Human dermal fibroblast subpopulations and epithelial mesenchymal transition signals in hidradenitis suppurativa tunnels are normalized by spleen tyrosine kinase antagonism in vivo.

Hidradenitis Suppurativa is a chronic inflammatory disease of which the pathogenesis is incompletely understood. Dermal fibroblasts have been previously identified as a major source of inflammatory cytokines, however information pertaining to the characteristics of subpopulations of fibroblasts in HS remains unexplored. Using in silico-deconvolution of whole-tissue RNAseq, Nanostring gene expression panels and confirmatory immunohistochemistry we identified fibroblast subpopulations in HS tissue and their relationship to disease severity and lesion morphology. Gene signatures of SFRP2+ fibroblast subsets were increased in lesional tissue, with gene signatures of SFRP1+ fibroblast subsets decreased. SFRP2+ and CXCL12+ fibroblast numbers, measured by IHC, were increased in HS tissue, with greater numbers associated with epithelialized tunnels and Hurley Stage 3 disease. Pro-inflammatory CXCL12+ fibroblasts were also increased, with reductions in SFRP1+ fibroblasts compared to healthy controls. Evidence of Epithelial Mesenchymal Transition was seen via altered gene expression of SNAI2 and altered protein expression of ZEB1, TWIST1, Snail/Slug, E-Cadherin and N-Cadherin in HS lesional tissue. The greatest dysregulation of EMT associated proteins was seen in biopsies containing epithelialized tunnels. The use of the oral Spleen tyrosine Kinase inhibitor Fostamatinib significantly reduced expression of genes associated with chronic inflammation, fibroblast proliferation and migration suggesting a potential role for targeting fibroblast activity in HS.

Infectious Disease Screening Prior to Systemic Immunomodulatory Therapy in Hidradenitis Suppurativa: Consensus Guidelines from the Asia-Pacific Hidradenitis Suppurativa Foundation.

BACKGROUND: Current infectious disease screening recommendations for hidradenitis suppurativa (HS) are adopted from recommendations in chronic plaque psoriasis. No HS-specific guidelines for infectious disease screening prior to immunomodulatory therapy have been developed. OBJECTIVES: To establish an expert Delphi consensus of recommendations regarding infectious disease screening prior to systemic immunomodulatory therapy in HS. METHODS: Participants were identified via recent publications in the field and were sent a questionnaire regarding infectious diseases encountered in the setting of HS, and opinions regarding infectious disease screening prior to various systemic immunomodulatory therapies. All questions were informed by a systematic literature review regarding infections exacerbated or precipitated by immunomodulatory therapy. Questionnaire responses were followed by round-table discussion with a core group of 8 experts followed by a final round of questionnaires resulting in achievement of consensus. RESULTS: 44 expert HS physicians from 12 countries on 5 continents participated in the development of the expert consensus recommendations. Consensus recommendations include screening for hepatitis B, hepatitis C and tuberculosis in all individuals with HS prior to therapy. All immunomodulatory therapies (biologic and systemic immunosuppressant therapy) should be preceded by infectious disease screening including patient and location specific considerations for endemic local diseases and high-risk activities and occupations. Clinical assessment has a significant role in determining the need for laboratory screening in the setting of many uncommon or tropical diseases such as leprosy, leishmaniasis and strongyloidiasis. CONCLUSIONS: The presented consensus recommendations are the first specifically developed for pre-treatment infectious disease screening in Hidradenitis Suppurativa.

A proof-of-concept open-label clinical trial of spleen tyrosine kinase antagonism using fostamatinib in moderate-to-severe hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is an autoinflammatory disorder of keratinization with a prominence of B cells and plasma cells. Fostamatinib is a spleen tyrosine kinase inhibitor targeting B cells and plasma cells. OBJECTIVES: To assess the safety, tolerability, and clinical response at week 4 and week 12 of fostamatinib in moderate-to-severe HS. METHODS: Twenty participants were administered fostamatinib 100 mg twice a day for 4 weeks, escalating to 150 mg twice a day thereafter until week 12. Participants were assessed for adverse events and clinical response assessed by HiSCR (Hidradenitis Suppurativa Clinical Response Score) and IHS4 (International Hidradenitis Suppurativa Severity Score) as well as other outcomes including DLQI (Dermatology Life Quality Index), visual analog scale, and physician global assessment. RESULTS: All 20 participants completed the week 4 and week 12 endpoints. Fostamatinib was well tolerated in this cohort with no grade 2/3 adverse events reported. A total of 85% achieved HiSCR at week 4 and 85% at week 12. The greatest reduction in disease activity was seen at weeks 4/5 with worsening in a proportion of patients thereafter. Significant improvements were seen in pain, itch, and quality of life. CONCLUSIONS: Fostamatinib was well tolerated in this HS cohort with no serious adverse events and improvement in clinical outcomes. Targeting B cells/plasma cells may be a viable therapeutic strategy in HS and requires further exploration.

