What is known about this subject in regard to women and their families? Hidradenitis suppurativa commonly affects women and significantly impairs quality of life, relationships, and daily functioning. Obesity and metabolic comorbidities are frequent in affected women and are associated with more severe disease. What is new from this article as messages for women and their families? This case demonstrates marked improvement of severe hidradenitis suppurativa with tirzepatide therapy. Targeting metabolic dysfunction may offer additional benefit in disease control and quality of life for women with hidradenitis suppurativa. Introduction Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease characterized by recurrent, painful abscesses, nodules, sinus tract formation, and scarring.1,2 It typically affects intertriginous areas, such as the axillary, anogenital, and inframammary regions.1,2 HS arises from follicular occlusion and immune dysregulation, with contributing roles from genetics, the cutaneous microbiome, and hormonal factors.1,2 Obesity plays an essential role in both the development and worsening of HS, and it is often associated with metabolic syndrome and type 2 diabetes.3 Treatment options include oral antibiotics, antiandrogens, and metformin. For more severe or refractory cases, Food and Drug Administration-approved biologics—such as Adalimumab (anti-tumor necrosis factor TNF-α), Secukinumab, and Bimekizumab (anti-interleukin IL-17)—are available. Surgical approaches, including wide excision or deroofing, may also be necessary.1 Glucagon-like peptide-1 receptor agonists (GLP-1RAs), developed initially for the treatment of type 2 diabetes, received Food and Drug Administration approval for obesity management in November 2023.4 Agents such as semaglutide and liraglutide, as well as tirzepatide—a dual GLP-1RA and glucose-dependent insulinotropic polypeptide receptor agonist (GIP-RA)—function as incretin analogues. They enhance glucose-dependent insulin secretion, suppress inappropriate glucagon release, slow gastric emptying, and promote satiety. Collectively, these mechanisms lead to significant weight reduction and improvements in obesity-related comorbidities.1,4 GLP-1 receptors are located in many tissues, including skin. This implies that GLP-1RA therapy may have effects in inflammatory skin conditions, such as psoriasis and HS.5 Case presentation We present the case of a 21-year-old female diagnosed with HS 5 years prior, who has been under regular follow-up at our institution. At the time of evaluation, she weighed 89 kilograms (kg) with a body mass index (BMI) of 32.3, classifying her as having Class I obesity. She is a nonsmoker, with no history of diabetes and no family history of HS. The disease involved multiple intertriginous areas, including the inframammary, intermammary, axillary, abdominal, inguinal, and gluteal folds. Clinical assessment revealed an International Hidradenitis Suppurativa Severity Score System of 21 points, Hurley stage II, Physician Global Assessment (PGA) of moderate severity, and Dermatology Life Quality Index (DLQI) score of 13. Her laboratory results showed a fasting blood glucose level of 106.2 mg/dL (normal range 70–100 mg/dL), with no HbA1c available. The lipid panel results were as follows: cholesterol, 4.49 mmol/dL (normal value less than 5.2 mmol/dL); and triglycerides, 0.68 mmol/L (normal value less than 1.7 mmol/dL). She had previously failed topical therapies, as well as systemic treatments with doxycycline and isotretinoin, which had been used intermittently over a 3-year period. Given the persistence of disease activity, adalimumab was considered. During the pretreatment evaluation for biologic therapy, however, the patient consulted an endocrinologist for obesity management and was initiated on tirzepatide, starting at 2.5 mg weekly with gradual titration to a target dose of 15 mg over 6 months. Adalimumab was ultimately not started, as the patient missed her scheduled appointment. The patient reported that over the course of tirzepatide titration, particularly at the 10 mg weekly dose, she noticed a