Hidradenitis Suppurativa

(Advertisement)

April 23, 2006 Articles Images CME Advanced Search Consumer Health Link to this site

You are in: eMedicine Specialties > Dermatology > Diseases Of The Adnexa Quick Find Author Information Introduction Rate this Article Hidradenitis Suppurativa Clinical Email to a Colleague Differentials Workup Last Updated: March 23, 2006 Get CME/CE for article Treatment Medication Synonyms and related keywords: HS, acne inversa, acne triad, acne tetrad, hidradenitis Follow-up axillaris, apocrinitis, intertriginous acne, pyoderma fistulans sinifica, Verneuil's disease, Miscellaneous Pictures Verneuil disease, dissecting cellulitis of scalp and neck, acne conglobata, follicular occlusion Bibliography triad, follicular occlusion tetrad, pilonidal sinus, acneiform disorder, apocrine occlusion Click for related AUTHOR INFORMATION Section 1 of 11 images.

Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography Related Articles Author: Marina Jovanovic, MD, PhD, Chief of Dermatology Ward and Contact Dermatitis Investigative Unit, Clinic Actinomycosis of Dermatoveneroleogic Diseases, Clinical Center, Novi Sad, Serbia and Montenegro; Associate Professor in Dermatology, Medical Faculty, University of Novi Sad, Vojvodina,Serbia and Montenegro Catscratch Coauthor(s): George Kihiczak, MD, Clinical Associate Professor, Department of Dermatology, New Jersey Disease Medical School University Hospital; Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical Erysipelas School Granuloma Inguinale Editor(s): Daniel Siegel, MD, MS, Director, Procedural Dermatology Fellowship Program, Clinical Professor of Dermatology, Department of Dermatology, State University of New York Downstate; David F Butler, MD, (Donovanosis) Professor, Texas A&M University College of Medicine; Director, Division of Dermatology, Scott and White Clinic; Jeff Miller, MD, Assistant Professor, Department of Dermatology, Penn State University, Milton S Hershey Lymphogranuloma Medical Center; Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University; Venereum and Dirk M Elston, MD, Teaching Faculty, Department of Dermatology, Geisinger Medical Center

Disclosure Continuing Education CME available for INTRODUCTION Section 2 of 11 this topic. Click Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography here to take this CME. Background: Hidradenitis suppurativa (HS) is a disorder of the terminal follicular epithelium in the apocrine gland–bearing skin. HS is characterized by comedolike follicular occlusion, chronic relapsing inflammation, mucopurulent discharge, and progressive scarring. Patient Education Skin, Hair, and Pathophysiology: HS has traditionally been considered a disorder of the apocrine glands. HS was first described Nails Center as a distinct entity in 1839, when Velpeau reported a patient with the superficial abscess formation in the axillary, mammary, and perianal regions. 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 Boils Overview subsequently became known as HS. Verneuil did not perform any histopathologic studies, and he conceded that his conclusions were based purely on the characteristic distribution of the condition. Causes of Boils

In 1922, Schiefferdecker classified the sweat glands as eccrine and apocrine, and he subsequently localized HS to Symptoms of Boils the apocrine glands. In 1939, Brunsting provided a detailed description of the histologic features of HS. He observed the primary cellular reaction in the lumen of the apocrine glands and in the neighboring periglandular Boils Treatment Boils Treatment connective tissue. Detailing the clinical features of the disease, Brunsting highlighted its frequent association with acne. He noted that HS, dissecting cellulitis of the scalp and 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.

In 1956, Pillsbury et al combined acne conglobata, HS, and dissecting cellulitis under the term follicular occlusion triad. The only flaw in their concept was the 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. Plewig and Kligman pointed out that HS 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. Eventually, HS was accepted as an acneiform disorder that begins with follicular occlusion rather than an infection of the sweat glands.

Because HS is actually a defect of follicular epithelium, some authorities have suggested excluding all outdated synonyms for this disease, including HS, and substituting the term acne inversa. The term acne inversa links the pathogenesis to acne and reflects the fact that the condition is an expression of follicular occlusion in localizations inverse to acne vulgaris.

Frequency:

In the US: In the United States, the prevalence of HS appears to be 1-2% in the general population.

Internationally: The prevalence of HS appears to be 1% of the general population; it was 4% in a group of young adults who were treated at a clinic for sexually transmitted diseases. HS is probably more common than once thought, but the diagnosis is frequently ignored or missed. HS has a worldwide distribution, although hot, humid environments tend to support its development.

Mortality/Morbidity: The death rate is similar to that in the general adult population. Although rare complications of the disease are described, little is known about the typical effects of HS. HS is a chronic disabling disorder that relentlessly progresses and leads to keloids, contractures, and immobility. Patients can become outcasts or at least have difficulty making social contact.

In an assessment of socioeconomic effects, Jemec et al noted that the most common problem in both sexes was soreness and that the average patient lost 2.7 days of work per year. In comparison, in Denmark, the average number of work days lost for all reasons was 7.5 days per year per employed person, whereas patients with eczema used 4 weeks of sick leave per year because of their disease. Although HS entails less morbidity than perhaps hand eczema, with regard to its prevalence, it significantly contributes to the average number of work days lost (Danish National Statistical Office, Copenhagen, Denmark, Jemec GB, written communication, 1996).

