Hidradenitis suppurativa.

Acne inversa is a chronic, progressive inflammatory skin disease. It is characterized by the occurrence of relapsing, painful, deep-seated nodules, abscesses, fistulae, sinus tracts, and scars in the axilla, inguinal area, submammary folds, and perianal area. The disease significantly affects patients’ quality of life and is often associated with severe, debilitating pain and depression. Pro-inflammatory cytokines such as TNF-α, interleukin 17 (IL-17), IL-23, IL-12, IL-1α, and IL-1β play a significant role in the pathogenesis of hidradenitis suppurativa. Treatment is difficult and often ineffective, based on both surgical and pharmacological methods. Biologic drugs in hidradenitis suppurativa are the subject of many clinical trials and may be effective in patients for whom other therapies have failed. The first biological drug approved by the Food and Drug Administration for the treatment of hidradenitis suppurativa was the TNF-α inhibitor — adalimumab. The advancement of knowledge of immune mechanisms in the pathogenesis of hidradenitis suppurativa has allowed the development of clinical trials of new therapeutic targets. In 2023, the Food and Drug Administration (FDA) approved the IL-17 inhibitor — secukinumab as the second biological drug in hidradenitis suppurativa. The aim of this review is an update of the biological treatment and its effectiveness in hidradenitis suppurativa.

BACKGROUND Studies have shown an association between inflammatory bowel disease (IBD) and hidradenitis suppurativa (HS), but there is conflicting data on whether it is more associated with Crohn’s disease (CD) versus ulcerative colitis (UC). In addition, the natural course and outcomes of patients with comorbid IBD and HS are unknown. The purpose of this study was to compare the clinical characteristics and disease course of patients with both IBD and HS compared with those of patients with isolated IBD or isolated HS. METHODS A retrospective chart review was conducted for patients who were seen at a single tertiary health system in New York City between 1/1/2016 and 5/31/2023. Of 970 patients diagnosed with HS by dermatologists, 35 had both confirmed IBD and HS. These patients were matched 1:1:1 with control cases having isolated IBD and isolated HS, based on age, sex, race, duration of the disease, and IBD type. Clinical variables related to HS and IBD were collected, including demographics, comorbid conditions, markers of disease severity, and treatment. RESULTS Of the 35 patients with both HS and IBD, 24 were female and 11 were male, with a median age of 34 years (range 14-81). Of patients with documented race, 16 were White (46%), 8 were Black (14%), and 5 were South Asian (23%). Six patients had UC, while 29 had CD. The median age at diagnosis of IBD was 19 (range 12-24) and of HS was 24 (range 20-36). IBD diagnosis preceded HS diagnosis in 26 patients, whereas HS preceded IBD in only 3 patients. When compared with the isolated IBD group, patients with comorbid CD and HS more often had perianal CD (55% vs 21%, p < 0.01). When compared for IBD-related outcomes, there were more frequent IBD-related hospitalizations in the comorbid IBD and HS group (0.29 vs 1.38, p = 0.02). The median number of biologics tried was 2 (p = 0.7), and anti-TNF biologics were used in 32 patients (p = 0.5). Combination therapy of biologics and immunomodulators was required in 13 patients (p = 0.04). As for extraintestinal manifestation, peripheral arthritis had a significant difference between the comorbid group and the isolated IBD group (p = 0.05). When compared for HS-related outcomes, the severity of HS assessed by the Hurley stage and the number of past surgical treatments did not significantly differ between the comorbid IBD and HS group and the isolated HS group. CONCLUSION In this single-center study with a diverse population, there was a high proportion of South Asian patients. Patients with comorbid IBD and HS more often had CD than UC, and the proportion of patients with PFCD was higher than in the isolated IBD group. IBD exhibited more severe disease progression, necessitating more frequent combination therapy and hospitalizations, while HS severity was similar when compared with patients with isolated IBD or HS, respectively.

