Hidradenitis suppurativa: Pathogenesis, clinical features, and diagnosis

INTRODUCTION — Hidradenitis suppurativa (HS; from the Greek hidros = sweat, and aden = glands) is a chronic inflammatory skin condition that is also known as acne inversa and, historically, as Verneuil's disease [1,2]. Although the name "hidradenitis suppurativa" implies a suppurative disorder that primarily involves sweat glands, increasing knowledge of the pathogenesis of the condition has led to the prevailing theory that HS is a chronic follicular occlusive disease involving the follicular portion of folliculopilosebaceous units (FPSUs).

The primary sites of involvement for HS are the intertriginous skin areas of the axillary, groin, perianal, perineal, and inframammary regions, though HS can occur in any skin area that contains FPSUs. The clinical manifestations vary, ranging from recurrent inflamed nodules and abscesses to draining skin tunnels (previously referred to as sinus tracts or fistulae) and bands of severe scar formation. The associated pain, malodor, drainage, and disfigurement that accompany HS contribute to a profound psychosocial impact of the disease on many patients [3].

Early HS lesions may mimic other disorders; misdiagnosis of HS as recurrent furunculosis or "boils" is common. Prompt recognition of the correct diagnosis is important. An early and accurate diagnosis facilitates the initiation of a treatment plan aimed at minimizing the risk of progression to disabling, severe disease.

The pathogenesis, clinical manifestations, and diagnosis of HS will be discussed here. Treatment is reviewed separately. (See "Hidradenitis suppurativa: Management" and "Surgical management of hidradenitis suppurativa".)

EPIDEMIOLOGY — Estimates of the prevalence of HS have varied, ranging from less than 1 percent to 4 percent [4,5]. Prevalence in the United Kingdom from a study using the nationwide Clinical Practice Research Datalink (CPRD), which also identified undiagnosed people with HS, was 0.77 percent [6]. Another population-based study that utilized data from a database of more than 48 million patients in the United States found an incidence of 11.4 per 100,000 population [7].

The onset of symptoms typically occurs between puberty and age 40, with usual onset in the second or third decade of life. Studies from North America and Europe suggest females are more likely to develop HS than males [7-9]. In a French series of 618 consecutive patients with HS, the sex ratio was 3.6:1 [8]. In addition, the large population-based study in the United States found that the incidence of HS was twice as high among women than among men; the highest age-specific incidence was among patients between the ages of 18 and 29 years [7]. The sex ratio may differ in other world regions; in a population-based study from Korea, the female-to-male ratio was 1:1.6 [10].

Epidemiologic data for children and adolescents are more limited than for adults. A cross-sectional analysis of more than 55 million patients in the United States found an overall prevalence of 0.028 percent in individuals under the age of 18 years and, similar to other studies, found a female predominance (sex ratio of 3.8:1) [11]. Of the individuals in this age group with HS, 97 percent were 10 years old or older [11]. In an international, multicenter, retrospective study of 481 pediatric patients with a diagnosis of HS, the mean age of disease onset was 12.5 years [9].

Race or ethnicity may influence susceptibility to HS. In the United States, the prevalence may be disproportionally high among African Americans [11,12].

PATHOGENESIS — The pathogenesis of HS is not fully understood; however, new evidence is emerging [13]. As opposed to early theories that implicated apocrine glands as the primary contributors to HS, most authors now support follicle-centered theories for the pathogenesis of HS. Follicular occlusion, follicular rupture, and an associated immune response appear to be important events in the development of the clinical manifestations of HS. The basic principles that underlie follicle-centered theories are reviewed below.

Mechanism — Follicular occlusion is the most likely event responsible for the initial development of HS lesions. Follicular occlusion appears to result from ductal keratinocyte proliferation (follicular epithelial hyperplasia of the ductal isthmus), causing follicular hyperkeratosis and plugging [14]. Proposed contributors have included the effects of hormones and nicotine on the follicular epithelium [14-16] (see 'Associated factors' below). It may be that that anoxia within the follicular duct secondary to follicular epithelial hyperplasia contributes to the disruption of normal terminal differentiation of follicular keratinocytes, leading to follicular plugging [17].