Jemec et al also found sex differences in morbidity. Women lost significantly more days of work (mean, 2.9 d) than men (mean, 1.7 d); this finding suggests that women have either a more fulminant course or other contributing factors. On the other hand, male patients experienced less delay in seeking care from a specialist or hospital; this finding could also suggest a more fulminant course or the presence of confounding factors.

The general self-reported level of health, which is well correlated with more objective parameters of morbidity, is significantly worse among HS patients than among healthy control subjects.

The mean Dermatology Life Quality Index score for HS is higher than for previously studied skin diseases and correlated with disease intensity as expressed by lesions per month. This suggests that the Dermatology Life Quality Index score may be a relevant outcome measure in future therapeutic trials in HS patients.

Race:

Although many authors report no racial predilection, an increased frequency is observed in blacks, possibly because blacks have a greater density of apocrine glands than whites.

Sex:

Although HS is widely considered to occur more frequently in females than in males, with a ratio as high as 2-5:1, reports on sex prevalence are controversial.

Active genitofemoral lesions occur significantly more often in female patients, whereas perianal involvement tends to be more common in men. No sex difference is seen in the axillary lesions. Large multiheaded comedones are characteristic findings of the disease. Comedones have been suggested as precursor lesions for HS. They appear to be equally distributed in both sexes and sites.

Age:

The onset of HS peaks in individuals aged 11-50 years, with an average patient age of 23 years. In less than 2% of patients, the disease appears before age 11 years.

In extremely rare cases, HS occurs before puberty or after menopause.

CLINICAL Section 3 of 11

Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography

History: HS usually occurs in otherwise healthy individuals, and it rarely begins before puberty.

The disease onset is insidious, with early symptoms of pruritus, erythema, and local hyperhidrosis.

Later, the lesions become painful.

Arthropathy associated with HS may manifest with variable clinical features, ranging from asymmetric pauciarticular arthritis to a symmetric polyarthritis and/or polyarthralgia syndrome.

Physical: The diagnosis is primarily clinical, and biopsy is rarely required, especially in well-developed lesions. Recently, the consensus approach deemed that 3 key elements are required to diagnose HS: typical lesions, characteristic distribution, and recurrence.

Based on 3 premises, a set of typical lesions, called primary lesions, was compiled, as follows:

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

Double-ended comedones

The characteristic sites were chosen in accordance with the 2 areas most frequently affected by HS: the axillae and the groin. These areas are defined by anatomical borders and are called designated sites. HS is diagnosed if the patient has either (1) 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 or (2) 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

Physical findings are as follows.

HS has a predilection for the intertriginous regions.

The axillary and inguinoperineal regions are most commonly affected (see Images 1-2).

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. One or both axillae can be affected. In addition, the inguinal region can be involved, often with spreading to the scrotum, the labia, the mons pubis, the mammary or perianal region, and the buttocks.

A firm pea-sized nodule can appear and may spontaneously rupture, yielding a purulent discharge. The lesion then heals, with fibrosis and eventual recurrence in the 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 HS; these sinuses periodically discharge 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 Images 3-4).

A draining sinus can be easily identified because of its linear or angular shape, its history of being present for a prolonged period, and its variable response to systemic isotretinoin.

Over time, multiple abscesses and sinus tracts form a subcutaneous honeycomb.

Occasionally, the involvement extends into the underlying fascia and muscles.

Ultimately, fibrosis, hypertrophic scarring, and induration develop.

Multiple open comedones and so-called bridged comedones are the hallmark finding of HS; 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, scars and contractures as large as a finger 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 fistulas.

In the upper anal fold, terminal hairs emerge from thickened scars.

Perianal HS 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 HS may be clinically identical to the cutaneous manifestations of Crohn disease (CD). CD may be complicated by a variety of skin manifestations, and HS has been reported to precede or complicate CD. In examining patients with perianal HS, Church et al noted that CD coexisted with perianal HS in 39% of the patients.

Local swelling and inflammation associated with CD may precipitate HS in patients already prone to it. However, the coexistence of CD and HS does not explain the frequent presence of axillary, groin, and buttock involvement, which may imply a constitutional or genetic predisposition to HS in patients with rectal CD.

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

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

Whether the association between HS and CD is more than a coincidence is unclear; however, the small proportion of patients with HS and epithelioid granulomatous inflammation may represent a group that is susceptible to systemic granulomatous disease, including CD.

The association of HS with several disorders in which poral occlusion is prominent supports the theory of a follicular origin of HS.

Such disorders include Fox-Fordyce disease, acanthosis nigricans, pityriasis rubra pilaris (PRP), steatocystoma multiplex, and Dowling-Degos disease.

HIV-associated PRP, or PRP type VI, is a new entity reported in patients with HIV disease. HIV- associated PRP is characterized by the cutaneous lesions of PRP and a variable association with the lesions of acne conglobata, HS, and lichen spinulosus. This disease can be designated by the wider term HIV-associated follicular syndrome. Although the pathogenesis of PRP type VI is unknown, follicular inflammation secondary to HIV infection of the hair follicle bulge area 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 HS, acne conglobata, perifolliculitis abscedens, and suffodiens capitis. Arthritis associated with acne fulminans, seronegative spondyloarthropathies of psoriatic arthritis, and Reiter disease are well-defined clinical entities. However, arthritis associated with HS, acne conglobata, perifolliculitis abscedens, suffodiens capitis, and SAPHO (synovitis, acne, palmoplantar pustulosis, hyperostosis, and osteitis) syndrome are less well defined; these conditions may be part of the spectrum of HLA-B27–negative spondyloarthropathies.