marked reduction in HS flare-ups and fewer abscess formations. However, when the dose was tapered down to 7.5 mg, she experienced a mild relapse, presenting with 4 inflamed but nonsuppurative nodules. Based on her experience, she resumed the 10 mg weekly dose and maintained it for an additional 3 months, during which her disease remained well-controlled. At her most recent clinic visit, approximately 9 months after initiating tirzepatide, the patient showed significant clinical improvement. On physical examination, a single inflammatory nodule was noted in the intermammary area. Her updated disease activity scores reflected substantial progress: the International Hidradenitis Suppurativa Severity Score System score decreased to 6, the Hurley stage was downgraded to I, and the PGA was downgraded to mild, with the DLQI reduced to 5. Her weight had decreased to 65.3 kg, reflecting a 26% total weight loss. Repeat laboratory results revealed a fasting glucose level of 71 mg/dL and an HbA1c of 4.8% (normal value less than 5.7%). Lipid panel showed cholesterol 4.8 mmol/L and triglycerides 0.8 mmol/L. Discussion HS is a chronic inflammatory skin disorder strongly associated with obesity, a condition characterized by low-grade systemic inflammation that can aggravate disease activity. The prevalence of HS is markedly higher among obese individuals, affecting up to 18-20% compared with 1-2% in the general population.3 Obesity contributes to metabolic dysfunction and is closely linked to cardiovascular disease and metabolic syndrome, conditions that share overlapping inflammatory pathways with HS.3,5 The pathogenesis of HS involves increased production of proinflammatory cytokines such as TNF-α, IL-1α, IL-1β, IL-12, IL-17, and IL-23.1,3 Skin samples from patients with a BMI greater than 30 demonstrate elevated levels of metabolic markers, including irisin, peroxisome proliferator-activated receptor gamma, and IGF-1R, as well as increased IL-17 receptor expression, a key proinflammatory marker.3 Moreover, obese individuals exhibit elevated levels of free fatty acids, which can bind to toll-like receptor 4 on monocytes, stimulating the release of proinflammatory cytokines such as IL-1β, IL-6, and IL-8, thereby amplifying systemic and local inflammation.3 Given this relationship, weight reduction is an essential measure in HS management. GLP-1RA, initially developed for the treatment of type 2 diabetes and obesity, has recently gained attention for its potential role in HS treatment.3,6 In addition to their roles in glycemic control and weight reduction, emerging evidence suggests that GLP-1RAs possess immunomodulatory properties, resulting in reductions in systemic inflammation and aging.5 Studies encourage the prescribing of these medications as an adjunctive approach for patients with a BMI greater than 27 kg/m2 and comorbidities or greater than 30 kg/m2 without comorbidities.6 At a cellular level, recent evidence suggests that GLP-1RAs suppress TNF-α activity through the nuclear factor kappa-light-chain-enhancer of activated B cells pathway, resulting in reduced cytokine production.3,5 The downregulation of proinflammatory mediators, such as IL-17 and IL-23, which are key contributors to HS pathogenesis, helps mitigate inflammation and promote disease remission.3,5 Additionally, GLP-1RAs have been shown to decrease secretion of monocyte chemotactic protein-1, thereby limiting monocyte recruitment and activation.5 The first published evidence of this association was reported by Emtestam et al. (2017), who described a 31-year-old obese female smoker with long-standing, extensive Hurley stage II HS and a HS-PGA score of 4. Treatment with liraglutide resulted in significant improvement after just 4 weeks, reducing her HS-PGA to 1 (minimal disease). After 8 weeks, her HS remained well-controlled, with notable improvements in weight, DLQI, and analgesic use (Table 1). This landmark case was the first to suggest that GLP-1 agonists could provide direct clinical benefit in HS.7 Table 1 - Summary of reported HS cases improved on GLP-1RA therapy Study Patient GLP-1RA treatment Previous failed treatment HS Scoring 1-Glucagon-like peptide-1 agonists for treatment of hidradenitis suppurativa. Emtestam et al. 2017. 