Hidradenitis Suppurativa

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Practice Essentials

Hidradenitis suppurativa is a disorder of the terminal follicular epithelium in the apocrine gland–bearing skin. This condition is a chronic disabling disorder that relentlessly progresses, frequently causing keloids, contractures, and immobility.

Signs and symptoms

Hidradenitis suppurativa usually occurs in otherwise healthy individuals and, very rarely, it can begin before puberty. This disease is characterized by comedolike follicular occlusion, chronic relapsing inflammation, mucopurulent discharge, and progressive scarring.

The onset of hidradenitis suppurativa is insidious, with early symptoms of pruritus, erythema, and local hyperhidrosis. Later, the lesions become painful. Arthropathy associated with this disease may present with variable clinical features, ranging from asymmetric pauciarticular arthritis to a symmetric polyarthritis and/or polyarthralgia syndrome.[1, 2]

See Clinical Presentation for more detail.

Diagnosis

The diagnosis is primarily clinical, and biopsy is rarely required, especially in well-developed lesions.[3] The consensus approach indicates that 3 key elements are required to diagnose hidradenitis suppurativa: typical lesions, characteristic distribution, and recurrence.

Typical lesions, called primary lesions, include the following:

The axillae and the groin are the 2 areas most frequently affected. These regions are defined by anatomic borders and are called designated sites. Hidradenitis suppurativa is diagnosed if the patient has 1 of the following:

Other authors have based the diagnosis on a series of questions, as follows[6] :

Staging

Clinical staging of hidradenitis suppurativa has diagnostic value and is as follows:

Dynamic staging systems have been used for assessing differences in treatment effects.[7] Uniform outcome variables should take into account the known characteristics of hidradenitis suppurativa, including the following:[7]

Laboratory testing

The following laboratory tests may be helpful in the evaluation of hidradenitis suppurativa:

Other studies that may be helpful include the following:

Imaging studies

Ultrasonography of the hair follicles and dermal thickness in hidradenitis suppurativa patients may reveal abnormalities in the deep part of the follicle.

See Workup for more detail.

Management

Medical management is recommended in early stages, whereas surgery should be performed as early as possible after the formation of abscesses, fistulas, scars, and sinus tracts.[6]

Conservative treatment may include the following:

The following medications are used in the management of hidradenitis suppurativa:

Surgery

Surgery is most valuable in the chronic and recurrent stages of hidradenitis suppurativa.[6, 8] Wide surgical excision, with margins well beyond the clinical borders of activity, remains the most definitive surgical therapy.[6, 9, 10] However, although recurrence rates may be lower with more aggressive surgery, recurrences continue.[11, 12] After radical excision, the disease has been reported to recur in 33% of patients,[12] and it may be as high as 50% in the submammary region.[13]

More limited surgical intervention may include the following[14, 15, 16] :

Radiotherapy

Irradiation may be a treatment option for hidradenitis suppurativa.[17] X-ray or laser epilation[18] has the potential for temporary epilation. In addition, nonablative radiofrequency therapy can be used for patients with Harley stage I and II disease.[19]

See Treatment and Medication for more detail.

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Vulvar hidradenitis suppurativa.

Background

Hidradenitis suppurativa (HS) is a disorder of the terminal follicular epithelium in the apocrine gland–bearing skin. Hidradenitis suppurativa is characterized by comedolike follicular occlusion, chronic relapsing inflammation, mucopurulent discharge, and progressive scarring.

Pathophysiology

Hidradenitis suppurativa (HS) has traditionally been considered a disorder of the apocrine glands. Hidradenitis suppurativa was first described as a distinct entity in 1839, when Velpeau reported a patient with superficial abscess formation in the axillary, mammary, and perianal regions.[20] In 1854, Verneuil associated the suppurative process with the sweat glands, and the condition was given its current name. For many years, the condition was described as Verneuil disease, but it subsequently became known as hidradenitis suppurativa. Not having performed any histopathologic studies himself, Verneuil conceded that his conclusion was based purely on the characteristic distribution of the condition.[21]

In 1922, Schiefferdecker classified the sweat glands as eccrine and apocrine, and he subsequently localized hidradenitis suppurativa to the apocrine glands.[22] In 1939, Brunsting provided a detailed description of the histologic features of hidradenitis suppurativa. He observed the primary cellular reaction in the lumen of the apocrine glands and in the neighboring periglandular connective tissue. Detailing the clinical features of the disease, Brunsting highlighted its frequent association with acne. He noted that hidradenitis suppurativa, dissecting cellulitis of the scalp and the neck, and acne conglobata commonly occur in the same patient. He thought that the central pathogenetic event in all 3 conditions was a tendency for follicular hyperkeratinization with secondary bacterial infection.[23]

In 1956, Pillsbury et al combined acne conglobata, hidradenitis suppurativa, and dissecting cellulitis under the term follicular occlusion triad.[24] The only flaw in their concept was their focus on apocrine sweat gland involvement. In 1975, Plewig and Kligman added pilonidal sinus as another component to the ensemble, and they introduced the term acne tetrad.[25] Plewig and Kligman pointed out that hidradenitis suppurativa is a misnomer because of the lack of apocrine gland involvement, but they did not present a detailed explanation. In 1989, Plewig and Steger suggested the term acne inversa as an inclusive and accurate name for what was previously called the follicular occlusion triad, or follicular occlusion tetrad.[26] Eventually, hidradenitis suppurativa was accepted as an acneiform disorder that begins with follicular occlusion rather than an infection of the sweat glands.[27, 28, 29]

Hidradenitis suppurativa is actually a defect of the follicular epithelium; therefore, there is a movement towards calling the disease acne inversa instead of hidradenitis suppurativa. The term acne inversa links the pathogenesis to acne and reflects the fact that it is an expression of follicular occlusion in localizations inverse to acne vulgaris.[30]

Frequency

United States

In the United States, the prevalence of hidradenitis suppurativa appears to be 1-2% in the general population.

