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. See the image below.



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

Signs and symptoms

Hidradenitis suppurativa usually occurs in otherwise healthy adolescents and adults. It rarely may begin before puberty. Hidradenitis suppurativa is characterized by comedolike follicular occlusion, chronic relapsing inflammation, mucopurulent discharge, and progressive scarring.

The onset of hidradenitis suppurativa is insidious, with the earliest sign being erythema. 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, as well as spondyloarthropathy. Moreover, epidemiological data also suggest an association of hidradenitis suppurativa with other diseases, including metabolic syndrome. Therefore, it is important to approach hidradenitis suppurativa as a systemic disease with an interprofessional team.[1, 2]

See Clinical Presentation for more detail.

Diagnosis

The diagnosis is primarily clinical, no pathognomonic test exists, and biopsy is rarely required, especially in well-developed lesions.[3] The consensus approach indicates that three key elements are required to diagnose hidradenitis suppurativa: typical lesions, characteristic distribution, and recurrence. Arbitrarily, two recurrences over a period of 6 months have been used as a qualifier for a diagnosis.[3] All three criteria must be present for the definitive diagnosis.[1]

Primary positive diagnostic criteria are as follows:

Suspicion of the diagnosis can be strengthened by other factors that are not, however, pathognomonic.[1, 3]

Secondary positive diagnostic criteria are as follows:

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[5] :

Staging

The Hurley clinical staging of hidradenitis suppurativa from 1989 is still relevant today; it has diagnostic value but is not suitable for monitoring the efficacy of interventions in clinical trials.[1] This staging is as follows:

Dynamic staging Sartorius Score systems have been used for assessing differences in treatment effects.[6] Uniform outcome variables should take into account the known characteristics of hidradenitis suppurativa, including the following[6] :

A recently developed six-stage physician global assessment (PGA) is defined as follows:

However, a Hurley severity grade‒relevant conservative and surgical treatment for hidradenitis suppurativa is recommended.[1, 7] In order to assess any treatment effectiveness, it is very important to standardize relevant endpoints. Defined as at least a 50% reduction in total abscess and inflammatory nodule count with no increase in abscess count and no increase in draining fistula count relative to baseline at week 12, the hidradenitis suppurativa clinical response (HiSCR) is currently the most appropriate clinical endpoint to assess treatment and effectiveness for hidradenitis suppurativa treatment. It does not contradict hidradenitis suppurativa response measured by the modified Sartorius Score or PGA, but rather represents a more sensitive measure of change in disease activity, resulting in a more accurate representation of patient response and treatment evaluation. The HiSCR does not take into account the size or severity of individual lesions and does not measure how treatment response affects a patient’s level of pain or quality of life. However, the threshold of 50% reduction in total abscess and inflammatory nodule count is the defined level that is clinically appropriate and meaningful to the patient regarding improvement in quality of life and pain level.[8]

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 after the formation of abscesses, fistulas, scars, and sinus tracts.[5]

Systemic treatment does not restore the skin’s original architecture; therefore, once the inflammation has been treated, epithelialized cysts and sinus tracts remain in the affected skin.[9]

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.[5, 7] Wide surgical excision, with margins well beyond the clinical borders of activity, remains the most definitive surgical therapy.[5, 8, 9] However, although recurrence rates may be lower with aggressive surgery, recurrences often continue.[10, 11] After radical excision, the disease has been reported to recur in 33% of patients,[11] and it may be as high as 50% in the submammary region.[12]

More limited surgical intervention may include the following[13, 14, 15, 16] :

Radiotherapy

Nonablative radiofrequency therapy can be used for patients with Harley stage I and II disease.[17]

See Treatment and Medication for more detail.

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.[18] 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.[19]

In 1922, Schiefferdecker classified the sweat glands as eccrine and apocrine, and he subsequently localized hidradenitis suppurativa to the apocrine glands.[20] 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.[21]

In 1956, Pillsbury et al combined acne conglobata, hidradenitis suppurativa, and dissecting cellulitis under the term follicular occlusion triad.[22] 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.[23] 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.[24] Eventually, hidradenitis suppurativa was accepted as an acneiform disorder that begins with follicular occlusion rather than an infection of the sweat glands.[25, 26]

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.[27] However, hidradenitis suppurativa differs from acne in that no increase in sebaceous secretions is seen in hidradenitis suppurativa.

Epidemiology

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[28, 10] ; it was 4% in a group of young adults who were treated at a clinic for sexually transmitted diseases.[10] 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%).[29] . Studies that provide prevalence or incidence estimations have been performed under different settings (hospital vs population-based) and in different periods.[28]

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.[12]

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,[4, 30] reports on sex prevalence are controversial.[4, 31, 32] . In fact, females were more likely to have a family history of hidradenitis suppurativa, and men had a tendency for more severe disease and associated severe acne.[32]

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.[33]

Age

The onset of hidradenitis suppurativa ranges from 11-50 years, with an average patient age of 23 years.[4] In less than 2% of patients, the disease appears before age 11 years.[34] In extremely rare cases, hidradenitis suppurativa occurs before puberty, but it has been suggested that a prepubertal onset is not uncommon in severely affected patients.[35, 36] or after menopause.[37]

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).[30] 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.[30] 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]

Prognosis

In general, hidradenitis suppurativa is a chronic disease, as underscored by the finding that 90% of patients in one large series still had active disease in the last year despite an average disease duration of nearly 19 years.[4]

The impression of a relentlessly progressive disorder may be explained by the finding that almost two thirds of patients acknowledged the existence of persistently painful boils that failed to heal. Possibly, new boils develop at an unchanged rate throughout the course of the disease, but some fail to subside in the usual manner and become chronic.[4]

With rare exceptions, surgical intervention is sufficient to stop the disease.[38] Shame, frustration, and despair may cause patients to delay radical surgical procedures.

No single treatment has shown overwhelmingly positive outcomes.[39]

Spontaneous resolution is rare.[7]

Specific factors appear to influence the prognosis. Larger excisions may offer a better outcome. Better results can be obtained by leaving wounds to secondary healing. Perianal surgery, axillary surgery, and older patient age are associated with lower recurrence rates, irrespective of the preoperative duration.[33]

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.[12] An overall recurrence rate of 2.5% have been estimated after wide surgical excision, with a median postoperative follow-up of 36 months.[7]

The postoperative relapse risk is higher in women after surgery under general anaesthesia in severe hidradenitis suppurativa.[36]

If untreated, the disease causes significant morbidity, particularly in women and patients with moderate and severe disease who are more likely to experience a significant diagnostic delay (>2 y).[40]

Patient Education

Patients should be educated about the initial treatments, which include the following[15] (see Medical Care):

Patients who are obese should be educated about weight loss (see Diet). Additionally, patients should be educated about activities that may provide some relief of their condition[4] (see Activity). These activities include swimming, bathing, and avoiding smoking.

