Hidradenitis suppurativa

 

Salient features

·        Hidradenitis suppurativa is a chronic and debilitating inflammatory disorder of the hair follicles with an underlying immune system imbalance that affects genetically predisposed individuals and that localizes to intertriginous and anogenital regions of the body. The course of disease can be modified by exogenous triggers or aggravating factors.

·        Lesions are characterized by inflammatory nodules, subcutaneous abscesses, and sinus tracts.

·        Reproductive-age women are disproportionately affected.

·        Hyperkeratotic plugging of the terminal hair follicle is a consistent histologic finding of early disease and is thought to be the primary pathophysiologic event.

 

Introduction

 

The first International Hidradenitis Suppurativa (HS) Research Symposium (2006, Dessau, Germany) formulated the following definition: HS is a chronic, inflammatory, recurrent, debilitating, skin disease that usually presents after pubertywith painful, deep‐seated inflamed lesions, primarily within the folded area of the skin that contain both terminal hairs and apocrine glands. The disease primarily affects terminal hair follicle. Approximately one‐third of patients have a family member with HS.

 

 

 

Epidemiology

Age

HS typically starts at or soon after puberty; the average age of onset is between second and third decade, with a sharp decline after the fifth decade.

Sex

Women are affected three times as often as men; estimated to affect 4% of the female population. Topographical distribution of lesions can vary between sexes. For example, perianal and gluteal disease are more common in males, whereas inguinal and submammary disease are more common in females. The most commonly affected site is axilla.

 

Associated diseases

Diseases associated with HS include disorders of the follicular occlusion tetrad, systemic inflammatory disorders and genodermatoses.

 

Follicular occlusion tetrad

 

Acne conglobata, dissecting cellulitis of the scalp and pilonidal sinus can coexist with HS; together they comprise the ‘follicular occlusion tetrad’.

 

Inflammatory disorders

 

The coexistence of HS and Crohn disease, particularly with perianal involvement, has been associated with a more fulminant course. Perianal Crohn disease may be clinically indistinguishable from perianal HS. Other associated inflammatory disorders include pyoderma gangrenosum and the syndromes SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis), PAPA (pyogenic arthritis, pyoderma gangrenosum and acne), PASH (pyoderma gangrenosum, acne conglobata and suppurative hidradenitis) and PAPASH (pyogenic arthritis, pyoderma gangrenosum, acne and suppurative hidradenitis).

 

Genodermatoses

 

Genodermatoses associated with HS or HS‐like lesions include keratosis ichthyosis deafness syndrome, pachyonychia congenita, steatocystoma multiplex and Dowling–Degos disease.

Most of these diseases belong to the group of auto inflammatory disorders, where Th17 cell cytokines seem to play a central role.

 

Pathophysiology

 

 

Proposed Pathogenesis

 

Recent studies propose the following mechanism:

 

1.   The process starts with the infiltration of lymphocytes around the terminal hair follicle (Perifolliculitis)

2.   Perifolliculitis may lead to infundibular hyperkeratinisation and subsequent blockage by keratin plugging.

3.   Dilatation of the hair follicle, followed by its rupture, leaking its contents, including keratin, bacteria,sebum and hairs into the surrounding dermis. This incites a vigorous chemotactic response and abscess formation with the formation of painful, deep dermal abscesses and apocrinitis as the inflammation spreads. The deep part of the follicle appears to be involved.

4.   The presence of secondary bacterial infection of inflamed hair follicles further promotes the infiltration of immune cells and inflammation, leading to the formation of pus. Epithelial strands are generated, possibly from ruptured follicular epithelia, and form sinus tracts with subsequent extensive scarring. Common secondary bacterial infections are staph aureus, streptococcus pyogens and gram negative organinsms.

