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Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). While MF generally follows an indolent course, a subset of patients will experience progressive and/or treatment-refractory disease; Sézary syndrome is an aggressive lymphoma associated with high morbidity and mortality. Although allogeneic hematopoietic cell transplant (allo-HCT) is the only currently available potentially curative treatment modality for MF/SS there is no published guidance on referral criteria, transplant timing orallo-HCT approach. To develop consensus clinical practice recommendations, we performed a Delphi survey of 32 specialists in dermatology (n = 9), transplant hematology/oncology (n = 10), non-transplant hematology/oncology (n = 8), and radiation oncology (n = 5) from across the United States. Consensus required agreement of ≥75% of participants. Sixteen consensus statements were generated on four topics: (1) criteria for referral for consideration for allo-HCT, (2) allo-HCT preparative regimens and procedures (3) disease status at the time of allo-HCT, and (4) multidisciplinary management in the pre- and post-transplant settings. These clinical practice guidelines provide a framework for decision-making regarding allo-HCT for MF/SS and highlight areas for future prospective investigation., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Autoimmune bullous disorders develop due to autoantibodies targeting intercellular adhesion proteins of hemidesmosomes and desmosomes and may be triggered by viral infections and vaccines. Recent reports suggest that the coronavirus disease 2019 vaccination may trigger flares or exacerbations of preexisting autoimmune diseases, including new onset autoimmune bullous disorders. There are less data on whether vaccination against severe acute respiratory syndrome coronavirus 2 may also exacerbate preexisting autoimmune bullous disorders., Case Presentation: Here we present three cases, two white males (ages 69 years and 88 years) with bullous pemphigoid and one white 50-year-old female with pemphigus foliaceus, wherein all individuals developed minor, tractable flares of their preexisting autoimmune bullous disorders after receiving the coronavirus disease 2019 vaccination, which were readily treatable with topical or low-dose systemic corticosteroids., Conclusions: Dermatologists managing patients with autoimmune bullous disorders should be cognizant of the uncommon potential for flares of the disorder following vaccination for severe acute respiratory syndrome coronavirus 2. Flares of bullous pemphigoid and pemphigus foliaceus following vaccination for severe acute respiratory syndrome coronavirus 2 in these cases were mild and tractable., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Importance: 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)., Objectives: 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., Design, Settings, and Participants: 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., Interventions: 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., Main Outcomes and Measures: 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., Results: 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., Conclusion and Relevance: 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., Trial Registration: ClinicalTrials.gov Identifier: NCT02448381.

Objective: To analyze the prognosis of cutaneous adnexal malignancies, survival relative to surgical management, and utility of lymph-node biopsy., Design: Population-based study of the SEER-18 database from 1975 to 2016., Participants: 7591 patients with sweat gland carcinoma, hidradenocarcinoma, spiradenocarcinoma, sclerosing sweat duct tumor/microcystic adnexal tumor (SSDT/MAC), porocarcinoma, eccrine adenocarcinoma, and sebaceous carcinoma RESULTS: Five-year OS ranged from 68.0 to 82.6%, while 5-year DSS ranged from 94.6 to 99.0%. The majority of patients were treated with narrow (42.4%) or wide local excision (16.9%). DSS at 5 years showed that patients with stage IV had significantly poorer survival (50.3%) than I, II, or III (99.3%, 97.8%, and 89.0% respectively). 5-year OS was significantly higher for narrow excision (excision with < 1 cm margin, 78.5%) than observation (65.0%), excisional biopsy (66.8%), or wide local excision (WLE, 73.2%). Lymph-node biopsy was performed in a minority of cases (8.1%) and patients showed no significant difference in survival based on nodal status. The sensitivity and specificity of lymph-node biopsy for all malignancies were 46% and 80%, respectively. The PPV and NPV for that group were 0.46 and 0.80, respectively. Invasion of deep extradermal structures was a poor predictor of nodal positivity., Conclusions: These malignancies have excellent DSS. Narrow excisions demonstrate better 5-year DSS and OS compared with WLE. Lymph-node biopsy is a poor predictor of survival in advanced stage disease and utility is limited., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Mycosis fungoides (MF) is associated with increased risk of second primary hematologic malignancies, but its association with second primary solid tumors is less well characterized., Objective: This retrospective analysis seeks to assess the risk of being diagnosed with a second primary hematologic or solid malignancy in patients with MF., Design: We performed an analysis of patients diagnosed with MF from 2000 through 2015 in the United States cancer registries of SEER-18 (N = 6742)., Results: Relative risks were estimated by using standardized incidence ratios (SIRs). Among 6742 patients, there were 511 (7.5%) second cancer events (SIR, 10.15; 95% confidence interval [CI], 9.29-11.07). These included 184 (36.0%) hematologic malignancies (SIR, 39.71; 95% CI, 34.05-46.05) and 327 (64.0%) solid tumor malignancies (SIR, 7.33; 95% CI, 6.56-8.17). Patients with MF were at increased risk for non-Hodgkin lymphoma; Hodgkin lymphoma; melanoma; and lung, female breast, prostate, colon, and renal cancers. Females were at higher risk than males (P < .05). All ethnic groups showed a statistically significant elevation in SIRs. Elevation of SIRs was observed across all stages of MF., Conclusions and Relevance: Patients with MF are at increased risk for diagnosis of second primary malignancies and should be carefully screened for discernable signs and symptoms of second malignancies., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Human papillomavirus (HPV) is the most common sexually transmitted infection in the world. It can lead to anogenital, cervical, and head and neck cancer, with higher risk of malignant disease in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients. In India, 73,000 of the 130,000 women diagnosed with cervical cancer die annually. Gardasil(®) , a vaccine available against HPV types 6, 11, 16, and 18, is approved for use in women in India but not men. A backlash to post-licensure trials has created a negative public opinion of the vaccine for women. Vaccinating boys and men is an alternate approach to prevent cervical cancer in women. This study gauges facilitators and barriers to vaccination acceptance among men in Bangalore, India., Materials and Methods: Young men presenting to a dermatology clinic or an ART center in Bangalore, India, answered a seven-point survey assessing acceptance of the HPV vaccine, perceived barriers to vaccination, and acceptance of vaccination for their children. Ninety-three general dermatology patients and 85 patients with HIV/AIDS participated., Results: There was a high degree of vaccine acceptance for both groups, 83 and 98%, respectively. Vaccine side effects and cost were cited as key barriers to vaccination, and doctor recommendation and government approval were the main facilitators., Conclusion: There is potential for high acceptability of the HPV vaccine among men in India. These results can facilitate further study of vaccine acceptance among males and physician opinion and knowledge about HPV vaccine use. Vaccination of males is a hopeful strategy to protect men and women from HPV-related malignancies., (© 2014 The International Society of Dermatology.)