For patient education resources, see the Skin Conditions and Beauty Center. Also see the patient education article Boils.

History

Hidradenitis suppurativa usually occurs in otherwise healthy individuals, and, very rarely, it can begin before puberty. The disease onset is insidious, with the earliest sign being erythema. 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, as well as spondyloarthropathy. Moreover, epidemiological data also suggest an association of hidradenitis suppurativa with other diseases, including metabolic syndrome. Therefore, it is important to approach hidradenitis suppurativa as a systemic disease with an interprofessional team.[1, 2]

Physical

The diagnosis is primarily clinical, no pathognomonic test exists, and biopsy is rarely required, especially in well-developed lesions.[3] The consensus approach indicates that three key elements are required to diagnose hidradenitis suppurativa: typical lesions, characteristic distribution, and recurrence. Arbitrarily, two recurrences over a period of 6 months have been used as a qualifier for a diagnosis.[3] All three criteria must be present for the definitive diagnosis.[1]

Primary positive diagnostic criteria are as follows:

Suspicion of the diagnosis can be strengthened by other factors that are not, however, pathognomonic.[1, 3]

Secondary positive diagnostic criteria are as follows:

Typical lesions, called primary lesions, include the following:

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[5] :

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.[12] 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 and its history of being present for a prolonged period. 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.[12, 41, 42] In examining patients with perianal hidradenitis suppurativa, Church et al noted that Crohn disease coexisted with perianal hidradenitis suppurativa in 39% of patients.[43] 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.[12]

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.[12]

The association of hidradenitis suppurativa with several disorders in which poral occlusion is prominent supports the theory of a follicular origin of hidradenitis suppurativa.[44] Such disorders include Fox-Fordyce disease, acanthosis nigricans,[35] pityriasis rubra pilaris (PRP),[45] steatocystoma multiplex, and Dowling-Degos disease.[46]

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.[45] 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.

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. 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.[47]

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.[48] 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.[47]

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.[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 hidradenitis suppurativa 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 hidradenitis suppurativa (see Imaging Studies).

The classic view of hidradenitis suppurativa 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 hidradenitis suppurativa occurred.[52]

In more recent studies, hidradenitis suppurativa is identified as a disorder of follicular occlusion rather than apocrine occlusion.[25, 26]  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.[25] 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.[26] Therefore, hidradenitis suppurativa is best considered a disorder of the terminal follicular epithelium in the apocrine gland–bearing skin.

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 hidradenitis suppurativa, bacterial infection seems to be a risk factor for the destructive scarring and extension of hidradenitis suppurativa 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 and anaerobic bacteria.[1, 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 hidradenitis suppurativa.[53]

The earliest inflammatory event in hidradenitis suppurativa 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 nonfollicular-based theories on what causes hidradenitis suppurativa, 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. More than 15 years ago, the existence of a familial form of hidradenitis suppurativa with autosomal dominant inheritance was proposed. The disease frequency among first-degree relatives of patients with familial hidradenitis suppurativa was 34%.[56]

Heterozygous mutations were recently reported in the gamma-secretase genes PSENEN, PSEN1, and NCSTN in some patients with hidradenitis suppurativa.[57] One member of this gene complex, termed nicastrin (NCSTN), lies on chromosome 1 within the previously reported region 1p21.1-1q25.3 on chromosome 1, where the AI (acne inversa) gene (until recently the only one putative genetic locus in hidradenitis suppurativa), was mapped.[58]

Gamma-secretase is a transmembrane protease composed of four essential protein subunits: one catalytic presenilin (PSEN1) subunit and three cofactor subunits [presenilin enhancer 2 (PSENEN), nicastrin (NCSTN), and anterior pharynx defective 1 (APH1)]. Gamma-secretase appears integral to normal skin function, through effects on notch signaling, such as the biological role in the hair follicle. The pattern of mutations suggests that loss of function of components of the gamma-secretase complex underlies the disease: follicular keratinization, follicular atrophy, the formation of epidermal cysts, absence of sebaceous glands, and epidermal hyperplasia. Most frequently, gamma-secretase mutations corresponded to nicastrin (NCSTN) mutant proteins.

Although these mutations only appear in a minority of cases of hidradenitis suppurativa, their identification delineated the first genetically defined clinical subgroup of patients with hidradenitis suppurativa and primary involvement of the hair follicle instead apocrine gland, suggesting that the primary event is follicular occlusion.[57] Owing to research efforts over the last 3 years, the genetic reasons for the disease are known in approximately 5% of the hidradenitis suppurativa patients. They are different heterozygous mutations in subunits of gamma-secretase. Genetic factors might influence not only the appearance of hidradenitis suppurativa, but also the phenotype of disease.[1]

Host-defense defects

Host-defense defects in patients with hidradenitis suppurativa are suspected but not proven.[59]

Hyperreactive neutrophils have been proposed to be of pathophysiologic importance in many chronic inflammatory diseases involving the destruction of the surrounding tissue by the simultaneous release of reactive oxygen species and active proteases.

The release of oxygen radicals from peripheral neutrophils that are activated in vitro was studied in patients with inactive hidradenitis suppurativa. The generation of free oxygen radicals after the stimulation of peripheral neutrophils with protein kinase C (PKC) activator and phorbolmyristate acetate (PMA) was significantly higher in patients with hidradenitis suppurativa than in healthy control subjects.

