RARE DISEASE
Autoinflammatory syndrome with acne and/or hidradenitis suppurativa
Autoinflammatory syndrome with acne and/or hidradenitis suppurativa
Autoinflammatory syndrome with acne and/or hidradenitis suppurativa
Drug discovery
0
drugs
With orphan designations
Overview
Autoinflammatory Syndromes with Acne/Hidradenitis Suppurativa (HS) are rare disorders characterized by dysregulated innate immunity, manifesting as chronic neutrophilic inflammation. Key features include recurrent HS (painful nodules, abscesses, scarring), acne, and pyoderma gangrenosum, often forming syndromes like PASH (pyoderma gangrenosum, acne, HS) or PAPASH (adding pyogenic arthritis). These conditions are linked to IL-1β pathway overactivation and polygenic factors, with symptoms persisting for decades without targeted treatment [3][6][9].
Burden
Chronic pain, disfiguring scars, and recurrent infections lead to impaired quality of life, with 40–60% reporting depression/anxiety [9][12][19].
Diagnostic delays average 4–6 years, increasing risks of amyloidosis, arthritis, and secondary infections [1][6][17].
High healthcare utilization due to frequent flares and multidisciplinary care needs [3][6][12].
Therapies
Biologics: IL-1 inhibitors (anakinra, canakinumab), TNF-α blockers (adalimumab, infliximab), and IL-17 antagonists (secukinumab) for moderate-severe cases [6][9][18].
Immunosuppressants: Colchicine, corticosteroids, or JAK inhibitors as adjuncts [3][6].
Surgical interventions: Incision/drainage or laser therapy for refractory HS lesions [9][12].
Categories: rare skin diseases, rare systemic and rheumatological diseases
Research Papers
1,300 drug discovery papers about Autoinflammatory syndrome with acne and/or hidradenitis suppurativa, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,300 drug discovery papers about Autoinflammatory syndrome with acne and/or hidradenitis suppurativa, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-13 | Real-World Experience with Janus Kinase Inhibitors in Severe Refractory Hidradenitis Suppurativa: A Retrospective Case Series.
Hidradenitis suppurativa (HS) is a chronic inflammatory disease with limited treatment options for patients with severe, treatment-refractory disease. The JAK-STAT pathway represents a potential therapeutic target, although real-world evidence for JAK inhibitors (JAKi) in HS remains limited. This retrospective case series describes eight male patients with Hurley stage III HS who received tofacitinib (n=3), upadacitinib (n=4), or ivarmacitinib (n=1) after inadequate response to conventional therapies. Clinical outcomes were assessed using the International Hidradenitis Suppurativa Severity Score System (IHS4) and a numerical rating scale (NRS) for pain at the latest available follow-up. Follow-up ranged from 1 week to 12 months. Seven patients showed improvement in inflammatory lesions and/or pain, whereas one patient receiving tofacitinib showed limited clinical benefit. The median reduction in IHS4 score was 9.5 points (range, 2-18), and the median reduction in NRS pain score was 4.0 points (range, 0-5). Temporary interruption of upadacitinib in one patient was followed by disease flare, with improvement again observed after treatment re-initiation. No severe infections, thromboembolic events, HBV reactivation, or treatment-limiting adverse events were identified during the available follow-up. These preliminary observations suggest that JAKi may have a potential role in selected patients with severe, treatment-refractory HS. However, responses and follow-up durations were heterogeneous, and the small sample size precludes comparisons between agents. Prospective controlled studies with standardized assessment timepoints and longer follow-up are needed to clarify efficacy, durability, and long-term safety.
2026-08-02 | Actinomyces neuii in chronic hidradenitis suppurativa: a case series highlighting the value of extended culture.
Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory skin disease characterized by painful nodules, sinus tract formation and scarring. Lesional skin is frequently colonized by diverse aerobic and anaerobic bacteria, with anaerobes such as Prevotella spp., Campylobacter ureolyticus, Staphylococcus epidermidis and Actinomyces spp. commonly isolated. Actinomyces neuii, a Gram-positive, slow-growing anaerobe, has been previously described only occasionally in deep HS abscesses. We present three cases of treatment-resistant HS in which extended incubation of cultures yielded A. neuii. All patients were subsequently treated with long-term amoxicillin (3-6 months), resulting in marked clinical improvement. These findings suggest a potential pathogenic role for A. neuii in severe HS. Further research is required to establish its clinical relevance, evaluate optimal antibiotic regimens and monitor for resistance development.
2026-08-01 | Effectiveness and Safety of 40 mg Modified-Release Doxycycline for the Treatment of Hidradenitis Suppurativa: A Single-Center Retrospective Observational Study.
Hidradenitis suppurativa (HS) is a chronic inflammatory follicular disorder commonly managed with antibiotics, despite increasing antimicrobial resistance (AMR). This single-center retrospective study evaluated the efficacy and safety of 40 mg modified-release doxycycline (MR-DC) in 66 adults with HS treated for 28 days. Response to treatment was assessed using the Hidradenitis Suppurativa Clinical Response (HiSCR) and the International Hidradenitis Suppurativa Severity Score System (IHS4) scales. Specifically, at 12 weeks, HiSCR50 and IHS4-55 responses were achieved in 75.8% and 87.9% of patients, respectively. Relapse occurred in 33% at 6 months. Lower baseline IHS4, shorter disease duration, lower BMI, higher total inflammatory nodule and abscess count, absence of involvement of the pubis and genital area, and use of concomitant treatment were associated with better outcomes; only shorter disease duration remained significant on multivariate analysis (P < 0.022). Compared to results from other studies using standard regimens of regular-release doxycycline (RR-DC), MR-DC appears to have similar efficacy and more favorable safety profile. Low-dose MR-DC may be an effective short-term treatment or adjunctive therapeutic option for HS flares, with a reduced risk of AMR and adverse events.
2026-07-24 | Povorcitinib for hidradenitis suppurativa: the randomized, double-blind, placebo-controlled STOP-HS1 and STOP-HS2 phase 3 trials.
Although therapeutic options for hidradenitis suppurativa (HS) continue to expand, unmet needs remain substantial. We evaluated the efficacy and safety of povorcitinib (an oral, highly selective Janus kinase 1 (JAK1) inhibitor) in patients with moderate to severe HS in two randomized trials. STOP-HS1 and STOP-HS2 were identically designed, randomized, double-blind, placebo-controlled phase 3 trials. Adults with moderate to severe HS were randomized 2:2:1:1 to once-daily treatment through week 54: povorcitinib 45 mg; povorcitinib 75 mg; placebo with crossover at week 12 to povorcitinib 45 mg; or placebo with crossover at week 12 to povorcitinib 75 mg. The primary endpoint was HiSCR50 (≥50% decrease in total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining tunnel count) at week 12. STOP-HS1/STOP-HS2 enrolled 608/619 patients, respectively. In both studies, both povorcitinib doses met the primary endpoint; in STOP-HS1, 82/204 (40%) patients in the povorcitinib 45-mg group and 82/202 (41%) in the 75-mg group versus 60/202 (30%) in the placebo group achieved HiSCR50 (OR (95% CI) 45 mg: 1.6 (1.1-2.5), P = 0.0240; 75 mg: 1.6 (1.1-2.4), P = 0.0214); corresponding values for STOP-HS2 were 88/208 (42%) and 88/208 (42%) versus 58/203 (29%; OR (95% CI) 45 mg: 1.8 (1.2-2.8), P = 0.0035; 75 mg: 1.9 (1.2-2.8); P = 0.0033). Through week 12, across STOP-HS1/STOP-HS2, serious treatment-emergent adverse events (AEs) occurred in 1-2% of patients across povorcitinib doses and in 2-3% with placebo; through week 54, serious AEs occurred in 5%/6% of patients receiving 45-mg/75-mg povorcitinib, respectively. The most frequent AEs among patients treated with 45-mg/75-mg povorcitinib were acne (17%/20%), nasopharyngitis (10%/12%) and upper respiratory tract infection (11%/10%). One death of undetermined etiology was reported and deemed unrelated to treatment. No new or unexpected safety findings were identified. Oral povorcitinib demonstrated significant improvements in HiSCR50 versus placebo and a favorable safety profile in patients with moderate to severe HS. ClinicalTrials.gov registration: NCT05620823 and NCT05620836 .
2026-07-22 | Epidemiology of hidradenitis suppurativa in a large institutional 15-year retrospective study.
Hidradenitis suppurativa (HS) is a chronic inflammatory disorder associated with substantial morbidity, yet large real-world studies evaluating prevalence and comorbidity patterns within single healthcare systems remain limited. We retrospectively reviewed adult patients diagnosed with HS across an institution-wide cohort from September 2010 through October 2025. Demographics, anxiety, depression, acne history, and median income category by zip code were analyzed. Among 1,882,631 patients, 15,275 had HS, corresponding to a prevalence of 0.81%. Women represented 77.8% of cases, and the highest prevalence occurred among patients aged 31 to 40 years. HS patients were more than twice as likely to have acne compared with non-HS patients (odds ratio = 2.16; 95% confidence interval, 2.09-2.23; P < 0.001). Anxiety or depression was documented in 26.9% of patients. Median household income was not significantly associated with HS. These findings reinforce the demographic and psychosocial burden associated with HS and may assist clinicians in earlier recognition and management.
antibodies
2026-08-13 | Successful treatment of hidradenitis suppurativa with vunakizumab: a case report and literature review.
Hidradenitis suppurativa (HS) is a chronic, recurrent, and disabling inflammatory skin disorder. To our knowledge, this study reports the first use of vunakizumab, a domestically developed anti-IL-17A monoclonal antibody, for the treatment of HS. We present the case of a 17-year-old boy with a 5-year history of recurrent painful nodules and abscesses on the buttocks who had been repeatedly misdiagnosed with common acute bacterial infections and had responded poorly to conventional antibiotics. After 8 weeks of treatment with vunakizumab, which offered a pharmacoeconomic advantage during the transition period before its inclusion in China's national insurance system, the patient showed marked improvement, with complete resolution of nodules, abscesses, and tunnels and no recurrence or significant adverse events during 10 months of follow-up. This case highlights the potential of vunakizumab in the treatment of HS and supports the pathogenic role of IL-17 in the disease.
