Hidradenitis suppurativa/Acne inversa (HS) is a chronic recurrent, inflammatory skin disease affecting mainly the intertriginous areas. The disease involving the apocrine – gland – bearing skin areas may be mild and limited or severe, causing widespread deep infection and resulting in abscesses, sinus tract formation, fistulas releasing malodorous discharge and subsequently in excessive scarring (1-4). Due to its chronicity, recurrent character and specific multifocal location of the lesions, HS is a physically, psychologically and socially disabling condition associated with considerable impairment of the quality of life (5).

There are some controversies about the epidemiology of HS. Despite the common opinion of HS being a rare disease, the exact prevalence is uncertain and probably different in various populations and groups of age. Literature data report the prevalence rate raging between 0.03-0.06 and 4%, but most authors suggest 1% in general population (1, 2, 4, 6). The onset of the disease is usually observed between 11 and 30 years of life (1, 4). Postmenopausal onset is rare, its prevalence among the subjects older than 55 years of age is about 5 times lower than in younger patients (1, 2, 4). What is interesting, some locations have distinct sexual predisposition, thus the perianal HS seems to affect male more than female patients (1, 7). Although the disease occurs in all human races, a higher prevalence is observed in black people than in Caucasians (1, 2).

Genetic background is being taken into consideration, although genetic studies conduce to conflicting results (4, 8). Clinical data, indicate that, 30-40% of HS patients have a family history, but the HLA association seems to be not significant (4, 8). An autosomal dominant pattern has been suggested with locus for the disease on chromosome 1p21.1-1q25.3, but a specific gene was not identified (1, 4).

Understanding of the HS pathogenesis has changed considerably over time, but still remains unclear. Due to the specific anatomical distribution of the disease, HS was initially believed to be a disorder of the apocrine glands (1, 2, 4). It is well known, that the apocrine sweat glands, mainly distributed in the axillary and anogenital skin, are evolutional analogues of an odour-producing organ found in lower animals (2). Early data suggested that the apocrine gland involvement is the primarily event leading to the development of the widespread inflammation in the skin and subcutis (1). In 1955, Shelley and Cahn evidenced that the primary event was a keratinous plugging of the apocrine sweat duct leading to the follicular occlusion, which eventually resulted in inflammation of the apocrine glands and neighbouring periglandular tissue (1). Further data suggested that inflammation of apocrine glands is not basic to HS pathogenesis, being only the secondary phenomenon (1). Pillsbury et al confirmed follicular occlusion as cause of HS, and what is more, the authors included this disease, together with acne conglobata and perifolliculitis capitis abscendens et suffodiens/dissecting cellulitis of the scalp, to so called “acne triad” or “follicular triad” (6). From this time, the similarity between the pathogenic mechanisms of acne and HS is being discussed. Plewig and Kligman added pilonidal sinus to “acne triad” and coined the term “acne tetrad” (9). In 1989 Plewig and Steger introduced the term “acne inversa” for the hidradenitis suppurativa, emphasizing a follicular origin of the disease (10).

The results of histologic study published by Yu and Cook in 1990 considerably influenced the contemporary understanding of the HS pathogenesis (1). The researchers showed that follicular occlusion and the dilated follicles were the most constant and probably primary feature and concluded that HS was a disease of follicular epithelium rather than a disease of apocrine glands.

Hidradenitis suppurativa is currently considered as an inflammatory disease of terminal hair follicles manifesting in intertriginous skin sites (2, 8). The accepted belief is that the initiating event is occlusion of the follicular ducts by keratinous plugging, leading to ductal dilatation and stasis in the pilosebaceous unit (1, 2, 3, 11). Bacteria entering the apocrine gland through the hair follicle, are entrapped under the keratinous plug and multiply rapidly (2). Subsequent follicular rupture leads to extrusion of follicular contents, into the dermis inducing a chemotactic inflammatory response (1). The resulting influx of neutrophils, lymphocytes and histiocytes lead to inflammation of the surrounding tissue and abscess formation (1, 2). Bacterial infection results in further local inflammation, suppuration, tissue destruction and skin damage (1, 2). Numerous recurrences and presence of ruptured epithelium lead to development of sinus tracts and fistulas (1, 2).