The higher sensitivity of PKC to PMA in patients with hidradenitis suppurativa is unlikely to have been induced by the disease and its local lesions because the systemic effects were minor in the quiescent state. Therefore, a defect in the function of the neutrophils might be of pathogenic importance in hidradenitis suppurativa.[59]

A reduction in the percentage of natural killer cells over time and a lower response of monocytes to triggering by bacterial components were found in patients with hidradenitis suppurativa. Further study is needed to elucidate if these changes are related to an autoimmune mechanism in the pathogenesis of hidradenitis suppurativa.[60]

Toll-like receptors play an integral role in the innate immune response to bacteria. A highly increased expression of toll-like receptor 2 (TLR2) by CD68+ macrophages and CD209+ dendritic cells in acne inverse skin lesions was found.[61]

Apart from Toll-like receptor 2 activating microbial products as an important trigger factor in the chronic inflammatory process, the inflammatory reactions leading to hidradenitis suppurativa are only poorly understood, but they show many similarities with other inflammatory reactions such as with psoriasis; proinflammatory cytokines interleukin (IL)‒12 and IL-23 are mediators in autoimmune tissue destruction and are abundantly expressed by macrophages in hidradenitis suppurativa; IL-23 has been shown to be involved in the induction of a T-helper cell subset named Th17; antimicrobial peptides beta-defensin 2, Psoriasin, and cathelicidin are highly up-regulated in lesions of psoriasis and in hidradenitis suppurativa, which may at least in part, explain the clinical finding that hidradenitis suppurativa patients only rarely have skin infections.[1]

Hormonal effects

Apocrine sweat glands are stimulated by androgen and suppressed by estrogen. Evidence for the hormonal effects in hidradenitis suppurativa exists; however, the exact roles of androgens in the pathogenesis of hidradenitis suppurativa remain controversial, and they may prove to be secondary.[10, 62, 63, 64]

Many women describe a worsening of the condition with menses, whereas others report alleviation with pregnancy, followed by postmenstrual flaring. These observations suggest that the low level of estrogen predisposes women to disease activity. Recently, premenstrual flare was shown to be unrelated to menstrual disturbances. These flares were not predictive of the overall course, and the effect of pregnancy was not constant.[37] The female preponderance may also be explained by other specific factors such as the estrogenic influence on inflammation.[33]

The following evidence supports the association of androgens and hidradenitis suppurativa: the disease is rarely present until after puberty begins,[34] Hidradenitis suppurativa is not present in eunuchs or eunuchoids, and hidradenitis suppurativa may occur as the presenting feature of premature adrenarche.[65] Also, antiandrogen therapy is of some benefit in patients with hidradenitis suppurativa.[66]

The relationship between hidradenitis suppurativa and hyperandrogenism is largely based on the finding that the free androgen index is increased due to a low level of sex hormone–binding globulin (SHBG). SHBG is now believed to be regulated by factors that influence body weight.[37]

Hirsutism and obesity are common findings among women with hidradenitis suppurativa.[67]  Obesity can alter sex hormone metabolism, leading to an androgen-excess state. Excessive androgens can enhance keratin production and coarsening of the hair shaft, promoting follicular occlusion.[26]  Although hirsutism, obesity, and acne among women with hidradenitis suppurativa are more common than expected,[37] the incidences are not significantly different from those in the general population.[62, 63, 68] However, neither evidence for biochemical hyperandrogenism nor suppression of SHBG has been shown in women with hidradenitis suppurativa when compared with age-, body weight-, and hirsuties-matched controls.[37]  In one study, obesity and oral contraceptive use were not common or pronounced among patients; this observation suggested that, while these parameters may influence preexisting disease, they are unlikely to be pathogenically important.[30]  In obesity, increased skin-to-skin contact may promote follicular hyperkeratosis.[26]

An abnormal end-organ response to normal circulating levels of androgens is proposed.[66] The normal apocrine gland contains 5-alpha reductase, which converts testosterone to the potent androgen dihydrotestosterone. Finasteride is a competitive inhibitor of the 5-alpha reductase type II isoenzyme. The benefits of finasteride in some patients with recalcitrant and persistent forms of hidradenitis suppurativa,[66] raised the issue of whether 5-alpha reductase type I or type II is expressed in this disease and whether this expression applies to the apocrine gland, sebaceous gland, or both. On the other hand, sebum excretion is not an important factor in the development of hidradenitis suppurativa.[68] Thus, hormonal influence remains controversial.

Other

Cigarette smoking may be among the major triggering factors in hidradenitis suppurativa, and its cessation should be encouraged, although whether cessation improves the course of disease is unknown.[10, 29] 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.[69]

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.[44] 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]

Hidradenitis suppurativa is rarely a side effect of drug use, but oral contraceptives and lithium have been associated with its development.[33]

Lung and buccal cancer are more common among hidradenitis suppurativa patients than in the general population as would be expected with increased tobacco smoking and chewing.[33]

Hidradenitis suppurativa may rarely be complicated by hidradenocarcinoma.[70]

In conclusion, being overweight and obesity are clearly associated factors in hidradenitis suppurativa; their role as severity factors is highly probable. The relationship between the severity of hidradenitis suppurativa and cigarette smoking has been studied, with conflicting results. Mechanical stress as a trigger for hidradenitis suppurativa has still to be proven.[1]

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. 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.[71] Among the most frequently found species are Staphylococcus aureus and coagulase-negative staphylococci, anaerobic streptococci (eg, microaerophilic Streptococcus milleri), and Bacteroides species.[53, 63]

The microbiologic florae are not consistent and change unpredictably.[71]

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.[72]

The noncornifying types II and III epithelia are characterized by the absence of the terminal differentiation markers CK10 and Dsc1 and by the strong expression of Dsg2 in the basal layer. Compared with the normal epidermis and type I epithelium, types II and III epithelia have Dsc2 and Dsg3 in all layers, whereas Dsc3 is restricted to the basal and parabasal layers. The inflammatory character of type III epithelium, as opposed to that of types I and II, is marked by the presence of CK7 and CK19 and the absence of Dsg1.[72]

All 3 types of epithelia are clearly distinct from the interfollicular epidermis because of the absence of CK2e and the presence of CKs 6, 13, 15, and 16; the presence of these proteins reflects the fact that the sinus tract epithelia have undergone the pathologically altered process of growth, differentiation, and inflammation.

CK19 is commonly found in the basal cells of noncornifying stratified squamous epithelia, such as in the outer root sheath (ORS) of the hair follicle. The strongly inflamed CK19-positive parts of the sinus epithelium show no signs of terminal squamous differentiation (ie, nuclei were present in the highest suprabasal layers, and keratohyalin granules were absent). Instead, the inflamed CK–positive parts resembled epidermal keratinocytes grown in organotypic culture, which can be induced to build a noncornifying epithelium and to express CK19 with the addition of retinoic acid to the culture medium.

In all specimens in one study, type I epithelium near the opening of the sinus showed strong similarities to the upper pilosebaceous duct from which the inflammation process seemed to emerge.