International

The prevalence of hidradenitis suppurativa appears to be 1% of the general population[29, 11] ; it was 4% in a group of young adults who were treated at a clinic for sexually transmitted diseases.[11] A 2008 study showed that the prevalence among persons aged 55 years and older was significantly lower than in younger age groups (0.5% vs 1.4%).[31]

Mortality/Morbidity

Hidradenitis suppurativa is a chronic disabling disorder that relentlessly progresses, frequently causing keloids, contractures, and immobility.

The disorder has significant socioeconomic effects as well. Jemec et al documented, in the Danish population, an average of 2.7 lost work days per year due to hidradenitis suppurativa (overall workdays lost was 7.5).[32] The general self-reported level of health, which is well correlated with more objective parameters of morbidity, was also significantly worse among hidradenitis suppurativa patients than healthy control subjects.[32] The mean Dermatology Life Quality Index (DLQI) score for hidradenitis suppurativa is higher than for previously studied skin diseases, indicating significant morbidity for those affected.[4]

Race

Most authors report no specific racial predilection. One report suggests an increased incidence is observed in blacks, possibly because blacks have a greater density of apocrine glands than whites.[13]

Sex

Although hidradenitis suppurativa is widely considered to occur more frequently in females than in males, with a ratio as high as 2-5:1,[32, 4] reports on sex prevalence are controversial.[4, 33, 34]

Active genitofemoral lesions occur significantly more often in females, whereas perianal involvement tends to be more common in males. No sex difference is seen in the axillary lesions. Comedones have been suggested as precursor lesions for hidradenitis suppurativa, and they appear to be equally distributed in both sexes and sites.[18]

Age

The onset of hidradenitis suppurativa ranges from 11-50 years,[3] with an average patient age of 23 years.[4] In less than 2% of patients, the disease appears before age 11 years.[35] In extremely rare cases, hidradenitis suppurativa occurs before puberty[36, 37] or after menopause.[38]

History

Hidradenitis suppurativa usually occurs in otherwise healthy individuals, and, very rarely, it can begin before puberty. The disease onset is insidious, with early symptoms of pruritus, erythema, and local hyperhidrosis. Later, the lesions become painful. Arthropathy associated with hidradenitis suppurativa may present with variable clinical features, ranging from asymmetric pauciarticular arthritis to a symmetric polyarthritis and/or polyarthralgia syndrome.[1, 2]

Physical

The diagnosis is primarily clinical, and biopsy is rarely required, especially in well-developed lesions.[3] The consensus approach has deemed that 3 key elements are required to diagnose hidradenitis suppurativa: typical lesions, characteristic distribution, and recurrence. Based on 3 premises, a set of typical lesions, called primary lesions, was compiled, as follows:

The characteristic sites were chosen in accordance with the 2 areas most frequently affected by hidradenitis suppurativa: the axillae and the groin. These areas are defined by anatomical borders and are called designated sites. Hidradenitis suppurativa is diagnosed if the patient has 1 of the following:

Others have based the diagnosis on a series of questions, as follows:[6]

Hidradenitis suppurativa has a predilection for the intertriginous regions. The axillary and inguinoperineal regions are most commonly affected (see the images below). Other zones that harbor terminal hair follicles and apocrine sweat glands are occasionally affected. These zones include the areola of the breast, the submammary fold, the periumbilical region, the scalp, the zygomatic and malar areas of the face, the nape of the neck, the external auditory meatus, and the shoulders. The extent and the severity of the disorder vary widely. Some patients have relatively mild forms of the disease that involve only one region.[13] In many patients, more than one major site is involved.


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Vulvar hidradenitis suppurativa.


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Vulvar and inguinal indurations.

A firm pea-size nodule appears and may spontaneously rupture, yielding a purulent discharge. The lesion then heals with fibrosis and eventual recurrence in an adjacent area. The progression from noninflamed nodules to painful, round, deep-seated lesions and subsequent scarring is highly diagnostic. The nodules tend to coalesce, and they may become infected, resulting in acute abscesses. These abscesses may temporarily resolve, or, alternatively, they may progress to multiple abscesses with persistent pain, fistula formation, and scarring. Infected ruptured apocrine glands coalesce, creating subcutaneous abscesses with discharge through multiple openings.

The inflamed nodules progress when spontaneously draining dermal sinus tracts appear. Draining sinuses represent a variant of persistent nodular hidradenitis suppurativa characterized by periodic discharge of pus or blood. If untreated, the draining sinuses persist for a long time, even years. They may seem to intermittently resolve, only to start draining again (see the images below). A draining sinus can be easily identified because of its linear or angular shape, its history of being present for a prolonged period, and its variable response to systemic isotretinoin.[39] Over time, multiple abscesses and sinus tracts form a subcutaneous honeycomb. Occasionally, the involvement extends into the underlying fascia and muscles. Fibrosis, hypertrophic scarring, and induration ultimately develop.


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Sinus tract.


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Draining sinus tract.

Multiple open comedones and so-called bridged comedones are the hallmark finding of hidradenitis suppurativa; they frequently progress to multiple abscesses and sinus tract formations. When 2 distant cutaneous orifices are interconnected through a subcutaneous fistula, they form bridging lesions. Adenopathy is rarely associated. With advanced disease, the destruction of most glands causes the apocrine glands to decrease in number or disappear. In the axillary region, 5- to 30-cm–long confluent infiltrations develop. These infiltrating lesions are firm and tend to merge at many points. As the disease becomes chronic, large scars and contractures develop with persistent erythema. The patient’s mobility is restricted, and the patient may not be able to fully raise his or her upper arm above the horizontal plane.

