Residency · Residency · Dermatology

Hidradenitis Suppurativa: A Paradigm Shift

Overview

Hidradenitis suppurativa (HS) is a chronic, debilitating, inflammatory skin disease affecting the apocrine gland-bearing areas, including the axillae, inguinal folds, and anogenital region. Characterized by recurrent painful nodules, abscesses, draining sinuses, and scarring, HS profoundly impairs quality of life. Once considered primarily an infection of apocrine glands, it is now understood as a disease of follicular occlusion with secondary inflammation.

Epidemiology

HS has an estimated prevalence of approximately 1 to 4 percent, though it is likely underdiagnosed due to stigma and delayed diagnosis. The average diagnostic delay is 7 to 10 years. There is a female predominance of approximately 3:1, although male patients are more commonly affected in the perianal region. Onset is typically post-pubertal, with peak incidence in the 20s and 30s, and the condition is rare before puberty. The strongest modifiable risk factor is smoking, with additional risk factors including obesity and family history (autosomal dominant with variable penetrance in approximately 40 percent of cases).

Pathogenesis

Follicular Occlusion (Primary Event)

Infundibular hyperkeratosis and follicular plugging are the initiating events in HS. Follicular rupture releases keratinous debris and bacteria into the dermis, triggering the inflammatory cascade. HS is part of the "follicular occlusion tetrad," which also includes acne conglobata, dissecting cellulitis of the scalp, and pilonidal cyst. Importantly, HS is not a primary apocrine gland disease, making the historical term "acne inversa" a misnomer.

Immune Dysregulation

Follicular rupture triggers a massive innate and adaptive immune response. Key cytokines include TNF-alpha (elevated in lesional skin, driving inflammation and tissue destruction), IL-1beta (inflammasome activation contributing to abscess formation), IL-17A (Th17-mediated inflammation), IL-23 (driving Th17 differentiation), and IL-12 and IL-36 (contributing to inflammation), along with complement activation. Neutrophilic infiltration is prominent, and deficiency of antimicrobial peptides, particularly reduced dermcidin, may contribute to secondary infection.

Genetic Factors

Gamma-secretase gene mutations (NCSTN, PSENEN, PSEN1) are found in familial HS, accounting for approximately 5 percent of cases. Gamma-secretase cleaves Notch receptors, and loss of Notch signaling impairs follicular differentiation. Genome-wide association studies have identified additional loci including IL-12B, IL-23R, and SOX9. Variable penetrance suggests that environmental cofactors play an important role.

Contributing Factors

Smoking promotes follicular plugging, alters keratinocyte differentiation, and activates innate immune pathways. Obesity contributes through mechanical friction, occlusion, and adipose-driven inflammation via adipokines. Hormonal factors are suggested by the post-pubertal onset and potential androgen influence (though this is debated), with perimenstrual flares being common. The follicular microbiome is altered in HS; while this is not a primary infection, secondary colonization contributes to disease chronicity.

Clinical Features

Distribution

The most common sites include the axillae, inguinal and groin folds, inframammary region, perianal and perineal area, and buttocks. Less common sites include the nape of the neck and waistband area.

Morphology (Progressive)

Disease progresses through characteristic stages. Recurrent inflammatory nodules are deep, painful, "boil-like" lesions. Abscesses are fluctuant and painful and may drain spontaneously. Sinus tracts (tunnels) are epithelialized tracts connecting nodules beneath the skin. Scarring includes hypertrophic and contracture scars with bridge scars ("tombstone" comedones). Double-ended comedones (open comedones) are pathognomonic for HS and represent re-epithelialized sinus openings.

Hurley Staging

Stage I is defined by recurrent abscess formation (single or multiple) without sinus tracts or scarring. Stage II features recurrent abscesses with sinus tract formation and scarring in single or few widely separated lesions. Stage III involves diffuse involvement across an entire anatomic area with multiple interconnected sinus tracts and abscesses.