In both normal pilosebaceous duct epithelium and cornifying type I sinus epithelium, CK5 and CK14 are restricted to the basal layer, CK10 and Dsc1 antibodies label the suprabasal cells, Dsg1 and Dsg3 are present in an epidermislike pattern, and CK2e is absent.

The relationship of the sinus epithelium to the hair follicles and the apocrine glands has long been debated.[55] The sinus epithelium is clearly distinct from the normal epithelium of the subinfundibular ORS of the hair follicle. Thus, CKs 5 and 14 and Dsg2 always remain restricted to the basal cell layer of the sinus epithelium, whereas in the subinfundibular ORS, they are also expressed in the suprabasal layer. The relationship of the sinus epithelium to hair follicles and apocrine glands is in agreement with the theory that hidradenitis suppurativa lesions are caused by follicular plugging and subsequent rupture of the follicular epithelia. The exact role of inflammation in such patterns of differentiation has yet to be elucidated.

Thus, in another study of the hidradenitis suppurativa cytokeratin expression reported by Kurokawa et al, the draining sinus tract epithelium of hidradenitis suppurativa lesions were divided into 3 components: infundibular-like keratinized epithelium (type-A), noninfundibular keratinized epithelium (type B), and nonkeratinized epithelium (type C).[73] Types A and B were similar to the types I and II reported by Kurzen et al,[72] although CK17 was not detected in type A, suggesting fragility of this epithelial type. CK17, which is normally present in the suprabasal layers of healthy skin, represents a useful marker for differentiation of epithelial cells. It is a spacial keratin and has a function related to the maintenance of the 3-dimensional cytoskeleton structure of human adnexal glands. Thus, the absence of CK17 may reflect a fragile follicular structure, resulting in rupture of the follicle, which subsequently forms a subcutaneous abscess.[74]

CK expression in pilonidal sinus is comparable with that in hidradenitis suppurativa, as previously reported. Moreover, in infundibularlike epithelium, CK17 is also absent.[74]

The overlying epidermis in hidradenitis suppurativa lesions has a more undifferentiated hyperproliferative state than that found in healthy epidermis.[73] In some cases, CK19 is present in the basal layer of the epidermis, and CK19 is thought to be associated with premalignant change.[75]

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.[71] Some evidence suggests that the occlusion of abnormal hair follicles may play an important part in the initiation of the lesions.[25, 76] Follicular occlusion was found in all specimens compared with controls and regardless of disease duration.[61] 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.[69]

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.[64] 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.[13]

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.[41]

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.[77] 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.[72]

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.[72] 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.

Staging

Clinical staging of hidradenitis suppurativa has diagnostic value. A study has shown that the soluble IL-2 receptor serum level in patients with hidradenitis suppurativa can be used as valuable marker for disease staging.[79] The Hurley clinical staging of hidradenitis suppurativa from 1989 is still relevant today; it has diagnostic value but is not suitable for monitoring the efficacy of interventions in clinical trials.[1] It is as follows:

Dynamic staging system have been used for assessing differences in treatment effects.[6] Uniform outcome variables should take into account the known characteristics of hidradenitis suppurativa, including the following:[6]

A recently developed six-stage physician global assessment (PGA) is defined as follows:

However, a Hurley severity grade‒relevant conservative and surgical treatment for hidradenitis suppurativa is recommended.[1, 7] In order to assess any treatment effectiveness, it is very important to standardize relevant endpoints. Defined as at least a 50% reduction in total abscess and inflammatory nodule count with no increase in abscess count and no increase in draining fistula count relative to baseline at week 12, the hidradenitis suppurativa clinical response (HiSCR) is currently the most appropriate clinical endpoint to assess treatment and effectiveness for hidradenitis suppurativa treatment. It does not contradict hidradenitis suppurativa response measured by the modified Sartorius Score or PGA, but rather represents a more sensitive measure of change in disease activity, resulting in a more accurate representation of patient response and treatment evaluation. The HiSCR does not take into account the size or severity of individual lesions and does not measure how treatment response affects a patient’s level of pain or quality of life. However, the threshold of 50% reduction in total abscess and inflammatory nodule count is the defined level that is clinically appropriate and meaningful to the patient regarding improvement in quality of life and pain level.[8]

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[5] (see Surgical Care). 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.[4]

Surgical Care

Surgery is necessary at times, especially in chronic hidradenitis suppurativa. Wide surgical excision, with margins well beyond the clinical borders of activity, remains the most definitive surgical therapy.[5] With this technique, sufficient resection of the lesion is the most important issue.[7] Although recurrence rates may be lower with surgery that is more aggressive, recurrences continue.[10, 11] After radical excision, the disease recurred in 33% of the patients.[11] Surgery is most valuable in the chronic and recurrent stages of hidradenitis suppurativa.[5, 7]

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.[5, 44, 7, 81] If the disease is diagnosed and treated early, secondary systemic complications can be prevented and the extent of surgery can be limited.[7]

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.[34] Patients should be warned that new lesions may develop at a site that was not apparent at the time of their initial surgery.[44]

Relatively minor surgical techniques

Numerous helpful and relatively minor surgical techniques include drainage; exteriorization; Nd:YAG laser treatment; 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.[13, 14, 15]

Local incision and drainage of purulent lesions are often required in the acute phase, and, although these procedures are helpful in providing short-term relief, recurrent inflammation is almost inevitable.[71] Deroofing of sinus tracts and curettage of fistulous tracts have distinct roles as preliminary treatments before more definitive intervention, and are especially suited for recurrent hidradenitis suppurativa lesions at fixed locations in Hurley I or II stage, particularly in the acute phase of perianal disease.[1] An alternative surgical approach may be used in so-called bridging lesions. These lesions have 2 distant cutaneous orifices connected by a subcutaneous fistula. Periorificial fusiform skin incisions are made parallel to the skin folds, followed by a viral blue dye injection for accurate visualization of the fistula tract, and the subcutaneous tubular fibrotic tissue is completely removed en bloc.[15]

When disease is chronic and extensive, removal of the affected area and the adjacent apocrine glandular zone to 2 cm beyond the diseased portion is the best option to minimize recurrence. The block of tissue excised should be adequately wide and sufficiently deep. To ensure that the deep coils of the apocrine gland are removed, the subcutaneous tissue down to the deep fascia, or at least 5 mm of subcutaneous fat, should be excised. The extent of the sinus tracts is intraoperatively marked by injecting 3-5 mL of a methyl-violet solution. Complete surgical excision is achieved when all color-coded areas are fully removed. In cases where blue-stained areas occurred in the operative field, further re-excisions must be performed to ensure complete clearance.[7]