The pathogenesis of the arthritis remains unknown but may include an inappropriate response to bacterial antigens involved in acne or some other autoimmune response.

Arthropathy associated with HS may manifest with variable clinical features, ranging from 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 also may be involved.

In many instances, the arthropathy worsens during flares of HS, and, conversely, it improves after HS resolves.

The concept of SAPHO syndrome includes 4 subgroups of osteoarticular disorders: (1) rheumatologic manifestations associated with acne conglobata or acne fulminans or inversa-HS, (2) pustulosis palmoplantaris, (3) sternocostoclavicular hyperostosis, and (4) chronic multifocal recurrent osteomyelitis.

SAPHO syndrome may encompass cases described as arthropathy associated with HS 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 HS and acne conglobata.

Recent reports raised the question of whether mammillary fistula or Zuska disease might be a manifestation of acne inversa.

Pyoderma gangrenosum has been rarely associated with HS and has occurred only after HS has been present for at least 2 decades, as can be seen in the authors' patient (see Images 5-15). Only 15 cases of coexistent pyoderma gangrenosum and HS were found in the English-language literature. More studies are required to support impaired neutrophil function as a common etiological pathway.

Causes: The exact etiology of HS remains obscure. All proposed etiologic factors, such as occlusion and bacterial infection, genetics, host defense defects, hormones, cigarette smoking, and irritants, are likely 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 HS (see Imaging Studies).

Classic HS 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 HS occurred.

In more recent studies, HS is identified as a disorder of follicular occlusion rather than apocrine occlusion. 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 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, HS 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 promotes perifolliculitis around the ducts. Whether this initial inflammatory change is due to a bacterial infection or factors similar to those involved in acne formation is not known.

In the later stages of HS, bacterial infection seems to be a risk factor for the destructive scarring and extension of HS lesions, and, once the sinuses have formed, the risk of secondary infection is obvious. Among the most commonly isolated bacteria are coagulase-negative staphylococci. 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 infection. Such strains induced miliaria under experimental conditions. A similar mechanism may be important in the pathogenesis of HS.

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

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 HS with autosomal dominant inheritance was proposed. The disease frequency among first-degree relatives of patients with familial HS was 34%. However, this finding does not seem to be widely accepted; why this finding is not accepted is unclear because it had repeatedly been recognized that a number of patients with HS have affected family members.

Findings from a recent review of the original study group supported the previous results, although conclusive proof is still lacking.

A search for the molecular genetic abnormality is now necessary. Mutation within the connexin 26 gene was recently reported in association with keratitis-ichthyosis-deafness syndrome and with the severe follicular occlusion triad. The notion that specific HLA antigens might be at the center of a genetic susceptibility to HS is not supported and remains questionable.

Host-defense defects in patients with HS 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 HS. The generation of free oxygen radicals after the stimulation of peripheral neutrophils with protein kinase C activator and phorbolmyristate acetate was significantly higher in patients with HS than in healthy control subjects.

The higher sensitivity of protein kinase C to phorbolmyristate acetate in patients with HS 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 HS.

Apocrine sweat glands are stimulated by androgen and suppressed by estrogen. Evidence is documented for hormonal effects in HS; however, the exact roles of androgens in the pathogenesis of HS remain controversial, and they may prove to be secondary.

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 flares were 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 HS: the disease is rarely present until after puberty begins, HS is not present in eunuchs or eunuchoids, and HS may occur as the presenting feature of premature adrenarche. Also, antiandrogen therapy is of some benefit in patients with HS.

The relationship between HS 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 HS.

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 are more common than expected among women with HS, the prevalence rates are not significantly different from those in the general population. However, neither evidence for biochemical hyperandrogenism nor suppression of SHBG has been shown in women with HS 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 HS 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 HS. Thus, hormonal influence remains controversial.

Cigarette smoking may be among the major triggering factors in persons with HS, and its cessation should be encouraged. However, whether cessation improves the course of disease is unknown. Precisely what pathogenetic mechanism is responsible for the effect of smoking on the manifestations of acne inversa remains unclear, but an altered chemotaxis of polymorphic neutrophils could play a role.

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 deterioration of their disease during the summer.

HS is rarely an adverse effect of drug use, but oral contraceptive use and lithium use have been associated with its development.

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

As reported by Wasik et al in 2001, HS may rarely be complicated by hidradenocarcinoma.

DIFFERENTIALS Section 4 of 11

Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography

Actinomycosis Catscratch Disease Erysipelas Granuloma Inguinale (Donovanosis) Lymphogranuloma Venereum

Other Problems to be Considered:

Abscesses Apocrine nevus Infection in a Bartholin cyst Carbuncle Crohn disease Infection in an epidermoid cyst Lymphadenitis Multiple trichoepitheliomas Tuberculosis Tularemia Ulcerative colitis

WORKUP Section 5 of 11

Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography

Lab Studies:

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

CBC count with differential and platelet counts Assessment of erythrocyte sedimentation rate

C-reactive protein assay

Urinalysis

Serum multiphasic analysis with determination of the serum iron level and serum protein electrophoresis

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 HS 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 HS than in healthy control subjects.