As a consequence of the failure of terminal differentiation, the keratinocytes do not separate and the follicular duct expands. Mechanical stress (pressure, friction, or shear) on skin, particularly in intertriginous areas, results in leakage of molecular-sized antigens that stimulate the adaptive immune system as well as stimuli for the innate immune system. Subsequent cytokine release leads to activation of keratinocytes that release their own proinflammatory mediators [18]. Perifolliculitis is detected at this stage [14,19]. If sufficient repair of the compromised follicular duct does not occur, the follicular duct may eventually rupture, leading to the release of macro follicular contents (eg, keratin fragments derived from corneocytes and hair, sebum products, bacteria), and the further recruitment of inflammatory cells [18]. Over time, the initial acute inflammatory response evolves into chronic foreign body-type granulomatous inflammation.

Defects in the support of the follicular wall may predispose individuals with HS to follicular rupture. A study that compared skin specimens from patients with HS to specimens from normal controls found that axillary specimens from patients with HS demonstrated a marked reduction in periodic acid-Schiff (PAS) staining of the basement membrane zone at the junction between the sebaceous gland and the follicle (sebofollicular junction) [20]. In contrast, continuous PAS staining was noted along the basement membrane zone of the folliculopilosebaceous unit (FPSU) in specimens from patients in the control group.

Follicular rupture may promote the formation of skin tunnels through the release of stem cells from the bulge area of the hair follicle that subsequently proliferate and form epithelial strands [18,20,21]. Established skin tunnels eventually open onto the skin surface and become chronically inflamed.

It is likely that dysregulation of the immune system is a contributor to HS etiology [22]. Although activation of the innate and adaptive immune systems is an expected response to the release of antigens and other proinflammatory stimuli from a ruptured follicular duct, a role for immune system dysregulation in HS is suggested by similarities between HS and Crohn disease, an inflammatory bowel disorder hypothesized to involve dysregulation of the innate and adaptive immune systems. HS and Crohn disease share histologic features, and there is a well-established epidemiologic association between the two conditions [23,24]. Moreover, the inflammatory processes of both diseases may respond to anti-tumor necrosis factor (TNF)-alpha therapies [18,25-28].

Further studies are necessary to explore whether immune dysregulation is a primary contributor to the initiation of HS. Interleukin (IL) 17 and the caspase-1-associated cytokines IL-1-beta and IL-18 may be involved in the disease pathogenesis [29]. Increased understanding of the role of the immune system may aid in the discovery of new treatments. The complement system has been implicated in HS pathogenesis, with increased levels of the C3a and C5a components [30]. Keratinocytes are also involved in the inflammatory cascade, with increased production of antimicrobial peptides, including human beta-defensin 2, psoriasin (S100A7), and calgranulin (S100A8) [31]. B cells and plasma cells may also play a role, with associated increases in immunoglobulin production and complement activation [32].

Associated factors — Genetic susceptibility, mechanical stresses on the skin, obesity, smoking, diet, and hormonal factors are repeatedly cited as factors that may be associated with the development or exacerbation of HS. The relationships between these factors and HS are discussed below:

●Genetics – Genetic susceptibility appears to be an important contributor to HS [33,34]. It is estimated that approximately 40 percent of patients with HS have an affected first-degree family member [9,35]. Compared with other HS patients, patients with early-onset HS (onset prior to age 13) may be more likely to have a family history of the disease [36]

Familial occurrences of HS resembling an autosomal dominant-like inheritance pattern have been documented (MIM #142690).

The finding of mutations in genes encoding the components of gamma-secretase, an intramembranous protease complex that cleaves multiple transmembrane proteins, in Han Chinese kindreds with HS may contribute to further understanding of the disease [37,38]. Gamma-secretase cleaves the intracellular domain of Notch, a transmembrane receptor protein involved in keratinocyte differentiation. However, pathogenic gamma-secretase mutations are present in only a small minority of patients. In one series of 48 European patients, pathogenic gamma-secretase mutations were found in only two individuals, neither of whom had a family history of HS [39]. Nevertheless, familial and mouse studies support the theory that inherited or acquired impairment of Notch signaling may play a key role in disease development [40]. The gamma-secretase mutations that have been reported in patients with HS include mutations in genes for presenilin-1 (PSEN1), presenilin enhancer-2 (PSENEN), and nicastrin (NCSTN) [41-45]. TNF gene polymorphisms also may play a role in susceptibility to HS [46].