Minor procedures can include exteriorization and laying open of tracts and electrocoagulation and excision and primary closure (eg, the Pollock procedure).[82] Total wide excision with healing by secondary intention or with the use of flaps and grafts can also be considered. Skin grafts could include Thiersch split-thickness grafts, meshed grafts, or Wolfe full-thickness grafts.[83, 84] Flaps could include rotation flaps or free flaps.[85, 86]

Surgical excision using the carbon dioxide laser and second-intention healing are often associated with good results and minimal complications. Healing usually occurs in 4-8 weeks. Use of the laser procedure is now advocated in patients with severe perianal hidradenitis suppurativa and the complex perianal fistula disease (PAD). With the carbon dioxide laser, lesions are ablated by vaporizing the tissue in layers until all macroscopically abnormal tissue is removed. This method effectively eradicates septic tracts and pockets while preserving sphincter function. The lesions are vaporized from the inside and out until surrounding healthy tissue is reached, superficially and deep. In this way, the technique can be tissue sparing and at the same time radical.[1] It also obviates diversion with or without proctectomy.[87]

Moreover, scanner-assisted carbon dioxide laser makes ablation quicker, smoother, and more precise and allows for early treatment of hidradenitis suppurativa lesions that were previously managed with less effective local conservative remedies.[88] Carbon dioxide laser treatment should be considered as a treatment option in patients with Hurley stage II.[89]

The goal of surgery is to achieve complete removal of lesional tissue, but it is important to spare as much healthy tissue as possible to prevent the formation of serious contractures. In order to gain both goals the Skin-Tissue sparing Excision with Electrosurgical Peeling (STEEP) procedure was developed. Wide excisions reach into the healthy deep subcutaneous fat, but the STEEP procedure with its successive tangential transsections leaves the epithelialized bottoms of the sinus tracts and a large extent of the subcutaneous fat intact, leading to more superficial and smaller defects. STEEP is done with the patient under general anesthesia. For the performance of the multiple transversal sections, electrosurgery has some important advantages over the carbon dioxide laser, since transversal electrosection is more easily controlled and adjusted by the surgeon. This leaves the epithelialized sinus bottom intact and allows deep excision of fibrotic and inflammatory tissue at the same time, while a carbon dioxide laser removes a continuous horizontal plane of one depth, making it less precise and less tissue sparing.[9]

A prospective, randomized, controlled study for patients with stage II to III hidradenitis suppurativa was designed in order to assess the 1064-nm Nd:YAG laser effectiveness in the treatment for hidradenitis suppurativa. After a 3-month laser session was administrated, the percentage change in severity of the disease from baseline was significant for all anatomic sites combined and each individual anatomic site as well. Thus, the effectiveness of this hair epilation device supports the primary follicular pathogenesis of hidradenitis suppurativa.[16] More research is needed before Nd:YAG laser can be established as a standard treatment for hidradenitis suppurativa.[1]

Other techniques

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.

The method of reconstruction depends on the size and the location of the defect.[7] In lesions that can be completely resected, the surgical procedure to cover the lesions should be selected to suit the size and the site of the defect. Negative-pressure dressings are particularly useful in the treatment of wounds requiring closure with skin grafts.[13, 90] However, in lesions that cannot be completely resected, the use of a musculocutaneous flap is recommended.[14] A reliable musculocutaneous perforator flap based on the musculocutaneous branches of the thoracodorsal vessels is very suitable for covering the axillary vessels and aesthetics of the axilla,[91] the option of choice for recurrent disease.[1] If the defect is too large for primary suturing or local cutaneous flaps, it can be covered with polyurethane foam sheets to induce formation of granulation tissue.[7]

Although accurate comparative assessment of the various surgical approaches is difficult because of the incomplete reporting of long-term results and the limited number of controlled clinical trials, skin grafting is generally considered unsuitable in the management of inguinoperineal disease. When compared with healing by secondary intention, split-thickness skin grafting is less preferred among patients, even those with axillary disease. Those who advocate excision and healing by secondary intention claim that this technique permits adequate disease clearance and results in a cosmetically acceptable scar, superior to that obtained by skin grafting, with little limitation of movement.[12]

A report on five patients treated for stage III vulvar hidradenitis suppurativa showed that the only one patient who was managed without split-thickness skin grafting developed an introital stricture and this was the only patient who regretted undergoing surgical excision for hidradenitis suppurativa.[92]

The width of the excision, and not the wound closure technique, influence the therapeutic outcome.[28] Recurrence after surgery is likely if excision is inadequate or if the distribution of apocrine glands is unusually wide.[12, 7, 14] 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.[12] An overall recurrence rate of 2.5% has been estimated after wide surgical excision, with a median postoperative follow-up of 36 months.[7]

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.[93] 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.[33]

Nonablative radiofrequency therapy can be used for patients with Harley stage I and II.[17]

Diet

Patients who are obese should be advised to lose weight.[5]

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, 5] In order to relieve symptoms, avoidance of excessive heat and humidity, which are known triggers, by staying indoors in air conditioning can be helpful. Other potential triggers, although not causative factors, include the use of deodorants, shaving, and depilation.[5]

Complications

Complications of hidradenitis suppurativa include local and systemic infections resulting from the spread of microorganisms[94] and, in rare cases, septicemia. Other complications may include the following:

Guideline Summary

In the published guidelines for hidradenitis suppurativa developed by the Guidelines Subcommittee of the European Dermatology Forum,[1] it is recommended that hidradenitis suppurativa be treated based on the subjective impact and objective severity of the disease, as follows:

A Hurley severity grade‒relevant treatment of hidradenitis suppurativa is recommended by the expert group with the following treatment algorithm:

Systemic treatment (clindamycin + rifampin/tetracycline or acitretin) with adjuvant therapy (pain management treatment of superinfections is proposed for Hurley II stage)

Based on expert opinion it is recommended that adjuvant therapy is offered to all patients in the form of general measures such as weight reduction, cessation of cigarette smoking, and specific help with bandaging lesions in order to improve the patients’ quality of life. Hidradenitis suppurativa‒specific bandages are not currently available.[1] Choice of dressing is based on clinical experience.[28] In addition, adhesive tape should be avoided to minimize trauma to inflamed skin, which can be overcome by using tubular net bandages or superabsorbent pads or materials in the seams of clothing.[2]

