Background: The use of thiazide diuretics is associated with skin cancer risk; however, whether this applies to all skin cancer types is unclear. Methods: In this meta-analysis, we searched multiple electronic databases and gray literature up to 10 April 2022, with no language restrictions, to identify relevant randomized controlled trials (RCTs) and non-randomized studies (cohort, case-control) that investigated the association between thiazide diuretics and skin cancer. The primary outcomes of interest were malignant melanoma and non-melanoma skin cancer (basal cell carcinoma [BCC], squamous cell carcinoma [SCC]). Secondary outcomes included other skin cancers (lip cancer, Merkel cell carcinoma, malignant adnexal skin tumors, oral cavity cancer, and precursors of skin cancer). We used a random-effects meta-analysis to estimate pooled adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: Thirty non-randomized studies (17 case-control, 13 cohort, no RCTs) were included. Thiazide diuretic users had a higher risk of malignant melanoma (17 studies; n = 10,129,196; pooled adjusted OR, 1.10; 95% CI, 1.04–1.15; p < 0.001; strength of evidence, very low; very small harmful effect), BCC (14 studies; n = 19,780,476; pooled adjusted OR, 1.05; 95% CI, 1.02–1.09; p = 0.003; strength of evidence, very low; very small harmful effect), and SCC (16 studies; n = 16,387,862; pooled adjusted OR, 1.35; 95% CI, 1.22–1.48; p < 0.001; strength of evidence, very low; very small harmful effect) than non-users. Thiazide diuretic use was also associated with a higher risk of lip cancer (5 studies; n = 161,491; pooled adjusted OR, 1.92; 95% CI, 1.52–2.42; p < 0.001; strength of evidence, very low; small harmful effect), whereas other secondary outcomes were inconclusive. Conclusions: Thiazide diuretics are associated with the risk of all skin cancer types, including malignant melanoma; thus, they should be used with caution in clinical practice.

Pemphigus vulgaris is an autoimmune blistering disease characterized by autoantibodies that target desmoglein adhesion proteins. Rituximab and corticosteroids are FDA-approved therapies for pemphigus vulgaris. As newer treatments for pemphigus enter clinical trials, analysis of clinical and serologic outcomes after rituximab therapy as a function of time is essential to guide clinical trial design. Here, we report detailed temporal and serological outcomes of rituximab treatment of pemphigus vulgaris. The maximal prevalence of complete remission off oral systemic therapy after a single cycle of rituximab was 32.4% at 12 months, or 43.1% by 36 months including additional rituximab cycles. Using receiver operating characteristic curves to develop prediction models for complete remission after a single cycle of rituximab, >90.7% reduction in average desmoglein 3 ELISA titers from baseline to months 3–9 was 94% sensitive, and an average absolute titer ≤130 RU/mL between months 3–9 was 96% specific, for achievement of complete remission off oral systemic therapy. All patients with negative titers at 6–9 months ultimately achieved complete remission off oral systemic therapy. This dataset of clinical and serological outcomes for pemphigus vulgaris patients after rituximab therapy will facilitate clinical trial planning and also guide clinician and patient expectations after rituximab therapy.

Capsaicin is an active compound in chili peppers (Capsicum chinense) that has been approved for chronic pain treatment. The topical application of high-strength capsaicin has been proven to reduce pain; however, skin irritation is a major drawback. The aim of this study was to investigate an appropriate and scalable technique for preparing nanostructured lipid carriers (NLCs) containing 0.25% capsaicin from capsicum oleoresin (NLC_C) and to evaluate the irritation of human skin by chili-extract-loaded NLCs incorporated in a gel formulation (Gel NLC_C). High-shear homogenization with high intensity (10,000 rpm) was selected to create uniform nanoparticles with a size range from 106 to 156 nm. Both the NLC_C and Gel NLC_C formulations expressed greater physical and chemical stabilities than the free chili formulation. Release and porcine biopsy studies revealed the sustained drug release and significant permeation of the NLCs through the outer skin layer, distributing in the dermis better than the free compounds. Finally, the alleviation of irritation and the decrease in uncomfortable feelings following the application of the Gel NLC_C formulation were compared to the effects from a chili gel and a commercial product in thirty healthy volunteers. The chili-extract-loaded NLCs were shown to be applicable for the transdermal delivery of capsaicin whilst minimizing skin irritation, the major noncompliance cause of patients.

Reactive neutrophilic dermatoses in adult‐onset immunodeficiency due to interferon‐γ autoantibody (AOID) are usually associated with concomitant active opportunistic infections. Data focusing on the treatment of these dermatoses with non‐immunosuppressive drugs are still lacking. The aim of this study was to assess the efficacy and safety of acitretin treatment of reactive neutrophilic dermatoses in AOID. We conducted a retrospective review of all patients with AOID who had reactive neutrophilic dermatoses and had been treated with acitretin from January 2008 to December 2018. In total, 23 patients had been diagnosed with AOID, with 27 episodes of reactive neutrophilic dermatoses (20 episodes of Sweet syndrome and seven episodes of generalized pustular eruption) and treated with acitretin. The median effective dose of acitretin was 10 mg/day. The mean initial response was 5.6 ± 2.3 days. The rash had almost or completely cleared within 2 weeks in 70.4% of patients. One case had developed a reversible acitretin‐induced liver injury with hepatocellular pattern. The median total duration of treatment was 3 months. In conclusion, this study demonstrates the potential role of acitretin as one of the treatments of choice for reactive neutrophilic dermatoses in AOID, attributable to its favorable response and good tolerability.

Klaewsongkram J, et al. Allergy Asthma Immunol Res. 2021 Nov;13(6):896-907. https://doi.org/10.4168/aair.2021.13.6.896