How I Treat: Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is classified as a progressive, inflammatory disease that appears to be primarily caused by inflammation of hair follicles and is most often found in areas of friction of the body, such as the axillae, groin, perineum, and medial thighs. The inflammation associated with HS presents clinically with recurrent inflamed painful nodules and abscesses, which often lead to both sinus tract and subsequent hypertrophic scar formation.             

Pathophysiology
The pathophysiology is believed to involve an inflammatory attack on the skin’s hair follicles, with specific targets of apocrine gland-bearing skin. This attack leads to follicular rupture, releasing keratin and bacterial flora into the dermis, which further propagates an elevated immune response. Sterile abscesses form, which may later progress into superinfections with bacterial flora, particularly Staphylococcus spp.

HS presents after puberty, with women being affected 3 times more than men.¹ A hormonal influence on disease has been suspected due to HS onset after puberty and because the disease rarely occurs after menopause in women. Interestingly, hormonal associations (and specifically androgen levels and receptors) have not been shown to influence disease development or progression.²

A synonym for HS is acne inversa, and although acneiform, deep, and scarring nodules can form, the evidence for an association between acne vulgaris and HS is weak. In addition, current or past history of acne vulgaris has not been shown to significantly affect HS severity,³ and so these conditions should be clinically regarded separately.

The majority of associated comorbidities in patients with HS are those seen with metabolic syndrome and obesity. Patients with HS have higher odds of being obese.³ Obesity-related comorbidities including hypertension, dyslipidemia, and polycystic ovary syndrome have been found to be independently associated with higher odds of developing HS, even after adjustment for all other comorbidities.³

Diagnosis
HS is diagnosed clinically in a setting of appropriate morphology, location, and clinical history. Patients will initially form nodules and sterile abscesses, which then become very tender and painful as they progress into sinus tracts, and then hypertrophic and/or keloidal scarring follows. These abscesses drain seropurulent material: they are recurrent and chronic, and are understandably a major source of embarrassment and depression in those affected. 

Disease severity is graded by Hurley staging I to III:

• Hurly Stage I: 1 or more abscesses with no sinus tract or scar
• Hurly Stage II: 1 or more widely separated recurrent abscess, with sinus tract and scar
• Hurly Stage III: multiple interconnected tracts and abscesses throughout an affected region

Treatment
Therapeutic management is empiric and begins with a lifestyle approach, which can be followed with medical and surgical management, depending on disease severity. All patients should be educated on the importance of weight management and tobacco cessation. Reduction of friction and moisture at the affected sites can help symptomatic management and reduce risk for external triggers on follicular inflammation. Patients should be instructed on how to appropriately care for suppurativa lesions at home (ie, warm compresses to affected sites, sitz baths, absorbent gauze, and regular dressing changes when nodules are suppurating). 

Treatment of any associated cultured bacterial infections should be followed with appropriate antibiotics. Recurrent infections (particularly Staphylococcus aureus) may be prophylactically treated with daily to biweekly antiseptic soaps and/or topical antibiotics to affected areas. Topical clindamycin (lotion, gel, solution) and topical gentamycin⁴ have both been reported to show efficacy in early disease, but patients must be reminded to use treatments along with topical benzoyl peroxide to decrease the risk of developing topical antibiotic resistance. For recurrent cultured Staphylococcus infections, intranasal mupirocin ointment can be considered to eradicate nasal carriage. 

Medical therapy with in-office intralesional triamcinolone 5 to 10 mg/mL often benefits the nonfluctuant inflammatory lesions. Fluctuant lesions (abscesses) often require local incision and drainage or lancing to resolve. Nonfluctuant nodules tend to respond well to intralesional steroids, which often mitigates development of painful and dysmorphic scarring. 

Oral antibiotics can be used more frequently for patients with stage II and III disease. Instructions can vary, and there is no standard dosing protocol existing for antibiotic use in HS. Treatment can be directed to be used as needed in 1- to 2-week courses for flare-ups, or as a daily suppressive dose for months to prevent frequency of suppuration. Tetracycline (TCN) class antibiotics, particularly doxycycline and minocycline, are used for both HS and acne/rosacea for their anti-inflammatory properties, in addition to their antibiotic properties. The author tends to favor a lower dosing daily use for frequently recurrent HS cases (more than 2 episodes of tender, painful cysts monthly) with the goal of the TCN being used primarily as more of an anti-inflammatory therapy than antibacterial (as the primary lesion is a sterile abscess), with dosing varying from 50 to 200 mg daily. Finding the lowest tolerated dose to maintain disease suppression tends to be patient-dependent and unpredictable. 

