Hidradenitis Suppurativa Clinical Presentation
- Author: Marina Jovanovic, MD, PhD; Chief Editor: William D James, MD more...
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]
The diagnosis is primarily clinical, no pathognomonic test exists, and biopsy is rarely required, especially in well-developed lesions. 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. All three criteria must be present for the definitive diagnosis.
Primary positive diagnostic criteria are as follows:
History: Recurrent painful or suppurating lesions more than twice in 6 months
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:
History: Family history of hidradenitis suppurativa
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:
Painful and/or tender erythematous papules smaller than 1 cm in diameter
Painful and/or tender erythematous nodules larger than 1 cm in diameter
Painful or tender abscesses and inflamed discharging papules or nodules
Dermal contractures and ropelike elevation of the skin
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:
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
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 
Others have based the diagnosis on a series of questions, as follows :
Is there more than a single inflamed lesion?
Is the course chronic, with new and recurrent lesions?
Are the lesions bilateral?
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. 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, 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. 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.
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.
The association of hidradenitis suppurativa with several disorders in which poral occlusion is prominent supports the theory of a follicular origin of hidradenitis suppurativa. Such disorders include Fox-Fordyce disease, acanthosis nigricans, pityriasis rubra pilaris (PRP), steatocystoma multiplex, and Dowling-Degos disease.
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. 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.
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. 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.
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.
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).
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.
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. 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. 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.
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. 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. 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.
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. Such strains induced miliaria under experimental conditions. A similar mechanism may be important in the pathogenesis of hidradenitis suppurativa.
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 :
The apocrine glands may play a role in hidradenitis suppurativa since an abnormal secretion (either the excess or absence) could be influencing an effect on the acroinfundibulum, distal from the gland itself.
The sinus tract formation is an early feature of hidradenitis suppurativa, arising not from hair follicles but rather from invaginations of epidermis as cysts.
Resident bacteria, such as coagulase-negative staphylococci may cause adherence of the epidermis in the closed serrated tissue of intertriginous areas, leading to the formation of cysts and hidradenitis suppurativa lesions.
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%.
Heterozygous mutations were recently reported in the gamma-secretase genes PSENEN, PSEN1, and NCSTN in some patients with hidradenitis suppurativa. 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.
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. 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.
Host-defense defects in patients with hidradenitis suppurativa are suspected but not proven.
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.
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.
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.
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.
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. The female preponderance may also be explained by other specific factors such as the estrogenic influence on inflammation.
The following evidence supports the association of androgens and hidradenitis suppurativa: the disease is rarely present until after puberty begins, Hidradenitis suppurativa is not present in eunuchs or eunuchoids, and hidradenitis suppurativa may occur as the presenting feature of premature adrenarche. Also, antiandrogen therapy is of some benefit in patients with hidradenitis suppurativa.
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.
Hirsutism and obesity are common findings among women with hidradenitis suppurativa. 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. Although hirsutism, obesity, and acne among women with hidradenitis suppurativa are more common than expected, 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. 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. In obesity, increased skin-to-skin contact may promote follicular hyperkeratosis.
An abnormal end-organ response to normal circulating levels of androgens is proposed. 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, 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. Thus, hormonal influence remains controversial.
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.
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. 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.
Hidradenitis suppurativa is rarely a side effect of drug use, but oral contraceptives and lithium have been associated with its development.
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.
Hidradenitis suppurativa may rarely be complicated by hidradenocarcinoma.
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.
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