●Mechanical stress – Increased mechanical stress (pressure, friction, shear) on intertriginous skin and other areas (eg, beltlines, brassiere straps, and other sites of clothing friction) likely contributes to the localization of HS. Mechanical stress on skin has been postulated to contribute to HS via increasing the chance of follicular occlusion and follicular rupture [18,47].

●Obesity – An elevated body mass index (BMI) is more common in patients with HS than in the general population; however, the disease is not limited to individuals who are overweight or obese. In a case-control study of 302 patients with HS and 906 controls, a BMI ≥30 was present in 21 percent of patients with HS versus only 9 percent of controls and a BMI between 25 and 29 was present in 22 percent of HS patients versus 17 percent of controls [48]. In an international, multicenter, retrospective study of pediatric patients with HS, obesity or overweight status were documented in most patients (65 and 14 percent of 406 children, respectively) [9].

Several studies have found a positive correlation between increasing BMI and disease severity [49-54].

As in acne vulgaris, hormonal changes associated with obesity may result in relative androgen excess and are proposed to increase follicular plugging [55]. Moreover, the comparatively larger size of intertriginous areas, local skin irritation from sweat retention, narrowed follicular orifices secondary to intrafollicular keratin hydration during skin occlusion, and obesity-related increases in levels of circulating proinflammatory cytokines may contribute [18,47,56]; however, these factors are also present in obese individuals without HS.

●Smoking – There is a strong relationship between smoking and HS, with higher rates of current and previous smoking in people with HS compared with controls [48,49,54,57,58]. An American retrospective cohort study that included approximately four million tobacco smokers and approximately eight million nonsmokers found the overall incidence of HS higher among tobacco smokers (0.2 versus 0.1 percent) [59]. In a French case-control study of 302 clinically assessed patients with HS and 906 controls, 76 percent of the patients with HS versus 25 percent of the controls were current smokers [48]. This particular study did not find a dose-response association between smoking and severity of disease; however, other studies have found more severe disease in smokers than nonsmokers [49,58]. In a study in which the modified Hidradenitis Suppurativa Score was used to assess disease severity in 115 patients with HS, the median score was significantly higher among the smokers than among the nonsmokers [49]. Stimulatory effects of nicotine and other components of tobacco on follicular occlusion, neutrophil chemotaxis, TNF-alpha production by keratinocytes, and Th17 cells have been cited as potential contributing factors [25,60].

●Hormones – An impact of hormones on HS is suggested by observations of the rarity of HS in prepubertal children and improvement in HS during treatment with antiandrogenic agents [61-65]. In addition, some women experience perimenstrual flares, and in this subgroup, amelioration of disease severity during pregnancy was found in a retrospective survey [66]. Hyperandrogenemia seems unlikely to be a contributor to HS based upon a series of 66 women with HS that found no evidence of biochemical hyperandrogenism when compared with controls matched for age, weight, and hirsutism [67].

Additional studies are necessary to determine the role of hormones in HS.

●Bacteria – The role of bacteria in HS is controversial. Cultures from early, unruptured HS lesions are usually sterile. Older and ruptured lesions and skin tunnels may demonstrate a wide variety of bacteria (eg, staphylococci, streptococci, Gram-negative rods, and anaerobic bacteria). Coagulase-negative staphylococci are frequently present [68,69]. Positive cultures may represent contaminants from normal skin flora or secondary infection. One theory suggests that bacteria may contribute to HS by promoting an inflammatory response [27], and a role for a bacterial biofilm in the persistence of the inflammatory process of HS has been proposed [70,71]. In addition, a case-control study found significant differences in the microbiome of lesional and nonlesional skin in 30 patients with HS compared with 24 healthy controls [72].