When TCN antibiotics fail to maintain disease control, a next step can be the regular dosing of a combination of oral clindamycin 300 mg twice a day and oral rifampicin 300 mg twice a day. Literature supports the safety and efficacy of this dosing, and I have found great success in my practice with this combination in TCN recalcitrant cases. Rifampin has also been used in combination with moxifloxacin and metronidazole, showing efficacy in patients with Hurley stage I to III.⁵ 

Hormonal therapy has shown to have a role in some cases of HS. Case series have shown efficacy with use of spironolactone (dosing range from 25-200 mg daily), oral contraceptives with estradiol plus cyproterone acetate, and finasteride.⁶ Monotherapy with metformin has shown a role in some case series, further supporting an underlying link between metabolic disease and HS activity.⁷ 

In 2015, the US Food and Drug Administration (FDA) approved adalimumab for moderate to severe HS dosed as given for inflammatory bowel disease (week 0: 160 mg, week 2: 80 mg, and week 4: 40 mg, every week). This is the first and currently only FDA-approved treatment for HS. For those whom adalimumab is contraindicated (or treatment failed), there are other biologics to consider that have been used off-label with efficacy, including infliximab, ustekinumab, and anakinra. 

Additional immunomodulatory therapies include prednisone, dapsone, cyclosporin, and acitretin. The limited duration of dosing and/or teratogenicity of these medications restrict them as a therapeutic option for many patients. Although a benefit has been seen with acitretin 25 mg twice a day/3 times a day, relapse is common after discontinuation of therapy. There has been no clear benefit of isotretinoin in HS disease modulation.^1,4 

Surgical therapy in milder, localized cases suggests performing a local excision of involved sinus tracts. Advanced cases with deep and multiple sinus tracts may require a wide excision followed by primary closure or grafting. Local “deroofing” with second intention healing might also be performed with resolution of disease often achieved in treated area. Laser stripping with CO2 laser to destroy lesions has also been utilized as another efficacious operative therapy.

Overview
In summary, HS is a disease that presents in both women and men following puberty and that runs a chronic, relapsing, painful, and often disfiguring course. Early diagnosis and appropriate clinical guidance toward therapeutic management is critical in maintaining higher quality of life and decreasing the morbidity of disease burden. Mainstays of early and moderate disease have been topical clindamycin, oral TCNs, and intralesional corticosteroids, with surgery being reserved for more advanced disease. Hormonal therapy may benefit some, but not all, cases. Currently, the only FDA-approved medication for HS is adalimumab, and this will hopefully lead the way for more anti-inflammatory and immunomodulating options to be accessible for patients in the future. There are several case reports and series that support various other lifestyle, medical, and surgical or laser options for patients. It is up to the dermatology provider to assess the risks vs benefits of these various therapies to customize the most appropriate HS disease management plan for their patients.

References

1. Bolognia JL, Jorizzo JL, Rapini RP. Dermatology. 3rd ed. Maryland Heights, MO: Elsevier; 2013:583-585.
2. Buimer M, Wobbes T, Klinkenbijl JH, Riejnen MM, Blokx WA. Immunohistochemical analysis of steroid hormone receptors in hidradenitis suppurativa. Am J Dermatopath. 2015;37(2):129-132.
3. Kohorst J, Kimball AB, Davis MD. Systemic associations of hidradenitis suppurativa. J Am Acad Dermatol. 2015;73(5):S27-S35.
4. Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I. Treatment of Skin Disease. 5^th ed. Toronto, Canada: Elsevier; 2019:344-346.
5. Join-Lambert O, Coignard H, Jais JP, et al. Efficacy of rifampin-moxifloxacin-metronidazole combination therapy in hidradenitis suppurativa. Dermatology. 2011;222(1):49-58.
6. Lee A, Fischer G. A case series of 20 women with hidradenitis suppurativa treated with spironolactone. Australas J Dermatol. 2015;56(3):192-196.
7. Verdolini R, Clayton N, Smith A, Alwash N, Mannello B. Metformin for the treatment of hidradenitis suppurativa: a little help along the way. J Eur Acad Dermatol Venereol.2013;27(9):1101-1108.