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Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by recurrent nodules, abscesses, and sinus tracts, resulting in scarring. Patients suffer significantly impacted quality of life (QoL), manifested by anxiety and depression. We describe microbial isolates identified from active sites in adults with HS, and explore associations between organisms isolated, disease severity, and QoL. Methods: Observational study over 2 years. Assessment was made of disease severity using the Hurley staging score and of QoL scores, and subjective assessment. Wound swab samples were obtained from sites of active disease. Descriptive summary statistics and tests of significance were used to analyse the data. Results: Two hundred and twelve patients participated, resulting in 352 episodes, and 501 lesion swab samples. 54% were female and 59% were obese, median age of 37 years. A lower proportion of Gram-negative organisms and more staphylococcal and streptococcal organisms were isolated from sites of disease in individuals with stage 3 disease compared to those with stage 1–2 disease (p = 0.001). We found no association between microbial isolation and QoL. Discussion/Conclusions: Hurley stage 3 disease is associated with more infected lesions than Hurley stage 1–2 disease, but the QoL experienced by patients with HS is determined by factors other than infection.

Chronic wounds present a major disease burden in people with recessive dystrophic epidermolysis bullosa (RDEB), an inherited blistering skin disorder caused by mutations in COL7A1 encoding type VII collagen, the major component of anchoring fibrils at the dermal-epidermal junction. Treatment of RDEB wounds is mostly symptomatic, and there is considerable unmet need in trying to improve and accelerate wound healing. In this study, we defined transcriptomic profiles and gene pathways in RDEB wounds and compared these to intact skin in RDEB and healthy control subjects. We then used a reverse transcriptomics approach to discover drugs or compounds, which might restore RDEB wound profiles towards intact skin. Differential expression analysis identified >2000 differences between RDEB wounds and intact skin, with RDEB wounds displaying aberrant cytokine-cytokine interactions, Toll-like receptor signalling, and JAK-STAT signalling pathways. In-silico prediction for compounds that reverse gene expression signatures highlighted methotrexate as a leading candidate. Overall, this study provides insight into the molecular profiles of RDEB wounds and underscores the possible clinical value of reverse transcriptomics data analysis in RDEB, and the potential of this approach in discovering or repurposing drugs for other diseases.

Background and Aims Metastatic Crohn’s disease is an extraintestinal cutaneous manifestation characterised by non-specific inflammatory lesions anatomically separate from the gut; genital involvement is rare. We conducted a systematic review of anogenital Crohn’s disease and granulomatosis, to provide a synthesis of epidemiology, clinical features, and treatment outcomes. Methods A systematic search of the literature was conducted via MEDLINE, EMBASE, and the Cochrane database from inception to December 1, 2020. Two investigators extracted and analysed study data. Response and remission were defined as partial improvement or complete resolution of symptoms and examination findings, respectively. Results Of 9381 screened studies, 185 articles, [410 cases: 273 female, 137 male] were included. The predominant clinical features were oedema, ulcers, fissures, and hypertrophic lesions. Adults and children present similarly. Luminal Crohn’s disease was diagnosed in nearly 80% of cases including 45–80% patients without gastrointestinal symptoms (time to inflammatory bowel disease [IBD] from anogenital Crohn’s disease diagnosis [range] –43 to 11 years). Antibiotics, corticosteroids, thiopurines, and anti-tumour necrosis factor [TNF] therapy were the most frequently prescribed agents. At final follow-up, non-response, response, and remission rates were 37/304 [12%], 267/304 [88%], and 114/304 [38%], respectively. Oedema was associated with a poor response to topical therapy. Greater response rates to anti-TNF therapy were seen in patients prescribed concomitant immunomodulation [24/25, 96% vs 67/90, 74%, p = 0.02]. Conclusions We provide an illustrative summary of the clinical presentation and treatment effectiveness of this rare, under-recognised condition, and a proposed algorithm for approach and management. Prospective studies with longer follow-up are required to define optimal treatment strategies.

Introduction Primary cutaneous marginal zone B-cell lymphoma (MZL) follows an indolent clinical course. Histopathologically, there is a polymorphous infiltrate that includes small lymphocyte-like and centrocyte-like B cells and plasma cells usually with a substantial T-cell fraction. Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, in which the signature cells have a follicular T-helper (TFH) phenotype and are admixed with numerous B cells. Thus, both present histologies of combined B-cell and T-cell infiltrates and represent differential diagnoses. The presence of TFH in MZL has yet to be elucidated. Methods Forty-one biopsies from 40 cases of MZL and 7 cases of lymphoid hyperplasia cutis (LCH) were stained with antibodies to follicular T-helper cells, including Bcl-6, PD-1, ICOS, and CD10, as part of their diagnostic workup, were reviewed, and the stained slides were evaluated semiquantitively. Five reactive lymph nodes were also evaluated as controls. Results All cases of MZL and LCH contained TFH, albeit usually in low proportions. There were repeated differences in levels of expression between TFH markers, with PD1 and Bcl-6 being the most prevalent. The pattern of involvement in MZL and LCH closely mirrored that observed in the reactive lymph nodes. Conclusion MZL includes TFH cells, similar to reactive lymph nodes, and a complexity of cell types. This provides evidence of an organoid immune response challenging its simple categorization as a malignancy.