Thickened skin may play a role in the pathogenesis of HS.

Other Tests:

Bacteriologic analysis should include bacteriologic sampling and cultivation.

Bacteriologic sampling should be performed at different depths in HS lesions.

A carbon dioxide laser can be used to evaporate the diseased tissue, level by level, from the surface downward. Samples can be concurrently obtained from each level, and contamination with bacteria from the level above can be minimized.

Almost every microorganism known to bacteriologists can be isolated from HS lesions; these microorganisms include streptococci, gram-positive and gram-negative rods, and the full range of fecal bacteria. Among the most frequently found species are Staphylococcus aureus and coagulase-negative staphylococci, anaerobic streptococci (eg, microaerophilic Streptococcus milleri), and Bacteroides species.

The microbiologic floras are not consistent and change unpredictably.

Kurzen et al reported immunohistochemical data obtained for various cytokeratins (CKs) and the 6 desmosomal cadherins (ie, desmoglein [Dsg] 1-3, desmecollin [Dsc] 1-3) showed 3 phenotypes of stratified squamous epithelia covering the sinus tracts in HS: type I cornifying, type II noncornifying and moderately inflamed, and type III noncornifying and strongly inflamed.

The noncornifying types II and III epithelia are characterized by the absence of the terminal differentiation markers CK 10 and Dsc 1 and by the strong expression of Dsg 2 in the basal layer. Compared with the normal epidermis and type I epithelium, types II and III epithelia have Dsc 2 and Dsg 3 in all layers, whereas Dsc 3 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 CK 7 and CK 19 and the absence of Dsg 1.

All 3 types of epithelia are clearly distinct from the interfollicular epidermis because of the absence of CK 2e 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.

CK 19 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 CK 19–positive parts of the sinus epithelium show no signs of terminal squamous differentiation. (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 CK 19 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, CK 5 and CK 14 are restricted to the basal layer, CK 10 and Dsc 1 antibodies label the suprabasal cells, Dsg 1 and Dsg 3 are present in an epidermislike pattern, and CK 2e is absent.

The relationship of the sinus epithelium to the hair follicles and the apocrine glands has long been debated. The sinus epithelium is clearly distinct from the normal epithelium of the subinfundibular ORS of the hair follicle. Thus, CKs 5 and 14 and Dsg 2 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 HS 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 HS-associated CK expression reported by Kurokawa et al, the draining sinus tract epithelium of HS lesions were divided into 3 components: infundibularlike keratinized epithelium (type A), noninfundibular keratinized epithelium (type B), and nonkeratinized epithelium (type C). Types A and B were similar to the types I and II reported by Kurzen et al, although CK 17 was not detected in type A, suggesting fragility of this epithelial type. CK 17, which is normally present in the suprabasal layers of normal 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 CK 17 may reflect a fragile follicular structure, resulting in the rupture of the follicle, which subsequently forms a subcutaneous abscess.

CK expression in the pilonidal sinus is comparable with that in HS, as previously reported. Moreover, CK 17 is also absent in infundibularlike epithelium.

The overlying epidermis in HS lesions has a more undifferentiated hyperproliferative state than that found in the normal epidermis. In some cases, CK 19 is present in the basal layer of the epidermis, and CK 19 is thought to be associated with premalignant change.

Histologic Findings: Histologically, the fundamental change in HS is the same as in acne vulgaris, namely, hyperkeratosis of the infundibulum that results in comedolike horny impactions. Some evidence suggests that the occlusion of abnormal hair follicles may play an important part in the initiation of the lesions. Follicular occlusion was found in all specimens compared with controls and regardless of disease duration. Folliculitis and perifollicular inflammation are common and occur in approximately 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.

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 revealed inflammation of the apocrine glands in only 33% of cases. Apocrinitis only evolves by extension of the inflammatory process. Apocrine gland destruction by neutrophils is occasionally observed. Abscess formation occurs, leading to the destruction of the pilosebaceous unit and, eventually, the other adnexal structures. Apocrine glands (present in axillae), which drain directly on the epidermal surface, appear intact and not inflamed.

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 HS should alert the examiner to the possibility of coexisting granulomatous disease, such as CD or sarcoidosis. 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. 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 HS.

Lipid rafts (membrane microdomains composed of cholesterol and gangliosides) have recently 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 HS, that emerge because of the influence of local inflammatory cytokines and are capable of nonmalignant infiltrative growth in the dermis and subcutis.

With regard to the expression of CK 19 in type II epithelium and overlying epidermis in HS 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. Free hair shafts can be found in the sinus and surrounding dermis, without apparent connection to the epithelium.

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

High-frequency ultrasound images show changes in the clinically uninvolved axillary and genitofemoral hair follicles. The follicles appear to be of larger diameter and have a distorted shape, with a wider deep follicular diameter, in agreement with the clinical impression that the primary event in HS is deeply seated in nature rather than superficial.

Staging:

Clinical staging of HS has diagnostic value.

The first stage is characterized by solitary or multiple, isolated abscess formation without scarring or sinus tracts.

The second stage is characterized by recurrent abscesses, single or multiple widely separated lesions with sinus tract formation, and cicatrization.

The third stage is characterized by diffuse or broad involvement with multiple interconnected sinus tracts and abscesses.