Inguinal-anogenital infiltration involves brown-red lesions with pus, blood, and a foul-smelling secretion that emerges from the numerous fistular openings. In the upper anal fold, terminal hairs emerge from thickened scars. Perianal hidradenitis suppurativa may cause pain, swelling, purulent discharge, bleeding, and fistulas. Progressive destruction of the normal skin architecture occurs; the malodorous discharge may be thin and serous or frankly purulent.

The signs of perianal hidradenitis suppurativa may be clinically identical to the cutaneous manifestations of Crohn disease. Crohn disease may be complicated by a variety of skin manifestations, and hidradenitis suppurativa has been reported to precede or complicate Crohn disease.[13, 40, 41] In examining patients with perianal hidradenitis suppurativa, Church et al noted that Crohn disease coexisted with perianal hidradenitis suppurativa in 39% of patients.[42] Local swelling and inflammation associated with Crohn disease may precipitate hidradenitis suppurativa in patients already prone to it. However, the coexistence of Crohn’s disease and hidradenitis suppurativa does not explain the frequent presence of axillary, groin, and buttock involvement, which may imply a constitutional or genetic predisposition to hidradenitis suppurativa in patients with rectal Crohn disease.[13]

The coexistence of the 2 conditions may have implications in the treatment of perianal sepsis in such patients. Each condition can mask the other. Hidradenitis suppurativa may adversely affect the clinical course of patients with Crohn disease. Furthermore, patients with both conditions are more prone to persistent sepsis and frequently require proctocolectomy and fecal diversion procedures.[13]

In patients with the chronic lesions due to so-called granulomatous hidradenitis suppurativa, as well as in 60% of patients with Crohn disease, the presence of noncaseating epithelioid-type granulomas suggests that hidradenitis suppurativa and Crohn disease are chronic inflammatory conditions. Epithelioid granulomas occur in patients with a constitutive tendency to form granulomas as a part of an immunologic abnormality.[40]

Whether the association between hidradenitis suppurativa and Crohn disease is more than a coincidence is unclear; however, the small proportion of patients with hidradenitis suppurativa and epithelioid granulomatous inflammation may represent a group that is susceptible to systemic granulomatous disease, including Crohn disease.[40, 41]

The association of hidradenitis suppurativa with several disorders in which poral occlusion is prominent supports the theory of a follicular origin of hidradenitis suppurativa.[43] Such disorders include Fox-Fordyce disease, acanthosis nigricans,[36] pityriasis rubra pilaris (PRP),[44] steatocystoma multiplex, and Dowling-Degos disease.[45]

HIV-associated pityriasis rubra pilaris, or pityriasis rubra pilaris type VI, is a new entity reported in patients with HIV infection. HIV-associated pityriasis rubra pilaris is characterized by the cutaneous lesions of pityriasis rubra pilaris and a variable association with the lesions of acne conglobata, hidradenitis suppurativa, and lichen spinulosus.[44] This disease can be designated by the broader term, HIV-associated follicular syndrome. Although the pathogenesis of pityriasis rubra pilaris type VI is unknown, follicular inflammation secondary to infection of the hair follicle bulge area by HIV has been suggested.[1]

Arthritis is a well-recognized, albeit uncommon, comorbidity of several chronic cutaneous inflammatory conditions that involve severe acne. Included in this group of conditions is the arthropathy associated with hidradenitis suppurativa, acne conglobata, perifolliculitis abscedens, and suffodiens capitis.[1, 2] Arthritis associated with acne fulminans, seronegative spondyloarthropathies of psoriatic arthritis, and reactive arthritis are well-defined clinical entities. However, arthritis associated with hidradenitis suppurativa; acne conglobata; perifolliculitis abscedens; suffodiens capitis; and synovitis, acne, palmoplantar pustulosis, hyperostosis, and osteitis (SAPHO) syndrome are less well defined; these conditions may be part of the spectrum of human leukocyte antigen B27(HLA-B27)–negative spondyloarthropathies.[46]

The pathogenesis of the arthritis remains unknown, but it may include an inappropriate response to bacterial antigens involved in acne, or it may be some other autoimmune response.[47] Arthropathy associated with hidradenitis suppurativa may manifest variable clinical features, ranging from an asymmetric pauciarticular arthritis to a symmetric polyarthritis and/or polyarthralgia syndrome. Arthropathy typically involves the large joints in the upper or lower extremities, particularly the knee joints. The axial skeleton may also be involved. In many instances, the arthropathy worsens during flares of hidradenitis suppurativa, and, conversely, it improves after hidradenitis suppurativa resolves.[46]

The concept of SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis) includes 4 subgroups of osteoarticular disorders: (1) rheumatologic manifestations associated with acne conglobata or acne fulminans or inversa hidradenitis suppurativa, (2) pustulosis palmoplantaris, (3) sternocostoclavicular hyperostosis, and (4) chronic multifocal recurrent osteomyelitis. SAPHO syndrome may encompass cases described as arthropathy associated with hidradenitis suppurativa and acne conglobata. However, aseptic osteitis with hyperostosis, particularly of the thoracic joints, is a hallmark of SAPHO syndrome, and it may represent a feature that distinguishes SAPHO syndrome from the arthropathy of hidradenitis suppurativa and acne conglobata.[2, 48]

Some reports raised the question of whether mammillary fistula or Zuska disease might be a manifestation of acne inversa.[49]

Pyoderma gangrenosum has been rarely associated with hidradenitis suppurativa, and this developed only after hidradenitis suppurativa had been present for at least 2 decades, just as in the authors' patient (see the images below).


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Vulvar hidradenitis suppurativa.


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Vulvar and inguinal indurations.


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Sinus tract.


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Draining sinus tract.


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Axillary hidradenitis suppurativa in a patient with pyoderma gangrenosum.


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Close-up view of axillary hidradenitis suppurativa in a patient with pyoderma gangrenosum.


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Submammary hidradenitis suppurativa in a patient with pyoderma gangrenosum.