The impact of psoriasis biologic therapy on HIV viral load and CD4+ cell counts in HIV-positive individuals: A real-world cohort study.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory disorder that also occurs in the setting of human immunodeficiency virus (HIV). Biological therapy has transformed the treatment landscape for psoriasis; however, individuals with HIV are excluded from clinical trials. The impact of biological therapy on blood parameters in HIV is unclear and is only observed in small case series. OBJECTIVE: The aim of this study was to assess the effect of biological therapy in psoriasis vulgaris in individuals with well-controlled HIV on CD4+ cell counts, CD4+ proportion and HIV viral load over 12 months. METHODS: This retrospective cohort study was conducted at a tertiary referral centre in Sydney, Australia and included 36 HIV-positive individuals with psoriasis treated with biological therapy, compared with 144 age-, gender- and HAART-matched individuals without psoriasis seen between 2010 and 2022. Outcomes of interest included HIV viral load, CD4+ cell count and incidence of infections. RESULTS: No statistically significant difference was seen in baseline HIV viral load and CD4+ count between individuals with and without psoriasis. No significant change in CD4+ count or HIV viral load was seen over the 12-month period of analysis in the HIV cohort without psoriasis. The HIV cohort treated with biological therapy for psoriasis also did not demonstrate any significant change in HIV viral load and CD4+ counts over the 12-month period examined. Stratification by type of biological therapy used did not identify any significant changes in these parameters. Rates of infections and adverse events were also not significantly different between cohorts. It is possible that minor blips seen in the biologics cohort may be a risk factor for future virological failure, and future prospective longitudinal studies are required. CONCLUSIONS: In individuals with well-controlled HIV, the use of biological therapy for psoriasis does not significantly impact HIV viral load, CD4+ cell count, CD4+ proportion and rates of infection over the first 12 months of therapy.

Neonatal lupus erythematosus presenting as a non-bullous histiocytoid neutrophilic dermatosis.

Histopathologic findings in neonatal lupus erythematosus (NLE) are usually congruent with those of subacute cutaneous lupus erythematosus. However, neutrophilic dermatosis-type histopathologic features are being increasingly recognized in the literature including rare cases with variant histiocytoid morphology. We report the case of a 7-week-old male presenting with figurate erythema. His mother was found to have elevated anti-nuclear antibodies and was positive for anti-SSA/Ro, anti-SSB/La antibodies and Ro52 autoantibodies. The infant had a similar serological profile. Skin biopsy showed a histiocytoid interstitial infiltrate with mild lichenoid features, sparse neutrophils and mild leukocytoclasis. The histiocytoid infiltrate showed prominent CD68, CD163, and myeloperoxidase expression. Isolated clusters of CD123+ histiocytes were also present. This case highlights the rare finding of non-bullous neutrophilic dermatosis with histiocytoid change in neonatal lupus. In neonates presenting with figurate erythemas with morphological histiocytic change on biopsy, NLE should be considered as a differential diagnosis and investigated for accordingly.

Pyoderma gangrenosum: A systematic review of the molecular characteristics of disease.

Pyoderma gangrenosum is a painful recurrent ulcerative neutrophilic dermatosis in which the pathogenesis is incompletely defined. Current evidence suggests that PG is associated with dysregulation of components of both the innate and adaptive immune system with dysregulation of neutrophil function and contribution of the Th17 immune axis. PG can be present in numerous heterogeneous clinical presentations and be associated with multiple inflammatory conditions including rheumatoid arthritis, inflammatory bowel disease and hidradenitis suppurativa. However, no critical evaluation of the observed molecular characteristics in PG studies in association with their clinical findings has been assessed. Additionally, emerging evidence suggests a potential role for other cell types and immune pathways including B cells, macrophages, autoantibodies and the complement system in PG, although these have not yet been integrated into the pathogenesis of disease. This systematic review aims to critically evaluate the current molecular observations regarding the pathogenesis of PG and discuss associations with clinical characteristics as well as the evidence supporting novel cell types and immune pathways in PG.

Dupilumab-associated head and neck dermatitis is associated with elevated pretreatment serum Malassezia-specific IgE: a multicentre, prospective cohort study.

Dupilumab associated head and neck dermatitis is incompletely understood. This prospective multicentre prospective study identified baseline Malassezia-specific IgE as associated with the development of Dupilumab associated head and neck dermatitis.

Clinical considerations in the management of hidradenitis suppurativa in women.

Hidradenitis suppurativa (HS) is a chronic, inflammatory disease of the skin with a predilection for women. The role of sex hormones, including estrogen and progesterone, is incompletely understood, but alterations in hormone levels may play a role in disease activity for many patients. Specific clinical considerations should be made for women with HS, particularly in the setting of pregnancy, childbirth, breastfeeding, and menopause. Current knowledge gaps regarding HS include the cumulative impact of disease across an individual's lifespan, as well as the mechanistic role of sex hormones in the disease. An improved understanding of the pathophysiologic role of hormones in HS would optimize our ability to use targeted therapies for hormonally driven disease. Psychological and psychosexual support for women with HS is an important facet of any holistic management strategy for the disease. This article integrates up-to-date pathogenic and mechanistic insights with evidence-based clinical management to optimize care for women with HS.

Patient and practitioner satisfaction with tele-dermatology including Australia's indigenous population: A systematic review of the literature.

BACKGROUND: Australia's health disparity, combined with evolving technologies, has evoked increasing interest and funding in health services that could address inequities. One such emerging service is tele-medicine. OBJECTIVE: The purpose of this report is to discuss and evaluate the current literature regarding patient and practitioner satisfaction with tele-medicine, and more specifically tele-dermatology. METHODS: We searched for literature relevant to tele-dermatology use among Australia's indigenous population. We synthesized the literature in our report and identified elements of tele-dermatology not yet researched. RESULTS: Most significantly, all available research is currently based on descriptive studies and there is no validated tool to assess the efficacy of tele-dermatology. LIMITATIONS: No published research currently exists on the use of tele-dermatology among Australia's indigenous population. CONCLUSION: A review of the literature shows that tele-dermatology is considered a valuable service, particularly to patients living in rural areas who might not otherwise have access to specialist care.