 

 

Predisposing factors

 

Obesity and smoking

 

Obesity and smoking are the two main exacerbating factors associated with HS. Obesity is often regarded as an exacerbating factor by increasing shearing forces, occlusion, keratinocyte hydration, and maceration and also increased pro‐inflammatory cytokine release from visceral fat at intertriginous skin sites.  Obesity may also exacerbate disease by creating a state of androgen excess. There is an increased prevalence of smoking amongst patients with HS. It is postulated that smoking affects polymorphonuclear cell chemotaxis. There is a strong association with current smoking. Smoking cessation may improve the clinical course of the disease.

 

Hormones and Androgens

The tendency of HS to develop at puberty or post puberty suggests an androgen influence. Hormonal influences are supported by a female preponderance, improvement during pregnancy and disease flares during postpartum, in association with the oral contraception pill, and in the premenstrual period (approximately 50% of patients). Antiandrogen therapy has also demonstrated therapeutic benefit in some studies. Clinical signs of virilization are, however, usually absent and circulating androgen levels are typically normal. Additionally, unlike the sebaceous glands, the apocrine glands are not affected by androgens. Thus, the influence of androgens on HS is unclear.

 

Host defense

 

Alterations of the innate immune system are thought to underlie disease pathogenesis. Overproduction of both IL-1β and tumor necrosis factor (TNF)-α has been observed lesional skin, suggesting the involvement of the innate immune system as well. In addition, a therapeutic response to TNF-α inhibitors and to IL-1 receptor antagonists has been noted in some studies. Increased serum levels of IL-2, which correlate with disease activity, have also been detected, as well as increased expression of IL-12, -17, and -23 within lesional skin. Lastly, high copy numbers of the beta-defensin cluster are noted to confer genetic susceptibility to hidradenitis suppurativa.

 

Pathology

There is a heavy mixed inflammatory cell infiltrate including histiocytes and giant cells in the lower half of the dermis that extends to interfollicular apocrine and eccrine structures and deep into the subcutis. Abscesses are present in active cases, and they may connect to the skin surface via a sinus tract. The sinus tracts contain inflammatory cells and keratinous debris. Granulation tissue with inflammatory and occasional foreign body giant cells is present in up to 25% of biopsies. In chronic disease, there may be extensive fibrosis with destruction of pilosebaceous follicles and eccrine and apocrine sweat glands.

 

Diagnostic criteria

 

All three diagnostic criteria must be met for a diagnosis of HS to be made.

1.   Typical lesions that are deep‐seated, painful nodules: ‘blind boils’ in early primary lesions; abscesses, draining sinus tracts, bridged scars and paired or multiheaded open pseudocomedones in secondary lesions.

2.   Typical topography: axillae, groin, perineal and perianal region, buttocks and infra‐ and intermammary folds.

3.   Chronicity and recurrence of lesions.

 

Clinical features

It is a chronic condition characterized by recurrent “boils” and draining sinus tracts with subsequent scarring. Initially, inflammatory nodules and sterile abscesses develop in the flexural areas. These lesions may be very tender and extremely painful. Over time, sinus tracts and scars may develop. This is accompanied by chronic drainage of malodorous discharge, leading to a marked degree of frustration, embarrassment, self-consciousness and depression. The discharged fluid is often a mixture of serous exudate, blood and pus, in varying proportions. Scarring is typically bridged or ‘rope‐like’, it can be hypertrophic or atrophic, producing depressions especially on the buttocks, and may be associated with contractures. Pseudo‐ (secondary) comedones are often seen, typically paired, polyporous and grouped. Lesions are localized to inverse (flexural) areas. The commonest sites are the axillae and inguinal and ano‐genital regions, including the external genitalia and the perineal, perianal and gluteal skin. Sub‐ and intermammary skin can also be affected, as can, less commonly, retroauricular, preauricular and occipital skin. The lesions are often bilateral.

 

Classification of severity

The Hurley staging system refers to three stages based on the presence and extent of sinus tracts and scarring.