2026-08-13 | Autoinflammatory Syndromes of Hidradenitis Suppurativa: Updates in Clinical Features, Emerging Associations, and Management.
To summarize and critically evaluate recent literature on autoinflammatory syndromes of hidradenitis suppurativa (HS). HS-associated autoinflammatory syndromes traditionally encompass pyoderma gangrenosum (PG), acne, and HS (PASH); pyogenic arthritis, PG, acne, and HS (PAPASH); psoriatic arthritis, PG acne, and HS (PsAPASH); and PG, acne, HS and ankylosing spondylitis (PASS). However, this spectrum continues to expand, with recent literature considering the inclusion of additional autoinflammatory diseases such as HS associated with SAPHO, including synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO); and Hyperimmunoglobulin D Syndrome (HIDS). HS-associated autoinflammatory syndromes are thought to be driven by dysregulation of the innate immune system and the subsequent overexpression of key inflammatory cytokines such as IL-1, and targeted IL-1 therapies have demonstrated particularly brisk and efficacious response. Multiple genes related to follicular keratinization or inflammatory regulation have been implicated, and sequencing methods such as whole-exome sequencing and variant enrichment analysis continue to identify novel genetic variants and are being used to further elucidate genotype-phenotype correlations. HS-associated autoinflammatory syndromes are an evolving spectrum of rare, severe, diseases in which HS coexists with other autoinflammatory conditions, most commonly PASH and related syndromes. They are driven by innate immune dysregulation and pathogenic genetic variants, with whole-exome sequencing aiding diagnosis and genotype-phenotype correlation. Management is often challenging and highly individualized, with targeted biologic therapies such as IL-1 inhibitors showing the most consistent and rapid clinical benefit.
2026-08-12 | Surgical Outcomes for Hidradenitis Suppurativa: Does Biologic Therapy Make a Difference?
Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that often requires both medical and surgical management. Biologic therapies are increasingly used for moderate-to-severe disease, but their effect on surgical outcomes remains unclear. The aim of this study was to evaluate the impact of biologic therapy on postoperative outcomes in patients undergoing excisional surgery for HS. The authors conducted a retrospective chart review of adult patients who underwent excisional surgery for HS at a single academic center with at least 6 months of postoperative follow-up. Demographic data, comorbidities, disease severity, biologic use at the time of surgery (adalimumab or infliximab), and surgical outcomes were collected. Statistical analyses compared postoperative outcomes between biologic and nonbiologic groups with false discovery rate correction for multiple testing. Seventy-seven patients undergoing 109 excisions were included, of which 27 (24.8%) occurred while on biologics. All biologic patients had Hurley Stage III disease and greater surgical burden, with more anatomic sites undergoing excision. Healing time, complication rates, recurrence, and need for revision surgery did not significantly differ between groups. Biologic therapy did not impair postoperative healing or increase complications, supporting the safety of combining biologics with surgery for HS.
2026-07-28 | From rheumatology to dermatology: cytokine signaling pathways as therapeutic targets at the skin-joint interface in inflammatory diseases: a narrative review.
Over the last two years, inflammatory dermatology has undergone a transition from morphology-based classification toward pathway-driven immune endotyping. Atopic dermatitis, psoriatic disease, and hidradenitis suppurativa have emerged as paradigmatic models of this transition, illustrating how epithelial dysfunction, involving autoinflammation and adaptive immunity, may lead to systemic inflammatory crosstalks, connecting cutaneous and musculoskeletal manifestations. Recent studies have refined the understanding of progressive immune maturation in atopic dermatitis, while psoriasis and juvenile psoriatic arthritis support skin-to-joint inflammatory models involving IL-23/IL-17 signaling. Hidradenitis suppurativa is increasingly recognized as a systemic autoinflammatory disease within a broader neutrophilic inflammatory spectrum. Parallel therapeutic advances involving IL-17, IL-23, TNF, and JAK inhibition reinforced the translational importance of these discoveries and accelerated the development of precision dermatology strategies.
2026-07-23 | Effect of adalimumab treatment on lesions and inflammatory factors in patients with moderate-severe hidradenitis suppurativa.
To investigate the efficacy and safety of adalimumab (ADA) in the treatment of hidradenitis suppurativa (HS). A retrospective analysis was conducted on the clinical data of 50 patients with HS. Patients were divided into ADA (n=30) and cyclosporine (CSA, n=20) groups. The Hidradenitis Suppurativa Clinical Response Criterion (HiSCR) and the International Hidradenitis Suppurativa Severity Score System (IHS4) were used to assess clinical efficacy. The Dermatology Life Quality Index (DLQI) was used to evaluate patients' quality of life, and peripheral blood inflammatory factor levels were measured. Safety was also assessed. After treatment, all scores in both groups decreased significantly (all P<0.05); the decrease in IHS4 score in the ADA group was significantly greater than that in the cyclosporine (CSA) group (P<0.05). From week 2 to week 12 of treatment, there was a significant difference in the clinical response rate between the groups (P<0.05). At week 12, the Patient Global Assessment Relief Rate (PtGA RR) for skin pain in the ADA group was significantly higher than that in the CSA group (P<0.05). After treatment, the levels of inflammatory cells, NLRP3, and caspase-1 in both groups were significantly lower than those before treatment (P<0.05), with the ADA group showing a greater decrease than the CSA group (P<0.05). Some patients experienced dry mouth, abdominal pain, and scalp, which improved after symptomatic treatment. No relapse or secondary infection occurred. ADA demonstrates good clinical efficacy and long-term safety in treating this population.
cell therapies
2026-08-07 | Reused skin grafts for treating hidradenitis suppurativa: A systematic review.
Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory disease in which wide excision remains the most reliable option for durable disease control in moderate to severe cases. Reconstruction after excision is challenging. Reused or recycled split-thickness skin grafts, harvested from excised HS tissue and reapplied after processing, have been proposed to reduce donor-site morbidity, but their clinical value remains uncertain. To systematically evaluate the outcomes of reused skin grafts following surgical excision of HS, with emphasis on recurrence, graft take and procedure-related morbidity. A PRISMA-compliant systematic review was conducted using PubMed, Web of Science and Google Scholar from inception to the final search date. Studies reporting HS excision followed by reused or recycled skin grafting were included. Outcomes of interest were recurrence, graft survival, complications and follow-up duration. Given heterogeneity, a narrative synthesis was performed. Risk of bias was assessed using design-appropriate tools. Sixteen studies met inclusion criteria, including five systematic reviews, two retrospective cohorts and nine case reports or small case series. Primary reused-graft reports comprised approximately 41 patients with follow-up ranging from 6 to 113 months. Across these series, no surgical-site recurrences were reported (0/41), corresponding to an exact 95% confidence interval of 0-7.0%. Complications were generally minor. However, in the largest reused-graft series, which included 18 patients, 8 (44%) required supplemental conventional donor grafts. Broader pooled estimates from conventional graft literature reported recurrence rates ranging from 2% to 18%, reflecting substantial heterogeneity. Reused skin grafting appears feasible and safe in selected HS patients, with encouraging short- to medium-term durability. Current evidence supports feasibility rather than definitive comparative effectiveness, underscoring the need for well-designed prospective studies.
2026-04-14 | Multidisciplinary Approach to Complex Lower Extremity Limb Salvage in Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne (PAPA) Syndrome: A Case Report.
Limb salvage using free tissue transfer in patients with rare autoinflammatory syndromes is poorly described, and the safety of microvascular reconstruction in this population remains uncertain. Hereditary pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is characterized by dysregulated inflammation, pathergy, and impaired wound healing, raising concern for flap compromise and postoperative complications. We report a rare case of lower extremity free tissue transfer in a patient with PAPA syndrome. A 66-year-old woman with rheumatoid arthritis and PAPA syndrome presented with rapid wound breakdown, violaceous ulceration, exposed hardware, and periprosthetic joint infection following left total knee arthroplasty (TKA). Examination revealed an approximately 9 × 7 cm anterior knee defect with subtotal patellar tendon necrosis. After multidisciplinary optimization, she underwent single-stage irrigation and debridement, hardware removal, revision TKA with patellar tendon reconstruction using gracilis autograft, and immediate coverage with a 22 × 14 cm free latissimus dorsi (LD) muscle flap. The flap was anastomosed end-to-side to the anterior tibial artery with venous outflow via the venae comitantes and loosely inset to preserve future surgical access. The donor site was closed primarily. A 21 × 13 cm staged split-thickness skin graft was performed 1 week later, with adjunctive postoperative hyperbaric oxygen therapy (HBOT). Initial healing was uncomplicated, with complete graft take and donor-site healing. Four months postoperatively, the patient developed chronic sinus tracts and recurrent periprosthetic infection requiring flap re-elevation, debridement, and hardware exchange; the flap pedicle was preserved, and coverage maintained. At one-year follow-up, all wounds had healed; flap coverage was durable with acceptable cosmesis, and the patient was ambulatory for short distances without assistance. She was last seen infection-free and full-weightbearing 4 months later. This case demonstrates that microvascular limb salvage is feasible in PAPA syndrome when guided by multidisciplinary planning and strategic flap design.
2026-03-26 | Two-Stage Surgical Management of Anogenital Hidradenitis Suppurativa in Patients on Biologic Therapy: A Retrospective Case Series.
Hidradenitis suppurativa is a chronic inflammatory skin disorder causing painful nodules, abscesses and scarring, with the anogenital region presenting particular functional and reconstructive challenges. Although biologic therapy is commonly used in moderate to severe disease, its limitations highlight the role of surgery in advanced cases. This single-centre retrospective case series included five male patients with Hurley stage III perineal, anorectal, genital or gluteal disease treated surgically between 2021 and 2023 following failure of biologic therapy. Management consisted of two-stage radical excision, negative-pressure wound therapy and reconstruction with meshed split-thickness skin grafts. All patients achieved more than 90% graft take and complete wound healing. No recurrence occurred during a median follow-up of 19.2 months. One patient developed a keloid scar at the donor site, and one experienced delayed healing. Functional and aesthetic results were satisfactory in all cases. Two-stage surgical excision with split-thickness skin graft reconstruction was associated with sustained wound healing and favourable functional outcomes in selected patients with severe anogenital hidradenitis suppurativa refractory to biologic therapy.
2026-03-06 | Intact Fish Skin Grafting in a Patient With Hidradenitis Suppurativa.