●Drugs – In support of a contribution of androgens to HS, there are reports of female patients in whom treatment with oral contraceptives containing androgenic progestins, intramuscular medroxyprogesterone acetate, or levonorgestrel in an intrauterine device may precipitate or worsen HS [73]. Lithium therapy has been linked to HS in a small number of patients [74,75]. Paradoxically, HS has been reported as an adverse effect of anti-TNF-alpha therapies and other biologic treatments given for other chronic inflammatory diseases [76].

CLINICAL MANIFESTATIONS — HS predominantly occurs in intertriginous areas. HS can affect the axillae (most common site), inguinal area, inner thighs, perianal and perineal areas, mammary and inframammary regions, buttocks, pubic region, scrotum, vulva, trunk, and, occasionally, the scalp and retroauricular areas (picture 1A-D) [77]. Early-onset HS may be associated with a greater risk for widespread disease [36].

Sex influences the distribution of HS. Primary sites of involvement in females are the groin or upper inner thigh, axilla, chest (including breast and inframammary regions), and the buttocks or gluteal clefts [58,78]. In males, primary sites of involvement are the groin or thigh, axilla, perineal or perianal regions, and buttocks or gluteal cleft [52,58,78]. Regardless of sex, involvement in nonintertriginous skin is common, particularly at sites of skin compression and friction. Beltlines, waistbands, abdominal folds, and brassiere straps or bands are common locations.

Given the heterogeneity in clinical presentation within the HS phenotype, attempts have been made to generate disease subclassifications [8]. However, these models have not been related to response to treatment.

The primary, visible lesions of HS are inflammatory nodules and abscesses. Skin tunnel formation, clusters of open comedones (tombstone comedones), and scarring are the result of recurrent or persistent disease:

●Inflammatory nodules – Most frequently, the first lesion is a solitary, painful, deep-seated inflamed nodule (0.5 to 2 cm in diameter), often in an intertriginous area. Onset can be insidious, with occasional solitary, painful nodules that can last for several days to months. Recurrent episodes of nodule formation may occur in the exact same location or in the same skin region.

The diagnosis of HS is frequently missed at this stage [79]. In a survey including 517 patients in 24 countries, diagnostic delay on average was seven years [79]. Diagnostic delay was also common in an international, multicenter, retrospective study of 481 pediatric patients with HS; the median disease duration at the time of diagnosis of HS was 2.5 years [9].

The inflammatory nodules are commonly misdiagnosed as "boils" or furunculosis. Unlike furuncles, primary HS lesions are deep-seated and round-topped, and lack the pointed appearance of furuncles [80]. The nodules are painful, and depending on the location and size of lesions, patients may be unable to raise their arms, walk, or sit without pain [81].

After a variable period of time, the nodule may progress to form an abscess that may open to the skin surface spontaneously (or as a result of manipulation by the patient), yielding purulent or serosanguineous drainage (picture 1E). Pain often improves after drainage. Other nodules regress without draining, usually within one to several weeks [35]. In a questionnaire-based study of 110 patients with HS, patients reported that the average duration of a single painful lesion was seven days, although approximately 60 percent of patients described at least one persistent painful nodule that failed to subside completely [35]. The number and frequency of nodules varies widely among patients. Patients in this study reported a median of two nodules per month (range 1 per year to 30 per month).

●Skin tunnels – Skin tunnels, previously known as sinus tracts or fistulae, are typical findings in HS that persist for months or years and contribute to symptomatology (picture 2) [82]. The development of multiple recurrent nodules within a limited area may predispose to the formation of intercommunicating tunnels. Patients with skin tunnels often experience intermittent release of blood-stained, seropurulent, malodorous discharge. Skin tunnels are not always palpable, and in some cases, a tunnel becomes apparent only when a substance (eg, local anesthetic) injected into a lesion appears at a site distant from the site of injection or when visualized by ultrasound. Ulceration may accompany skin tunnel formation. Occasionally, pyogenic granulomas develop at skin tunnel openings [83]. (See "Pyogenic granuloma (lobular capillary hemangioma)".)