31 years old, femaleObese (BMI 45.3),Smoker. Liraglutide (1.8 mg/week) for 2 months. Combined rifampicin and clindamycin, metformin, spironolactone, adalimumab, etanercept, and dapsone. IHS4:Hurley:PGA:DLQI: Before treatment After treatment - II - 4 1 24 14 2-Liraglutide for the treatment of obesity among patients with hidradenitis suppurativa. Nicolau et al.9 14 patients with obesity Liraglutide (3 mg/week) for 3 months. - IHS4:Hurley:PGA:DLQI: Before treatment After treatment - 2.6 ± 0.5 1.1 ± 0.3 - 12.3 ± 2.8 9.7 ± 6.9 3-Semaglutide for weight loss in people with obesity as an adjunctive treatment for hidradenitis suppurativa: its impact on disease control and quality of life. Lyons et al.10 30 patients with obesity Semaglutide (2.4 mg/week) for 2 months. - IHS4:Hurley:PGA:DLQI: Before treatment After treatment - - - 13 9 4-A case of recalcitrant hidradenitis suppurativa concomitantly treated with tirzepatide. Chan et al.8 20-year-old female, obese (BMI 41.3), T2DM, PCOS. Tirzepatide (7.5 mg/week) for 3 months.(concurrent with infliximab). Antibiotics, OCP, SCS, spironolactone, and adalimumab. IHS4:Hurley:PGA:DLQI: Before treatment After treatment - - 3 2 14 3 5-GLP-1 Agonists in patients with hidradenitis suppurativa: a case series. Rames et al.2 3 patients, smokers, obese (average BMI 45.5), T2DM. 2 with dulaglutide.1 with tirzepatide.(One patient had bariatric surgery, and another patient started IL-17 inhibitors). - IHS4:Hurley:PGA:DLQI: Before treatment After treatment - III II - - 6-Glucagon-like peptide-1 receptor agonists in hidradenitis suppurativa, retrospective multicenter cohort study. Gouvrion et al.11 HS exposed to GLP-1 RAs from 2017 to 2024, a total of 66 patients:-Median age 46.-38 were females.-Median BMI 39.4.-57 had DM.-30 patients had Hurley stage I, 21 had Hurley II, and 15 had Hurley III. -48 received semaglutide.-13 received dulaglutide.-5 received liraglutide. 53% were undergoing treatment for HS when GLP-1 RA was initiated:-23 suspensive antibiotic therapy.-3 broad-spectrum antibiotics.-9 biologic. IHS4:Hurley:PGA:DLQI:Flares:NRS-Pain:NRS-suppuration: At initiation 6 months follow-up - - 2.8 2.1 16.2 11.8 4.8 3.2 5 3.5 5.6 4.2 BMI, body mass index; DLQI, Dermatology Life Quality Index; IHS4, International Hidradenitis Suppurativa Severity Score System; NRS, Numerical Rating Scale; OCP, oral contraceptive pills; PCOS, polycystic ovary syndrome; PGA: Physician’s Global Assessment; SCS, systemic corticosteroids; T2DM, type 2 diabetes mellitus. More recently, Chan et al.8 described a 20-year-old female with HS, polycystic ovarian syndrome, type 2 diabetes, and obesity (BMI 41.36 kg/m2). She initially responded to infliximab, but following the initiation of tirzepatide for diabetes and obesity, she achieved marked additional improvements within 3 months. Her DLQI decreased from 14 to 3, her HS-PGA improved from moderate to mild, and she experienced a 16% reduction in body weight.8 In the same year, Nicolau et al.9 reported significant decreases in HS severity among 14 obese patients treated with liraglutide. After 3 months of therapy, both Hurley stage and DLQI scores improved markedly (Hurley: 2.6 ± 0.5 vs 1.1 ± 0.3; P = .002; DLQI: 12.3 ± 2.8 vs 9.7 ± 6.9; P = .04).9 Similar results were also observed in a study by Lyons et al.10 Tirzepatide is a dual GLP-1RA and GIP-RA.3 Similar to our case, this case highlights the innovative application of dual incretin co-agonists in obese patients with or without type 2 diabetes, offering a valuable complement to biologic therapy. In our case, we observed a relapse when the patient tapered the dose below 10 mg weekly, which suggests that spontaneous remission is unlikely given the relapsing–remitting nature of the disease. Remission was reestablished and maintained upon resuming a 10 mg weekly dose. Further research is warranted to determine the optimal dosing strategy for patients with HS. Most recently, Rames et al.2 published a case series evaluating GLP-1RA in HS. One