Wound management in hidradenitis suppurativa (HS) patients is often challenging due to worsening infections and impaired circulation, which can lead to prolonged hospitalization and poorer quality of life. Traditionally, autografting-a leading option in skin grafting-exhibits risks, including donor site morbidity. However, xenograft products, such as KerecisTM, derived from North Atlantic Cod fish, offer a novel solution for conditions with chronic wounds by promoting natural tissue regeneration. This case report presents a 35-year-old woman with HS who presented with persistent abscesses and fistulas in bilateral axillary regions. Following multiple surgical incisions and drainage procedures, the patient was treated with intact fish skin grafting, which resulted in significant granulation tissue deposition and wound edge approximation. The successful outcome in this case suggests that intact fish skin grafting is a viable option for non-healing wounds, particularly HS wounds, and can be integrated into surgical and wound care practices.
2025-11-26 | Beyond excision: modern plastic surgery techniques for hidradenitis suppurativa reconstruction.
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder characterized by recurrent abscesses, sinus tract formation and extensive scarring. In severe cases, surgical excision and complex reconstruction are often required. This case report aims to highlight the role of modern plastic surgical techniques, including regenerative technologies, in managing severe HS. A 37-year-old Hispanic male with a 17-year history of HS presented with extensive lesions involving the buttocks, groin, genitalia, thighs and perianal region. He underwent staged wide excisions totaling over 2,400 cm2. Reconstruction included split-thickness skin grafts (STSG), NovoSorb® BTM (Biodegradable Temporizing Matrix) and RECELL® autologous skin cell suspension. Postoperative recovery was marked by successful graft take, wound healing and return to normal function, including physical activity and sexual function, by postoperative day 69. This case underscores both the complexity of managing stage III HS and the evolving role of regenerative technologies in improving outcomes. While wide local excision remains the cornerstone of treatment for extensive disease, adjunctive use of BTM and RECELL enhances dermal regeneration, reduces donor-site morbidity and optimizes aesthetic and functional results. These innovations reflect a shift in reconstructive strategy, emphasizing a more tailored, patient-centered approach. The integration of regenerative modalities such as Biodegradable Temporizing Matrix (BTM) and RECELL autologous cell suspension technology into contemporary plastic surgical reconstruction offers significant benefits in treating severe hidradenitis suppurativa. By complementing traditional excisional techniques, these technologies contribute to improved healing, minimized morbidity and restored function, aligning with the goals of modern, multidisciplinary HS management.
proteins
2026-08-13 | The Metabolic Revolution in Dermatology: Obesity, Insulin Resistance, and Ultra-Processed Diets as Drivers of Skin Inflammation.
Inflammatory dermatoses are increasingly linked to systemic metabolic factors. Obesity and insulin resistance create a pro-inflammatory milieu that affects the skin. Adipose tissue functions as an endocrine organ secreting adipokines and cytokines that drive chronic inflammation with notable skewing toward T-helper 1 (Th1)/Th17 signaling. Hyperinsulinemia, elevated insulin-like growth factor-1 promote keratinocyte proliferation, sebum production, and autoinflammation, contributing to a multitude of skin diseases including hidradenitis suppurativa, acne, psoriasis, atopic dermatitis (AD), acanthosis nigricans, hirsutism, scarring alopecias, intertrigo, and chronic idiopathic urticaria. Concomitantly, ultra-processed diets low in fiber and high in additives detrimentally affect the gut-skin axis. Diets rich in emulsifiers, sugars, and fructose alter the gut microbiome and increase intestinal permeability, leading to metabolic endotoxemia and increased systemic inflammation. High-fructose corn syrup in sweetened beverages is metabolized via hepatic fructokinase, promoting de novo lipogenesis and excess uric acid, a cascade implicated in metabolic fatty liver disease and heightened inflammation. These dietary factors have been correlated with aggravated skin diseases, where fast-food intake (≥3× weekly) is associated with increased risk of severe AD in children. Emerging evidence suggests that dietary modifications may help mitigate skin inflammation in select patients. At the same time, the advent of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists may improve metabolic parameters and could represent promising adjunctive therapies in select inflammatory dermatoses. Dermatologists can serve as sentinels, identifying cutaneous signs of insulin resistance (eg, acanthosis nigricans, acrochordons, and other skin diseases driven by insulin resistance) and addressing lifestyle factors as part of routine care.
2026-08-12 | Trained immunity in autoinflammatory diseases: Cellular reprogramming across the monogenic-polygenic spectrum.
Trained immunity, an innate immunological memory induced by epigenetic and metabolic reprogramming, has changed the paradigm of host defense and pathogenesis of chronic inflammatory disease. Unlike adaptive immunological memory, trained immunity is characterized by the ability of innate immune cells and their progenitors to respond more robustly or differently to subsequent stimulations and contributes to chronic inflammatory conditions. Emerging data suggests that this process might be essential in autoinflammatory and immune-mediated inflammatory illnesses by enhancing sterile inflammation, decreasing activation thresholds, and boosting disease chronicity. This narrative review summarizes the existing evidence relating trained immunity to monogenic and polygenic autoinflammatory diseases. The greatest evidence in monogenic disease is for mevalonate kinase deficiency, where dysregulated mevalonate metabolism directly overlaps with conventional trained immunity pathways. Moderate evidence exists for familial Mediterranean fever, cryopyrin-associated periodic syndromes, and tumor necrosis factor receptor-associated periodic syndrome. For other rare hereditary autoinflammatory diseases, data are still inadequate. There is convincing evidence for a role of trained immunity in polygenic disorders like gout, atherosclerosis, obesity-associated "metaflammation", and type 2 diabetes and increasing evidence in Behçet's disease, adult-onset Still's disease, psoriasis, hidradenitis suppurativa, inflammatory bowel disease, and related inflammatory spectrum disorders. A major conceptual finding is that autoinflammatory illnesses may be a dynamic interplay between hereditary susceptibility and dysfunctional innate immune memory, rather than isolated static inflammatory abnormalities. However, information gaps still exist in reprogramming at the progenitor level, disease-specific epigenetic markers, and the reversibility of trained states. Understanding these systems may allow the development of therapeutic techniques to de-train abnormal innate immunological memory and obtain resilience for diseases.
2026-08-11 | Skin Impacts and Tradeoffs of GLP-1 Therapy: Improved Patient-Reported Outcomes of Inflammatory Skin Disease in the Era of "Ozempic Face".
With the surge in use of glucagon-like peptide 1-receptor agonists (GLP-1RAs) for weight management, "Ozempic Face," one of the dermatologic effects describing facial hollowing, sinking cheeks, and skin laxity, has drawn public attention. While substantial media discourse has surrounded certain dermatologic effects, patient-reported data is needed to more accurately characterize them. This study identifies patient-reported changes in skin, hair, and nails associated with weight management treatment with GLP-1RAs, including the frequency of dermatologic effects relative to weight loss. Our study was conducted through an IRB-approved, voluntary, anonymous survey developed via collaboration between obesity medicine physicians and dermatologists. The survey was then distributed to patients of a virtual cardio-kidney-metabolic treatment program. Responses (n = 1226) were sorted by the percent body weight lost and categorized by medication regimen (glucagon-like peptide 1-receptor agonists; GLP-1RA, nonGLP-1RA, or combination therapy). Patients reported dermatologic and overall physical changes. Dermatologic effects were reported more frequently with greater weight loss. Of respondents reporting greater than 20% body weight loss, (n = 325) 233 (72%; 95% CI 67-76) reported skin sagging, (n = 325) 170 (52%; 95% CI 47-58) reported hair loss, (n = 325) 163 (50%; 95% CI 45-55) reported decreased facial volume, and (n = 325) 107 (33%; 95% CI 28-38) reported reduced strength. Of respondents reporting 10-20% weight loss, (n = 395) 172 (44%; 95% CI 39-49) reported skin sagging, (n = 395) 119 (30%; 95% CI 26-35) reported hair loss, (n = 395) 147 (37%; 95% CI 33-42) reported decreased facial volume, and (n = 395) 76 (19%; 95% CI 16-23%) reported reduced strength. In comparison, of respondents reporting less than 10% weight loss, only (n = 380) 57 (15%; 95% CI 12-19) reported skin sagging, (n = 380) 65 (17%; 95% CI 13-21) reported hair loss, (n = 380) 48 (13%; 95% CI 10-16) reported decreased facial volume, and (n = 380) 35 (9%; 95% CI 7-13) reported reduced strength. The frequency of adverse patient-reported outcomes increased significantly with increasing percentage of body weight loss. Cochran-Armitage trend testing identified significant positive trends across the < 10%, 10-20%, and > 20% body weight loss categories for skin sagging (Z = 15.22), hair loss (Z = 9.91), decreased facial volume (Z = 10.70), and reduced strength (Z = 7.85), with P values of < 0.001. Among survey respondents on at least one GLP-1RA medication therapy, improvement was reported in certain preexisting inflammatory and hormonally driven skin conditions, including hidradenitis suppurativa (n = 15), 13 (87%; 95% CI 60-98); acanthosis nigricans (n = 12), 9 (75%; 95% CI 43-93); psoriasis (n = 47), 22 (47%; 95% CI 32-62); acne (n = 41), 17 (41%; 95% CI 27-57); eczema (n = 64), 17 (27%; 95% CI 17-39); hirsutism (n = 14), 4 (29%; 95% CI 10-56); seborrheic dermatitis (n = 16), 4 (25%; 95% CI 8-52); and skin tags (n = 57), 14 (25%; 95% CI 15-37). This large analysis of patient-reported outcomes suggests that greater weight loss, which often occurred with GLP-1RA treatment regimens versus other weight management therapies, was associated with higher reports of negative aesthetic impacts, most notably skin laxity, facial volume loss, and hair shedding, although with improvement in preexisting inflammatory and hormonally driven dermatological conditions. This calls for further studies to determine the potential mechanisms and incidence behind patient-reported outcomes associated with significant weight loss on GLP-1RA medications.
2026-07-25 | Integrated Proteogenomics and Single-Cell Transcriptomics Prioritize Putative Protective Plasma Proteins for Hidradenitis Suppurativa.