Regarding local wound care, superabsorbent dressings are best to treat actively draining lesions or postoperative wounds, but there are no trials or studies to support this recommendation.[1] In order to prevent the primary dressing from sticking to the wound, white petrolatum, zinc oxide paste, or film-forming liquid acrylate should be extensively and generously applied on the marginal skin as the best ways to keep the wound dressings in place.[2]

Algorithm

In 2016, an algorithm with respect to all aspects of hidradenitis suppurativa therapy included in the aforementioned guidelines was developed by using Grading of Recommendations Assessment and Evaluation (GRADE) methodology based on the Category of Evidence and Strength of Recommendation.[1, 28]

The need for surgical intervention should be assessed in all patients depending on the type and extent of scarring.[28]

The proposed dosing regimen as a first-line treatment option in patients with mild hidradenitis suppurativa PGA or localized Hurley I/mild Hurley II stage, especially when there are no deep inflammatory lesions (abscesses), is topical clindamycin 1% solution/gel twice daily for 12 weeks and/or tetracycline 500 mg orally twice daily for 4 months.

If patient fails to exhibit a response to treatment or for a PGA of moderate-to-severe disease with moderate and severe hidradenitis suppurativa PGA or Hurley II stage, considered clindamycin 300 mg orally twice daily with rifampin 600 orally twice daily for 10 weeks.

If the patient is not improved, then adalimumab is recommended as a first-line treatment option in patients with moderate-to-severe hidradenitis suppurativa who were unresponsive to or intolerant of oral antibiotics. Dosing is adalimumab 160 mg at week 0, 80 mg at week 2, and then 40 mg subcutaneously weekly.

If improvement occurs, then therapy should be maintained as long as hidradenitis suppurativa lesions are present. If the patient fails to exhibit response, then consideration of second- or third-line therapy is required.

The second-line therapies include the following:

If clinical response is not achieved after 12 weeks of treatment, other treatment modalities must be considered.

Third line therapies evaluated include the following:

Benefit-to-Risk Ratio

A relevant benefit-to-risk ratio analysis can be performed only for the phase 2 trial of adalimumab, since that is the only randomized controlled trial with an appropriate safety analysis that provides the basis to recommend adalimumab as the first-line treatment option in patients with moderate-to-severe hidradenitis suppurativa who were unresponsive to or intolerant of oral antibiotics.[28, 100]

There is very limited or absent randomized controlled trial data in hidradenitis suppurativa for antibiotic therapy, retinoids, oral immunomodulators, and, in particular, there are no randomized controlled trial data investigating the timing of surgery or type of surgical procedure. Interventions currently under investigation include topical antiseptics, the Nd:YAG and carbon dioxide lasers, anakinra (a newer biological treatment that inhibits IL-1, and the PIONEER I and II studies of adalimumab therapy.[100]

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.[14]

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 symptoms.

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 including biologics 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.[5]

Mild topical steroid creams in combination with topical antibiotics in the aminoglycoside group, such as clindamycin 1-2% solution/gel, gentamicin collagen sponge, and erythromycin 3% gel, have been favored.[15]

Systemic treatment is indicated when more severe or widely spread lesions are present.[1] Some authors advocate long-term treatment with systemic antibiotics (eg, tetracycline, doxycycline, minocycline, clindamycin, trimethoprim-sulfamethoxazole, erythromycin in combination with metronidazole), but long-term outcomes are often poor.[4, 5]

The aim of one study was to evaluate the efficacy of hyperbaric oxygen therapy as an adjunctive therapy in patients treated with a combination of rifampin and clindamycin. Adjunctive hyperbaric oxygen therapy was considered effective to significantly improve the efficacy of antibiotic treatment of hidradenitis suppurativa.[101]

Clindamycin at 300 mg twice daily in combination with rifampin at 300 mg twice daily has been recommended in a 2012 clinical practice article by Jemec, especially in light of the emerging presence of methicillin-resistant Staphylococcus aureus (MRSA).[102]

Systemic treatment with a combination of rifampin-moxifloxacin-metronidazole, either alone or preceded by systemic ceftriaxone treatment, is recommended for resistant stage II and III disease. After 12 weeks of initial treatment, the therapy should be continued for an additional 12 weeks using a combination of moxifloxacin and rifampin.[1]

Dapsone therapy with 25-200 mg/day should be initiated if standard first- or second-line agents fail. There are no data on maximum duration of therapy (reported range, 3-48 months).[1]

Some patients have dramatic responses to isotretinoin 1 mg/kg/day as monotherapy.[47] Retinoids may also be useful only as an adjunct to reduce inflammation before and after surgery.[44, 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.[103] The dose of isotretinoin has not been found to be important in treating hidradenitis suppurativa. 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.[104] In general, the results from the use of oral retinoids are disappointing.[2]

The suggested dosage and duration of treatment with isotretinoin is similar to those proposed for severe forms of acne vulgaris (0.5-1.2 mg/kg/day for 4-12 months). However, the presence of acne vulgaris or of a history of previous acne had no impact on outcome. An absence or reduced volumes of the sebaceous glands are observed in hidradenitis suppurativa. Its usage in hidradenitis suppurativa is often disappointing; patients were assessed as nonresponders in 64.4%, the observed response (evaluated as moderate to significant) among the rest of the patients was mainly restricted to those with mild hidradenitis suppurativa forms (Hurley I). In general, the literature data are inconsistent, but it is currently recommended not to use isotretinoin in the treatment of hidradenitis suppurativa.[1]

Caution should be taken if liver enzyme or serum lipid levels increase during therapy; it should avoided/stopped if these values increase three and two times over the upper normal range limit, respectively. Since both retinoids and tetracyclines can increase intracranial pressure, their combined use is also contraindicated.

Pregnancy testing should be done monthly during the whole period of drug intake and for 5 weeks after therapy cessation.[1] .