●Comedones – Open comedones often appear in long-standing HS, commonly as double-headed or multi-headed open comedones [84]. These structures are often described as "tombstone comedones" because they reflect end stage damage to the folliculopilosebaceous unit (FPSU) with associated loss of the sebaceous gland and hair [85].

Closed comedones may also develop in HS. The closed comedones of HS are essentially tiny cysts that result from continued keratin production by the follicular epithelium lining the residual stub of the follicle above the destroyed sebofollicular junction. Closed comedones are not primary lesions and therefore, are not present in early cases of HS. The presence of comedones is not required for the diagnosis of HS.

●Scarring – The appearance of healed areas ranges from individual, pitted, acneiform scars after resolution of small nodules to dense, fibrotic, rope-like bands or indurated, thick, scarred plaques involving the whole affected area. Scars may also be atrophic (particularly on the trunk) or keloidal, and scarring on the buttocks sometimes manifests as multiple pitted scars. In patients with active disease, scarring is accompanied by inflammatory nodules and draining skin tunnels.

In areas of lax flexural skin, such as the axilla, scarring can result in thick, linear, rope-like bands. Severe scarring in the axilla may result in reduced mobility of the arm or lymphatic obstruction leading to lymphedema. Groin involvement may lead to lymphedema of the pubis or the entire vulvar area in women or penile and/or scrotal lymphedema in men [86].

HS has a significant impact on patient quality of life [3,87]. Pain is a major cause of disutility, along with scarring, the unpredictable discharge, the necessary dressings, and the accompanying odor, which are embarrassing and humiliating [88]. As a result, patients may experience social isolation, depression, failed relationships, and loss of (or failure to gain) employment [89,90]. An increased suicide risk has also been reported among patients with HS [91]. Prodromal symptoms may also be experienced prior to disease flares, including fatigue and localized pruritus or paresthesias [92].

CLINICAL STAGING — The Hurley clinical staging system frequently is used to divide patients with HS into three disease severity groups [93,94]:

●Stage I – Abscess formation (single or multiple) without skin tunnels or cicatrization/scarring (picture 3)

●Stage II – Recurrent abscesses with skin tunnels and scarring, single or multiple widely separated lesions (picture 4)

●Stage III – Diffuse or almost diffuse involvement, or multiple interconnected skin tunnels and abscesses across the entire area (picture 8B)

The majority of patients with HS exhibit stage I disease. In a French series of 302 consecutive patients with HS, stage I, II, and III disease were observed in 68, 28, and 4 percent of patients, respectively [50].

ASSOCIATED DISORDERS AND SYNDROMES — A variety of disorders have been linked to HS:

●Emerging data indicate that patients with HS may have increased incidence of (and risk for) certain diseases, such as metabolic syndrome and related comorbidities, a constellation of metabolic and secondary disorders including diabetes, obesity, insulin resistance, dyslipidemia, hyperglycemia, hypertension, myocardial infarction, and cerebrovascular accidents [53,95-101]. In combination with higher rates of smoking in HS, these factors contribute to a higher risk of cardiovascular-associated death; in a population-based cohort study of over 35,000 Danish individuals (including approximately 6000 patients with HS), the risk of this outcome among individuals with HS was nearly double that of a control group [102].

Moreover, a United States cross-sectional analysis of 5000 patients with HS, 14,000 patients with psoriasis, and 1.7 million controls found a higher overall comorbidity burden among patients with HS compared with patients with psoriasis and the control group [103].

●Multiple studies suggest an association between HS and inflammatory bowel disease (IBD), particularly Crohn disease [6,24,27,104-106]. A systematic review and meta-analysis of case-control, cross-sectional, and cohort studies assessing the relationship between HS and IBD found increased odds of both Crohn disease (pooled odds ratio [OR] 2.12, 95% CI 1.46-3.08) and ulcerative colitis (pooled OR 1.51, 95% CI 1.25-1.82) among study participants with HS [107]. In addition, a United States population-based cohort study of 679 patients with Crohn disease or ulcerative colitis found these patients more likely to develop HS than the general population (incidence rate ratio 8.9, 95% CI 3.6-17.5) [105]. Data from observational studies suggest patients with IBD and HS tend to be younger than patients with IBD alone and are more likely to be smokers and have other comorbid conditions (eg, obesity, diabetes mellitus) [108,109]. (See "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults" and "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults".)