Translating hidradenitis suppurativa (HS) genetic susceptibility into actionable targets remains challenging, as most genome-wide association study loci lie in non-coding regions and tissue-level transcriptomics cannot easily distinguish causal drivers from secondary inflammation. In this study, we aimed to prioritize plasma proteins whose genetically predicted levels are causally associated with HS risk and to localize them within human skin at single-cell resolution. We performed two-sample Mendelian randomization (MR) using cis-pQTL instruments for 2923 plasma proteins from the UK Biobank Pharma Proteomics Project against HS summary statistics from FinnGen R12. Following multiple-testing correction and Bayesian colocalization with a prior-sensitivity grid, the intersection of false-discovery rate (FDR)-significant MR with colocalization evidence (PP.H4 ≥ 0.5) yielded three putative protective candidates: TNFRSF6B (OR = 0.748, 95% CI 0.666-0.840; PP.H4 = 0.648), FCRL2 (OR = 0.896, 95% CI 0.819-0.979; PP.H4 = 0.550), and APOD (OR = 0.789, 95% CI 0.647-0.963; PP.H4 = 0.503). All sensitivity MR tests were concordant. Single-cell transcriptomic analysis localized FCRL2 and APOD to specific cell populations. FCRL2 was predominantly expressed in B cells and NK cells, while APOD showed multi-cellular expression across cornified keratinocytes, macrophages, and dendritic cells. Furthermore, TNFRSF6B was below the skin detection threshold, supporting its biological role as a circulating decoy receptor. Together, our integrated proteogenomic and single-cell approach prioritizes TNFRSF6B, FCRL2, and APOD as putative protective plasma proteins for HS, with TNFRSF6B emerging as the most genetically robust candidate for future translational follow-up.
2026-07-15 | GLP-1 Receptor Agonists in Hidradenitis Suppurativa: Time to Treat the Whole Patient.
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a disproportionately high burden of metabolic comorbidities, including obesity, metabolic syndrome, type 2 diabetes mellitus (T2DM), dyslipidaemia, and polycystic ovary syndrome. Despite this, clinical management of HS has historically remained siloed within dermatology, with insufficient integration of cardiometabolic risk management. GLP-1 receptor agonists (GLP-1 RAs) - a drug class now established for T2DM, obesity, and cardiovascular risk reduction - have recently emerged as candidate agents for HS. A systematic review published in 2024 and two pivotal real-world studies published in 2025 provide preliminary evidence that GLP-1 RAs improve HS disease activity through both weight loss and direct anti-inflammatory mechanisms. We argue that this evidence base is already sufficient to justify a paradigm shift: GLP-1 RAs should be considered as adjunctive components of a multidisciplinary treatment strategy for HS patients with concurrent cardiometabolic disease. We propose a practical clinical framework for patient selection and monitoring and call for dedicated randomised controlled trials. Metabolic comorbidities are mechanistically linked to HS pathogenesis and are inadequately addressed in current clinical practice. GLP-1 RAs offer dual benefit in HS - improving both metabolic outcomes and HS disease activity. Dermatologists should screen every HS patient for cardiometabolic comorbidities and advocate for GLP-1 RA therapy in eligible patients as part of a multidisciplinary approach.
other
2024-12-16 | Unlocking the Mechanisms of Hidradenitis Suppurativa: Inflammation and miRNA Insights.
Inflammatory skin diseases impose a significant burden on patients and healthcare systems worldwide. Among these, hidradenitis suppurativa (HS) is particularly notable for its chronic and recurrent nature. Recurrent nodules, abscesses, and scarring in apocrine gland-rich areas characterize the disease, including the groin, axillae, and perianal regions. Despite its considerable physical and psychological impact, the precise mechanisms driving HS remain elusive. Recent advancements in understanding the inflammatory processes involved in HS have highlighted the TNF-alpha, IL-1β, and IL-17/IL-23 pathways, which play crucial roles in initiating and perpetuating the disease. Moreover, specific microRNAs (miRNAs), such as miR-24-1-5p, miR146a-5p, mirR-26a-5p, miR-206, miR-338-3p, and miR-338-5p, are involved in these inflammatory processes. Dysregulation of these miRNAs contributes to aberrant cytokine expression and persistent inflammation, foreseeably exacerbating HS disease progression. This narrative review hypothesizes that miRNA dysregulation triggers aberrant expression in specific inflammatory pathways, contributing to HS's clinical manifestations and progression. We explore the implicated miRNAs' potential as biomarkers for earlier disease detection and as novel therapeutic targets. Identifying miRNA dysregulation offers new opportunities for earlier and more accurate diagnosis, potentially allowing clinicians to intervene before severe disease manifestations occur. Furthermore, therapeutic strategies to modulate miRNA expression could target the inflammatory pathways driving HS, leading to more personalized and effective treatments. This review also discusses future research directions to enhance the clinical management of HS. A better understanding of miRNA involvement in HS offers new avenues for research and management, ultimately improving patient outcomes and quality of life.
2024-05-17 | LncRNA microarray profiling identifies novel circulating lncRNAs in hidradenitis suppurativa.
Long noncoding RNAs (lncRNAs) have been demonstrated to be involved in biological processes, both physiological and pathological, including cancer, cardiovascular diseases, multiple sclerosis, autoimmune hepatitis and types I and II diabetes. LncRNAs are also known to have a critical role in the physiology of skin, and in the pathology of cutaneous diseases. LncRNAs are involved in a wide range of biological activities, including transcriptional post‑transcriptional processes, epigenetics, RNA splicing, gene activation and or silencing, modifications and/or editing; therefore, lncRNAs may be useful as potential targets for disease treatment. Hidradenitis suppurativa (HS), also termed acne inversa, is a major skin disease, being an inflammatory disorder that affects ~1% of global population in a chronic manner. Its pathogenesis, however, is only partly understood, although immune dysregulation is known to have an important role. To investigate the biological relevance of lncRNAs with HS, the most differentially expressed lncRNAs and mRNAs were first compared. Furthermore, the lncRNA‑microRNA regulatory network was also defined via reverse transcription‑quantitative PCR analysis, whereby a trio of lncRNA expression signatures, lncRNA‑TINCR, lncRNA‑RBM5‑ASI1 and lncRNA‑MRPL23‑AS1, were found to be significantly overexpressed in patients with HS compared with healthy controls. In conclusion, the three lncRNAs isolated in the present study may be useful for improving the prognostic prediction of HS, as well as contributing towards an improved understanding of the underlying pathogenic mechanisms, thereby potentially providing new therapeutic targets.
2023-11-29 | Epigenetic switch reshapes epithelial progenitor cell signatures and drives inflammatory pathogenesis in hidradenitis suppurativa.
Hidradenitis suppurativa (HS) is a complex inflammatory skin disease with undefined mechanistic underpinnings. Here, we investigated HS epithelial cells and demonstrated that HS basal progenitors modulate their lineage restriction and give rise to pathogenic keratinocyte clones, resulting in epidermal hyperproliferation and dysregulated inflammation in HS. When comparing to healthy epithelial stem/progenitor cells, in HS, we identified changes in gene signatures that revolve around the mitotic cell cycle, DNA damage response and repair, as well as cell-cell adhesion and chromatin remodeling. By reconstructing cell differentiation trajectory and CellChat modeling, we identified a keratinocyte population specific to HS. This population is marked by S100A7/8/9 and KRT6 family members, triggering IL1, IL10, and complement inflammatory cascades. These signals, along with HS-specific proinflammatory cytokines and chemokines, contribute to the recruitment of certain immune cells during the disease progression. Furthermore, we revealed a previously uncharacterized role of S100A8 in regulating the local chromatin environment of target loci in HS keratinocytes. Through the integration of genomic and epigenomic datasets, we identified genome-wide chromatin rewiring alongside the switch of transcription factors (TFs), which mediated HS transcriptional profiles. Importantly, we identified numerous clinically relevant inflammatory enhancers and their coordinated TFs in HS basal CD49fhigh cells. The disruption of the S100A enhancer using the CRISPR/Cas9-mediated approach or the pharmacological inhibition of the interferon regulatory transcription factor 3 (IRF3) efficiently reduced the production of HS-associated inflammatory regulators. Our study not only uncovers the plasticity of epidermal progenitor cells in HS but also elucidates the epigenetic mechanisms underlying HS pathogenesis.
2022-10-14 | Methylated miRNAs may serve as potential biomarkers and therapeutic targets for hidradenitis suppurativa.
Hidradenitis suppurativa (HS) is a chronic inflammatory disease influenced by genetics, non-genetic and environmental factors that modulate miRNA expression. Currently, no miRNA data are available for HS. In this study, we profiled DNA methylation patterns of miRNA genes associated with HS susceptibility. Identify miRNA gene methylation profiles associated with HS susceptibility. This study examined the methylation patterns of DNAs from 24 healthy controls and 24 patients with HS using Illumina Infinium MethylationEPIC BeadChip array analysis. Methylation patterns of miRNA genes were analysed using KEGG pathway analysis to explore the inversely correlated pathways regulated by miRNAs. We identified 60 CpG sites representing 65 unique microRNA genes including 54 hypomethylated and 6 hypermethylated CpGs as potentially associated with HS. Some of these CpGs were found to be critical for skin function, such as miR-29, miR-200, miR-205, miR-548 and miR-132. The miR-192 is implicated in non-alcoholic fatty liver disease. The miR-200c gene was identified as a vital determinant in regulating skin repair after injury and may contribute to age-associated alterations in wound repair. miR-132 was significantly upregulated during the inflammation phase of wound repair, enhancing the activity of STAT3 and ERK pathways that promote keratinocyte proliferation. Epigenetically altered microRNA genes are implicated in wound healing, inflammation, keratinocyte proliferation and wound modulation. This is the first study to analyse methylation profiles of miRNA genes in the HS population, highlighting the unique role that miRNAs might play in diagnosing and treating HS.
2020-08-21 | Association of pyrin mutations and autoinflammation with complex phenotype hidradenitis suppurativa: a case-control study.