Background Recessive dystrophic epidermolysis bullosa (RDEB) is a hereditary blistering disorder due to a lack of type VII collagen. At present, treatment is mainly supportive. Objectives To determine whether intravenous allogeneic bone marrow–derived mesenchymal stromal/stem cells (BM-MSCs) are safe in RDEB adults and if the cells improve wound healing and quality of life. Methods We conducted a prospective, phase I/II, open-label study recruiting 10 RDEB adults to receive 2 intravenous infusions of BM-MSCs (on day 0 and day 14; each dose 2-4 × 106 cells/kg). Results BM-MSCs were well tolerated with no serious adverse events to 12 months. Regarding efficacy, there was a transient reduction in disease activity scores (8/10 subjects) and a significant reduction in itch. One individual showed a transient increase in type VII collagen. Limitations Open-label trial with no placebo. Conclusions MSC infusion is safe in RDEB adults and can have clinical benefits for at least 2 months.

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is a severe form of skin fragility disorder due to mutations in COL7A1 encoding basement membrane type VII collagen (C7), the main constituent of anchoring fibrils (AFs) in skin. We developed a self-inactivating lentiviral platform encoding a codon-optimized COL7A1 cDNA under the control of a human phosphoglycerate kinase promoter for phase I evaluation. METHODS: In this single-center, open-label phase I trial, 4 adults with RDEB each received 3 intradermal injections (~1 × 10(6) cells/cm(2) of intact skin) of COL7A1-modified autologous fibroblasts and were followed up for 12 months. The primary outcome was safety, including autoimmune reactions against recombinant C7. Secondary outcomes included C7 expression, AF morphology, and presence of transgene in the injected skin. RESULTS: Gene-modified fibroblasts were well tolerated, without serious adverse reactions or autoimmune reactions against recombinant C7. Regarding efficacy, there was a significant (P < 0.05) 1.26-fold to 26.10-fold increase in C7 mean fluorescence intensity in the injected skin compared with noninjected skin in 3 of 4 subjects, with a sustained increase up to 12 months in 2 of 4 subjects. The presence of transgene (codon-optimized COL7A1 cDNA) was demonstrated in the injected skin at month 12 in 1 subject, but no new mature AFs were detected. CONCLUSION: To our knowledge, this is the first human study demonstrating safety and potential efficacy of lentiviral fibroblast gene therapy with the presence of COL7A1 transgene and subsequent C7 restoration in vivo in treated skin at 1 year after gene therapy. These data provide a rationale for phase II studies for further clinical evaluation. TRIAL REGISTRATION: ClincalTrials.gov NCT02493816. FUNDING: Cure EB, Dystrophic Epidermolysis Bullosa Research Association (UK), UK NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, and Fondation René Touraine Short-Exchange Award.

Advances in DNA sequencing technologies have had a major impact on disease gene discovery strategies, including for many genodermatoses.1 Notably, for inherited forms of ichthyosis, whole exome sequencing (WES) has been used to identify new genes contributing to genetically heterogeneous phenotypes such as autosomal recessive congenital ichthyosis.2,3 This article is protected by copyright. All rights reserved.

Epidermolysis bullosa (EB) is a group of inherited disorders characterized by trauma-induced fragility of skin and mucosal surfaces. EB affects approximately 1 in 17,000 live births and is classifi...

Naevus sebaceus has recently been shown to result from post-zygotic mutations in HRAS, KRAS or occasionally NRAS. We present details of a neonate with extensive naevus sebaceus in whom we identified a pathogenic mutation in HRAS (c.37G > C; p.Gly13Arg), but only in lesional skin DNA, consistent with a mosaic RASopathy. This case highlights the clinicopathological and molecular findings of this naevoid disorder as well as the key issues in the clinical assessment and management of such patients.

Naevus sebaceus has recently been shown to result from post-zygotic mutations in HRAS, KRAS or occasionally NRAS. We present details of a neonate with extensive naevus sebaceus in whom we identified a pathogenic mutation in HRAS (c.37G C; p.Gly13Arg), but only in lesional skin DNA, consistent with a mosaic RASopathy. This case highlights the clinicopathological and molecular findings of this naevoid disorder as well as the key issues in the clinical assessment and management of such patients.