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Double-ended-comedones. Hidradenitis suppurativa in a patient with pyoderma gangrenosum.


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Inguinal hidradenitis suppurativa in a patient with pyoderma gangrenosum.


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Close-up view of inguinal hidradenitis suppurativa in a patient with pyoderma gangrenosum.


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Pyoderma gangrenosum in a patient with hidradenitis suppurativa.


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Close-up view of pyoderma gangrenosum in a patient with hidradenitis suppurativa.


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Coexisting hidradenitis suppurativa and pyoderma gangrenosum.


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Coexisting hidradenitis suppurativa and pyoderma gangrenosum.


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Hidradenitis suppurativa in a patient with pyoderma gangrenosum.

Fifteen cases of coexisting pyoderma gangrenosum and hidradenitis suppurativa were found in the English-language literature. More studies are required to support impaired neutrophil function as a common etiological pathway.[50]

Causes

The exact etiology of HS remains obscure. All proposed etiologic factors, such as occlusion and bacterial infection, genetics, host defense defects, hormones, cigarette smoking, and irritants, are likely to be only secondary factors. The primary events in the hair follicles of the affected areas remain unidentified.[51] Also, thickened skin may play a role in the pathogenesis of HS (see Imaging Studies).

The classic view of HS is that it is an occlusive and pyogenic disease of the apocrine glands, a hypothesis that seemed to be confirmed with its experimental reproduction by Shelley and Cahn in 1955.[52] After manually depilating the skin and applying atropine-impregnated tape, they induced initial keratinous obstruction, dilatation, and inflammation of the apocrine duct, which occurred in only 25% of the experimental lesions. No progression to the characteristically chronic condition of HS occurred.[52]

In more recent studies, HS is identified as a disorder of follicular occlusion rather than apocrine occlusion.[27, 28, 29] Yu and Cook found inflammatory changes involving the apocrine glands in only one third of cases; these occurred only when the inflammation extensively involved the hair follicles and eccrine glands.[27] Attanoos et al reported follicular occlusion in all specimens, when compared with controls, regardless of the disease duration. The inflammation of the apocrine glands did not occur in the absence of an adjacent folliculitis; thus, apocrine gland involvement was incidental or secondary.[28] Therefore, HS is best considered a disorder of the terminal follicular epithelium in the apocrine gland–bearing skin.[3]

The earliest change is plugging, which occurs in follicular hyperkeratosis with infundibulofolliculitis. This obstructs the apocrine gland ducts and perifolliculitis around the ducts. Whether this initial inflammatory change is due to a bacterial infection or factors similar to those involved in acne formation is not known.

In the later stages of HS, bacterial infection seems to be a risk factor for the destructive scarring and extension of HS lesions, and, once the sinuses have formed, the risk of secondary infection is obvious.[53]

Among the most commonly isolated bacteria are coagulase-negative staphylococci.[53] Sweat ducts can become occluded with periodic acid-Schiff (PAS)–positive extracellular polysaccharide substance, the cause of which was recently suggested to be Staphylococcus epidermidis.[54] Such strains induced miliaria under experimental conditions. A similar mechanism may be important in the pathogenesis of HS.[53]

The earliest inflammatory event in HS is the rupture of the follicular epithelium. The cause of the rupture is not known, although friction in intertriginous locations may be a contributing factor. The rupture is followed by the spillage of foreign-body material into the dermis, which initiates an inflammatory response, resulting in foreign-body granuloma formation. Epithelial strands form draining sinuses in this inflammatory tissue. Colonization with bacteria, usually coagulase-negative staphylococci, can aggravate the chronic inflammation.[51, 53]

Regarding the current controversies non-follicular-based theories on what causes HS, some authors suggest the following:[55]

Although the inciting influences for the follicular occlusion and sinus tract formation have not been fully elucidated, genetic factors may play a role.

A search for the molecular genetic abnormality is now necessary.[5] Mutation within the connexin 26 gene was recently reported in association with keratitis-ichthyosis-deafness syndrome, and severe follicular occlusion triad.[57] A study of a large four-generation Chinese family with HS indicates a locus for the disease on chromosome 1q21.1-1q25.3.[58]

The notion that specific HLA antigens might be at the center of a genetic susceptibility to HS is not supported and remains questionable.[59]

Host-defense defects in patients with HS are suspected but not proven.[60]

Apocrine sweat glands are stimulated by androgen and suppressed by estrogen. Evidence for the hormonal effects in HS exists; however, the exact roles of androgens in the pathogenesis of HS remain controversial, and they may prove to be secondary.[11, 3, 63, 64, 65]

Cigarette smoking may be among the major triggering factors in HS, and its cessation should be encouraged, although whether cessation improves the course of disease is unknown.[11, 31] It remains unclear precisely what pathogenetic mechanism would be responsible for the effect of smoking in the manifestation of acne inversa, but an altered chemotaxis of polymorphic neutrophils could play a part.[70]

Chemical irritants (eg, deodorants) and mechanical irritation (eg, depilation, shaving) have been considered risk factors. However, in one study, no significant difference was found in patients who were exposed to these factors compared with age-matched control subjects.[43] Factors associated with disease activity, such as heat, sweating, stress, and menstruation in females, are the most commonly cited factors that exacerbate the disease. In one study, 32% of responders observed a deterioration in their disease during the summer.[4]

HS is rarely a side effect of drug use, but oral contraceptives and lithium have been associated with its development.[18]

Lung and buccal cancer are more common among HS patients than in the general population as would be expected with increased tobacco smoking and chewing.[18]

Hidradenitis suppurativa may rarely be complicated by hidradenocarcinoma.[71]

Laboratory Studies

The following laboratory tests may be helpful in the evaluation of hidradenitis suppurativa (HS):

Patients with acute lesions may have an elevated erythrocyte sedimentation rate, elevated white blood cell count (occasionally), a low serum iron level, and serum protein abnormalities on electrophoresis.