Purpose: To demonstrate the efficacy of the UVAR XTS Photopheresis System and evaluate health-related quality of life in patients with early-stage mycosis fungoides (MF)., Patients and Methods: Extracorporeal photopheresis was administered 2 days every 4 weeks for 6 months. Patients with partial responses by skin weighted assessment continued for 6 months; nonresponders added oral bexarotene and/or interferon α. Health-related quality of life was assessed at baseline and every 3 months with 3 validated tools., Results: Nineteen patients with early-stage MF (7 men, 12 women; 16 white, 3 African Americans) with median age of 63.5 years (range, 46-85 years) participated. Their stages were IA (n = 3), IB (n = 14), and IIA (n = 2). The overall response rate for extracorporeal photopheresis (ECP) alone, was 42% (8/19; including 7 partial response, 1 complete response), with a median of 12 ECP sessions (range, 3-32) given over a median of 12 months (3-32 months) and with an overall duration of response of 6.5 months (range, 1-48 months). Seven patients with stable disease at 3 months received additional bexarotene (3/5; 1 complete response) or bexarotene plus interferon α (1/2), and 4 (57%) of 7 responded. Treatment-related adverse effects were limited to those expected with interferon (fatigue, nausea, vomiting, and diarrhea), or with hypertriglyceridemia and bexarotene. Trends in health-related quality of life indicated an improvement in emotional scores over time., Conclusions: ECP is effective for patients with early-stage MF alone or in combination with biologic response modifiers with low toxicity and improved quality of life., (2011 Elsevier Inc. All rights reserved.)

Background: Our patient presented with an unusual case of rapidly growing palpebral tumors, which obstructed his vision and caused professional and social impairment., Objectives: The objective was to report the role of surgical management in a case of the d'emblee variant of cutaneous T-cell lymphoma and to provide a literature review., Methods: Tumors of the eyelids previously treated with topical and oral retinoids, indomethacin, dapsone, systemic chemotherapy, and high-dose systemic corticosteroids respond finally to conservative excision and second intention healing., Results: Surgical debulking of palpebral tumors achieved remission of a locally aggressive form of cutaneous T-cell lymphoma and significant restoration of the sight, eyelid function, and social/professional function., Conclusion: In selected cases, surgical excision of tumor tissue may be of significant assistance in managing d'emblee variant cutaneous T-cell lymphoma.

Immunomodulatory effects of retinoids may be part of their anti-carcinogenic and anti-inflammatory properties. We studied the in vivo effects of retinoic acid (RA) on antigen-presenting activity of human epidermal Langerhans cells and on accessory cell activity of keratinocytes. Two skin sites from each volunteer were treated in vivo with 0.1% RA or vehicle, respectively, once a day for 4 d. RA-treated epidermal cell (RA-EC) alloantigen presentation to CD4+ T cells in each volunteer tested was consistently greater than that induced by vehicle EC. However, this increased antigen-presenting activity did not lead to autoreactive CD4+ T-lymphocyte proliferation. Elevated unfractionated epidermal antigen-presenting activity of RA-EC was not due to increased keratinocyte major histocompatibility complex (MHC) or intercellular adhesion molecule expression or to other keratinocyte accessory signaling, because incubation of CD1a-fluoroscence-activated cell sorter (FACS)-purified RA-EC inhibited alloantigen presentation, presumably through increased keratinocyte transforming growth factor-beta. By contrast, Langerhans cell function was upregulated; FACS-purified CD1a+ Langerhans cells derived from RA-EC displayed a markedly increased ability, relative to Langerhans cells from vehicle EC, to present alloantigen to T cells. Triple color flow-cytometric analysis of RA-EC and vehicle EC suspensions revealed that RA treatment did not modify the number of DR+ and CD1a+DR+EC, but did result in statistically significant increases in Langerhans cells expression of HLA-DR, CD11c, and CD1c. Another novel finding was that HLA-DR-dependent Langerhans cells antigen-presenting activity in both normal and RA-treated skin was completely blocked by anti-CD11c antibody. Thus, retinoid upregulation of antigen-presenting activity may be due to upregulation of Langerhans cell CD11c, as well as class II MHC. Upregulation of cutaneous immune responsiveness in human skin without autoreactivity has not (to our knowledge) been reported previously, and the Langerhans cell phenotypic and functional state achieved is distinct from previously reported states of Langerhans cell activation.