A uniform staging system should be used for assessing differences in treatment effects. Uniform outcome variables should take into account the known characteristics of HS. The following variables should be included: The anatomical region involved (axilla, groin, genital, gluteal, or other inflammatory region, including left and/or right designation) is scored at 3 points per region involved.

The number and severity of lesions (ie, abscesses, nodules, fistulas, scars) is scored based on points per lesion of all regions involved. The scoring system is 2 points for nodules, 4 points for fistulas, 1 point for scars, and 1 point for other types).

The longest distance between 2 relevant lesions (ie, nodules and fistulas) in each region, or size if only 1 lesion is present, is scored. Lesions smaller than 5 cm score 2 points, lesions of 5-10 cm score 4 points, and lesions larger than 10 cm score 8 points.

If all lesions are clearly separated by normal skin in each region, 0 points are scored. If they are not clearly separated by normal skin in each region, 6 points are scored.

TREATMENT Section 6 of 11

Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography

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

Initial treatment consists of the following:

Practicing local hygiene and ordinary hygiene

Instituting weight reduction in patients who are obese

Using ordinary soaps and antiseptic and antiperspirant agents (eg, 6.25% aluminum chloride hexahydrate in absolute ethanol)

Applying warm compresses with sodium chloride solution or Burow solution

Wearing loose-fitting clothing

In one series, radiation therapy with single doses of 0.5-1.5 Gy to total doses of 3-8 Gy was given as a treatment option for HS. The use of x-rays in depilating doses for temporary epilation has also been suggested. The possible beneficial effects of laser epilation do, however, suggest that hair removal may be of independent importance.

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 HS are, on the whole, still unsatisfactory. Surgical approaches, which were used in almost one half of patients, were included in those treatments.

Surgical Care: Surgery is the sine qua non treatment, especially in persons with chronic HS. Wide surgical excision, with margins well beyond the clinical borders of activity, remains the most definitive surgical therapy. With this technique, sufficient resection of the lesion is the most important issue. Surgery has hitherto been considered a curative treatment, but specific studies have suggested otherwise, and, although recurrence rates may be lower with more aggressive surgery, recurrence continues to be reported. After radical excision, the disease recurred in 33% of the patients. Surgery can be regarded as the treatment of choice in the chronic and recurrent stages of the disease.

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.

Nonsurgical procedures are important both before and after surgery. If the disease is diagnosed and treated early, secondary systemic complications can be prevented and the extent of surgery can be limited.

Numerous helpful and relatively minor surgical techniques include drainage, exteriorization, curettage, electrocoagulation of the sinus tracts, and simple excision of the troublesome areas with direct closure. More extensive procedures include placement of local cutaneous flaps, musculocutaneous flaps, pedicled and free flaps, and skin grafts.

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. Deroofing of sinus tracts and curettage of fistulous tracts have distinct roles as preliminary treatments before more definitive intervention, particularly in the acute phase of perianal disease. 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.

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.

To define the apocrine gland–bearing area, the iodine-starch method is used to reveal the little black spots that are usually in the vicinity of hair follicles where the sweat makes contact with the iodine-starch interface. 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 in which blue-stained areas occurred in the operative field, further reexcisions must be performed to ensure complete clearance.

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. It has been used successfully in patients with severe perianal HS and the complex perianal fistula disease. 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. It also obviates diversion with or without proctectomy. Moreover, use of a scanner-assisted carbon dioxide laser makes ablation quicker, smoother, and more precise and allows early treatment of HS lesions that were previously managed with less-effective local conservative remedies.

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. 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 contoured wounds that require closure with skin grafts. However, in lesions that cannot be completely resected, the use of a musculocutaneous flap is recommended. 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. 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.

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.

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. Recently, an overall recurrence rate of 2.5% was estimated after wide surgical excision, with a median postoperative follow-up of 36 months.

Diet: Patients who are obese should be advised to lose weight.

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.

MEDICATION Section 7 of 11

Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography

Treatment of HS remains a considerable challenge. Therapeutic options for HS were long restricted to the use of local disinfectants and systemic antibiotics and repeated incision and drainage, which produce only short-term benefits. Medical management is recommended in early stages, whereas surgery should be performed as early as possible after the formation of abscesses, fistulas, scars, and sinus tracts (see Surgical Care). Alternatively, draining sinuses can be treated by the application of spray liquid nitrogen for several seconds until bleaching occurs. The spray is preferred over the cryoprobe for this indication. In draining sinuses, cryotherapy works by accelerating the resorption of the inflammation. However, patients must be warned about pain and the prolonged healing time and risk of infection after the procedure; also, they should be informed that the treatment is unlikely to influence disease progression.