Hurley staging system
1.   Stage I – One or more recurrent abscess formation with no sinus tract or scar formation 2.   Stage II – One or more widely separated recurrent abscesses, with sinus tract and scar formation 3.   Stage III – Multiple interconnected abscesses, sinus tracts and scarring diffusely involving an entire region

 

Complications and co‐morbidities

 

Secondary bacterial infection should be suspected when flares are preceded by smarting pain or associated with the development of pustules. Anal, urethral, or rectal strictures may develop from chronic inflammation. Fistula formation to the gastrointestinal tract (anal canal and rectum), genito‐urinary tract (urethra, bladder and vagina) and peritoneum are extremely rarely described, and when seen should trigger examination for Crohn disease. Additionally, disfiguring persistent penile, scrotal, or vulvar lymphedema due to blockade or destruction of local lymph drainage routes subsequent to chronic and recurrent inflammation may develop, giving rise to significant functional impairment. Once this complication appears, no medical treatment is effective and surgical reconstruction may be necessary. Squamous cell carcinoma (SCC) may rarely develop in chronically inflamed and scarred areas in individuals with long-standing disease. Malignant transformation occurs most commonly on the gluteal skin of male patients, and carries a poor prognosis.

 

 

Disease course and prognosis

 

Chronicity is the hallmark. The mean duration is 18.8 years. Milder forms (Hurley stage I) are more frequent and affect approximately two‐thirds of patients, with intermediate disease (Hurley stage II) affecting one‐quarter and severe disease (Hurley stage III) about one‐fifth of patients. In patients older than 50 years, spontaneous remission may occur over time.

Treatment

 

Hidradenitis suppurativa – grading systems and therapeutic ladder. Additional scoring systems are used in clinical trials. In the Revuz modification of the Sartorius grading system, five regions (axilla, breast, inguino-femoral, perianal, perineal) are scored, with additional modifications including the addition of abscesses to fistulae. Both Hidradenitis Suppurativa Clinical Response (HiSCR) and a Physician’s Global Assessment (PGA) Scale have been utilized as has a refinement of the Hurley staging system in which stages I and II are subdivided into A,B,C subtypes.

HIDRADENITIS SUPPURATIVA – GRADING SYSTEMS AND THERAPEUTIC LADDER
Hurley staging system
.   Stage I – one or more abscesses with no sinus tract or scar formation .     .   Stage II – one or more widely separated recurrent abscesses, with sinus tract and scar formation .     .   Stage III – multiple interconnected sinus tracts and abscesses throughout an affected region; more extensive scarring
Sartorius grading system
·       Anatomical regions involved: axilla (left +/or right), groin (left +/or right), gluteal (left +/or right) or other region (e.g. inframammary): 3 points per region involved   ·       Number and scores of lesions for each region: nodules = 1; fistulae = 6   ·       The longest distance between two relevant lesions*, i.e. nodules and fistulae, in each region: <5 cm = 1; 5–10 cm = 3; >10 cm = 9   ·       Are all lesions clearly separated by normal skin? In each region – yes 0/no (Hurley III) 9
Therapeutic ladder
Indication	Therapeutic interventions
General measures	·       If obese or overweight, weight reduction   ·       Reduce friction and moisture via loose undergarments, absorbent powders, and topical aluminum chloride   ·       Antiseptic soaps   ·       Smoking cessation
Hurley Stage I	·       Intralesional triamcinolone (5 mg/ml) injections into early inflammatory lesions   ·       Topical clindamycin   ·       Eradication of S. aureus carriage with topical mupirocin in nose, axillae, umbilicus, and perianal regions   ·       Oral antibiotics tailored to results of bacterial cultures from pustular discharge or abscess contents   ·       Oral antibiotic therapy (alone or in combination) for its anti-inflammatory effect (rifampin + clindamycin, tetracycline, doxycycline, minocycline, dapsone, trimethoprim–sulfamethoxazole)   ·       Oral anti-androgen therapy (e.g. finasteride)
Hurley Stage II	·       Oral antibiotic therapy (see Stage I)   ·       Acitretin   ·       Systemic immunosuppressive agents including adalimumab^, infliximab, and cyclosporine   Surgical treatments†   ·       Limited local excisions with second intention healing   ·       CO2 laser ablation with second intention healing   ·       Nd:YAG laser treatments, at least 3–4 monthly sessions
Hurley Stage III	Medical treatments outlined for Stages I and II Surgical treatments†   ·       Early wide surgical excision of involved areas   ·       CO2 laser ablation with second intention healing

