreement for uniformity and change, 12 of 16 melanomas (including all 5 superficially invasive tumors) were graded as nonuniform and changed. The 4 melanomas not included in this category were in situ. The predicted odds of melanoma for lesions scored as both nonuniform and changed was 4.06 (P >.0195). If 3 out of 3 agreement was used, the odds ratio increased to 6 (P >.0010). CONCLUSION: An algorithm on the basis of dermoscopic nonuniformity and change suggestive of growth as determined by total body photography segregates melanocytic neoplasms most likely to be malignant.

Pruritus in systemic disease: mechanisms and management.

Pruritus is the most common symptom of skin disease. Even in the absence of primary cutaneous findings, severe and extensive pruritus often is associated with systemic disease. This review considers briefly the physiology of pruritus and discusses the various systemic diseases often accompanied by this bothersome symptom. In addition to exploring the possible mechanisms and potential therapies of itching in selected disorders, this review presents general recommendations for evaluating patients with unexplained pruritus and management guidelines for alleviating their discomfort.