Shared pathogenic mechanisms have been proposed as contributors to an association between HS and IBD [107]. Certain genes have been associated with the presence of both conditions, including SULT1B1 and SULT1E1 [110]. Immune dysregulation and altered microbiota are also postulated to contribute to both HS and IBD [72,111]. (See 'Pathogenesis' above and "Immune and microbial mechanisms in the pathogenesis of inflammatory bowel disease".)

●Acne vulgaris is a common condition that occurs with increased frequency in HS [112]. Acne vulgaris can be particularly severe and difficult to treat in patients with HS [47]. (See "Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris".)

●HS is a component of the follicular occlusion tetrad. The follicular occlusion tetrad consists of four diagnoses: HS, acne conglobata, dissecting cellulitis of the scalp, and pilonidal sinus. These four conditions are considered to share follicular occlusion as a key pathogenic event and may appear in conjunction with one another in individual patients [113-115]. (See "Evaluation and diagnosis of hair loss", section on 'Cicatricial alopecia' and "Pilonidal disease" and "Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris", section on 'Acne conglobata'.)

●There are isolated reports of patients in whom HS has appeared to develop within a syndrome-like presentation consisting of several inflammatory diseases. PAPASH syndrome (pyogenic arthritis, pyoderma gangrenosum, acne, and suppurative hidradenitis) has been described in an adolescent in whom a mutation in the PSTPIP1 gene was detected [116]. The term PASH syndrome has been used to refer to patients with pyoderma gangrenosum, acne, and suppurative hidradenitis [117-119]. Genetic analysis has revealed a PSTPIP1 mutation in a patient with PASH syndrome [120]; however, in two other patients with PASH syndrome PSTPIP1 mutations were absent [117].

Other conditions, including inflammatory, neoplastic, and genetic disorders have been associated with HS [121]. A table listing examples of associated disorders is provided (table 1).

Patients with HS may benefit from a multidisciplinary approach to aid in prevention, detection, and management of comorbid disease. (See "Hidradenitis suppurativa: Management", section on 'Assessment and management of comorbidities'.)

HISTOPATHOLOGY — The histopathologic findings in HS vary according to the stage of the lesion (picture 5). Common early features include follicular hyperkeratosis, follicular plugging, follicular dilation, and lymphocytic perifolliculitis [14]. Biopsies of established areas of disease can demonstrate additional features, including psoriasiform hyperplasia of the interfollicular epithelium [14] or a dense, mixed inflammatory infiltrate involving the lower half of the dermis and subcutis [122]. In addition, chronic abscesses, skin tunnels lined by stratified squamous epithelium, and granulation tissue with or without foreign body giant cells may be present. Destruction of folliculopilosebaceous units (FPSUs), fibrosis, and incidental peri-apocrine and perieccrine inflammation also may be evident [56,83].

DIAGNOSIS — The diagnosis of HS is made from the patient history and recognition of characteristic clinical manifestations [80].

History and physical examination — The three main clinical features that support a diagnosis of HS are as follows:

●Typical lesions (multiple deep-seated inflamed nodules, tombstone comedones, skin tunnels, abscesses and/or fibrotic scars)

●Typical locations (in particular, axillae, groin, inframammary areas; often bilateral distribution)

●Relapses and chronicity

A diagnosis of HS is straightforward in patients who demonstrate the constellation of recurrent inflammatory nodules, skin tunnels, and hypertrophic scarring in intertriginous areas. However, the location, type, number, and severity of typical lesions vary widely among patients with HS. Thus, clinicians should maintain high suspicion for the diagnosis for all patients who present with recurrent inflammatory nodules, particularly when intertriginous involvement is present. Recognition of this feature and the characteristic patterns of scarring may allow for treatment of the disease at early stages.