Hidradenitis suppurativa (HS) is a rare, debilitating neutrophilic dermatosis characterized by chronic inflammation of hair follicles. Many inflammatory conditions may accompany HS. To investigate the association of variants of the MEFV gene with a complex HS phenotype. Firstly, we identified the clinical characteristics of 119 patients with HS with a complex phenotype (Hurley stage III disease and/or additional inflammatory symptoms). Then, we searched for MEFV variants among these patients. The odds ratios (ORs) for pathogenic MEFV mutations were calculated using data from these patients with HS and 191 healthy controls. The male/female ratio was higher, and the mean age of onset was earlier, in our complex HS group compared with patients with HS in general. Five of the patients with HS (4·2%) had a diagnosis of familial Mediterranean fever (FMF) with a standardized morbidity ratio of 45 [95% confidence interval (CI) 16·50-99·84, P < 0·001] when compared with the frequency of FMF in the general Turkish population. Of the patients with complex HS, 38% were positive for pathogenic variants of MEFV. The OR for carrying a pathogenic MEFV allele was 2·80 (95% CI 1·31-5·97, P < 0·001). The frequency of MEFV mutations in the group of patients with complex HS was higher than that in healthy controls, suggesting that MEFV mutations may contribute to the pathogenesis of HS. Understanding the role of autoinflammation in HS is of fundamental importance for the development of novel therapies.
small molecules
2026-08-13 | Real-World Experience with Janus Kinase Inhibitors in Severe Refractory Hidradenitis Suppurativa: A Retrospective Case Series.
Hidradenitis suppurativa (HS) is a chronic inflammatory disease with limited treatment options for patients with severe, treatment-refractory disease. The JAK-STAT pathway represents a potential therapeutic target, although real-world evidence for JAK inhibitors (JAKi) in HS remains limited. This retrospective case series describes eight male patients with Hurley stage III HS who received tofacitinib (n=3), upadacitinib (n=4), or ivarmacitinib (n=1) after inadequate response to conventional therapies. Clinical outcomes were assessed using the International Hidradenitis Suppurativa Severity Score System (IHS4) and a numerical rating scale (NRS) for pain at the latest available follow-up. Follow-up ranged from 1 week to 12 months. Seven patients showed improvement in inflammatory lesions and/or pain, whereas one patient receiving tofacitinib showed limited clinical benefit. The median reduction in IHS4 score was 9.5 points (range, 2-18), and the median reduction in NRS pain score was 4.0 points (range, 0-5). Temporary interruption of upadacitinib in one patient was followed by disease flare, with improvement again observed after treatment re-initiation. No severe infections, thromboembolic events, HBV reactivation, or treatment-limiting adverse events were identified during the available follow-up. These preliminary observations suggest that JAKi may have a potential role in selected patients with severe, treatment-refractory HS. However, responses and follow-up durations were heterogeneous, and the small sample size precludes comparisons between agents. Prospective controlled studies with standardized assessment timepoints and longer follow-up are needed to clarify efficacy, durability, and long-term safety.
2026-08-02 | Actinomyces neuii in chronic hidradenitis suppurativa: a case series highlighting the value of extended culture.
Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory skin disease characterized by painful nodules, sinus tract formation and scarring. Lesional skin is frequently colonized by diverse aerobic and anaerobic bacteria, with anaerobes such as Prevotella spp., Campylobacter ureolyticus, Staphylococcus epidermidis and Actinomyces spp. commonly isolated. Actinomyces neuii, a Gram-positive, slow-growing anaerobe, has been previously described only occasionally in deep HS abscesses. We present three cases of treatment-resistant HS in which extended incubation of cultures yielded A. neuii. All patients were subsequently treated with long-term amoxicillin (3-6 months), resulting in marked clinical improvement. These findings suggest a potential pathogenic role for A. neuii in severe HS. Further research is required to establish its clinical relevance, evaluate optimal antibiotic regimens and monitor for resistance development.
2026-08-01 | Effectiveness and Safety of 40 mg Modified-Release Doxycycline for the Treatment of Hidradenitis Suppurativa: A Single-Center Retrospective Observational Study.
Hidradenitis suppurativa (HS) is a chronic inflammatory follicular disorder commonly managed with antibiotics, despite increasing antimicrobial resistance (AMR). This single-center retrospective study evaluated the efficacy and safety of 40 mg modified-release doxycycline (MR-DC) in 66 adults with HS treated for 28 days. Response to treatment was assessed using the Hidradenitis Suppurativa Clinical Response (HiSCR) and the International Hidradenitis Suppurativa Severity Score System (IHS4) scales. Specifically, at 12 weeks, HiSCR50 and IHS4-55 responses were achieved in 75.8% and 87.9% of patients, respectively. Relapse occurred in 33% at 6 months. Lower baseline IHS4, shorter disease duration, lower BMI, higher total inflammatory nodule and abscess count, absence of involvement of the pubis and genital area, and use of concomitant treatment were associated with better outcomes; only shorter disease duration remained significant on multivariate analysis (P < 0.022). Compared to results from other studies using standard regimens of regular-release doxycycline (RR-DC), MR-DC appears to have similar efficacy and more favorable safety profile. Low-dose MR-DC may be an effective short-term treatment or adjunctive therapeutic option for HS flares, with a reduced risk of AMR and adverse events.
2026-07-24 | Povorcitinib for hidradenitis suppurativa: the randomized, double-blind, placebo-controlled STOP-HS1 and STOP-HS2 phase 3 trials.
Although therapeutic options for hidradenitis suppurativa (HS) continue to expand, unmet needs remain substantial. We evaluated the efficacy and safety of povorcitinib (an oral, highly selective Janus kinase 1 (JAK1) inhibitor) in patients with moderate to severe HS in two randomized trials. STOP-HS1 and STOP-HS2 were identically designed, randomized, double-blind, placebo-controlled phase 3 trials. Adults with moderate to severe HS were randomized 2:2:1:1 to once-daily treatment through week 54: povorcitinib 45 mg; povorcitinib 75 mg; placebo with crossover at week 12 to povorcitinib 45 mg; or placebo with crossover at week 12 to povorcitinib 75 mg. The primary endpoint was HiSCR50 (≥50% decrease in total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining tunnel count) at week 12. STOP-HS1/STOP-HS2 enrolled 608/619 patients, respectively. In both studies, both povorcitinib doses met the primary endpoint; in STOP-HS1, 82/204 (40%) patients in the povorcitinib 45-mg group and 82/202 (41%) in the 75-mg group versus 60/202 (30%) in the placebo group achieved HiSCR50 (OR (95% CI) 45 mg: 1.6 (1.1-2.5), P = 0.0240; 75 mg: 1.6 (1.1-2.4), P = 0.0214); corresponding values for STOP-HS2 were 88/208 (42%) and 88/208 (42%) versus 58/203 (29%; OR (95% CI) 45 mg: 1.8 (1.2-2.8), P = 0.0035; 75 mg: 1.9 (1.2-2.8); P = 0.0033). Through week 12, across STOP-HS1/STOP-HS2, serious treatment-emergent adverse events (AEs) occurred in 1-2% of patients across povorcitinib doses and in 2-3% with placebo; through week 54, serious AEs occurred in 5%/6% of patients receiving 45-mg/75-mg povorcitinib, respectively. The most frequent AEs among patients treated with 45-mg/75-mg povorcitinib were acne (17%/20%), nasopharyngitis (10%/12%) and upper respiratory tract infection (11%/10%). One death of undetermined etiology was reported and deemed unrelated to treatment. No new or unexpected safety findings were identified. Oral povorcitinib demonstrated significant improvements in HiSCR50 versus placebo and a favorable safety profile in patients with moderate to severe HS. ClinicalTrials.gov registration: NCT05620823 and NCT05620836 .
2026-07-22 | Epidemiology of hidradenitis suppurativa in a large institutional 15-year retrospective study.
Hidradenitis suppurativa (HS) is a chronic inflammatory disorder associated with substantial morbidity, yet large real-world studies evaluating prevalence and comorbidity patterns within single healthcare systems remain limited. We retrospectively reviewed adult patients diagnosed with HS across an institution-wide cohort from September 2010 through October 2025. Demographics, anxiety, depression, acne history, and median income category by zip code were analyzed. Among 1,882,631 patients, 15,275 had HS, corresponding to a prevalence of 0.81%. Women represented 77.8% of cases, and the highest prevalence occurred among patients aged 31 to 40 years. HS patients were more than twice as likely to have acne compared with non-HS patients (odds ratio = 2.16; 95% confidence interval, 2.09-2.23; P < 0.001). Anxiety or depression was documented in 26.9% of patients. Median household income was not significantly associated with HS. These findings reinforce the demographic and psychosocial burden associated with HS and may assist clinicians in earlier recognition and management.
antibodies
2026-08-13 | Successful treatment of hidradenitis suppurativa with vunakizumab: a case report and literature review.
Hidradenitis suppurativa (HS) is a chronic, recurrent, and disabling inflammatory skin disorder. To our knowledge, this study reports the first use of vunakizumab, a domestically developed anti-IL-17A monoclonal antibody, for the treatment of HS. We present the case of a 17-year-old boy with a 5-year history of recurrent painful nodules and abscesses on the buttocks who had been repeatedly misdiagnosed with common acute bacterial infections and had responded poorly to conventional antibiotics. After 8 weeks of treatment with vunakizumab, which offered a pharmacoeconomic advantage during the transition period before its inclusion in China's national insurance system, the patient showed marked improvement, with complete resolution of nodules, abscesses, and tunnels and no recurrence or significant adverse events during 10 months of follow-up. This case highlights the potential of vunakizumab in the treatment of HS and supports the pathogenic role of IL-17 in the disease.
2026-08-13 | Autoinflammatory Syndromes of Hidradenitis Suppurativa: Updates in Clinical Features, Emerging Associations, and Management.
To summarize and critically evaluate recent literature on autoinflammatory syndromes of hidradenitis suppurativa (HS). HS-associated autoinflammatory syndromes traditionally encompass pyoderma gangrenosum (PG), acne, and HS (PASH); pyogenic arthritis, PG, acne, and HS (PAPASH); psoriatic arthritis, PG acne, and HS (PsAPASH); and PG, acne, HS and ankylosing spondylitis (PASS). However, this spectrum continues to expand, with recent literature considering the inclusion of additional autoinflammatory diseases such as HS associated with SAPHO, including synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO); and Hyperimmunoglobulin D Syndrome (HIDS). HS-associated autoinflammatory syndromes are thought to be driven by dysregulation of the innate immune system and the subsequent overexpression of key inflammatory cytokines such as IL-1, and targeted IL-1 therapies have demonstrated particularly brisk and efficacious response. Multiple genes related to follicular keratinization or inflammatory regulation have been implicated, and sequencing methods such as whole-exome sequencing and variant enrichment analysis continue to identify novel genetic variants and are being used to further elucidate genotype-phenotype correlations. HS-associated autoinflammatory syndromes are an evolving spectrum of rare, severe, diseases in which HS coexists with other autoinflammatory conditions, most commonly PASH and related syndromes. They are driven by innate immune dysregulation and pathogenic genetic variants, with whole-exome sequencing aiding diagnosis and genotype-phenotype correlation. Management is often challenging and highly individualized, with targeted biologic therapies such as IL-1 inhibitors showing the most consistent and rapid clinical benefit.
