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 Examination
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:
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History: Recurrent painful or suppurating lesions more than twice in 6 months
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Signs: Involvement of axilla, genitofemoral area, perineum, gluteal area and inframammary area of women; presence of nodules (inflamed or noninflamed), sinus tracts (inflamed or noninflamed), abscesses, and scarring (atrophic, meshlike, red, hypertrophic or linear)
Suspicion of the diagnosis can be strengthened by other factors that are not, however, pathognomonic. [1, 3]
Secondary positive diagnostic criteria are as follows:
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History: Family history of hidradenitis suppurativa
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Microbiology: A negative swab or the presence of normal skin microbiota (may be indicative of hidradenitis suppurativa)
Typical lesions, called primary lesions, include the following:
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Painful and/or tender erythematous papules smaller than 1 cm in diameter
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Painful and/or tender erythematous nodules larger than 1 cm in diameter
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Painful or tender abscesses and inflamed discharging papules or nodules
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Dermal contractures and ropelike elevation of the skin
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Double-ended comedones
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:
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Active disease with 1 or more primary lesion in a designated site, plus a history of 3 or more discharging or painful lumps (not specified) in designated sites since age 10 years
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Inactive disease with a history of 5 or more discharging or painful lumps (unspecified) in designated sites since age 10 years, in the absence of current primary lesions [4]
Others have based the diagnosis on a series of questions, as follows [5] :
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Is there more than a single inflamed lesion?
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Is the course chronic, with new and recurrent lesions?
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Are the lesions bilateral?
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Are the lesions located primarily in the milk line?
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.
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.
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, 62, 63] In examining patients with perianal hidradenitis suppurativa, Church et al noted that Crohn disease coexisted with perianal hidradenitis suppurativa in 39% of patients. [64] 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. [52] Such disorders include Fox-Fordyce disease, acanthosis nigricans, [57] pityriasis rubra pilaris (PRP), [65] steatocystoma multiplex, and Dowling-Degos disease. [66]
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. [65] 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. [67]
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. [68] 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. [67]
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. [69]
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).
Close-up view of axillary hidradenitis suppurativa in a patient with pyoderma gangrenosum.
Double-ended-comedones. Hidradenitis suppurativa in a patient with pyoderma gangrenosum.
Close-up view of inguinal hidradenitis suppurativa in a patient with pyoderma gangrenosum.
Close-up view of pyoderma gangrenosum in a patient with hidradenitis suppurativa.
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. [70]
Complications
Complications of hidradenitis suppurativa include local and systemic infections resulting from the spread of microorganisms [71] and, in rare cases, septicemia.
Restricted mobility of the limbs resulting from marked fibrosis and scarring may occur, particularly with axillary disease. [57]
With perianal disease, anal fistula formation is common. Although the etiology of anal fistulas remains unknown, the infection theory is widely accepted. Repeated or persistent abscess formation in the anal glands between the external and internal sphincters may be required for fistula formation. [72] Rectal and urethral fistulas are rare. [40]
Swelling and elephantiasis nostras that occur after streptococcal infection may be superimposed on hidradenitis suppurativa lesions, leading to severe enlargement and distortion of the external genitalia. [73]
In male patients, severe ulcerative genital disease can cause destruction of the prepuce. [74]
Chronic inflammatory reactions, such as anemia, proteinuria, hypoproteinemia, amyloidosis, interstitial keratitis, and renal disease, rarely occur. [40, 73]
It was shown by standard incidence rate (SIR) that hidradenitis suppurativa patients have a higher overall incidence of cancer (SIR = 1.5; 1.1-1.8) compared with the general population. The incidence of nonmelanoma skin cancer (SIR = 4.6; 1.5-10.7), buccal (SIR = 5.5; 1.8-12.9), and hepatic cancer (SIR = 10.0; 2.1-29.1) was increased. [75]
Squamous cell carcinoma (SCC) is a rare but serious consequence. Most SCCs occur in men and in the anogenital region, perhaps because these tumors are hard to detect. SCC tumors show endophytic growth along the sinus tracts once they occur. Most patients with SCC have a history of hidradenitis suppurativa for 10 years or longer; the prevalence of SCC among patients with perianal hidradenitis suppurativa lasting 20-30 years is approximately 3.2%. [76] The diagnosis of perianal SCC is often delayed owing to chronic scarring and the endophytic nature of its growth pattern. Metastases and death may result.
The first case of vulvar SCC as a complication of hidradenitis suppurativa was reported in the English-language literature in 1999. [55] All 5 previously reported cases of SCC with hidradenitis suppurativa in women involved the buttocks or the perianal region. Maclean and Coleman suggest that hidradenitis suppurativa arising in extra-axillary sites is a premalignant condition and that it should not be treated conservatively. [77] SCC that arises in chronically scarred and inflamed skin (Marjolin ulcer) tends to be more aggressive than that resulting from actinic damage, and it is associated with local invasion or recurrence after excision, distant metastasis, and a higher mortality rate. [78]
Attention should also be given to the development of anal cancer.
The draining sinus tract is a late complication of hidradenitis suppurativa and leads to extensive periodically inflamed lesions that are lined by a variably thickened stratified epithelium.
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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.