The patient history can be a valuable tool in the diagnosis of HS. Onset in adolescence or young adulthood, a history of recurrent or persistent disease, or a family history of HS offer support for a diagnosis. Patients with atypical features also should be questioned about gastrointestinal symptoms to identify patients who may benefit from an evaluation for Crohn disease. (See 'Differential diagnosis' below and "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults".)

A full skin examination should be performed in patients with suspected HS. This allows for an assessment of the extent and severity of involvement and the recognition of features that are more or less consistent with this disease.

Laboratory studies — A skin biopsy usually is not necessary for diagnosis. However, in cases in which the diagnosis is uncertain, a biopsy can be useful for excluding other disorders. A biopsy should also be performed if features suggestive of squamous cell carcinoma (SCC) are present. SCC may appear as a slowly growing, firm, nonfluctuant and nondraining mass that is superficially eroded or ulcerated and is located in an area of chronic HS, particularly in the perianal region.

Routine bacterial cultures are not indicated [80,94]. Cultures are reserved for cases in which the clinical findings are suggestive of a primary infectious disorder rather than HS or if there is clinical evidence of secondary cellulitis [80,94]. No serologic studies confirm a diagnosis of HS.

Imaging — Radiologic imaging is not necessary for the diagnosis of HS. However, ultrasound may be useful for preoperative assessment of the subclinical extent of disease, particularly to identify skin tunnels [80,123-125]. Magnetic resonance imaging may be helpful for delineating extensive anogenital disease [126].

DIFFERENTIAL DIAGNOSIS — A few diseases produce inflamed nodules, recurrent abscesses, or skin tunnels that may be mistaken for HS. The patient history and clinical findings are usually sufficient for distinguishing HS from other diseases:

●Follicular pyodermas (folliculitis, furuncles, carbuncles) – Folliculitis, furuncles ("boils"), and carbuncles are infections arising from hair follicles. Infectious folliculitis usually presents with multiple, superficial, inflammatory papules, each surrounding a hair follicle, with or without an overlying pustule. Infection that progresses to a nodular abscess is termed a furuncle. Carbuncles occur when several inflamed follicles converge into a single inflammatory mass with purulent drainage emanating from multiple areas. Unlike HS, which typically exhibits a chronic and recurrent course, follicular pyodermas are transient lesions that usually respond rapidly to appropriate antibiotic therapy. In addition, the follicular pyodermas do not cause the comedones, persistent skin tunnels, and hypertrophic scarring observed in HS. (See "Cellulitis and skin abscess: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

●Acne vulgaris – Like HS, acne vulgaris demonstrates follicular hyperkeratinization leading to comedones, inflammatory nodules, and scarring. Although there is some overlap in the distribution of the two diseases, acne vulgaris primarily occurs on the face, upper chest, and back, whereas HS primarily involves the axillae, groin, buttocks, and inframammary folds. In addition, HS typically causes more deep-seated lesions, and several of its consequences, including skin tunnels and "rope-like" scars, provide characteristic clinical features. (See "Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris".)

●Intergluteal pilonidal disease – Intergluteal pilonidal disease manifests as a cavity, pit, or skin tunnel in the area of the natal cleft that may become inflamed, swollen, and painful with associated mucoid, purulent, or bloody drainage. Along with HS, acne conglobata, and dissecting cellulitis of the scalp, pilonidal disease is a member of the follicular occlusion tetrad. Thus, pilonidal disease and HS may occur in the same patient, and it is likely that pilonidal disease is a phenotypic variant of HS [127]. (See "Pilonidal disease".)

●Crohn disease – Perianal and vulvar manifestations of Crohn disease include abscesses, rectoperineal and rectovaginal fistulae, skin tunnels, fenestrations, and scarring, as well as classic "knife-cut" ulcers in the inguinal, genitocrural, or interlabial folds (picture 6A-B). A history of gastrointestinal Crohn disease supports this diagnosis; however, the simultaneous development of Crohn disease and HS has been reported [26,27]. (See "Perianal Crohn disease".)