2026-08-12 | Surgical Outcomes for Hidradenitis Suppurativa: Does Biologic Therapy Make a Difference?
Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that often requires both medical and surgical management. Biologic therapies are increasingly used for moderate-to-severe disease, but their effect on surgical outcomes remains unclear. The aim of this study was to evaluate the impact of biologic therapy on postoperative outcomes in patients undergoing excisional surgery for HS. The authors conducted a retrospective chart review of adult patients who underwent excisional surgery for HS at a single academic center with at least 6 months of postoperative follow-up. Demographic data, comorbidities, disease severity, biologic use at the time of surgery (adalimumab or infliximab), and surgical outcomes were collected. Statistical analyses compared postoperative outcomes between biologic and nonbiologic groups with false discovery rate correction for multiple testing. Seventy-seven patients undergoing 109 excisions were included, of which 27 (24.8%) occurred while on biologics. All biologic patients had Hurley Stage III disease and greater surgical burden, with more anatomic sites undergoing excision. Healing time, complication rates, recurrence, and need for revision surgery did not significantly differ between groups. Biologic therapy did not impair postoperative healing or increase complications, supporting the safety of combining biologics with surgery for HS.
2026-07-28 | From rheumatology to dermatology: cytokine signaling pathways as therapeutic targets at the skin-joint interface in inflammatory diseases: a narrative review.
Over the last two years, inflammatory dermatology has undergone a transition from morphology-based classification toward pathway-driven immune endotyping. Atopic dermatitis, psoriatic disease, and hidradenitis suppurativa have emerged as paradigmatic models of this transition, illustrating how epithelial dysfunction, involving autoinflammation and adaptive immunity, may lead to systemic inflammatory crosstalks, connecting cutaneous and musculoskeletal manifestations. Recent studies have refined the understanding of progressive immune maturation in atopic dermatitis, while psoriasis and juvenile psoriatic arthritis support skin-to-joint inflammatory models involving IL-23/IL-17 signaling. Hidradenitis suppurativa is increasingly recognized as a systemic autoinflammatory disease within a broader neutrophilic inflammatory spectrum. Parallel therapeutic advances involving IL-17, IL-23, TNF, and JAK inhibition reinforced the translational importance of these discoveries and accelerated the development of precision dermatology strategies.
2026-07-23 | Effect of adalimumab treatment on lesions and inflammatory factors in patients with moderate-severe hidradenitis suppurativa.
To investigate the efficacy and safety of adalimumab (ADA) in the treatment of hidradenitis suppurativa (HS). A retrospective analysis was conducted on the clinical data of 50 patients with HS. Patients were divided into ADA (n=30) and cyclosporine (CSA, n=20) groups. The Hidradenitis Suppurativa Clinical Response Criterion (HiSCR) and the International Hidradenitis Suppurativa Severity Score System (IHS4) were used to assess clinical efficacy. The Dermatology Life Quality Index (DLQI) was used to evaluate patients' quality of life, and peripheral blood inflammatory factor levels were measured. Safety was also assessed. After treatment, all scores in both groups decreased significantly (all P<0.05); the decrease in IHS4 score in the ADA group was significantly greater than that in the cyclosporine (CSA) group (P<0.05). From week 2 to week 12 of treatment, there was a significant difference in the clinical response rate between the groups (P<0.05). At week 12, the Patient Global Assessment Relief Rate (PtGA RR) for skin pain in the ADA group was significantly higher than that in the CSA group (P<0.05). After treatment, the levels of inflammatory cells, NLRP3, and caspase-1 in both groups were significantly lower than those before treatment (P<0.05), with the ADA group showing a greater decrease than the CSA group (P<0.05). Some patients experienced dry mouth, abdominal pain, and scalp, which improved after symptomatic treatment. No relapse or secondary infection occurred. ADA demonstrates good clinical efficacy and long-term safety in treating this population.
cell therapies
2026-08-07 | Reused skin grafts for treating hidradenitis suppurativa: A systematic review.
Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory disease in which wide excision remains the most reliable option for durable disease control in moderate to severe cases. Reconstruction after excision is challenging. Reused or recycled split-thickness skin grafts, harvested from excised HS tissue and reapplied after processing, have been proposed to reduce donor-site morbidity, but their clinical value remains uncertain. To systematically evaluate the outcomes of reused skin grafts following surgical excision of HS, with emphasis on recurrence, graft take and procedure-related morbidity. A PRISMA-compliant systematic review was conducted using PubMed, Web of Science and Google Scholar from inception to the final search date. Studies reporting HS excision followed by reused or recycled skin grafting were included. Outcomes of interest were recurrence, graft survival, complications and follow-up duration. Given heterogeneity, a narrative synthesis was performed. Risk of bias was assessed using design-appropriate tools. Sixteen studies met inclusion criteria, including five systematic reviews, two retrospective cohorts and nine case reports or small case series. Primary reused-graft reports comprised approximately 41 patients with follow-up ranging from 6 to 113 months. Across these series, no surgical-site recurrences were reported (0/41), corresponding to an exact 95% confidence interval of 0-7.0%. Complications were generally minor. However, in the largest reused-graft series, which included 18 patients, 8 (44%) required supplemental conventional donor grafts. Broader pooled estimates from conventional graft literature reported recurrence rates ranging from 2% to 18%, reflecting substantial heterogeneity. Reused skin grafting appears feasible and safe in selected HS patients, with encouraging short- to medium-term durability. Current evidence supports feasibility rather than definitive comparative effectiveness, underscoring the need for well-designed prospective studies.
2026-04-14 | Multidisciplinary Approach to Complex Lower Extremity Limb Salvage in Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne (PAPA) Syndrome: A Case Report.
Limb salvage using free tissue transfer in patients with rare autoinflammatory syndromes is poorly described, and the safety of microvascular reconstruction in this population remains uncertain. Hereditary pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome is characterized by dysregulated inflammation, pathergy, and impaired wound healing, raising concern for flap compromise and postoperative complications. We report a rare case of lower extremity free tissue transfer in a patient with PAPA syndrome. A 66-year-old woman with rheumatoid arthritis and PAPA syndrome presented with rapid wound breakdown, violaceous ulceration, exposed hardware, and periprosthetic joint infection following left total knee arthroplasty (TKA). Examination revealed an approximately 9 × 7 cm anterior knee defect with subtotal patellar tendon necrosis. After multidisciplinary optimization, she underwent single-stage irrigation and debridement, hardware removal, revision TKA with patellar tendon reconstruction using gracilis autograft, and immediate coverage with a 22 × 14 cm free latissimus dorsi (LD) muscle flap. The flap was anastomosed end-to-side to the anterior tibial artery with venous outflow via the venae comitantes and loosely inset to preserve future surgical access. The donor site was closed primarily. A 21 × 13 cm staged split-thickness skin graft was performed 1 week later, with adjunctive postoperative hyperbaric oxygen therapy (HBOT). Initial healing was uncomplicated, with complete graft take and donor-site healing. Four months postoperatively, the patient developed chronic sinus tracts and recurrent periprosthetic infection requiring flap re-elevation, debridement, and hardware exchange; the flap pedicle was preserved, and coverage maintained. At one-year follow-up, all wounds had healed; flap coverage was durable with acceptable cosmesis, and the patient was ambulatory for short distances without assistance. She was last seen infection-free and full-weightbearing 4 months later. This case demonstrates that microvascular limb salvage is feasible in PAPA syndrome when guided by multidisciplinary planning and strategic flap design.
2026-03-26 | Two-Stage Surgical Management of Anogenital Hidradenitis Suppurativa in Patients on Biologic Therapy: A Retrospective Case Series.
Hidradenitis suppurativa is a chronic inflammatory skin disorder causing painful nodules, abscesses and scarring, with the anogenital region presenting particular functional and reconstructive challenges. Although biologic therapy is commonly used in moderate to severe disease, its limitations highlight the role of surgery in advanced cases. This single-centre retrospective case series included five male patients with Hurley stage III perineal, anorectal, genital or gluteal disease treated surgically between 2021 and 2023 following failure of biologic therapy. Management consisted of two-stage radical excision, negative-pressure wound therapy and reconstruction with meshed split-thickness skin grafts. All patients achieved more than 90% graft take and complete wound healing. No recurrence occurred during a median follow-up of 19.2 months. One patient developed a keloid scar at the donor site, and one experienced delayed healing. Functional and aesthetic results were satisfactory in all cases. Two-stage surgical excision with split-thickness skin graft reconstruction was associated with sustained wound healing and favourable functional outcomes in selected patients with severe anogenital hidradenitis suppurativa refractory to biologic therapy.
2026-03-06 | Intact Fish Skin Grafting in a Patient With Hidradenitis Suppurativa.
Wound management in hidradenitis suppurativa (HS) patients is often challenging due to worsening infections and impaired circulation, which can lead to prolonged hospitalization and poorer quality of life. Traditionally, autografting-a leading option in skin grafting-exhibits risks, including donor site morbidity. However, xenograft products, such as KerecisTM, derived from North Atlantic Cod fish, offer a novel solution for conditions with chronic wounds by promoting natural tissue regeneration. This case report presents a 35-year-old woman with HS who presented with persistent abscesses and fistulas in bilateral axillary regions. Following multiple surgical incisions and drainage procedures, the patient was treated with intact fish skin grafting, which resulted in significant granulation tissue deposition and wound edge approximation. The successful outcome in this case suggests that intact fish skin grafting is a viable option for non-healing wounds, particularly HS wounds, and can be integrated into surgical and wound care practices.
2025-11-26 | Beyond excision: modern plastic surgery techniques for hidradenitis suppurativa reconstruction.