Disclosure: S.R. Vasavada: None. K.A. Chopra: None. L. Philipson: Grant Recipient; Self; Novo Nordisk. Background: Hidradenitis suppurativa (HS) is an inflammatory skin condition of the pilosebaceous unit characterized by subcutaneous nodules that if untreated can form purulent abscesses, fistulae, and sinus tracts. HS may result from dysregulated autoimmune response to skin flora with overexpression of inflammatory cytokines, such as IL-17A, TNF-a, IL-1B (Shah et al 2017). Although HS and type 1 diabetes both share underlying autoimmune etiologies, and autoimmune diseases have been reported in higher frequencies in HS than controls, co-incidence with type 1 diabetes is extremely rare (Straalen et al 2022). Herein, we describe a case of a patient with type 1 diabetes with recurrent admissions for diabetic ketoacidosis (DKA) secondary to HS flares. Clinical Case: 37-year-old female with medical history of type 1 diabetes, hypogammaglobulinemia, and HS presented with rectal pain and hematochezia. Previously, she had several hospitalizations due to HS flares complicated by episodes of DKA and 20+ corrective surgeries for infected HS lesions. Prior to admission, patient was treated with clindamycin lotion, spironolactone, and weekly adalimumab for HS. Patient’s initial labs showed DKA with glucose 494 mg/dL (RR 60-99 mg/dL), bicarbonate 21 mmol/L (RR 23-30 mmol/L), anion gap 16 mmol/L (RR 6-15 mmol/L), and beta hydroxybutyrate level 1.44 mmol/L (N <0.3 mmol/L). Hemoglobin A1c was 10.4% (RR <5.7%). Physical exam showed Hurley Stage 2 HS with multiple atrophic scars, boils, and double comedones on bilateral axillae. She was treated with insulin infusion and IV fluids. After anion gap closed and bicarbonate improved to 24 mmol/L (RR 23-30 mmol/L), she transitioned to regimen of insulin glargine 38 units and started mealtime insulin lispro using a ratio of 1 unit of lispro for 6 grams of carbs. Subsequent glucose values stabilized, ranging 120-200 mg/dL (RR 60-99 mg/dL) during hospitalization. She underwent colonoscopy due to concern for colonic involvement of HS, however pathology was normal. After multidisciplinary discussion with endocrinology and dermatology specialists, HS treatment with prednisone was avoided due to concern of worsening patient’s glycemic control. Patient started infliximab treatment and reported mild symptom improvement. Conclusion: This case showing a patient with multiple episodes of DKA triggered by flares of HS has demonstrated the importance of further study to improve our current understanding of the potential overlap of these two conditions to help guide future treatment decisions and improve patients’ overall quality of life. Reference: Shah A, Alhusayen R, Amini-Nik S. The critical role of macrophages in the pathogenesis of hidradenitis suppurativa. Inflamm Res. 2017;66(11):931-945. Straalen KR van, Prens EP, Gudjonsson JE (2022) Insights into hidradenitis suppurativa. J Allergy Clin Immun 149(4):1150–1161. Presentation: Thursday, June 15, 2023

Hidradenitis Suppurativa and Pediatric Crohn Disease

Hidradenitis suppurativa (HS) is a chronic inflammatory disease, characterized by painful, purulent and destructive skin alterations in intertriginous areas. We investigated the expression and role in HS of granulocyte colony-stimulating factor (G-CSF), the regulator of neutrophil biology, as clinical signs of a neutrophilic granulocyte-driven inflammation are distinctive in the disease. Skin and blood samples obtained from different cohorts of patients with HS and control individuals were assessed by RNA sequencing, quantitative polymerase chain reaction on reverse transcribed mRNA, and/or enzyme-linked immunosorbent assay. Mechanistic studies using keratinocytes, dermal fibroblasts, immune cell populations and skin biopsies were performed. G-CSF was abundant in HS skin, particularly in inflamed nodules and abscesses. Its levels even exceeded those found in other inflammatory skin diseases. Interleukin (IL)-1 and IL-17, respectively, induced G-CSF production by fibroblasts and keratinocytes. These effects were enhanced by tumour necrosis factor (TNF)-α and IL-36. Accordingly, fibroblasts separated from HS lesions expressed G-CSF, and IL-1 receptor antagonist reduced G-CSF levels in explanted HS skin. G-CSF blood levels positively correlated with severity of HS. Elevated lesional G-CSF receptor levels were linked to upregulation of molecules that contribute to prolonged activation of neutrophils by components of bacteria and damaged host cells [formyl peptide receptor 1 (FPR1), FPR2 and free fatty acid receptor 2 (FFAR2)], neutrophil survival [TNF receptor superfamily member 10C (TNFRSF10C/TRAIL-R3) and TNF receptor superfamily member 6B], kinases (tyrosine-protein kinase HCK and hexokinase 3), and skin destruction [MMP25 (matrix metalloproteinase 25) and ADAM8 (disintegrin and metalloproteinase domain-containing protein 8)]. G-CSF elevated the expression of FPR1, FFAR2, and TNFRSF10C/TRAIL-R3 in neutrophils and synergized with bacterial components to induce skin-destructive enzymes. The G-CSF pathway engages both tissue and immune cells, is strongly activated in HS lesions, and offers the opportunity to target the neutrophil-driven inflammation.