●Granuloma inguinale – Granuloma inguinale (donovanosis) is a sexually transmitted infection caused by Klebsiella granulomatis that usually occurs on the vulva, penis, scrotum, glans, inguinal folds, or perianal skin (picture 7) [128]. Lesions usually present as succulent red ulcers with granulation tissue that bleeds easily and with a foul odor. The presence of an enlarging ulcer with an undermined border suggests this diagnosis over HS. The causative organism cannot be cultured. Diagnosis requires visualization of Donovan bodies on tissue crush preparation or biopsy.

Examples of other disorders that may enter the differential diagnosis of HS include actinomycosis, anal fistula, cat-scratch disease, cellulitis, inflamed epidermoid cyst, ischiorectal abscess, lymphogranuloma venereum, nocardiosis, noduloulcerative syphilis, perirectal abscess, tuberculous abscess, and tularemia [47].

COMPLICATIONS — Long-standing, poorly controlled HS may lead to significant physical and emotional consequences. Complications include:

●Strictures and contractures [47]

●Lymphatic obstruction, lymphedema of limbs and genitalia

●Malaise, depression, and suicide

●Long-term effects of chronic inflammation including anemia, hypergammaglobulinemia, hypoproteinemia, and amyloidosis

●Infectious complications (eg, lumbosacral epidural abscess, sacral bacterial osteomyelitis) [47]

●Arthritis [129]

●Squamous cell carcinoma (SCC)

●Anemia [130]

Fistulae into the urethra, bladder, rectum, and peritoneum are a reported complication of HS [77]. However, confusion with Crohn disease or coexistence of HS with Crohn disease may be responsible for some of these reports.

SCC arising in HS is rare but has been reported in multiple case reports and appears to be more common in males with longstanding perianal HS [131-137]. A 2011 review of published cases of cutaneous SCC arising in HS found that SCC primarily occurred 20 to 30 years after the onset of HS (range 2 to 50 years) [136]. Approximately one-half of these patients died of metastatic disease [136]. Human papilloma virus infection may be an important contributing factor to the development of SCC in lesions of HS [135].

Limited data suggest that AA amyloidosis, a condition associated with chronic inflammatory disease, may be a rare complication [138,139]. (See "Overview of amyloidosis", section on 'AA amyloidosis'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hidradenitis suppurativa".)

SUMMARY AND RECOMMENDATIONS

●Pathogenesis – Hidradenitis suppurativa (HS) refers to a painful, chronic, suppurative process involving the skin and subcutaneous tissue (picture 1A-D). The clinical manifestations of HS appear to result from infra-infundibular follicular occlusion and secondary rupture of the sebofollicular junction of folliculopilosebaceous units (FPSUs), resulting in an inflammatory cascade. HS is neither contagious nor due to poor hygiene. (See 'Pathogenesis' above.)

●Clinical manifestations:

•Distribution – HS primarily occurs on intertriginous skin. The axilla is the most common site; the inguinal area, inner thighs, perineal and perianal areas, mammary and inframammary skin, and buttocks are additional common sites for involvement. Nonintertriginous skin involvement also can occur. (See 'Clinical manifestations' above.)

•Skin lesions – Initial presentation of HS typically involves recurrent, painful, and inflamed nodules (picture 1A, 1E). The nodules may rupture, discharging purulent, sometimes malodorous material. Persistent disease leads to coalescence of nodules into inflammatory plaques, epithelialized skin tunnels, end-stage "tombstone" comedones, and characteristic "rope-like" scarring (picture 8A-B). (See 'Clinical manifestations' above.)

●Diagnosis – Diagnosis of HS is based upon the recognition of characteristic clinical manifestations, including typical lesions in intertriginous sites occurring on a chronic, recurrent basis. A skin biopsy usually is not necessary for diagnosis. Routine performance of bacterial cultures is not indicated. (See 'Diagnosis' above.)

The diagnosis of early-stage HS is often missed. The clinician should have a high index of suspicion for the disease in individuals misdiagnosed with recurrent furuncles or "boils" in intertriginous areas after puberty. (See 'Diagnosis' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Lynette Margesson, MD, FRCPC, FAAD, who contributed to an earlier version of this topic review.

The UpToDate editorial staff acknowledges F. William Danby, MD, FRCPC, FAAD, now deceased, who contributed to an earlier version of this topic review.