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder characterized by recurrent abscesses, sinus tract formation and extensive scarring. In severe cases, surgical excision and complex reconstruction are often required. This case report aims to highlight the role of modern plastic surgical techniques, including regenerative technologies, in managing severe HS. A 37-year-old Hispanic male with a 17-year history of HS presented with extensive lesions involving the buttocks, groin, genitalia, thighs and perianal region. He underwent staged wide excisions totaling over 2,400 cm2. Reconstruction included split-thickness skin grafts (STSG), NovoSorb® BTM (Biodegradable Temporizing Matrix) and RECELL® autologous skin cell suspension. Postoperative recovery was marked by successful graft take, wound healing and return to normal function, including physical activity and sexual function, by postoperative day 69. This case underscores both the complexity of managing stage III HS and the evolving role of regenerative technologies in improving outcomes. While wide local excision remains the cornerstone of treatment for extensive disease, adjunctive use of BTM and RECELL enhances dermal regeneration, reduces donor-site morbidity and optimizes aesthetic and functional results. These innovations reflect a shift in reconstructive strategy, emphasizing a more tailored, patient-centered approach. The integration of regenerative modalities such as Biodegradable Temporizing Matrix (BTM) and RECELL autologous cell suspension technology into contemporary plastic surgical reconstruction offers significant benefits in treating severe hidradenitis suppurativa. By complementing traditional excisional techniques, these technologies contribute to improved healing, minimized morbidity and restored function, aligning with the goals of modern, multidisciplinary HS management.
proteins
2026-08-13 | The Metabolic Revolution in Dermatology: Obesity, Insulin Resistance, and Ultra-Processed Diets as Drivers of Skin Inflammation.
Inflammatory dermatoses are increasingly linked to systemic metabolic factors. Obesity and insulin resistance create a pro-inflammatory milieu that affects the skin. Adipose tissue functions as an endocrine organ secreting adipokines and cytokines that drive chronic inflammation with notable skewing toward T-helper 1 (Th1)/Th17 signaling. Hyperinsulinemia, elevated insulin-like growth factor-1 promote keratinocyte proliferation, sebum production, and autoinflammation, contributing to a multitude of skin diseases including hidradenitis suppurativa, acne, psoriasis, atopic dermatitis (AD), acanthosis nigricans, hirsutism, scarring alopecias, intertrigo, and chronic idiopathic urticaria. Concomitantly, ultra-processed diets low in fiber and high in additives detrimentally affect the gut-skin axis. Diets rich in emulsifiers, sugars, and fructose alter the gut microbiome and increase intestinal permeability, leading to metabolic endotoxemia and increased systemic inflammation. High-fructose corn syrup in sweetened beverages is metabolized via hepatic fructokinase, promoting de novo lipogenesis and excess uric acid, a cascade implicated in metabolic fatty liver disease and heightened inflammation. These dietary factors have been correlated with aggravated skin diseases, where fast-food intake (≥3× weekly) is associated with increased risk of severe AD in children. Emerging evidence suggests that dietary modifications may help mitigate skin inflammation in select patients. At the same time, the advent of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonists may improve metabolic parameters and could represent promising adjunctive therapies in select inflammatory dermatoses. Dermatologists can serve as sentinels, identifying cutaneous signs of insulin resistance (eg, acanthosis nigricans, acrochordons, and other skin diseases driven by insulin resistance) and addressing lifestyle factors as part of routine care.
2026-08-12 | Trained immunity in autoinflammatory diseases: Cellular reprogramming across the monogenic-polygenic spectrum.
Trained immunity, an innate immunological memory induced by epigenetic and metabolic reprogramming, has changed the paradigm of host defense and pathogenesis of chronic inflammatory disease. Unlike adaptive immunological memory, trained immunity is characterized by the ability of innate immune cells and their progenitors to respond more robustly or differently to subsequent stimulations and contributes to chronic inflammatory conditions. Emerging data suggests that this process might be essential in autoinflammatory and immune-mediated inflammatory illnesses by enhancing sterile inflammation, decreasing activation thresholds, and boosting disease chronicity. This narrative review summarizes the existing evidence relating trained immunity to monogenic and polygenic autoinflammatory diseases. The greatest evidence in monogenic disease is for mevalonate kinase deficiency, where dysregulated mevalonate metabolism directly overlaps with conventional trained immunity pathways. Moderate evidence exists for familial Mediterranean fever, cryopyrin-associated periodic syndromes, and tumor necrosis factor receptor-associated periodic syndrome. For other rare hereditary autoinflammatory diseases, data are still inadequate. There is convincing evidence for a role of trained immunity in polygenic disorders like gout, atherosclerosis, obesity-associated "metaflammation", and type 2 diabetes and increasing evidence in Behçet's disease, adult-onset Still's disease, psoriasis, hidradenitis suppurativa, inflammatory bowel disease, and related inflammatory spectrum disorders. A major conceptual finding is that autoinflammatory illnesses may be a dynamic interplay between hereditary susceptibility and dysfunctional innate immune memory, rather than isolated static inflammatory abnormalities. However, information gaps still exist in reprogramming at the progenitor level, disease-specific epigenetic markers, and the reversibility of trained states. Understanding these systems may allow the development of therapeutic techniques to de-train abnormal innate immunological memory and obtain resilience for diseases.
2026-08-11 | Skin Impacts and Tradeoffs of GLP-1 Therapy: Improved Patient-Reported Outcomes of Inflammatory Skin Disease in the Era of "Ozempic Face".
With the surge in use of glucagon-like peptide 1-receptor agonists (GLP-1RAs) for weight management, "Ozempic Face," one of the dermatologic effects describing facial hollowing, sinking cheeks, and skin laxity, has drawn public attention. While substantial media discourse has surrounded certain dermatologic effects, patient-reported data is needed to more accurately characterize them. This study identifies patient-reported changes in skin, hair, and nails associated with weight management treatment with GLP-1RAs, including the frequency of dermatologic effects relative to weight loss. Our study was conducted through an IRB-approved, voluntary, anonymous survey developed via collaboration between obesity medicine physicians and dermatologists. The survey was then distributed to patients of a virtual cardio-kidney-metabolic treatment program. Responses (n = 1226) were sorted by the percent body weight lost and categorized by medication regimen (glucagon-like peptide 1-receptor agonists; GLP-1RA, nonGLP-1RA, or combination therapy). Patients reported dermatologic and overall physical changes. Dermatologic effects were reported more frequently with greater weight loss. Of respondents reporting greater than 20% body weight loss, (n = 325) 233 (72%; 95% CI 67-76) reported skin sagging, (n = 325) 170 (52%; 95% CI 47-58) reported hair loss, (n = 325) 163 (50%; 95% CI 45-55) reported decreased facial volume, and (n = 325) 107 (33%; 95% CI 28-38) reported reduced strength. Of respondents reporting 10-20% weight loss, (n = 395) 172 (44%; 95% CI 39-49) reported skin sagging, (n = 395) 119 (30%; 95% CI 26-35) reported hair loss, (n = 395) 147 (37%; 95% CI 33-42) reported decreased facial volume, and (n = 395) 76 (19%; 95% CI 16-23%) reported reduced strength. In comparison, of respondents reporting less than 10% weight loss, only (n = 380) 57 (15%; 95% CI 12-19) reported skin sagging, (n = 380) 65 (17%; 95% CI 13-21) reported hair loss, (n = 380) 48 (13%; 95% CI 10-16) reported decreased facial volume, and (n = 380) 35 (9%; 95% CI 7-13) reported reduced strength. The frequency of adverse patient-reported outcomes increased significantly with increasing percentage of body weight loss. Cochran-Armitage trend testing identified significant positive trends across the < 10%, 10-20%, and > 20% body weight loss categories for skin sagging (Z = 15.22), hair loss (Z = 9.91), decreased facial volume (Z = 10.70), and reduced strength (Z = 7.85), with P values of < 0.001. Among survey respondents on at least one GLP-1RA medication therapy, improvement was reported in certain preexisting inflammatory and hormonally driven skin conditions, including hidradenitis suppurativa (n = 15), 13 (87%; 95% CI 60-98); acanthosis nigricans (n = 12), 9 (75%; 95% CI 43-93); psoriasis (n = 47), 22 (47%; 95% CI 32-62); acne (n = 41), 17 (41%; 95% CI 27-57); eczema (n = 64), 17 (27%; 95% CI 17-39); hirsutism (n = 14), 4 (29%; 95% CI 10-56); seborrheic dermatitis (n = 16), 4 (25%; 95% CI 8-52); and skin tags (n = 57), 14 (25%; 95% CI 15-37). This large analysis of patient-reported outcomes suggests that greater weight loss, which often occurred with GLP-1RA treatment regimens versus other weight management therapies, was associated with higher reports of negative aesthetic impacts, most notably skin laxity, facial volume loss, and hair shedding, although with improvement in preexisting inflammatory and hormonally driven dermatological conditions. This calls for further studies to determine the potential mechanisms and incidence behind patient-reported outcomes associated with significant weight loss on GLP-1RA medications.
2026-07-25 | Integrated Proteogenomics and Single-Cell Transcriptomics Prioritize Putative Protective Plasma Proteins for Hidradenitis Suppurativa.
Translating hidradenitis suppurativa (HS) genetic susceptibility into actionable targets remains challenging, as most genome-wide association study loci lie in non-coding regions and tissue-level transcriptomics cannot easily distinguish causal drivers from secondary inflammation. In this study, we aimed to prioritize plasma proteins whose genetically predicted levels are causally associated with HS risk and to localize them within human skin at single-cell resolution. We performed two-sample Mendelian randomization (MR) using cis-pQTL instruments for 2923 plasma proteins from the UK Biobank Pharma Proteomics Project against HS summary statistics from FinnGen R12. Following multiple-testing correction and Bayesian colocalization with a prior-sensitivity grid, the intersection of false-discovery rate (FDR)-significant MR with colocalization evidence (PP.H4 ≥ 0.5) yielded three putative protective candidates: TNFRSF6B (OR = 0.748, 95% CI 0.666-0.840; PP.H4 = 0.648), FCRL2 (OR = 0.896, 95% CI 0.819-0.979; PP.H4 = 0.550), and APOD (OR = 0.789, 95% CI 0.647-0.963; PP.H4 = 0.503). All sensitivity MR tests were concordant. Single-cell transcriptomic analysis localized FCRL2 and APOD to specific cell populations. FCRL2 was predominantly expressed in B cells and NK cells, while APOD showed multi-cellular expression across cornified keratinocytes, macrophages, and dendritic cells. Furthermore, TNFRSF6B was below the skin detection threshold, supporting its biological role as a circulating decoy receptor. Together, our integrated proteogenomic and single-cell approach prioritizes TNFRSF6B, FCRL2, and APOD as putative protective plasma proteins for HS, with TNFRSF6B emerging as the most genetically robust candidate for future translational follow-up.