Drug Category: Antibiotics -- Acute episodes and relapses of HS should be treated in a fashion similar to nodulocystic acne. Some authors advocate long-term treatment with systemic antibiotics (eg, tetracycline, minocycline, clindamycin, erythromycin in combination with metronidazole). Although many patients clearly benefit from such therapy, note that no published evidence suggests that the long-term use of antibiotics alters the natural course of HS. Randomized controlled trials are needed. Some patients have had a beneficial response to biological agents, especially anti-TNF alpha biologicals. Tetracycline (Panmycin, Sumycin, Tetracap) -- Used to treat gram-positive and gram-negative organisms and Drug Name mycoplasmal, chlamydial, and rickettsial infections. Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunits. Adult Dose 250-500 mg PO q6h <12 years: Not recommended Pediatric Dose >12 years: Administer as in adults Documented hypersensitivity; severe hepatic dysfunction; Contraindications severe renal impairment; pregnancy; children <12 y; SLE Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives, Interactions causing breakthrough bleeding and increasing risk of pregnancy; can increase hypoprothrombinemic effects of anticoagulants Pregnancy X - Contraindicated in pregnancy Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in Precautions prolonged therapy; use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines Doxycycline (Doryx, Vibramycin, Bio-Tab) -- Inhibits protein Drug Name synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. Adult Dose 200 mg PO initially, followed by 100 mg PO qd/bid <12 years: Not recommended Pediatric Dose >12 years: Administer as in adults Documented hypersensitivity; pregnancy; children <12 y; Contraindications SLE; severe hepatic dysfunction Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can increase hypoprothrombinemic effects of Interactions anticoagulants; can decrease effects of oral contraceptives, causing breakthrough bleeding and increasing risk of pregnancy Pregnancy D - Unsafe in pregnancy Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in Precautions prolonged therapy; use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines Clindamycin (Cleocin) -- Lincosamide for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except Drug Name enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Adult Dose 150-300 mg PO q6h Pediatric Dose 3-6 mg/kg PO q6h Documented hypersensitivity; regional enteritis; ulcerative Contraindications colitis; hepatic impairment; antibiotic-associated colitis; diarrhea Increases duration of neuromuscular blockade induced by Interactions tubocurarine and pancuronium; erythromycin may antagonize effects; antidiarrheals may delay absorption Pregnancy B - Usually safe but benefits must outweigh the risks. Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and Precautions possibly fatal colitis by allowing overgrowth of Clostridium difficile Erythromycin (EES, E-Mycin, Eryc) -- Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis Drug Name to arrest. In children, age, weight, and severity of infection determine proper dosage. When bid dosing is desired, half the total daily dose may be taken q12h. For more severe infections, double the dose. Adult Dose 250-500 mg PO q6h or 0.5-1 g PO q12h <2 years: Not established Pediatric Dose 2-8 years: 250 mg PO q6h >8 years: Administer as in adults Documented hypersensitivity; hepatic impairment; Contraindications porphyria; liver disease (estolate) Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with Interactions lovastatin and simvastatin increases risk of rhabdomyolysis; decreases metabolism of repaglinide, increasing serum levels and effects Pregnancy B - Usually safe but benefits must outweigh the risks. Caution in liver disease; estolate formulation may cause cholestatic jaundice; adverse GI effects are common (give Precautions doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occurs Drug Category: Retinoids -- Vitamin A derivatives have many roles. They encourage cellular differentiation, they are antiproliferative, and they serve as immunomodulators. Although some patients have dramatic responses to isotretinoin at 1 mg/kg/d as monotherapy or combined with prednisolone (ie, when isotretinoin was introduced after 8 wk of prednisolone and erythromycin therapy), retinoids may be useful only as an adjunct to reduce inflammation before and after surgery.