 

* Or size if only one lesion.

^FDA- approved dosing regimen: 160 mg (four 40 mg injections) on day 1 –or- 80 mg daily on days 1 and 2 followed by 80 mg  on day 15 then 40 mg on day 29 and weekly thereafter

† Incision and drainage is discouraged given high rate of recurrence.

 

Adjuvant treatment

 

1.   Weight reduction (if overweight) and smoking cessation

2.   Reduce friction and moisture (loose-fitting clothing and undergarments, absorbent powders, topical aluminum chloride)

 

Analgesics

 

 

HS is painful and patients should be offered appropriate analgesic therapy, including non‐steroidal anti‐inflammatory therapy and paracetamol.

 

Topical therapy

 

Antiseptic soaps and topical antibiotics (e.g. clindamycin lotion 0.1% may reduce Staphylococcus aureus colonization and secondary infection). Intranasal mupirocin (5-day course for nasal carriers of S. aureus).

 

 

Systemic antibiotics

 

Combined treatment with clindamycin 300 mg b.d. and rifampicin 300 mg b.d. given for 10 weeks resulted in remissions of up to 1 to 4 years regardless of disease severity (Hurley stage I, II, or III). The combination is well tolerated, as the most common adverse effects are gastrointestinal discomfort and diarrhea (generally mild).

 

Other antibiotics used to treat HS are doxycycline, minocycline, and rifampicin associated with moxifloxacin and/or metronidazole, with variable response.

 

 

Anti‐inflammatory treatment

 

For isolated number of tender lesions, intralesional triamcinolone (3–5 mg) often ameliorates symptoms rapidly. For more severe disease, short‐term systemic prednisolone (0.5–1.0 mg/kg body weight) or ciclosporin (3–5 mg/kg body weight), or longer term treatment using dapsone (100 mg daily), have all been reported to be useful for disease control.

 

Biological agents

 

Tumour necrosis factor‐α antibodies appear to have a beneficial effect in moderate to severe HS. The most effective tumor necrosis factor α (TNF-α) blocker in HS is adalimumab. Adalimumab is considered the most specific treatment for HS. Based on the data available, it is currently the main drug for the treatment of refractory Hurley stage II disease or moderate to severe Hurley stage III disease.

Adalimumab (a loading dose of 160mg at week 0 and 80mg at week 2, followed at week 4 by 40mg every week, for a total of 12 weeks).

Physical intervention

Surgical removal of all involved tissue, beyond clinically involved margins, is an effective treatment modality.

 

Surgery is indicated for the treatment of nodules and isolated fistulas and for severe, extensive disease that does not respond to medical treatment. The choice of surgery and size of margins are determined by the area affected and the degree of involvement.

Several surgical techniques are indicated for HS:

1.      Incision and drainage

2.      Unroofing and marsupialization

3.      Localized excision

4.      Wide excision

 

Incision and Drainage

Incision with drainage is a simple technique that can be performed under local anesthesia on an outpatient basis. It tends to result in rapid relief of pain in the case of isolated nodules, but recurrence is common.

Punch debridement has also been proposed as a modification of this technique. This procedure involves centering a biopsy punch with a diameter of 5 to 7mm over an inflamed pilosebaceous unit, which is then debrided by digital pressure followed by curettage. The goal is to remove the remains of the sebaceous gland and/or the follicle containing cells involved in the generation of fistulas and fibrous tracts. Preliminary data suggest that recurrences are relatively infrequent with this technique.