patient treated with dulaglutide demonstrated a reduction in Hurley stage from III to II, a decrease in HS sites from 4 to 2, and improvements in inflammatory markers; however, this improvement coincided with bariatric surgery. Two additional patients, 1 on dulaglutide and 1 on tirzepatide, also showed improvements in Hurley stage and subjective disease activity (III to II and II to I, respectively). However, one of these patients started secukinumab during the same timeframe, complicating the interpretation of therapeutic effect.2Table 1 summarizes all reported cases of HS that have improved with GLP-1RA therapy. A retrospective multicenter study from France by Gouvrion et al.11 evaluated patients with HS treated with GLP-1RA between 2017 and 2024, with assessments performed at treatment initiation, at 6 months, and at discontinuation.11 Among 66 patients treated across 8 French hospitals with semaglutide, dulaglutide, or liraglutide, significant reductions were observed in HS severity scores (Table 1). By the time of discontinuation, 62% of patients achieved a ≥1-point improvement in HS-PGA, and 32% achieved a ≥2-point improvement. Additionally, 67% showed a reduction in flares, while 60% experienced decreased pain, 58% had reduced suppuration, and 52% reported improved quality of life compared with treatment initiation. A subgroup analysis of 34 patients whose HS treatments had remained stable for the preceding 12 months before GLP-1RA initiation showed similar improvements, supporting that the results were not solely attributable to other concurrent therapies. GLP-1RA represents a promising therapeutic avenue in HS, particularly as an early intervention and before the initiation of biologic therapy.1,3 Their dual effects on weight reduction and systemic inflammation position them to address 2 key drivers of HS pathogenesis: metabolic dysfunction and chronic inflammation.3 Early use of GLP-1RAs may reduce or delay the need for biologics, which are costly and associated with adverse outcomes, including inflammatory bowel disease in the context of IL-17 inhibition.1 Moreover, the concurrent administration of GLP-1RAs and biologics may yield synergistic benefits by targeting distinct yet complementary pathways. GLP-1RAs primarily modulate metabolic and systemic inflammatory processes, whereas biologics inhibit specific immune mediators, such as TNF-α and IL-17. This combinatorial strategy could be particularly advantageous in patients with severe or refractory HS and those with significant metabolic comorbidities.3,5 In summary, we report the first case of HS improvement with tirzepatide monotherapy in a 21-year-old female with obesity and no diabetes, who achieved significant disease control and 26% weight loss without biologic therapy or bariatric surgery. This case highlights tirzepatide’s potential as a novel therapeutic option for obese HS patients, irrespective of diabetes status. However, our report is limited by the fact that the patient was evaluated only once after 9 months of treatment; more frequent follow-up visits, consistent with the 3-month assessment intervals recommended by the HiSTORIC consensus, would have allowed a more reliable evaluation of treatment response. Additionally, we did not obtain inflammatory biomarker measurements, and the proposed immunological mechanisms by which GLP-1RAs may improve HS remain speculative, as current evidence is limited and observational. Weight reduction alone may explain the clinical improvement observed in this case. Further studies and controlled clinical trials are required to define the efficacy, safety, and long-term outcomes of GLP-1RA monotherapy and combination therapy strategies in the management of HS. Conflicts of interest None. Funding None. Study approval N/A Author contributions GBA and MMA: Involved in patient care, data collection, and manuscript preparation. Both authors critically reviewed the manuscript and approved the final version. Patient consent Written informed consent was obtained from the patient for publication of this case report.
Alqefari et al. (Thu,) studied this question.