Imaging Studies

Ultrasonography of the hair follicles and dermal thickness in hidradenitis suppurativa patients may reveal abnormalities in the deep part of the follicle. In the genitofemoral region, perilesional clinically normal hair follicles have an abnormal shape and are significantly wider in the deep part of the dermis, compared with control samples. Mean axillary and genitofemoral skin is significantly thicker in patients with hidradenitis suppurativa than in healthy control subjects. Thickened skin may play a role in the pathogenesis of hidradenitis suppurativa.

Other Tests

Bacteriologic analysis should include bacteriologic sampling and cultivation. Bacteriologic sampling should be performed at different depths in hidradenitis suppurativa lesions. A carbon dioxide laser can be used to evaporate the diseased tissue, level by level, from the surface downward. Samples can be concurrently obtained from each level, and contamination with bacteria from the level above can be minimized. Almost every microorganism known to bacteriologists can be isolated from hidradenitis suppurativa lesions; these microorganisms include streptococci, gram-positive and gram-negative rods, and the full range of fecal bacteria.[72] Among the most frequently found species are Staphylococcus aureus and coagulase-negative staphylococci, anaerobic streptococci (eg, microaerophilic Streptococcus milleri), and Bacteroides species.[53, 64]

The microbiologic florae are not consistent and change unpredictably.[72]

Immunohistochemical data obtained for various cytokeratins (CKs) and the 6 desmosomal cadherins (ie, desmogleins [Dsgs] 1-3, desmocollins [Dscs] 1-3) showed 3 phenotypes of stratified squamous epithelia covering the sinus tracts in hidradenitis suppurativa: type I cornifying, type II noncornifying and moderately inflamed, and type III noncornifying and strongly inflamed.[73]

Histologic Findings

Histologically, the fundamental change in hidradenitis suppurativa is the same as in acne vulgaris, namely, hyperkeratosis of the infundibulum that results in comedolike horny impactions.[72] Some evidence suggests that the occlusion of abnormal hair follicles may play an important part in the initiation of the lesions.[27, 77] Follicular occlusion was found in all specimens compared with controls and regardless of disease duration.[62] Folliculitis and perifollicular inflammation are common and occur in about two thirds of cases, with or without follicular occlusion.

The earliest inflammatory event is a segmental rupture of the follicular epithelium, followed by spilling of foreign body material. The apocrine glands are not involved in the earliest stage of follicular hyperkeratosis and infundibulofolliculitis.[70]

The inflammatory infiltrate is composed of neutrophils, lymphocytes, plasma cells, and, occasionally, eosinophils. Active inflammation around the sweat glands is less common than inflammation around the hair follicles. The histologic features reveal inflammation of the apocrine glands in only 33% of cases. Apocrinitis only evolves by extension of the inflammatory process.[65] Apocrine gland destruction by neutrophils is occasionally observed. Abscess formation occurs, leading to destruction of the pilosebaceous unit and, eventually, the other adnexal structures. Apoeccrine glands (present in axillae), which drain directly on the epidermal surface, appear intact and not inflamed.[14]

Chronic lesions have a dermis with an inflammatory cell infiltrate and foreign body–type granulomas around the hair follicles and the sinus tracts. The presence of epithelioid granulomas in so-called granulomatous hidradenitis suppurativa should alert to the possibility of coexisting granulomatous disease, such as Crohn disease or sarcoidosis.[40]

The draining sinus tracts extend predominantly into the dermis and are lined by a variably thickened stratified epithelium; they extend in the form of dissecting tracts, which burrow through the necrotic tissue. The epithelium is constantly breaking down; therefore, the sinus tract is not completely lined with epithelium.[39] As previously mentioned, the 3 phenotypes (see Other Tests) of stratified squamous epithelia reflect the dynamic processes of inflammation, proliferation, and stratification that occur in hidradenitis suppurativa.[73]

Lipid rafts (membrane microdomains composed of cholesterol and gangliosides) have been described and appear to have potentially relevant functions in the formation of sinus tracts. The lipid rafts provide anchor points for growth factor receptors and are expressed on migrating cells such as keratinocytes involved in wound healing. Thus, sinus tract formation may represent an aberrant epidermal repair response executed by the lipid raft-enriched stem cell–like keratinocytes in the epidermis and hair follicles, as well as in sinus tracts in hidradenitis suppurativa, that emerge due to the influence of local inflammatory cytokines and are capable of nonmalignant infiltrative growth in the dermis and subcutis.[78]

With regard to the expression of CK19 in type II epithelium and overlying epidermis in hidradenitis suppurativa lesions (which can also be induced in epidermal keratinocytes grown in organotypic culture medium with the addition of retinoic acid), study of the expression of retinoic acid and retinoid X receptors in the different epithelial phenotypes of the draining sinus would be interesting.

Retinoids are known to induce a differentiation shift in keratinocytes, which thereby acquire certain features of simple glandular epithelia. Type III epithelium expresses some markers of such epithelia. This finding may be interpreted as a kind of metaplasia toward glandular differentiation.[73] Free hair shafts can be found in the sinus and surrounding dermis, without apparent connection to the epithelium.

Difficulty may arise in distinguishing well-differentiated squamous cell carcinoma (SCC) and florid pseudoepitheliomatous hyperplasia. Pseudoepitheliomatous hyperplasia is usually associated with chronic irritation, unlike SCC. Tissue destruction, necrosis, and, often, keratin pearls, are associated with SCCs. Vascular and lymphatic invasion may be present in SCC. Mitotic activity is seen in both conditions, although abnormal mitoses are only seen in SCCs.