Recent results from a long-term follow-up study indicate that the response of HS to isotretinoin is only moderate and related to the severity of the disease. The dose of isotretinoin is unlikely to be important in treating HS. Others propose that long-term treatment with isotretinoin is more successful than the usual 4- to 6-month regimen. Acitretin may be useful, at least in some cases. These agents are contraindicated in pregnancy. Isotretinoin (Accutane) -- Affects epidermal differentiation, especially at the follicular infundibulum. Also has Drug Name immunomodulating effects. Has been used as chemoprophylaxis for skin cancers. Adult Dose 1 mg/kg PO qd or divided bid Pediatric Dose Administer as in adults Documented hypersensitivity; breastfeeding; renal or Contraindications hepatic impairment, pregnancy Toxicity may occur with vitamin A coadministration; pseudotumor cerebri or papilledema may occur when Interactions coadministered with tetracyclines; may reduce plasma levels of carbamazepine Pregnancy X - Contraindicated in pregnancy May decrease night vision; inflammatory bowel disease may occur; may be associated with hepatitis; occasional exaggerated healing response of acne lesions (excessive granulation with crusting) may occur; patients with diabetes may have difficulty controlling their blood glucose levels; Precautions avoid exposure to UV light or sunlight until tolerance achieved; discontinue treatment if rectal bleeding, abdominal pain, or severe diarrhea occur; mood swings or depression may occur; caution in patients with history of depression; avoid pregnancy Drug Category: Sulfones -- These agents have anti-inflammatory effects. Because dapsone is less teratogenic than other drugs, it may be the preferred option in young women with HS. Dapsone (Avlosulfon) -- Bactericidal and bacteriostatic against mycobacteria; mechanism of action similar to that of Drug Name sulfonamides, in which competitive antagonism of PABA prevents formation of folic acid, inhibiting bacterial growth. Adult Dose 100 mg PO qd Pediatric Dose 1-1.5 mg/kg PO qd Documented hypersensitivity; severe anemia; G-6-PD Contraindications deficiency May inhibit anti-inflammatory effects of clofazimine; hematologic reactions may increase with folic acid antagonists (eg, pyrimethamine) (monitor for Interactions agranulocytosis during second and third mo of therapy); probenecid increases toxicity; trimethoprim may increase toxicity of both drugs; concurrent rifampin may significantly decrease levels (increased renal clearance) C - Safety for use during pregnancy has not been Pregnancy established. Perform weekly blood cell counts (first month), then WBC counts monthly (for 6 mo), then semiannually; discontinue if hematopoiesis occurs or if platelet or leukocyte counts significantly decrease; caution in methemoglobin reductase deficiency, G-6-PD deficiency (>200 mg/d), or hemoglobin Precautions M because of high risk of hemolysis and Heinz body formation; caution in patients exposed to other agents or conditions (eg, infection, diabetic ketosis) capable of producing hemolysis; peripheral neuropathy can occur (rare); phototoxicity may occur with UV light exposure Drug Category: Corticosteroids -- These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli. Intralesional injection with either a syringe or an automatic needleless injector usually decreases the size of draining sinuses. The injection of 0.05-0.25 mL of triamcinolone acetonide suspension (2.5- 10 mg/mL) into each lesion is recommended for its anti-inflammatory effects. This treatment can be repeated every 2-3 weeks if necessary. The anti-inflammatory effects of systemic corticosteroids may be useful in acute exacerbations. Prednisolone at 60 mg/d with lower maintenance doses provides some long-term control. Triamcinolone acetonide (Amcort, Aristospan Intra- Articular) -- For inflammatory dermatosis responsive to steroids; decreases inflammation by suppressing migration steroids; decreases inflammation by suppressing migration Drug Name of polymorphonuclear leukocytes and reversing capillary permeability. Intramuscular injection may be used for widespread skin disorder. Intralesional injections may be used for localized skin disorder. Adult Dose 0.05-0.25 mL intralesionally q2-3wk Pediatric Dose Administer as in adults Documented hypersensitivity; fungal, viral, and bacterial Contraindications skin infections Coadministration with barbiturates, phenytoin, and rifampin Interactions decreases effects C - Safety for use during pregnancy has not been Pregnancy established. Multiple complications (eg, severe infections, hyperglycemia, edema, osteonecrosis, myopathy, peptic Precautions ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression) may occur; abrupt discontinuation of may cause adrenal crisis Prednisolone (Prelone) -- Decreases autoimmune Drug Name reactions, possibly by suppressing key components of immune system. 60 mg/d PO in single or divided doses until remission; Adult Dose thereafter, reduce dose to lowest amount that produces acceptable clinical response Pediatric Dose Use lowest dose that produces acceptable clinical response Documented hypersensitivity; viral, fungal, or tubercular Contraindications skin lesions Decreases effects of salicylates and toxoids (for Interactions immunizations); phenytoin, carbamazepine, barbiturates, and rifampin decrease effects C - Safety for use during pregnancy has not been Pregnancy established. Caution in hyperthyroidism, osteoporosis, cirrhosis, Precautions nonspecific ulcerative colitis, peptic ulcer, diabetes, and myasthenia gravis Drug Category: Hormones -- Combined treatment with the antiandrogen cyproterone acetate and ethinyl oestradiol has been shown to be of benefit to women with long-standing HS. 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 HS, but many conditions fail to respond to these treatments. Finasteride, a competitive inhibitor of 5- alpha reductase type II isoenzyme, may be beneficial in HS. Cyproterone acetate (Androcur) -- Inhibits androgen binding Drug Name to target cells. Adult Dose 50 mg PO bid on days 5-14 of menstrual cycle Pediatric Dose Not established Documented hypersensitivity; <18 y (may arrest bone Contraindications maturation); malignant and hepatic diseases; severe depression; history of thromboembolic disorders Interactions None reported Pregnancy X - Contraindicated in pregnancy Precautions Caution in breastfeeding and liver function abnormalities Ethinyl estradiol (Estinyl) -- Reduces secretion of LH and Drug Name FSH from pituitary gland by decreasing amount of gonadotropin-releasing hormones. 50 mcg PO qd on days 5-25 of each menstrual cycle; Adult Dose administer in combination with cyproterone acetate Pediatric Dose Not established Documented hypersensitivity; thrombophlebitis; Contraindications undiagnosed vaginal bleeding May reduce hypoprothrombinemic effects of anticoagulants; coadministration of barbiturates, rifampin, and other agents that induce hepatic microsomal enzymes may reduce estrogen levels; may increase corticosteroid levels; use with Interactions hydantoins may cause spotting, breakthrough bleeding, and reduced contraceptive effectiveness; increased fluid retention caused by estrogen intake may reduce seizure control; antibiotics may alter GI flora and reduce absorption of oral contraceptives, reducing their effectiveness Pregnancy X - Contraindicated in pregnancy May interfere with thyroid function test results and serum cortisol test results by increasing concentrations of hormone Precautions binding; caution in hepatic impairment, migraine, seizure disorders, cerebrovascular disorders, breast cancer, and thromboembolic disease Drug Category: Immunosuppressants -- Because of the concurrent presentation of HS and CD, as well as the morphological and histological similarities, these 2 conditions have been suggested to share the same pathogenesis, namely excess TNF-alpha production. This was supported by several reports in the literature of patients with HS and CD who responded to infliximab. Infliximab is an inhibitor of TNF-alpha.

Although approved by the US Food and Drug Administration for the treatment of CD and rheumatoid arthritis, infliximab has been used with generally good efficacy in HS. The benefits outweigh the risks associated with its use, especially when it is administrated in severe chronic cases resistant to standard therapies. Patients self-reported 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 h. Although the efficacy has proven impressive and short-term adverse effects have been few and relatively benign, long-term adverse effects have not been studied. Further trials are needed to assess effects of its prolonged use.