Summary: Introduction: Association between hidradenitis suppurativa (HS) and chronic inflammatory bowel disease (IBD) exists. Prevalence of IBD in patients with HS is not clear. The aim of this paper is to determine the prevalence of IBD in patients with HS, evaluate risk factors and possible phenotype of patients with HS and IBD. Methods: Single center retrospective analysis of 241 patients with HS was carried out and medical files were searched for inflammatory bowel disease accordingly. Epidemiologic data of HS were collected. Results: IBD had a prevalence of 5.8%. Out of this number 13 (92.9%) suffered from Crohn’s disease (CD) and 1 (7.1%) from ulcerative colitis (UC). Eight patients (57.1%) were referred to the dermatologist by gastroenterologist and in six patients (42.9%) history of IBD was detected by dermatologist during routine examination. Special phenotype of the disease associated with IBD was not confirmed. The study points out possible existence of common comorbidities and risk factors such as smoking and obesity. Discussion: Our study confirmed similar data like those available in literature, where strong association between CD and HS is present and weaker with UC and HS. Conclusion: The prevalence of IBD in HS patients (5.8%) however these patients do not have a distinct HS phenotype. Key words: hidradenitis suppurativa – chronic inflammatory bowel disease – Crohn’s disease – ulcerative colitis – comorbidities – association – risk factors

The pathogenesis of hidradenitis suppurativa (HS) is largely unknown and the disease is difficult to treat. Patients are in high need of an effective treatment. Although it is not known whether the levels of tumour necrosis factor (TNF)-α are aberrant in HS skin, anti-TNF-α biologics are used, with variable clinical efficacy. To determine the cytokine profile in lesional and perilesional HS skin. We cultured 20 lesional and 10 normal-appearing perilesional HS skin samples, seven psoriasis and six healthy control skin samples in a transwell culture system. Two distinct cytokine bead arrays were used to measure the spectrum of inflammatory cytokines in the culture supernatant. Results from HS skin samples were compared with those of healthy and psoriasis skin. The proinflammatory cytokines interleukin (IL)-1β and TNF-α as well as the anti-inflammatory cytokine IL-10 were significantly elevated in HS skin. Elevated levels of these cytokines were also found in perilesional HS skin. Fold increases relative to control skin of IL-1β, TNF-α and IL-10 in HS were 31, 5 and 34, compared with psoriasis: 4, 1 and 2, respectively. Levels of all three cytokines showed a trend towards a positive correlation with disease severity. IL-2, IL-4, IL-5 and interferon-γ were hardly detectable in HS or healthy control skin. This study shows for the first time that IL-1β, TNF-α and IL-10 levels are elevated in HS skin. These data provide a rationale for therapies with biologics targeting cytokines such as TNF-α and IL-1.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease defined clinically by multiple, painful inflammatory lesions occurring predominantly in flexural sites. Onset is typically soon after puberty; however, it remains unknown whether the menopause induces remission. In North American and European patients with HS the female-to-male ratio is approximately 3:1 but the ratio is 1:2 in South Korean patients. It may be that some elements of HS epidemiology cannot be generalized across all populations. Elements of HS epidemiology in the USA and Europe are well established, including strong associations with obesity and smoking, which may increase disease severity. There are associations between HS and other cardiovascular disease (CVD) risk factors, including type 2 diabetes and metabolic syndrome. People with HS have double the risk of death from CVD compared with those without HS and 1·5 times the risk compared with patients with psoriasis. Depression and anxiety are associated with HS and completed suicide rates in those with HS are more than double the rates in controls. Associations exist between HS and other chronic inflammatory conditions, particularly inflammatory bowel disease and inflammatory arthritis. Case-control studies demonstrate associations with pilonidal sinus, polycystic ovary syndrome, Down syndrome, obstructive sleep apnoea and pyoderma gangrenosum. Population-based studies using routinely collected healthcare data from the USA estimate a prevalence of 0·1%, suggesting HS is relatively uncommon. European studies include undiagnosed patients and typically estimate prevalence of 1% or more, suggesting a common condition. Resolving the controversy surrounding a greater than 10-fold difference in HS prevalence estimates remains a high priority.