High-frequency ultrasonography shows changes in the clinically uninvolved axillary and genitofemoral hair follicles. The follicles appear to be larger diameter and a distorted shape with a wider deep follicular diameter, in agreement with the clinical impression that the primary event in hidradenitis suppurativa is deep seated rather than superficial.[18]

Staging

Clinical staging of hidradenitis suppurativa has diagnostic value. A recent study has shown that the soluble interleukin-2 receptor serum level in patients with hidradenitis suppurativa can be used as valuable marker for disease staging.[79]

Dynamic staging system have been used for assessing differences in treatment effects.[7] Uniform outcome variables should take into account the known characteristics of hidradenitis suppurativa, including the following:[7]

Medical Care

The ideal treatment of hidradenitis suppurativa (HS) should provide a high likelihood of cure with a low recurrence rate, as well as minimal inconvenience and loss of work time. Medical management is recommended in early stages, whereas surgery should be performed as early as possible after the formation of abscesses, fistulas, scars, and sinus tracts (see Surgical Care).[6] Treatment may include the following:

In one study, nearly one quarter of patients were unable to list any measure that helped their condition, despite an average disease duration of nearly 19 years. This outcome indicates that the available treatments for hidradenitis suppurativa are, on the whole, still unsatisfactory. Surgical approaches, which were used in almost half the patients, were included in those treatments.[5]

Surgical Care

Surgery is the sine qua non treatment, especially in chronic hidradenitis suppurativa. Wide surgical excision, with margins well beyond the clinical borders of activity, remains the most definitive surgical therapy.[6, 9, 10] With this technique, sufficient resection of the lesion is the most important issue.[8] Surgery has hitherto been considered a curative treatment, but specific studies have suggested otherwise. Although recurrence rates may be lower with surgery that is more aggressive, recurrences continue.[11, 12] After radical excision, the disease recurred in 33% of the patients.[12] Surgery is most valuable in the chronic and recurrent stages of hidradenitis suppurativa.[6, 8]

More limited surgical intervention, consisting of unroofing abscesses and sinus tracts, with vigorous curettage of the base, and secondary-intention healing can be valuable in some cases.

Electrosurgery should be considered a top alternative in the treatment algorithm of hidradenitis suppurativa.[80]

Nonsurgical procedures are only supportive, but they are important either before or after surgery.[6, 43, 8, 81] If the disease is diagnosed and treated early, secondary systemic complications can be prevented and the extent of surgery can be limited.[8]

Radical surgery is considered by many to be the only cure for hidradenitis suppurativa, although a cure can be achieved only in the particular area excised.[3, 35] Patients should be warned that new lesions may develop at a site that was not apparent at the time of their initial surgery.[43]

Numerous helpful and relatively minor surgical techniques include drainage; exteriorization; curettage; electrocoagulation of the sinus tracts; simple excision of the troublesome areas with direct closure; placement of local cutaneous flaps, musculocutaneous flaps, pedicled and free flaps, or skin grafts; and secondary-intention healing.[14, 15, 16]

Adequate excision to eradicate the disease often results in a defect that precludes primary closure; therefore, other techniques must be used to achieve wound healing.

Recurrence after surgery is likely if excision is inadequate or if the distribution of apocrine glands is unusually wide.[13, 8, 15] The recurrence rate in patients treated with radical surgery varies considerably depending on the site affected; the highest rate is 50% in the submammary region.[13] An overall recurrence rate of 2.5% has been estimated after wide surgical excision, with a median postoperative follow-up of 36 months.[8]

Radiological Care

In one series, radiation therapy by irradiation with single doses of 0.5-1.5 Gy to total doses of 3.0-8.0 Gy was given as a treatment option for hidradenitis suppurativa.[17] The use of x-rays in depilating doses to achieve temporary epilation has been suggested. The possible beneficial effects of laser epilation do, however, suggest that hair removal may be of independent importance.[18]

Nonablative radiofrequency therapy can be used for patients with Harley stage I and II.[19]

Diet

Patients who are obese should be advised to lose weight.[6]

Activity

Some patients can obtain relief from their condition by making certain lifestyle changes and by engaging in activities such as swimming, bathing, avoiding smoking, and wearing loose-fitting clothing.[4, 6]

Medication Summary

Treatment of hidradenitis suppurativa remains a considerable challenge. Therapeutic options for hidradenitis suppurativa were long restricted to the use of local disinfectants and systemic antibiotics, as well as repeated incision and drainage, which produce only short-term benefits. Medical management is recommended in early stages, whereas surgery should be performed as early as possible after the formation of abscesses, fistulas, scars, and sinus tracts (see Surgical Care).[15]

Treatment should be individualized according to the state and extent of the disease. Absolute cessation of smoking is essential in the treatment of hidradenitis suppurativa. Management with antibiotics or other medications may relieve early symptoms, but radical surgery may be necessary for control and prevention of recurrence.[10]

Alikhan et al suggest a treatment algorithm based upon the Hurley classification or a tiered approach. For patients in Hurley stage I, antibiotics and intralesional injections of corticosteroids represent a good first-line therapy, while flares should be treated with short courses of systemic corticosteroids. If this regimen fails, zinc, or, in females of non-childbearing age, antiandrogen, therapy may be effective. Long-term immunosuppressive therapy or surgical therapy may be required in some patients. For patients in Hurley stage III, wide excision may prove to be the only effective treatment.[6]

Cryotherapy has also been used as adjunctive therapy. In draining sinuses, cryotherapy works by accelerating the resorption of the inflammation. However, patients must be warned about pain, prolonged healing time, and risk of infection after the procedure, and they must be informed that the treatment is unlikely to influence disease progression.[88]

Tetracycline

Clinical Context:  Used to treat gram-positive and gram-negative organisms and mycoplasmal, chlamydial, and rickettsial infections. Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunits.

Doxycycline (Doryx, Vibramycin, Adoxa)

Clinical Context:  Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Clindamycin (Cleocin)

Clinical Context:  Lincosamide for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Erythromycin (E.E.S., Ery-Tab, Erythrocin)

Clinical Context:  Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. In children, age, weight, and severity of infection determine proper dosage. When twice daily dosing is desired, half the total daily dose may be taken q12h. For more severe infections, double the dose.

