ABSTRACT
Tattoos can lead to a variety of cutaneous conditions such as allergic or contact dermatitis, lichenoid dermatitis, pseudolymphomatous reactions and granulomatous responses such as foreign body granulomas that may have a sarcoidal histology simulating sarcoidosis. Pseudolymphomatous reactions are less common and may clinically and histologically resemble cutaneous lymphomas. Pseudolymphomatous reactions may develop in response to injections, Borrelia infections and arthropod bites. Diagnosis of cutaneous pseudolymphoma is usually based on clinicopathologic correlation coupled with skin biopsy and ancillary tests such as immunoperoxidase stains and genetic testing when necessary. Treatment is generally successful with application of topical corticosteroid preparation or injection of intralesional corticosteroids and in some cases, surgical excision. Here, we describe the case of a 61-year-old male who presented with 3-4 mm papules contained within the blue region of a multicolored tattoo on his upper right arm that had been present for several years. The reaction developed shortly following a Covid vaccination. © 2022 THE AUTHORS.
ABSTRACT
Background: Rheumatoid arthritis (RA) is independently associated with an increased risk of cardiovascular disease (CVD). One of the early stages of atherosclerosis is endothelial dysfunction, which is increased in RA. Using drugs to target endothelial dysfunction is a promising novel strategy for CVD prevention in RA. Sildenafil has been shown to improve endothelial function in diabetics, who have similar increased CVD risk. Our hypothesis was that sildenafil use may be a novel primary CVD prevention strategy in RA. Objectives: To determine if sildenafil use in RA patients improves endothelial dysfunction (as measured by brachial artery flow-mediated dilation [FMD] and peripheral arterial tone [PAT]), as well as serum inflammatory and atherosclerosis biomarkers. Methods: This NIH-funded study was a phase II, randomized double-blind placebo-controlled crossover efficacy trial of 25 RA patients, with no known history of CVD, but at least one traditional CVD risk factor. Patients were randomized 1:1 to receive either sildenafil or placebo for 3 months, then after a 2-week washout, crossed over to each respective group for an additional 3 months. Vascular studies (FMD and PAT) and serum atherosclerosis biomarkers (e-Selectin, ICAM-1, VCAM-1) were performed at baseline, 3 months pre-and post-washout, and 6 months. Adverse events were collected. Given the cross-over design, analyses included a random effects model for within-subject comparisons of sildenafil versus placebo periods, adjusting for the baseline (FMD or EndoPAT) within that period and a term for treatment order. All tests were 2-sided with α=0.05. Results: A total of 233 subjects were assessed for eligibility, with 25 subjects being randomized after written informed consent. A total of 13 subjects were randomized to placebo first, and 12 to sildenafil first. Baseline characteristics were similar between those randomized to Placebo vs. Sildenafil first. Mean age was 62.0+/-10.9 years;84% were female;and 92% were white. A total of 6 adverse events experienced in 3 subjects occurred. The primary endpoint (increase in %FMD in Sildenafil period vs. Placebo period) was not significant (p=0.19). However, note the study was powered at 80% to detect an effect size of 0.37 for change in %FMD or biomarker with a sample size of 60, not 25. However, sildenafil use was associated with a significant increase (improvement) by 0.200 units of PAT ratio (p=0.003) compared with placebo, adjusted by treatment order and baseline PAT ratio (within the given treatment period). Exploratory linear mixed models comparing e-Selectin, ICAM-1, and VCAM-1 between Sildenafil vs. Placebo periods, adjusted for treatment order and the baseline biomarker level, did not show any significant differences except for ICAM-1 (55.3 units higher in Sildenafil vs. Placebo periods, p=0.011). Conclusion: In this pilot trial of 25 RA subjects, sildenafil use was associated with a significant increase (improvement) in endothelial function as measured by PAT. However, there was no significant difference in FMD. The study is limited due to the small sample size, which was impacted by slow recruitment as well as the COVID-19 pandemic. Future larger studies are required to assess whether other PDE5 inhibitors may improve endothelial dysfunction in RA and other autoimmune disease patients at high risk of CVD.