Intralesional steroid 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 (up to 3-6 mL per visit) is recommended for its anti-inflammatory effects. This treatment can be repeated every 2-3 weeks if necessary.[77] These injections should be avoided if there is clinical evidence of infection.[2]

Data on the use of corticosteroids in hidradenitis suppurativa are limited.[1] The anti-inflammatory effects of systemic corticosteroids may be useful in acute exacerbations. Prednisolone at 60 mg/day with lower maintenance doses provides some long-term control.[63] Oral prednisone reduces inflammation, facilitates the healing of existing hidradenitis suppurativa lesions, and prevents future lesions from forming.[2] A dose of 0.5–0.7 mg/kg oral prednisolone is recommended for short-term use for acute flares; the dose should be rapidly tapered to stop over weeks.[1]

This was supported by several reports in the literature of patients with hidradenitis suppurativa and Crohn disease who responded to infliximab.[42, 105, 106, 107, 108] 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.[109] The benefits outweigh the risks associated with its use, especially when it is administrated in severe chronic cases resistant to standard therapies.[87]

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.[109, 110] 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.[110, 111]

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.[112] In a study in the United Kingdom, the authors looked at 134 responses to an online survey of dermatology consultants, nurses, and general practitioners who treat patients with hidradenitis suppurativa, in order to see how much variation there is in the types of treatment patients receive; 46% of responders included infliximab in their top 10 treatments.[113] Moderate-quality evidence suggests that infliximab is effective in hidradenitis suppurativa.[114]

Other TNF-alpha 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 been studied. For etanercept, not enough information is available to assess the true risks of TNF-alpha inhibitor use as therapy for hidradenitis suppurativa. Thus, randomized controlled studies are necessary to determine the risk-to-benefit ratio of TNF-alpha inhibitor therapy in the treatment of hidradenitis suppurativa.[114, 115, 116, 117, 118] On September 11, 2015, the FDA approved adalimumab to treat moderate-to-severe hidradenitis suppurativa in adult patients showing inadequate response to conventional therapy. Adalimumab is recommended as a first-line treatment option in patients with moderate-to-severe hidradenitis suppurativa who were unresponsive to or intolerant of oral antibiotics.[100]

More, larger randomized controlled studies are required to investigate most hidradenitis suppurativa interventions, particularly oral treatments with biologics. Moderate-quality evidence suggests that adalimumab given weekly and infliximab are effective, whereas adalimumab every other week is ineffective.[114] No definitive conclusions regarding the most effective biological drug for hidradenitis suppurativa could be drawn. Higher dosage schedules seem to be associated with higher response rates. The lack of response of one particular drug does not preclude the potential efficacy of another biological treatment.

Therapeutic experience with nonspecific immunosuppression in hidradenitis suppurativa using methotrexate is unlikely to offer any significant advance. Different immunosuppressive medications, including methotrexate and cyclosporin A, have been used in case reports.[2] 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. Data assessing the appropriate dose or duration of cyclosporin A for hidradenitis suppurativa are limited. Beneficial effects of cyclosporin A are reported in limited cases. Use should therefore be reserved for cases in which standard first-, second-, and third-line therapies have failed until further evidence is available. Daily doses of 2-6 mg/kg have been used for variable duration (6 weeks to 7 months).[1]

The therapy is mainly indicated for female patients with menstrual abnormalities, signs of hyperandrogenism, or upper normal or high serum levels of dehydroepiandrosterone, androstenedione, and/or sexual hormone-binding protein.[1]

Finasteride might be a suitable additive therapy for refractory female hidradenitis suppurativa cases[2] .

Despite the fact that severe pain causes high morbidity, hidradenitis suppurativa has been essentially ignored in the pain medicine literature.[1]

No clinical evidence exists on the use of nonsteroidal anti-inflammatory drugs in the treatment of pain and inflammation in hidradenitis suppurativa. It was suggested that ketoprofen topical preparations, especially the patch one, could be useful mostly because of its good skin permeability.[1] Except aspirin, COX-2 inhibitors should probably be avoided because they are associated with a higher risk for major adverse cardiovascular events compared with the other nonsteroidal anti-inflammatory drugs.

No clinical evidence exists for the use of opioids in the amelioration of pain in hidradenitis suppurativa. Their use should be restricted and limited to cases in which all other options have failed. Codeine should be the first treatment option.[1] A fentanyl patch can be used for resistant pain.[2]

Gabapentin and pregabalin should be first-line therapy of neuropathic pain because they have fewer adverse effects.[1]

Exfoliants and peels with topical 15% resorcinol cream, which is the only exfoliant formulated as an oil/water cream with emulsifying waxes, exhibits keratolytic, antipruritic, and antiseptic activities. Resorcinol is indicated in recurrent lesions in patients with Hurley stage I or II hidradenitis suppurativa. 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.[119]  No formal studies or guidelines are available on the use of resorcinol in pregnancy.

Other therapies, including the use of adapalene or azelaic acid, may occasionally be beneficial based on expert opinion. No formal studies have been conducted and therapies must currently be considered experimental.[1]

Metformin can be used as an alternative to current treatments, including long-term antibiotics.[2]

Zinc seems to be a maintenance therapy and second-line treatment for Hurley stage I and II hidradenitis suppurativa.[1, 28]

Tetracycline

Clinical Context:  Tetracycline is used to treat gram-positive and gram-negative organisms and mycoplasmal, chlamydial, and rickettsial infections. It inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunits. It can be prolonged if clinically indicated.

Doxycycline (Doryx, Vibramycin, Adoxa)

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

Clindamycin (Cleocin)

Clinical Context:  Clindamycin is a lincosamide for the treatment of serious skin and soft tissue staphylococcal infections. It is also effective against aerobic and anaerobic streptococci (except enterococci). It inhibits bacterial growth, possibly by blocking the dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Rifampin (Rifadin, Rimactane)

Clinical Context:  Rifampin inhibits DNA-dependent RNA polymerase activity in bacteria, by interacting with bacterial RNA polymerase.

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

Clinical Context:  Erythromycin 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 the severity of infection determine the proper dosage. When twice-daily dosing is desired, half the total daily dose may be taken every 12 hours. For more severe infections, double the dose.

Dapsone

Clinical Context:  Dapsone is bactericidal and bacteriostatic against mycobacteria; its mechanism of action similar to that of sulfonamides, in which competitive antagonism of PABA prevents the formation of folic acid, inhibiting bacterial growth. Dapsone therapy with 25-200 mg/day should be initiated if standard first- or second-line agents fail. There are no data on maximum duration of therapy (reported range, 3-48 months).

Minocycline (Minocin, Solodyn)

Clinical Context:  Minocycline can be used for the treatment of infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible rickettsial, chlamydial, and mycoplasmal organisms.

Trimethoprim/sulfamethoxazole (Bactrim, Bactrim DS, Septra DS, Sulfatrim)

Clinical Context:  This combination agent inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid. The antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except Pseudomonas aeruginosa.

Class Summary

Acute episodes and relapses of hidradenitis suppurativa should be treated as bacterial infections.