Therapeutic experience with nonspecific immunosuppression in HS using methotrexate is unlikely to offer any significant advance. Before finally determining the value (or lack of value) of methotrexate in HS, investigating different dosage schedules in patients with HS may be of value. Infliximab (Remicade) -- Inhibits TNF-alpha activity and triggers complement-mediated lysis of TNF- alpha–expressing cells in vitro. Monoclonal chimeric antibody made from human constant and mouse variable regions of IgG, with binding specificity for human TNF- Drug Name alpha. Binds to inactive TNF-alpha and can bind specifically to both membrane-bound and soluble TNF-alpha. Binds to inactive TNF-alpha monomers, preventing their association into active trimers. Used to treat severe inflammatory diseases that do not respond to systemic corticosteroids or immunosuppressants. Adult Dose 3-5mg/kg per infusion q4-6wk Pediatric Dose Not established Documented hypersensitivity; congestive heart failure; Contraindications tuberculosis Interactions None reported Pregnancy B - Usually safe but benefits must outweigh the risks. Perform tuberculosis skin testing prior to initiating treatment, and, if results are positive, perform chest radiography; check a full panel of laboratory studies, including CBC count with differential, basic metabolic panel, liver function tests, ANA, and HIV serology; search for any active infections, including cutaneous infections; consider potential for patients' own immune system to mount an potential for patients' own immune system to mount an Precautions immune response to the foreign murine portion of the drug; concern of long-term development of antibodies to the drug because these lead to loss of clinical efficacy; acute and delayed infusion reactions may develop; anaphylaxis and bronchospasm can occur (rarely); lupuslike syndrome may occur; congestive heart failure may develop; caution in personal or family history of neurological symptoms or disease (demyelinating)

FOLLOW-UP Section 8 of 11

Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography

In/Out Patient Meds:

Discharge patients and prescribe oral isotretinoin at 1 mg/kg/d.

Complications:

Complications of HS include local and systemic infections due to the spread of microorganisms and, in rare cases, septicemia.

Restricted mobility of the limbs due to marked fibrosis and scarring may occur, particularly with axillary disease.

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. Rectal and urethral fistulas are rare.

Swelling and elephantiasis nostras that occur after streptococcal infection may be superimposed on HS lesions, leading to severe enlargement and distortion of the external genitalia.

In male patients, severe ulcerative genital disease can cause destruction of the prepuce.

Chronic inflammatory reactions, such as anemia, proteinuria, hypoproteinemia, amyloidosis, interstitial keratitis, and renal disease, are rare.

Based on the standard incidence rate (SIR), HS 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 cancer (SIR = 5.5; 1.8-12.9), and hepatic cancer (SIR = 10.0; 2.1-29.1) is increased.

SCC is a rare but serious consequence. Most SCCs are noted in men and in the anogenital region, perhaps because these tumors are hard to detect. Once they occur, SCC tumors show endophytic growth along the sinus tracts.

Most patients with SCC have a history of HS for 10 years or longer; the prevalence of SCC among patients with perianal HS lasting 20-30 years is approximately 3.2%.

Recently, the first case of vulvar SCC as a complication of HS was reported in the English-language literature. All 5 previously reported cases of SCC with HS in women involved the buttocks or the perianal region.

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.

In addition to SCC, attention should be given to the development of anal cancer. Extensive invasion of mucinous carcinoma, which probably originates from the anal gland in relation to the anal fistula, may occur in persons with HS.

The draining sinus tract is a late complication of HS and leads to extensive, periodically inflamed lesions lined by a variably thickened stratified epithelium.

Prognosis:

In general, HS 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.

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.

New boils develop at a rate of approximately 2 per month, and individual boils resolve in approximately 1 week, which is almost the average duration of a course of antibiotics. The observed improvement seems to result not from the antibiotics but simply from the natural history of the disease. With rare exceptions, surgical intervention is sufficient to stop the disease. Shame, frustration, and despair may cause patients to delay radical surgical procedures.

Spontaneous resolution is rare.

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 and axillary surgery, as well as surgery in older patients, have lower recurrence rates, irrespective of the preoperative duration.

Patient Education:

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

Practicing proper hygiene

Using soaps and antiseptic and antiperspirant agents

Using warm compresses

Wearing loose-fitting clothing

Patients who are obese should be educated about weight loss (see Diet).

Patients should be educated about activities that may provide some relief of their condition (see Activity). These activities include swimming, bathing, and avoiding smoking.

For excellent patient education resources, visit eMedicine's Skin, Hair, and Nails Center. Also, see eMedicine's patient education article Boils.

MISCELLANEOUS Section 9 of 11

Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography

Medical/Legal Pitfalls:

Failure to consider the diagnosis, especially in patients with atypical presentations, results in misdiagnoses, which are numerous. However, the diagnosis has a significant influence on the health of the average patient, even before the development of complications such as scarring and chronic suppuration. The crucial point in HS is early diagnosis and correct classification with subsequent early and radical surgical excision. If the disease is diagnosed and treated early, secondary systemic complications are avoided.

PICTURES Section 10 of 11

Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography

Caption: Picture 1. Vulvar hidradenitis suppurativa.

View Full Size Image