Dapsone

Clinical Context:  Bactericidal and bacteriostatic against mycobacteria; mechanism of action similar to that of sulfonamides, in which competitive antagonism of PABA prevents formation of folic acid, inhibiting bacterial growth.

Class Summary

Acute episodes and relapses of hidradenitis suppurativa should be treated as bacterial infections. Mild topical steroid creams in combination with topical antibiotics in the aminoglycoside group, such as clindamycin 2% solution, gentamicin collagen sponge, and erythromycin 3% gel, have been favored.[16, 89] Some authors advocate long-term treatment with systemic antibiotics (eg, tetracycline, minocycline, clindamycin, erythromycin in combination with metronidazole), but long-term outcomes are often poor.[5, 6]

Isotretinoin (Amnesteem, Claravis, Sotret)

Clinical Context:  Affects epidermal differentiation, especially at the follicular infundibulum. Also has immunomodulating effects. Has been used as chemoprophylaxis for skin cancers.

A US Food and Drug Administration–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.

Class Summary

Vitamin A derivatives have many roles. They encourage cellular differentiation, are antiproliferative, and serve as immunomodulators. Although some patients have dramatic responses to isotretinoin 1 mg/kg/day as monotherapy[46] or combined with prednisolone (ie, when isotretinoin was introduced after 8 wk of prednisolone and erythromycin therapy),[34] retinoids may be useful only as an adjunct to reduce inflammation before and after surgery.[43, 81]

Results from a long-term follow-up study indicate that although the response of hidradenitis suppurativa to isotretinoin is only moderate and is related to the severity of the disease, the promising effects of acitretin therapy described in this case series suggests the need for a randomized, controlled trial.[90] The dose of isotretinoin is unlikely to be important in treating hidradenitis suppurativa.

Others propose that long-term treatment with isotretinoin is more successful than the usual 4-month to 6-month regimen.[34] Isotretinoin does not affect the size of the apocrine gland, and etretinate or acitretin (25 mg bid) may be more useful, at least in some cases. The fact that some conditions do not respond to isotretinoin, yet do respond to etretinate and acitretin, suggests that the suppression of hyperkeratinization is more important than glandular shrinkage. In parous women, a prolonged course of isotretinoin is probably a safer initial choice; however, severe complications, such as acute pancreatitis associated with hyperlipidemia, may occur, even in patients without an identifiable risk factor.[91]

Triamcinolone (Aristospan, Kenalog-10, Kenalog-40)

Clinical Context:  For inflammatory dermatosis responsive to steroids; decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability. Intramuscular injection may be used for widespread skin disorder. Intralesional injections may be used for localized skin disorder.

Prednisolone (Millipred, Pediapred)

Clinical Context:  Decreases autoimmune reactions, possibly by suppressing key components of immune system.

Prednisone

Clinical Context:  Prednisone is useful for treating inflammatory and allergic reactions; it may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte (PMN) activity. Decreases autoimmune reactions, possibly by suppressing key components of immune system.

Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli. Intralesional injection with either a syringe or an automatic needleless injector usually decreases the size of draining sinuses. The injection of 0.05-0.25 mL of triamcinolone acetonide suspension (2.5-10 mg/mL) into each lesion is recommended for its anti-inflammatory effects. This treatment can be repeated every 2-3 weeks if necessary.[39] The anti-inflammatory effects of systemic corticosteroids may be useful in acute exacerbations. Prednisolone 60 mg/day with lower maintenance doses provides some long-term control.[64]

Cyproterone acetate

Clinical Context:  Inhibits androgen binding to target cells.

Class Summary

Combined treatment with the antiandrogen cyproterone acetate and ethinyl oestradiol has been shown to be of benefit to women with long-standing hidradenitis suppurativa.

Infliximab (Remicade)

Clinical Context:  Inhibits TNF-alpha activity and triggers complement-mediated lysis of TNF-alpha–expressing cells in vitro. Monoclonal chimeric antibody made from human constant and mouse variable regions of IgG, with binding specificity for human TNF-alpha. Binds to inactive TNF-alpha and can bind specifically to both membrane-bound and soluble TNF-alpha. Binds to inactive TNF-alpha monomers, preventing their association into active trimers. Used to treat severe inflammatory diseases that do not respond to systemic corticosteroids or immunosuppressants.

Class Summary

Because of the concurrent presentation of hidradenitis suppurativa and Crohn disease, as well as the morphological and histological similarities, these 2 conditions may share the same pathogenesis, namely excess tumor necrosis factor-alpha (TNF-alpha) production. This was supported by several reports in the literature of patients with hidradenitis suppurativa and Crohn disease who responded to infliximab.[41, 92, 93, 94, 95] Infliximab is an inhibitor of TNF-alpha. Although approved by the US Food and Drug Administration (FDA) for the treatment of Crohn disease and rheumatoid arthritis, infliximab has also been used in hidradenitis suppurativa.[96] The benefits outweigh the risks associated with its use, especially when it is administrated in severe chronic cases resistant to standard therapies.[82]

Patients self-report that pain significantly decreased following infliximab treatment. This correlated with significant physician-observed clinical improvement (P = .0001). Patients reported a rapid response after the first infusion, and some of them noticed decreased pain after 24 hours.[96, 97] Although the efficacy has proven impressive and short-term adverse effects have been few and relatively benign, the long-term adverse effects have not been studied. Further multicenter studies are needed to assess effects of its prolonged use, as well as to determine safety, optimal frequency of dosing, and time to relapse after cessation of therapy.[97, 98]

Moreover, the existing prospective studies have described variable patient responses and significant adverse reactions, including hypersensitive reactions, lupuslike reactions, and abdominal pain secondary to colon cancer, tuberculosis, and motor neuropathy. The studies varied in their outcome assessment, population studied, and dose of infliximab used in patients with hidradenitis suppurativa.[99, 100, 101]