IHS4 (International Hidradenitis Suppurativa Severity Score)

The IHS4 is a point-based scoring system calculated as the number of nodules times 1, plus the number of abscesses times 2, plus the number of draining tunnels times 4. Scores below 4 indicate mild disease, 4 to 10 indicate moderate disease, and 11 or greater indicate severe disease. This system is more granular than Hurley staging for clinical trial use and monitoring.

Comorbidities

HS is associated with metabolic syndrome (obesity, dyslipidemia, insulin resistance, hypertension), inflammatory bowel disease (especially Crohn disease, which shares IL-17/IL-23 pathways), spondyloarthropathy, depression and anxiety (with DLQI scores among the highest of any dermatologic disease), polycystic ovary syndrome, and rarely squamous cell carcinoma arising in chronic sinus tracts (usually perianal). Anemia of chronic disease, hypoalbuminemia in severe cases, and substance abuse and chronic pain syndromes are additional comorbidities.

Diagnosis

The diagnosis is clinical, based on typical lesions (nodules, abscesses, sinus tracts, scarring), typical locations (intertriginous, apocrine-bearing areas), and chronicity with recurrence (two or more episodes in six months). Biopsy is rarely needed but shows follicular occlusion, perifollicular inflammation, sinus tracts lined by stratified squamous epithelium, and granulation tissue. Ultrasound is helpful for identifying subclinical sinus tracts and guiding surgical planning. Wound cultures typically reveal polymicrobial biofilms with anaerobes and coagulase-negative staphylococci, but routine cultures are not needed.

Management

Lifestyle Modifications

Smoking cessation is the most impactful modifiable intervention. Even modest weight reduction improves disease. Additional measures include wearing loose-fitting clothing, using gentle skin cleansing with antiseptic washes (chlorhexidine, benzoyl peroxide wash), and zinc gluconate supplementation (90 mg/day) for its anti-inflammatory properties.

Medical Therapy

Topical

Clindamycin 1% lotion or solution is appropriate for mild disease (Hurley I). Resorcinol 15% cream is a keratolytic used in some European protocols.

Antibiotics (Anti-Inflammatory, Not Just Antimicrobial)

Tetracyclines (doxycycline 100 mg daily) are used for mild-to-moderate disease in three-month courses. Clindamycin plus rifampin (300 mg each twice daily) is used for moderate-to-severe disease in 10- to 12-week courses, with monitoring for C. difficile and rifampin drug interactions from CYP450 induction. Dapsone has anti-neutrophilic properties and can be used adjunctively, requiring G6PD screening.

Biologics

Adalimumab (anti-TNF-alpha) is the first FDA-approved biologic for HS, dosed at 160 mg at week 0, 80 mg at week 2, and 40 mg weekly thereafter (a higher dose than used for psoriasis). It achieves HiSCR50 (50 percent or greater reduction in abscess and nodule count) in approximately 50 to 60 percent of patients at 12 weeks, with monitoring for TB and hepatitis B reactivation. Secukinumab (anti-IL-17A) was FDA-approved for HS in 2023 at 300 mg every two weeks after loading and is effective in moderate-to-severe disease. Bimekizumab (anti-IL-17A/F) has positive phase III data for HS. Infliximab (anti-TNF-alpha) is used off-label at 5 mg/kg IV at 0, 2, and 6 weeks then every 8 weeks and may be more effective than adalimumab in severe HS.

Hormonal Therapies

Options include combined oral contraceptives with anti-androgenic progestin (cyproterone acetate), spironolactone at 50 to 200 mg/day (which may benefit some female patients), and finasteride (with limited evidence from case reports).

Other Systemic Agents

Metformin may help HS independent of diabetes when metabolic syndrome is present. Cyclosporine serves as bridging therapy. Colchicine has anti-neutrophilic properties with anecdotal benefit. Oral retinoids (acitretin, isotretinoin) provide modest benefit, and isotretinoin is notably less effective in HS than in acne.

