Faculty Bibliography

BACKGROUND:Psoriasis is an inflammatory skin disease associated with increased cardiovascular (CV) risk, whose pathogenesis is not fully known. OBJECTIVE:We identified a transcriptomic signature in psoriasis and investigated its association with prevalent and future risk of a CV event to understand the connection between psoriasis and CV disease (CVD). METHODS:Psoriasis patients (n = 37) with a history of moderate-severe skin disease without CVD and 11 matched controls underwent whole blood RNA sequencing. This transcriptomic signature in psoriasis versus controls was evaluated in two CVD cohorts: Women referred for cardiac catheterization with (n = 76) versus without (n = 97) myocardial infarction (MI), and patients with peripheral artery disease (n = 106) followed over 2.5 years for major adverse CV or limb events (MACLE). The association between genes differentially expressed in psoriasis and prevalent and incident CV events was assed. RESULTS:In psoriasis, median age was 44 (IQR; 34-51) years, 49% male and ACC/AHA ASCVD Risk Score of 1.0% (0.6-3.4) with no significant difference versus controls. The median psoriasis area and severity index score (PASI) was 4.0 (IQR 2.9-8.2) with 36% on biologic therapy. Overall, 247 whole blood genes were upregulated and 228 downregulated in psoriasis versus controls (p < 0.05), and 1302 genes positively and 1244 genes negatively correlated with PASI (p < 0.05). Seventy-three genes overlapped between psoriasis prevalence and PASI with key regulators identified as IL-6, IL-1β and interferon gamma. In the CVD cohorts, 50 of 73 genes (68%) identified in psoriasis associated with prevalent MI, and 29 (40%) with incident MACLE. Key regulator transcripts identified in psoriasis and CVD cohorts included SOCS3, BCL3, OSM, PIM2, PIM3 and STAT5A. CONCLUSIONS:A whole blood transcriptomic signature of psoriasis diagnosis and severity associated with prevalent MI and incident MACLE. These data have implications for better understanding the link between psoriasis, systemic inflammation and CVD.

BACKGROUND:Hidradenitis suppurativa (HS) is a chronic inflammatory disorder of hair follicles characterized by recurrent, painful nodules, abscesses, and sinus tracts ("tunnels") typically refractory to treatment. This debilitating condition results in poor quality of life due to high disease burden. Intralesional triamcinolone (ILTAC) is a standard of care for acute inflammation and drainage associated with HS; however, the optimal therapeutic dose has not been determined. We investigated the utility of high-dose ILTAC 20 mg/ml (ILTAC-20) or 40 mg/ml (ILTAC-40), for inflammatory lesions of HS. METHODS:A retrospective chart review and telephone questionnaire included HS patients treated with high-dose ILTAC-20 or ILTAC-40 between April and December 2018. Patients with Hurley stages I-III were included. Data were obtained from electronic medical records and telephone interviews. A short questionnaire pertained to satisfaction with therapy, changes of disease state, and modifications in quality of life. RESULTS:Of 54 patients interviewed, the average age was 36.9 ± 11.6 years; 36 (66.7%) were female. Forty patients (76.9%) were very satisfied (n = 19) or satisfied (n = 21) with high-dose ILTAC therapy. Fifty patients (92.6%) demonstrated improvements in disease state, and 41 patients (75.9%) experienced enhanced quality of life. Forty-four patients (86.3%) were amenable to additional injections of high-dose ILTAC, if clinically indicated. No adverse effects of therapy were reported. CONCLUSIONS:The majority of patients reported improvements in disease state, quality of life, and overall satisfaction after administration of high-dose ILTAC (20-40 mg/ml). These findings support the use of high-dose ILTAC for acute lesions of HS.

Cutaneous vasculitis has many underlying causes, and the clinical and histological findings often overlap. Inflammatory vasculitis can mimic infection; however, distinction is critical for the timely institution of appropriate therapy. We present two patients who had generalized polymorphous eruptions whose cutaneous pathology showed vasculitis with unusual haloed yeast-like cells within the inflammatory infiltrate, mimicking Cryptococcus. The unusual cells stained negatively with Gomori methenamine silver and periodic acid-Schiff fungal stains, but positively for CD68 and had cytoplasmic reactivity with antibody to myeloperoxidase (MPO). Both patients had positive serum anti-MPO antibodies. The first patient experienced a rapidly fatal course, whereas the second patient improved with prompt initiation of systemic corticosteroids. Interestingly, the second case had prior biopsy showing Sweet syndrome with crypotoccoid-appearing cells. Cryptococcoid cells have been described previously in association with neutrophilic dermatoses, but not in the setting of vasculitis as was seen in our patients. Our cases add to the existing literature on crypotoccoid mimickers, and are the first to be reported in association with vasculitis.

Topical cantharidin is a commonly used treatment for molluscum contagiosum (MC). However, studies validating its safety and efficacy are limited. We conducted a 6-week, randomized, double-blind, placebo-controlled trial with subsequent open-label extension to assess the safety and effectiveness of cantharidin in treating pediatric MC. Ninety-four participants with MC were randomized to receive cantharidin or placebo, with or without occlusion. The primary outcome was complete lesion clearance. Secondary outcomes included post-treatment lesion count, adverse events, and side effects. No significant differences between the study arms, including baseline lesion count, were observed. The overall mean (SD) baseline lesion count was 22.2 (12.9). The number of participants achieving total clearance is as follows: 7/23 (30.4%) in the cantharidin only arm, 10/24 (41.7%) in the cantharidin with occlusion arm, 2/25 (8.0%) in the placebo with occlusion arm, and 3/22 (13.6%) in the placebo only arm. Post hoc analysis demonstrated that 17/47 (36.2%) participants in the combined cantharidin arms achieved clearance compared to 5/47 (10.6%) in the placebo arms (P = 0.0065). The mean (SD) lesion count change from baseline was -5.1 (12.2) in the placebo only arm; the mean change (SD) was -17.4 (12.8) in the cantharidin only arm (P = 0.0033) and -15.9 (11.6) in the cantharidin with occlusion arm (P = 0.0101). No serious adverse events or side effects were observed. Topical cantharidin was well-tolerated and associated with the resolution of MC.

INTRODUCTION/BACKGROUND:Microcystic adnexal carcinoma (MAC) is a rare malignant cutaneous neoplasm presenting as a slow-growing, indurated nodule, papule or plaque. Clinically, the lesion can blend into the surrounding skin, obscuring borders and consequently delaying diagnosis histologically. Surgical and histologic techniques that emphasize examination of all margins may optimize management through early diagnosis and prevention of recurrences. OBJECTIVE:This review aims to assess the current surgical and histology techniques that result in lower rates of tumor recurrence and, consequently, better clinical outcomes. METHODS:A literature search of the PubMed database was conducted to identify studies examining wide local excision (WLE), Mohs micrographic surgery (MMS), radiotherapy (RT) and chemotherapy in the treatment of MAC. RESULTS:WLE had a high likelihood of positive margins and local recurrence. MMS was found to have the lowest recurrence rates. Definitive RT could be considered for elderly patients or those who are poor surgical candidates, as large surgical defects may be required to obtain free margins with either WLE or MMS. Chemotherapy was found to be ineffective. CONCLUSION/CONCLUSIONS:Complete margin evaluation with MMS permits complete tumor removal with subsequently low recurrence rate.