Deroofing

Unroofing (or deroofing) with marsupialization is a simple technique that can also be performed on an outpatient basis.

Deroofing is a tissue‐saving technique, whereby the ‘roof’ of an abscess or sinus tract is surgically removed either through electrosurgery (using a loop) or conventional surgery. The ensuing defect is left open to heal by secondary intention.

Unroofing is suitable for recurrent painful stage I or II lesions, and results in acceptable cosmetic results. Approximately 17% of lesions treated using this technique has been found to recur within a mean of 4 to 6 months.

 

Localized surgery

Patients with few, clinically stable, non‐inflamed lesions (nodules or sinus tracts) are most suitable for localized surgery. Generally, complete surgical removal of the lesion is required, suggesting that wider excisions have a better result than more limited excision.

 

Extensive surgery

 

In severe disease when entire sites are involved with multiple interconnecting sinus tracts, the only curative method is excision of the entire area involved.

 

Wide excision involves removing an entire affected area with margins extending beyond the visibly affected region. When used in combination with medical measures and treatments, wide excision is the technique that is most likely to achieve disease control in patients with chronic, extensive stage III disease. The surgical defect can be reconstructed using simple local or free flaps, skin grafts, tissue expanders, or simply closure by secondary intention.

 

 

Lasers and Light

 

CO₂ laser evaporation provides a method whereby all visibly affected tissue can be vaporized (i.e. evaporating abnormal tissue under visual guidance until healthy tissue is reached everywhere). The technique offers radical treatment whilst still being tissue‐sparing. Postsurgical defects are usually left to heal by secondary intention. Patient satisfaction with the technique is high.

Hair removal lasers and intense-pulsed light systems also result in clinical improvement by reducing the number of hair follicles and associated inflammation. Long-pulsed (1064nm) Nd:YAG 1064 laser therapy has also been described as effective for the treatment of Hurley stage II and III disease.

 

Radiotherapy

 

In selected patients with particularly recalcitrant disease, radiotherapy may be considered.

 

PSYCHOLOGICAL MANAGEMENT

Patients become very depressed because of pain, soiling of clothing by draining pus, odor and the site of occurrence (anogenital area). Therefore, every effort should be made to deal with the disease, using every modality possible.

 

Approach to the treatment of hidradenitis suppurativa, based on the European guidelines for hidradenitis suppurativa

 

Therapy	Category of Evidence	Strength of Recommendation
1st Line
Clindamycin (topical)	IIb	Possible B
Clindamycin/Rifampicin (oral)	III	C
Adalimumab (subcutaneous)	Ib	A
Tetracycline (oral)	IIb	B
Surgery
Excision or Curettage of Individual Lesions	III	C
Total Excision of the Lesions and Surrounding Hair-Bearing Skin	IIb	B
Second Intention Healing	IIb	B
Primary Closure	III	C
Reconstruction with Skin Grafting & NPWT	III	C
Reconstruction with Flap Plasty	Ia/IIa	A/B
Deroofing	IV	D
Carbon Dioxide Laser Therapy	Ib	A
Nd:YAG Laser	Ib	A
IPL	IV	D
2nd Line
Zinc Gluconate	III	C
Resorcinol	III	C
Intralesional Corticosteroids	IV	D
Systemic Corticosteroids	IV	D
Infliximab	Ib/IIa	B
Acitretin/Etretinate	III	C
3rd Line
Colchicine	IV	D
Botulinum Toxin	IV	D
Isotretinoin	IV	D
Dapsone	IV	D
Cyclosporine	IV	D
Hormones	IV	D
Pain Control
NSAIDS	IV	D
Opiates	IV	D
Dressings
No studies have been published to date on the use of specific dressing or wound care methodology in HS. Choice of dressing is based on clinical experience.	IV	D