Isotretinoin (Amnesteem, Claravis, Absorica, Myorisan, Zenatane)

Clinical Context:  Isotretinoin affects epidermal differentiation, especially at the follicular infundibulum, has immunomodulating effects, and 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.

Acitretin (Soriatane)

Clinical Context:  Acitretin is a metabolite of etretinate. Specifically, acitretin helps to normalize cell differentiation and thin the cornified layer, by directly reducing the keratinocytes’ rate of proliferation. This is why it is reasonable to suggest acitretin usage in early hidradenitis suppurativa stages (Hurley I or mild II), and perhaps even in the later stages of hidradenitis suppurativa. Recommended doses administered over 3-12 months for acitretin and etretinate ranged from 0.25-0.88 mg/kg and 0.35-1.1 mg/kg, respectively. Pregnancy testing should be done monthly during the whole period of treatment and preferably at 1-3 monthly intervals after therapy cessation for a period of at least 2 years (3 years according to US labelling).

Class Summary

Vitamin A derivatives have many roles. They encourage cellular differentiation, are antiproliferative, and serve as immunomodulators.

Triamcinolone (Aristospan, Kenalog)

Clinical Context:  Triamcinolone is used for inflammatory dermatoses responsive to steroids; it decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability. Intramuscular injection may be used for widespread skin disorders. Intralesional injections may be used for localized skin disorders.

Prednisolone (Millipred, Pediapred, Veripred, Prelone)

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

Prednisone (Deltasone, Rayos)

Clinical Context:  Prednisone is useful for treating inflammatory and allergic reactions; it may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity. It 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.

Cyproterone acetate

Clinical Context:  Cyproterone is not available in the United States. It inhibits androgen binding to target cells.

Spironolactone (Aldactone)

Clinical Context:  Spironolactone is an aldosterone antagonist that inhibits ovarian and adrenal production of androgens. It competes with dihydrotestosterone binding at hormone receptor sites on hair follicle cells. It also reduces 17-alpha-hydroxylase activity, lowering plasma levels of testosterone and androstenedione.

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.

Adalimumab (Humira)

Clinical Context:  Adalimumab is a recombinant human anti-TNF-alpha IgG1 monoclonal antibody; it blocks the inflammatory activity of TNF-alpha; it specifically binds to TNF-alpha and blocks its interaction with p55 and p75 cell surface TNF receptors; it also lyses surface TNF-expressing cells in vitro and modulates biologic responses responsible for leukocyte migration.

Infliximab (Remicade)

Clinical Context:  Infliximab inhibits TNF-alpha activity and triggers complement-mediated lysis of TNF-alpha–expressing cells in vitro. It is a monoclonal chimeric antibody made from human constant and mouse variable regions of IgG, with binding specificity for human TNF-alpha. It binds to inactive TNF-alpha and can bind specifically to both membrane-bound and soluble TNF-alpha. Infliximab binds to inactive TNF-alpha monomers, preventing their association into active trimers. It is 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 two conditions may share the same pathogenesis, namely excess tumor necrosis factor-alpha (TNF-alpha) production.

Norgestrel/ethinyl estradiol (Cryselle 28, Elinest, Lo-orgestrel, Orgestrel)

Clinical Context:  Norgestrel/ethinyl estradiol reduces secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary gland by decreasing the 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. The therapy is mainly indicated for female patients with menstrual abnormalities, signs of hyperandrogenism, or upper normal or high serum levels of dehydroepiandrosterone, androstenedione, and/or sexual hormone-binding protein.

Finasteride (Proscar)

Clinical Context:  Finasteride 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 the genital region contains type 2. Finasteride has been effective in treating hirsutism. Finasteride might be a suitable additive therapy for refractory female hidradenitis suppurativa cases.

Class Summary

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

Zinc (Galzin, ZnCl2)

Clinical Context:  Zinc gluconate alters an innate immunity in lesional skin since partially restores Toll-like receptors 2, 3, 4, 7, and 9; intercellular adhesion molecule 1; IL-6; TNF; alpha-melanocyte-stimulating hormone; transforming growth factor-beta; b-defensin 2 and 4; and insulinlike growth factor 1. Zinc seems to be a maintenance therapy and second-line treatment for Hurley stage I and II hidradenitis suppurativa.

Class Summary

These are essential to normal growth and development, and they play a role in many metabolic processes.

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 of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Disclosure: Nothing to disclose.

Specialty Editors

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

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.

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.

Additional Contributors

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

Disclosure: Received consulting fee from Galderma for consulting; Received consulting fee from Valeant for consulting; Received consulting fee from Promius for consulting; Received consulting fee from Anacor for consulting; Received grant/research funds from Stiefel for investigator; Received grant/research funds from Astellas for investigator; Received grant/research funds from Ranbaxy for other; Received consulting fee from Ranbaxy for consulting.

Acknowledgements

Diana Fite, MD, FACEP Clinical Assistant Professor, Department of Emergency Medicine, University of Texas Medical School at Houston, Hermann Hospital

Diana Fite, MD, FACEP is a member of the following medical societies: American Association of Women Emergency Physicians, American College of Emergency Physicians, American Medical Association, Society for Academic Emergency Medicine, and Texas Medical Association

Disclosure: Nothing to disclose.

John Geibel, MD, DSc, MA Vice Chair and Professor, Department of Surgery, Section of Gastrointestinal Medicine, and Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director, Surgical Research, Department of Surgery, Yale-New Haven Hospital

John Geibel, MD, DSc, MA is a member of the following medical societies: American Gastroenterological Association, American Physiological Society, American Society of Nephrology, Association for Academic Surgery, International Society of Nephrology, New York Academy of Sciences, and Society for Surgery of the Alimentary Tract

Disclosure: AMGEN Royalty Consulting; Ardelyx Ownership interest Board membership

Ravi Pokala Kiran, MBBS, MS, FRCS (Eng), FRCS (Glas) Staff Physician, Department of General Surgery, St Mary's Hospital

Disclosure: Nothing to disclose.

David L Morris, MD, PhD, FRACS Professor, Department of Surgery, St George Hospital, University of New South Wales, Australia

David L Morris, MD, PhD, FRACS is a member of the following medical societies: British Society of Gastroenterology

Disclosure: RFA Medical None Director; MRC Biotec None Director

Naveen Pokala, MBBS, MS, FRCS Staff Physician, Department of Surgery, Bronx Lebanon Hospital

Disclosure: Nothing to disclose.

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

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.