Last years studies have brought new data concerning the extent of skin inflammation in HS. In 2011 van der Zee et al (12) investigated the cytokine profile in lesional and perilesional HS skin and have shown that TNF-α, IL-1β and IL-10 levels are elevated in HS skin. Moreover, it was also demonstrated that HS inflammation extend beyond the visibly affected inflammatory lesions, and that likely can be the cause of recurrences. These results are in agreement with those obtained earlier by Matusiak et al. (13), who evidenced the elevated TNF-α level in the peripheral blood of HS patients. Recently, alterations in leukocyte subsets in normal-appearing perilesional skin and in HS lesions have been found (14). Moreover, psoriasiform hyperplasia, follicular plugging and mild mixed infiltration consisted of T cells, plasma cells dendritic cells and mast cells, was observed in perilesional “normal” skin (14).

A variety of etiologic factors is suspected of a causal relationship in the pathogenesis of HS. First of all, the role of hormones, especially androgens in HS is still being investigated, but with conflicting results provided by many studies (1). Some researchers present opinion of the disorder being androgen dependent in adults, but others believe that hyperandrogenism probably does not play a role in HS (2). It is worth to stress, that the influence of androgens on the formation of terminal hair follicles in the axillae and anogenital regions may be important in the development of HS, as it is primarily an inflammatory disease of terminal hair follicles (8). A relationship between onset of hidradenitis and androgen levels is strongly suggested by clinical observations of the disease occurring with puberty and its persisting in females up to menopause, rarity of onset thereafter (1, 2). What is more, HS may decline substantially following menopause, also suggesting a hormonal role (1, 8). However, there is no substantial evidence to support hyperandrogenism in women with HS (2). No change in the peripheral blood hormone levels, including testosterone and dehydrotestosterone was observed in HS patients (1, 4). Revuz considering the etiopathogenesis of HS stresses that some important facts concerning the role of androgens remain still unexplained, among them the high female prevalence, the frequent improvement during pregnancy, and the termination of the disease in post-menopausal women (4).

Bacterial infection was suggested as a important etiologic factor contributing to HS pathogenesis. Various aerobic and anaerobic species have been cultured from samples taken from the HS lesions, among them Streptococcus viridans, Staphylococcus aureus, Staphylococcus milleri, Staphylococcus epidermidis, Peptostreptococcus spp., Bacteroides melaninogenicus and Bacteroides corrodens, coryneform bacteria (1, 4). In perineal and perianal locations of HS the Gram-negative bacteria are more commonly found, such as Escherichia coli, Klebsiella, and Proteus (1, 4). Very heterogeneous spectrum of pathogens indicates that the disease is not associated with the presence of a specific pathogen because no single species is dominant (1, 8). Most researchers believe that the bacteria implicated in HS are the secondary colonizers, which may exacerbate the disease, but should not be regarded as the primary etiologic factors (1, 4, 8).

The possible role of numerous exogenous factors in HS development are also taken into consideration. Among them, the mechanical and chemical irritation of the local skin in the areas typically involved, especially caused by shaving and friction (1, 2, 4). The use of chemical irritants, such as deodorants, depilatory chemicals, antiperspirants, talcum powder have been suggested as triggering or exaggerating factors (1, 2, 4, 8).

The role of pharmacological agents is also being considered and it seems that it can not be completely ruled out as yet. Onset or exacerbation following lithium therapy has been reported (1, 4). The suggested mechanism is not only the known lithium ability to induce inflammation but also to facilitate follicular plugging through its direct effect on follicular keratinocytes (1).