2026-07-15 | GLP-1 Receptor Agonists in Hidradenitis Suppurativa: Time to Treat the Whole Patient.
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a disproportionately high burden of metabolic comorbidities, including obesity, metabolic syndrome, type 2 diabetes mellitus (T2DM), dyslipidaemia, and polycystic ovary syndrome. Despite this, clinical management of HS has historically remained siloed within dermatology, with insufficient integration of cardiometabolic risk management. GLP-1 receptor agonists (GLP-1 RAs) - a drug class now established for T2DM, obesity, and cardiovascular risk reduction - have recently emerged as candidate agents for HS. A systematic review published in 2024 and two pivotal real-world studies published in 2025 provide preliminary evidence that GLP-1 RAs improve HS disease activity through both weight loss and direct anti-inflammatory mechanisms. We argue that this evidence base is already sufficient to justify a paradigm shift: GLP-1 RAs should be considered as adjunctive components of a multidisciplinary treatment strategy for HS patients with concurrent cardiometabolic disease. We propose a practical clinical framework for patient selection and monitoring and call for dedicated randomised controlled trials. Metabolic comorbidities are mechanistically linked to HS pathogenesis and are inadequately addressed in current clinical practice. GLP-1 RAs offer dual benefit in HS - improving both metabolic outcomes and HS disease activity. Dermatologists should screen every HS patient for cardiometabolic comorbidities and advocate for GLP-1 RA therapy in eligible patients as part of a multidisciplinary approach.
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2024-12-16 | Unlocking the Mechanisms of Hidradenitis Suppurativa: Inflammation and miRNA Insights.
Inflammatory skin diseases impose a significant burden on patients and healthcare systems worldwide. Among these, hidradenitis suppurativa (HS) is particularly notable for its chronic and recurrent nature. Recurrent nodules, abscesses, and scarring in apocrine gland-rich areas characterize the disease, including the groin, axillae, and perianal regions. Despite its considerable physical and psychological impact, the precise mechanisms driving HS remain elusive. Recent advancements in understanding the inflammatory processes involved in HS have highlighted the TNF-alpha, IL-1β, and IL-17/IL-23 pathways, which play crucial roles in initiating and perpetuating the disease. Moreover, specific microRNAs (miRNAs), such as miR-24-1-5p, miR146a-5p, mirR-26a-5p, miR-206, miR-338-3p, and miR-338-5p, are involved in these inflammatory processes. Dysregulation of these miRNAs contributes to aberrant cytokine expression and persistent inflammation, foreseeably exacerbating HS disease progression. This narrative review hypothesizes that miRNA dysregulation triggers aberrant expression in specific inflammatory pathways, contributing to HS's clinical manifestations and progression. We explore the implicated miRNAs' potential as biomarkers for earlier disease detection and as novel therapeutic targets. Identifying miRNA dysregulation offers new opportunities for earlier and more accurate diagnosis, potentially allowing clinicians to intervene before severe disease manifestations occur. Furthermore, therapeutic strategies to modulate miRNA expression could target the inflammatory pathways driving HS, leading to more personalized and effective treatments. This review also discusses future research directions to enhance the clinical management of HS. A better understanding of miRNA involvement in HS offers new avenues for research and management, ultimately improving patient outcomes and quality of life.
2024-05-17 | LncRNA microarray profiling identifies novel circulating lncRNAs in hidradenitis suppurativa.
Long noncoding RNAs (lncRNAs) have been demonstrated to be involved in biological processes, both physiological and pathological, including cancer, cardiovascular diseases, multiple sclerosis, autoimmune hepatitis and types I and II diabetes. LncRNAs are also known to have a critical role in the physiology of skin, and in the pathology of cutaneous diseases. LncRNAs are involved in a wide range of biological activities, including transcriptional post‑transcriptional processes, epigenetics, RNA splicing, gene activation and or silencing, modifications and/or editing; therefore, lncRNAs may be useful as potential targets for disease treatment. Hidradenitis suppurativa (HS), also termed acne inversa, is a major skin disease, being an inflammatory disorder that affects ~1% of global population in a chronic manner. Its pathogenesis, however, is only partly understood, although immune dysregulation is known to have an important role. To investigate the biological relevance of lncRNAs with HS, the most differentially expressed lncRNAs and mRNAs were first compared. Furthermore, the lncRNA‑microRNA regulatory network was also defined via reverse transcription‑quantitative PCR analysis, whereby a trio of lncRNA expression signatures, lncRNA‑TINCR, lncRNA‑RBM5‑ASI1 and lncRNA‑MRPL23‑AS1, were found to be significantly overexpressed in patients with HS compared with healthy controls. In conclusion, the three lncRNAs isolated in the present study may be useful for improving the prognostic prediction of HS, as well as contributing towards an improved understanding of the underlying pathogenic mechanisms, thereby potentially providing new therapeutic targets.
2023-11-29 | Epigenetic switch reshapes epithelial progenitor cell signatures and drives inflammatory pathogenesis in hidradenitis suppurativa.
Hidradenitis suppurativa (HS) is a complex inflammatory skin disease with undefined mechanistic underpinnings. Here, we investigated HS epithelial cells and demonstrated that HS basal progenitors modulate their lineage restriction and give rise to pathogenic keratinocyte clones, resulting in epidermal hyperproliferation and dysregulated inflammation in HS. When comparing to healthy epithelial stem/progenitor cells, in HS, we identified changes in gene signatures that revolve around the mitotic cell cycle, DNA damage response and repair, as well as cell-cell adhesion and chromatin remodeling. By reconstructing cell differentiation trajectory and CellChat modeling, we identified a keratinocyte population specific to HS. This population is marked by S100A7/8/9 and KRT6 family members, triggering IL1, IL10, and complement inflammatory cascades. These signals, along with HS-specific proinflammatory cytokines and chemokines, contribute to the recruitment of certain immune cells during the disease progression. Furthermore, we revealed a previously uncharacterized role of S100A8 in regulating the local chromatin environment of target loci in HS keratinocytes. Through the integration of genomic and epigenomic datasets, we identified genome-wide chromatin rewiring alongside the switch of transcription factors (TFs), which mediated HS transcriptional profiles. Importantly, we identified numerous clinically relevant inflammatory enhancers and their coordinated TFs in HS basal CD49fhigh cells. The disruption of the S100A enhancer using the CRISPR/Cas9-mediated approach or the pharmacological inhibition of the interferon regulatory transcription factor 3 (IRF3) efficiently reduced the production of HS-associated inflammatory regulators. Our study not only uncovers the plasticity of epidermal progenitor cells in HS but also elucidates the epigenetic mechanisms underlying HS pathogenesis.
2022-10-14 | Methylated miRNAs may serve as potential biomarkers and therapeutic targets for hidradenitis suppurativa.
Hidradenitis suppurativa (HS) is a chronic inflammatory disease influenced by genetics, non-genetic and environmental factors that modulate miRNA expression. Currently, no miRNA data are available for HS. In this study, we profiled DNA methylation patterns of miRNA genes associated with HS susceptibility. Identify miRNA gene methylation profiles associated with HS susceptibility. This study examined the methylation patterns of DNAs from 24 healthy controls and 24 patients with HS using Illumina Infinium MethylationEPIC BeadChip array analysis. Methylation patterns of miRNA genes were analysed using KEGG pathway analysis to explore the inversely correlated pathways regulated by miRNAs. We identified 60 CpG sites representing 65 unique microRNA genes including 54 hypomethylated and 6 hypermethylated CpGs as potentially associated with HS. Some of these CpGs were found to be critical for skin function, such as miR-29, miR-200, miR-205, miR-548 and miR-132. The miR-192 is implicated in non-alcoholic fatty liver disease. The miR-200c gene was identified as a vital determinant in regulating skin repair after injury and may contribute to age-associated alterations in wound repair. miR-132 was significantly upregulated during the inflammation phase of wound repair, enhancing the activity of STAT3 and ERK pathways that promote keratinocyte proliferation. Epigenetically altered microRNA genes are implicated in wound healing, inflammation, keratinocyte proliferation and wound modulation. This is the first study to analyse methylation profiles of miRNA genes in the HS population, highlighting the unique role that miRNAs might play in diagnosing and treating HS.
2020-08-21 | Association of pyrin mutations and autoinflammation with complex phenotype hidradenitis suppurativa: a case-control study.
Hidradenitis suppurativa (HS) is a rare, debilitating neutrophilic dermatosis characterized by chronic inflammation of hair follicles. Many inflammatory conditions may accompany HS. To investigate the association of variants of the MEFV gene with a complex HS phenotype. Firstly, we identified the clinical characteristics of 119 patients with HS with a complex phenotype (Hurley stage III disease and/or additional inflammatory symptoms). Then, we searched for MEFV variants among these patients. The odds ratios (ORs) for pathogenic MEFV mutations were calculated using data from these patients with HS and 191 healthy controls. The male/female ratio was higher, and the mean age of onset was earlier, in our complex HS group compared with patients with HS in general. Five of the patients with HS (4·2%) had a diagnosis of familial Mediterranean fever (FMF) with a standardized morbidity ratio of 45 [95% confidence interval (CI) 16·50-99·84, P < 0·001] when compared with the frequency of FMF in the general Turkish population. Of the patients with complex HS, 38% were positive for pathogenic variants of MEFV. The OR for carrying a pathogenic MEFV allele was 2·80 (95% CI 1·31-5·97, P < 0·001). The frequency of MEFV mutations in the group of patients with complex HS was higher than that in healthy controls, suggesting that MEFV mutations may contribute to the pathogenesis of HS. Understanding the role of autoinflammation in HS is of fundamental importance for the development of novel therapies.
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