Although the pathogenesis of hidradenitis suppurativa (HS) remains enigmatic, several factors point to potential involvement of the cutaneous microbiome. Insight into the cutaneous microbiome in HS using next-generation sequencing may provide novel data on the microbiological diversity of the skin. To investigate the follicular skin microbiome in patients with HS and in healthy controls. This case-control study obtained punch biopsy specimens from patients with HS (lesional and nonlesional) and healthy controls between October 1, 2014, and August 1, 2016. Data were analyzed from March to November 2016. Patients with HS were recruited from the Department of Dermatology, Zealand University Hospital, Roskilde, Denmark. Biopsy specimens were analyzed at the Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark. None of the participants received any antibiotics (systemic or topical therapy) within 1 month before the study. In patients with HS, biopsy specimens were obtained from lesional skin (axilla or groin) and nonlesional skin. Only nodules containing at least 1 visible hair follicle were biopsied. Biopsy specimens from healthy controls were obtained from the axilla only. The different microbiomes were investigated using next-generation sequencing targeting 16S and 18S ribosomal RNA. The skin microbiome was characterized in 30 patients with HS (mean [SD] age, 46.9 [14.0] years; 19 [63% female]) and 24 healthy controls (mean [SD] age, 32.2 [12.0] years; 13 [54% female]). The next-generation sequencing data provided a previously unreported (to our knowledge) characterization of the skin microbiome in HS. The study demonstrated that the microbiome in HS differs significantly from that in healthy controls in lesional and nonlesional skin. Overall, the following 5 microbiome types were identified: Corynebacterium species (type I), Acinetobacter and Moraxella species (type II), Staphylococcus epidermidis (type III), Porphyromonas and Peptoniphilus species (type IV), and Propionibacterium acnes (type V). In lesional skin, microbiome types consisted predominantly of type I or type IV. Microbiome type IV was not detected in healthy controls. Several taxa, including Propionibacterium, showed a significantly higher relative abundance in healthy controls vs HS skin, indicating that Propionibacterium may be part of the pathogenesis in HS. The study findings suggest a link between a dysbiotic cutaneous microbiome and HS.

Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disease of apocrine gland-bearing skin which affects approximately 1–4% of the population. The disease is more common in women and patients of African American descent and approximately one-third of patients report a family history. Obesity and smoking are known risk factors, but associations with other immune disorders, especially inflammatory bowel disease, are also recognized. The pathogenesis of HS is poorly understood and host innate or adaptive immune response, defective keratinocyte function, and the microbial environment in the hair follicle and apocrine gland have all been postulated to play a role in disease activity. While surgical interventions can be helpful to reduce disease burden, there is a high recurrence rate. Increasingly, data supports targeted immune therapy for HS, and longitudinal studies suggest benefit from these agents, both when used alone and as an adjunct to surgical treatments. The purpose of this review is to outline the current data supporting use of targeted immune therapy in HS management.

Crohn's disease (CD) is an inflammatory bowel disease (IBD) with major extraintestinal manifestations. Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that has previously been described to have a strong association with CD. Though the pathophysiology remains uncertain, this case series highlights the different aspects of disease presentation, similarities, severity, current treatment modalities, and the relational conflict between HS as a paradoxical side effect of biologic agents (BA) that is not well established.We identified a total of three patients with CD and HS and described their clinical presentation and management. A systematic search of the literature with PubMed and Ovid MEDLINE was done in 2021. Two patients were initially diagnosed with CD prior to developing skin manifestations. The third patient was diagnosed with HS first, then was found to have gastrointestinal symptoms. All patients had HS requiring surgical intervention. One patient failed a biological agent but responded to another. The second patient was treated with cytotoxic agents with acceptable results. The third patient was managed without the use of biologics. One of three patients’ clinical courses may suggest a paradoxical side effect of BA. The relationship between CD and HS is based on several case reports. A prospective study will help establish the relationship as well as shed light on the treatment of both conditions simultaneously. In addition, further evaluation of the causal relationship between BA, specifically adalimumab and infliximab as treatment for CD and HS are warranted to effectively manage Crohn’s disease, evaluate paradoxical HS, and improve outcomes of both HS and CD. CD and HS impact a patient's quality of life and physicians should therefore have a high degree of awareness upon diagnosis.

Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin condition that manifests as painful, deep-seated, inflamed nodules and abscesses in the axillary, groin, perianal, perineal, and inframammary regions. The associated pain, malodour, and disfigurement contribute to its profound negative impact on psychosocial spheres and overall quality of life in affected individuals. Although the symptoms of HS classically begin in the second or third decade of life, HS affects children and adolescents as well. Despite this, there are limited pediatric data on treatment, which are largely based on expert opinion, extrapolation of efficacy data in adults with HS, and safety information from medication use in other pediatric diseases. On this basis, there exist several pharmacological modalities in the treatment of children and adolescents with HS including topical therapies, systemic therapies, and biologics. The goals of this review article are to: (1) review the efficacy of different pharmacological treatment modalities in children and adolescents with HS, and (2) review the safety and monitoring considerations of the different treatment options in children and adolescents with HS.

Complement inhibition has been identified as a potential therapeutic target for multiple inflammatory disorders including Hidradenitis Suppurativa (HS). It is currently unclear how complement integrates into our current model of molecular pathogenesis in HS and whether it represents a central component of pathogenesis, or a neutrophil-associated bystander. Levels of C5a in serum and tissue correlate with disease activity and degree of neutrophilic infiltrates in HS. C5a has been associated with Th17 immune axis activation in psoriasis, rheumatoid arthritis and Crohn's disease with strong similarities to TH17 activation in HS. Porphyromonas species (which are identified in the HS microbiome) are able to cleave inactive C5 into C5a implicating the cutaneous microbiome as an activator of complement. C3a and C5a are associated with activation of the NLRP3 inflammasome, implicated in the inflammatory drive in HS. Complement receptors are present upon dendritic cells, monocytes, fibroblasts and adipocytes, which may broaden the potential contribution of complement to multiple aspects of HS pathogenesis. Dysregulation of complement receptor pathways has been documented in obesity, insulin resistance and polycystic ovarian syndrome leading to the possibility that complement may explain the epidemiological associations between these conditions and HS. The therapeutic potential of complement inhibitors in HS may be related to the therapeutic target (complement receptor or complement subunit) and the presence of alternate receptors (such as C5aR2) or ligands (including C3a, PAMPs and DAMPs). Integrating complement into the known pathogenesis of HS may aid in explaining the contradictory results between Phase 2 studies of C5a antagonists. It also allows for the identification of existing knowledge gaps to target further clinical investigation and research.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory condition of the skin that mainly affects the apocrine gland-rich intertriginous areas. The disease manifests as painful nodules, abscesses, and pus-filled tunnels, which can severely impact patient’s quality of life. While diagnosis is clinical, successful treatment options for this condition are limited. There has been an increase in research and clinical trials focusing on biomarkers and cytokines for clinical use. Understanding the potential biomarkers and cytokines implicated in HS pathogenesis may allow efficacious and safe treatment options. Summary: A literature review was conducted on nine biomarkers and cytokines. IL-1, IL-10, IL-17, IL-23, TNF-α, YKL-40, G-CSF, NOD2, and the complement system were identified due to their potential clinical utilization and pathophysiological involvement in HS. Key Messages: With further research expanding our understanding of the pathophysiology of HS and the roles these cytokines and biomarkers play, there is potential for utilization as diagnostic markers or development of antagonists against these specific agents for HS management.

Hidradenitis suppurativa (HS) is a chronic auto-inflammatory skin disease with a complex and multifactorial pathogenesis involving both the innate and adaptive immune system. Despite limited evidence for local complement activation, conflicting results have been published on the role of systemic complement activation in HS. It was hypothesized that complement was consumed in highly inflamed HS skin, trapping complement from the circulation. Therefore, the aim of this study was to evaluate this local complement deposition in HS skin lesions using routine and commonly used complement antibodies.Direct immunofluorescence for C1q, C3c, C4d, C5b-9, and properdin was performed on frozen tissue sections of 19 HS patients and 6 controls. C5a receptor 1 (C5aR1) was visualized using immunohistochemistry.Overall, we found no significant local complement deposition in HS patients versus controls regarding C1q, C3c, C4d, C5b-9, or properdin on either vessels or immune cells. C5aR1 expression was exclusively found on immune cells, predominantly neutrophilic granulocytes, but not significantly different relatively to the total infiltrate in HS lesions compared with controls. In conclusion, despite not being able to confirm local complement depositions of C1q, C3c, C4d, or properdin using highly sensitive and widely accepted techniques, the increased presence of C5aR1 positive immune cells in HS suggests the importance of complement in the pathogenesis of HS and supports emerging therapies targeting this pathway.