Given that mycosis fungoides-cutaneous T-cell lymphoma (MF/CTCL) is chronic, there is a need for additional therapies with minimal short- and long-term adverse effects. Topical synthetic hypericin ointment, 0.25%, activated with visible light is a novel, nonmutagenic photodynamic therapy (PDT).To determine the efficacy and safety of topical synthetic hypericin ointment, 0.25%, activated with visible light as a nonmutagenic PDT in early-stage MF/CTCL.This was a multicenter, placebo-controlled, double-blinded, phase 3 randomized clinical trial (FLASH study) conducted from December 2015 to November 2020 at 39 academic and community-based US medical centers. Participants were adults (≥18 years) with early-stage (IA-IIA) MF/CTCL.In cycle 1, patients were randomized 2:1 to receive hypericin or placebo to 3 index lesions twice weekly for 6 weeks. In cycle 2, all patients received the active drug for 6 weeks to index lesions. In cycle 3 (optional), both index and additional lesions received active drug for 6 weeks.The primary end point was index lesion response rate (ILRR), defined as 50% or greater improvement in modified Composite Assessment of Index Lesion Severity (mCAILS) score from baseline after 6 weeks of therapy for cycle 1. For cycles 2 and 3, open label response rates were secondary end points. Adverse events (AEs) were assessed at each treatment visit, after each cycle, and then monthly for 6 months. Data analyses were performed on December 21, 2020.The study population comprised 169 patients (mean [SD] age, 58.4 [16.0] years; 96 [57.8%] men; 120 [72.3%] White individuals) with early-stage MF/CTCL. After 6 weeks of treatment, hypericin PDT was more effective than placebo (cycle 1 ILRR, 16% vs 4%; P = .04). The ILRR increased to 40% in patients who received 2 cycles of hypericin PDT (P < .001 vs cycle 1 hypericin) and to 49% after 3 cycles (P < .001 vs cycle 1 hypericin). Significant clinical responses were observed in both patch and plaque type lesions and were similar regardless of age, sex, race, stage IA vs IB, time since diagnosis, and number of prior therapies. The most common treatment-related AEs were mild local skin (13.5%-17.3% across cycles 1-3 vs 10.5% for placebo in cycle 1) and application-site reactions (3.2%-6.9% across cycles 1-3 vs 4% for placebo in cycle 1). No drug-related serious AEs occurred.The findings of this randomized clinical trial indicate that synthetic hypericin PDT is effective in early-stage patch and plaque MF/CTCL and has a favorable safety profile.ClinicalTrials.gov Identifier: NCT02448381.
The increase in popularity of tattoos has coincided with an increase in reports of cutaneous inoculation of nontuberculous (atypical) mycobacteria (NTM) during the tattooing process. We report 3 NTM infections in otherwise healthy persons who received tattoos, which prompted a multiagency epidemiologic investigation. Tattoo artists involved were contacted and interviewed regarding practices, ink procurement and use, and other symptomatic clients. Additional patients were identified from their client lists with an Internet survey. Thirty-one cases of suspected or confirmed NTM inoculation from professional tattooing were uncovered, including 5 confirmed and 26 suspected cases. Clinical biopsy specimens from 3 confirmed infections grew Mycobacterium abscessus strains that were indistinguishable by pulsed-field gel electrophoresis testing. Another 2 skin specimens grew Mycobacterium chelonae, which also grew from a bottle of graywash ink obtained from the tattoo artist. The pathogenicity and antibiotic resistance patterns of certain NTM isolates highlight the importance of correct diagnosis and potential difficulty in treating infections. Enforcement of new standards for the regulation and use of tattoo inks should be considered.
Tattooing for ornamental purposes is an ancient practice that remains popular in modern times. Tattoos are encountered by the dermatopathologist either as incidental findings on skin biopsies or because of complications specific to the tattoo. A range of neoplasms and inflammatory conditions are seen in association with tattoos, many of which may be attributed to hypersensitivity to tattoo inks. The composition of tattoo inks is highly variable, and inks can contain numerous potentially allergenic or carcinogenic compounds. Infections with bacterial, viral and fungal species can occur after tattooing, sometimes after substantial delay. Atypical mycobacterial infections in particular are increasingly reported; special stains for mycobacteria should be performed and cultures recommended particularly when dense, mixed or granulomatous infiltrates are present.
Transient acantholytic dermatosis (TAD; Grover disease) is an inflammatory immune condition characterized by small, erythematous papules most commonly affecting the trunk and extremities of middle-aged men with a history of sun exposure. Skin pathology characteristically demonstrates acantholytic dyskeratosis within the epidermis with varying degrees of associated dermal inflammation, often with eosinophils. Lesions typically last for weeks to months, though there is a propensity for recurrence.
Background: Continuous subcutaneous insulin infusion (CSII) for type 1 diabetes is increasing in use. Pump site failures are common, yet little is known about the skin changes from pump use. Using noninvasive optical coherence tomography (OCT), OCT angiography (OCTA), and skin biopsies, we evaluated the skin changes of chronic insulin infusion.Methods: OCT operating at 1310nm central wavelength with a bandwidth of 100 nm was performed immediately before skin punch biopsies were collected at three sites: a “current site”, a “recovery site” used 3 days prior to biopsy, and a “control” site never used for any insulin infusion or injection.Findings: OCT and OCTA identified characteristics of increased inflammation and vessel density at pump sites compared to control sites. Histological analysis of pump sites showed differences in skin architecture including fibrosis, inflammation including increased tissue eosinophils and fat necrosis. Immunohistochemical staining showed differences between infusion sites and the control sites for staining of insulin-like-growth factor-1 and transforming growth factor β-3.Interpretation: These findings support allergic sensitization as a potentially common reaction at CSII sites. The leading candidates include insulin preservatives, plastic materials, or adhesive glue used in device manufacturing. The inflammatory response caused by these common allergic responses may result in tissue changes responsible for the infusion site failures seen frequently in clinical practice.Funding: Funding was provided by the Leona M. and Harry B. Helmsley Charitable Trust.Declaration of Interests: AK, MMS, RW, JDB, XD, DK, JL and IBH report support for the present manuscript from Leona M. and Harry B. Helmsley Charitable Trust paid to their institution. RW reports grants from National Institutes of Health, Carl Zeiss Meditec Inc, Colgate-Palmolive Company and Estee Lauder Inc outside of the submitted work; consulting fees from Cyberdontics Inc, Carl Zeiss Meditec Inc outside of the submitted work; patents planned, issued or pending (US8,750,586, US8,180,134, US9,282,905, US9,759,544, US 10,354,378, US10,529,06) outside of the submitted work; and received equipment from Carl Zeiss Meditec Inc to his institution and a gift support from Washington Research Foundation to his institution outside of the submitted work. IBH reports grants and contracts from Insulet, Medtronic and Dexcom outside of the submitted work; consulting fees from Abbott Diabetes Care, Roche, Big Foot, Lifescan and Hagar outside of the submitted work; and honoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from Section editor: UpToDate outside of the submitted work.Ethics Approval: The University of Washington Human Subjects Division reviewed and approved the study. Because of the COVID-19 pandemic, minor modifications to the protocol became necessary, including remote visits for consenting and screening.