Other inhibitors, including etanercept (a human fusion protein receptor consisting of 2 human TNF-alpha receptors and Fc domain of human immunoglobulin G1) and adalimumab (a fully humanized recombinant anti-TNF-alpha monoclonal antibody) have also produced variable patient responses and significant adverse reactions. Enough information is not yet available to assess the true risks of TNF-alpha inhibitor use as therapy for hidradenitis suppurativa. None of the studies used a control group. Thus, randomized controlled studies are necessary to determine the risk-to-benefit ratio of TNF-alpha inhibitor therapy in the treatment of hidradenitis suppurativa.[102, 103, 104, 105]

Therapeutic experience with nonspecific immunosuppression in hidradenitis suppurativa using methotrexate is unlikely to offer any significant advance. Before finally determining the value (or lack of value) of methotrexate in hidradenitis suppurativa, investigation of different dosage schedules in future patients with hidradenitis suppurativa would be worthwhile.[106]

Ethinyl estradiol (Estinyl)

Clinical Context:  Reduces secretion of LH and FSH from pituitary gland by decreasing amount of gonadotropin-releasing hormones.

Class Summary

Treatment with the antiandrogen cyproterone acetate in combination with estrogen ethinyl estradiol and ethinyl estradiol in combination with the low-dose progestin norgestrel may significantly improve disease activity, especially in patients with mild forms of hidradenitis suppurativa, but many conditions do not respond to these treatments.

Finasteride (Proscar)

Clinical Context:  Inhibits steroid 5alpha-reductase, which converts testosterone into 5alpha-dihydrotestosterone (DHT), causing serum DHT levels to decrease.

All skin tissue predominantly contains type 1 isoenzyme, and genital region contains type 2. Finasteride has been effective in treating hirsutism.

Class Summary

Agents in this class decrease dihydrotestosterone serum levels and may be beneficial to hidradenitis suppurativa.

Inpatient & Outpatient Medications

In a 2010 study, topical treatment with 15% resorcinol reduced pain from painful nodules in all patients with hidradenitis suppurativa. However, more trials are needed to confirm its efficacy.[107]

Complications

Complications of hidradenitis suppurativa include local and systemic infections resulting from the spread of microorganisms[108] and, in rare cases, septicemia. Other complications may include the following:

Prognosis

Author

Marina Jovanovic, MD, PhD, Chief of Dermatology Ward and Contact Dermatitis Investigative Unit, Clinic of Dermatoveneroleogic Diseases, Clinical Center, Novi Sad, Serbia; Professor in Dermatology, Medical Faculty, University of Novi Sad, Vojvodina, Serbia

Disclosure: Nothing to disclose.

Coauthor(s)

George Kihiczak, MD, Clinical Associate Professor, Department of Dermatology, New Jersey Medical School and University Hospital

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School

Disclosure: Nothing to disclose.

Specialty Editors

Andrea Leigh Zaenglein, MD, Professor of Dermatology and Pediatrics, Department of Dermatology, Hershey Medical Center, Pennsylvania State University College of Medicine

Disclosure: Galderma Consulting fee Consulting; Valeant Consulting fee Consulting; Promius Consulting fee Consulting; Anacor Consulting fee Consulting; Stiefel Grant/research funds Investigator; Astellas Grant/research funds Investigator

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Jeffrey J Miller, MD, Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center

Disclosure: Nothing to disclose.

Catherine M Quirk, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

Disclosure: Nothing to disclose.

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Vulvar hidradenitis suppurativa.

Vulvar hidradenitis suppurativa.

Vulvar and inguinal indurations.

Sinus tract.

Draining sinus tract.

Vulvar hidradenitis suppurativa.

Vulvar and inguinal indurations.

Sinus tract.

Draining sinus tract.

Axillary hidradenitis suppurativa in a patient with pyoderma gangrenosum.

Close-up view of axillary hidradenitis suppurativa in a patient with pyoderma gangrenosum.

Submammary hidradenitis suppurativa in a patient with pyoderma gangrenosum.

Double-ended-comedones. Hidradenitis suppurativa in a patient with pyoderma gangrenosum.

Inguinal hidradenitis suppurativa in a patient with pyoderma gangrenosum.

Close-up view of inguinal hidradenitis suppurativa in a patient with pyoderma gangrenosum.

Pyoderma gangrenosum in a patient with hidradenitis suppurativa.

Close-up view of pyoderma gangrenosum in a patient with hidradenitis suppurativa.

Coexisting hidradenitis suppurativa and pyoderma gangrenosum.

Coexisting hidradenitis suppurativa and pyoderma gangrenosum.

Hidradenitis suppurativa in a patient with pyoderma gangrenosum.

Vulvar hidradenitis suppurativa.

Vulvar and inguinal indurations.

Sinus tract.

Draining sinus tract.

Axillary hidradenitis suppurativa in a patient with pyoderma gangrenosum.

Close-up view of axillary hidradenitis suppurativa in a patient with pyoderma gangrenosum.

Submammary hidradenitis suppurativa in a patient with pyoderma gangrenosum.

Double-ended-comedones. Hidradenitis suppurativa in a patient with pyoderma gangrenosum.

Inguinal hidradenitis suppurativa in a patient with pyoderma gangrenosum.

Close-up view of inguinal hidradenitis suppurativa in a patient with pyoderma gangrenosum.

Pyoderma gangrenosum in a patient with hidradenitis suppurativa.

Close-up view of pyoderma gangrenosum in a patient with hidradenitis suppurativa.

Coexisting hidradenitis suppurativa and pyoderma gangrenosum.

Coexisting hidradenitis suppurativa and pyoderma gangrenosum.

Hidradenitis suppurativa in a patient with pyoderma gangrenosum.