Surgical Management

Surgery is a critical component of HS management, as medical therapy alone is often insufficient for advanced disease. Incision and drainage provides temporary relief only, with a high recurrence rate. Deroofing involves removing the sinus tract roof with marsupialization and is effective for limited sinus tracts. Wide local excision is the gold standard for Hurley II and III, excising all affected tissue down to fascia with healing by secondary intention or flap/graft closure; it has the lowest recurrence rate but significant morbidity. Laser therapy using CO2 laser for sinus tract excision/ablation and Nd:YAG laser for hair removal and inflammation reduction are additional options.

Pain Management

Pain is often undertreated in HS, yet chronic pain is a major driver of disability. NSAIDs and acetaminophen are first-line, with intralesional triamcinolone (10 mg/mL) effective for acute nodules. Lidocaine patches provide localized relief. Chronic opioid use should be avoided when possible, with referral to pain management when needed.

Controversy: Inflammatory vs. Follicular Keratinization Disorder

The historical view of HS as an infection of apocrine glands has been disproven. The current debate centers on whether HS is primarily a disorder of follicular keratinization (analogous to acne) or primarily an inflammatory and immune-mediated disease. Evidence supports both perspectives: follicular occlusion initiates disease, but immune dysregulation drives chronicity and tissue destruction. This has treatment implications, as the keratinization view favors retinoids and deroofing while the inflammatory view favors biologics and immunosuppression. The reality is likely a continuum requiring a multimodal approach.

<image>Clinical photograph panel of hidradenitis suppurativa showing: (A) early Hurley stage I with inflammatory nodules in the axilla, (B) Hurley stage II with draining sinus tracts and scarring in the inguinal fold, (C) Hurley stage III with diffuse interconnected sinus tracts, abscesses, and severe scarring in the axillary and inframammary regions, (D) close-up of double-ended (bridged) comedones, which are pathognomonic for HS. Show on diverse skin tones.</image>

<image>Pathogenesis diagram of hidradenitis suppurativa showing the sequence: follicular hyperkeratosis and plugging leading to follicular rupture, release of keratin and bacteria into dermis, triggering innate immune activation (neutrophils, TNF-alpha, IL-1beta, IL-17), formation of abscesses and sinus tracts, and eventual fibrosis and scarring. Map therapeutic targets: adalimumab (anti-TNF), secukinumab (anti-IL-17), antibiotics (anti-inflammatory), and surgery (sinus tract removal).</image>

<image>Treatment algorithm for hidradenitis suppurativa organized by Hurley stage: Stage I (topical clindamycin, tetracyclines, lifestyle modification), Stage II (clindamycin-rifampin, adalimumab or secukinumab, deroofing), Stage III (biologic therapy plus wide local excision). Include lifestyle modifications and pain management at every stage.</image>

Key Clinical Pearls

The average diagnostic delay for HS is 7 to 10 years, so maintaining a high index of suspicion for recurrent "boils" in intertriginous areas is critical. Double-ended comedones and sinus tracts are pathognomonic, and incision and drainage alone has near-100 percent recurrence and should not be the definitive treatment. Adalimumab dosing for HS (40 mg weekly) is higher than for psoriasis (40 mg every two weeks), and underdosing is a common cause of treatment failure. Smoking cessation is the single most impactful modifiable risk factor and should be counseled at every visit. Wound cultures are generally not helpful because HS is not a primary infection; routine antibiotics in HS target inflammation, not bacteria. All HS patients should be screened for depression, metabolic syndrome, and inflammatory bowel disease given the high comorbidity rates.

References

• Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa. J Am Acad Dermatol. 2019;81(1):76-90.
• Kimball AB, et al. Adalimumab for the treatment of moderate to severe hidradenitis suppurativa: results of PIONEER I and II. Ann Intern Med. 2012;157(12):846-855.
• Sabat R, Jemec GBE, Matusiak L, et al. Hidradenitis suppurativa. Nat Rev Dis Primers. 2020;6(1):18.
• Kimball AB, et al. Secukinumab in moderate-to-severe hidradenitis suppurativa (SUNSHINE and SUNRISE). Lancet. 2023;401(10378):747-761.

Read this lecture as Markdown