The Pathophysiology of Hidradenitis Suppurativa

Sara M. James, MD, and Barbara B. Wilson, MD

Part 3 of this 4-part series discusses the pathophysiology of hidradenitis suppurativa. The first and second part discussed the clinical presentation of the disease and grading systems used to score its severity.


Research into the pathogenesis of hidradenitis suppurativa (HS) is ongoing. As suggested by its name, HS was originally believed to be a disorder of the apocrine (hidro-) glands (aden-), because disease occurs in apocrine gland-bearing areas. Apocrine glands, which are concentrated in the axillae, groin, buttocks, and inframammary regions, empty into the follicular canal above the entrance of the sebaceous gland. In comparison, eccrine sweat glands are present throughout the entire body and open directly onto the skin surface.1 However, research has disproved this theory and instead has demonstrated that occlusion of the terminal hair follicle is the key event in disease pathogenesis.6

HS is part of the follicular occlusion tetrad, which consists of HS, acne conglobata, pilonidal sinus, and dissecting cellulitis of the scalp. Patients may simultaneously present with 2 or more of the diseases within the tetrad.3 In HS, hyperplasia of the follicular epithelium causes follicular hyperkeratosis and follicle plugging. The follicle dilates and expands, releasing antigens that stimulate the immune system, causing a lymphocytic perifolliculitis.7 If repair does not occur, the follicle may rupture secondary to mechanical stress on the skin.3 Rupture of the follicle releases bacteria, sebum, and hair follicles into the connective tissue, which results in further inflammation.5

Infection. Bacterial infection does not cause the formation of HS lesions but is instead a secondary feature of the disease.5 Studies have failed to isolate a single dominant organism in cultures from the surfaces of the lesions. Cultures from deeper aspiration of lesions were frequently sterile (51% of cultures), with Staphylococcus epidermidis and Staphylococcus aureus otherwise most frequently isolated.1 Treatment with antibiotics does not cure the disease but often results in temporary improvement. Infection further increases inflammation, which contributes to scarring and sinus tract formation.

Genetics. HS can be familial or sporadic, with one-third of patients reporting a relative with the disease.2 A familial form of HS has been described with an autosomal dominant mode of transmission. Incomplete penetrance and hormonal factors explain why fewer than 50% of patients report having a first-degree relative with HS.8 A single culprit gene has not been identified.5

Patient characteristics. A clear association exists between obesity and HS.4 In one study, 69% of women were overweight (33% obese) and 77% of men were overweight (26% obese).9 Obesity is not causative but contributes to and exacerbates the disease through several mechanisms, including increased areas of friction between body folds, relative androgen excess, and irritation from sweat retention.1,3 In addition to obesity, HS patients have a higher prevalence of metabolic syndrome compared with controls, with increased rates of hypertriglyceridemia and insulin resistance.10

Smoking is also closely linked to HS. Smoking was significantly more likely in patients with HS (88.9%) than controls (46%).11 Within a subset of patients suffering from HS, disease was more severe in smokers compared with nonsmokers.5 It has been proposed that nicotine may release toxins into sweat and alter neutrophilic granulocytes and sweat gland activity, contributing to follicular plugging and inflammation.3

Literature reviews have revealed that a number of other diseases are commonly comorbid with HS, including inflammatory bowel disease (mainly Crohn disease), spondyloarthropathy, SCC, and genetic keratin disorders (eg, paronychia congenita).4 Crohn disease may present similarly to HS with perianal fistulae and sinus tracts. The diagnosis is particularly challenging if skin disease precedes gastrointestinal tract symptoms.

Hormones. There is conflicting evidence about the role of sex hormones in HS. An association with acne vulgaris and hirsutism suggests that androgens contribute to disease. Moreover, postpubertal onset, premenstrual flares, and improvement during pregnancy and after menopause argue for a role of hormones in disease pathogenesis. However, other studies have found normal androgen profiles in women with HS. Additionally, androgens principally affect the sebaceous glands, which have not been implicated in the development of HS.1 Further research is needed to clarify the role of hormones in HS.

The final part of this 4-part series will discuss methods of treatment.


  1. Slade DEM, Powell BW, Mortimer PS. Hidradenitis suppurativa: pathogenesis and management. Br J Plast Surg. 2003;56(5):451-461.
  2. Jemec GBE. Hidradenitis suppurativa. N Engl J Med. 2012;366(2):158-164.
  3. Alikhan A, Lynch PJ, Eisen DB: Hidradenitis suppurativa: a comprehensive review. J Am Acad Dermatol. 2009;60(4):539-561.
  4. Gill L, Williams M, Hamzavi I. Update on hidradenitis suppurativa: connecting the tracts. F1000Prime Rep. 2014;6:112. doi:10.12703/P6-112.
  5. Dessinioti C, Katsambas A, Antoniou C. Hidradenitis suppurrativa (acne inversa) as a systemic disease. Clin Dermatol. 2014;32(3):397-408.
  6. Yu CC-W, Cook MG. Hidradenitis suppurativa: a disease of follicular epithelium, rather than apocrine glands. Br J Dermatol. 1990;122(6):763-769.
  7. von Laffert M, Stadie V, Wohlrab J, Marsch WC. Hidradenitis suppurativa/acne inversa: bilocated epithelial hyperplasia with very different sequelae. Br J Dermatol. 2011;164(2):367-371.
  8. Von Der Werth JM, Williams HC, Raeburn JA. The clinical genetics of hidradenitis suppurativa revisited. Br J Dermatol. 2000;142(5):947-953.
  9. Harrison BJ, Read GF, Hughes LE. Endocrine basis for the clinical presentation of hidradenitis suppurativa. Br J Surg. 1988;75(10):972-975.
  10. Gold DA, Reeder VJ, Mahan MG, Hamzavi IH. The prevalence of metabolic syndrome in patients with hidradenitis suppurativa. J Am Acad Dermatol. 2014;70(4):699-703.
  11. König A, Lehmann C, Rompel R, Happle R. Cigarette smoking as a triggering factor of hidradenitis suppurativa. Dermatology. 1999;198(3):261-264.