REVIEW

Hidradenitis Suppurativa: A Guide for the

Practicing Physician
Carina M. Woodruff, MD; Abbas M. Charlie, BS, MPH;
and Kieron S. Leslie, MBBS, FRCP

Abstract

Hidradenitis suppurativa is a chronic inflammatory disease of apocrine glandebearing skin. Although immu-
nologic derangements, genetic predisposition, obesity, and smoking are likely important factors, the patho-
genesis of the disease and the effect of available treatments on disease course have not been fully elucidated. In the
absence of proper treatment, chronic inflammation results in diffuse scarring and a wide array of complications,
including the development of cutaneous squamous cell carcinoma. This severe and chronic disease can have
detrimental effects on self-esteem and quality of life. No ideal treatment regimen has been defined, but several
therapies have been found to reduce lesion severity and improve symptoms. We reviewed the literature through
July 2014 for existing treatments. Published articles were obtained via systematic review of medical databases
(PubMed, Embase, Google Scholar) and scrutiny of citation lists using the search terms “hidradenitis suppu-
rativa” and “acne inversa”. Given the scarce literature on treatment strategies, we also reviewed data from any case
reports or prospective and retrospective studies that were located. On the basis of the existing literature, we
provide an evidence-based algorithm for the management of this disease in the primary care setting. More
research is needed to evaluate the comparative effectiveness of topical and systemic treatments and to better
understand the pathogenesis, natural history, and subtypes of hidradenitis suppurativa.
ª 2015 Mayo Foundation for Medical Education and Research n Mayo Clin Proc. 2015;90(12):1679-1693

From the Department of

H
idradenitis suppurativa (HS) is an in- At present, there are few double blinded ran-
Dermatology, University
flammatory disease of apocrine domized trials and no official algorithm to of California, San Fran-
glandebearing skin with a chronic inform the treatment of HS. This leads to hetero- cisco, San Francisco.
intermittent course and a devastating effect on geneity in treatment practices because physi-
quality of life. It is characterized by tender, cians are left to dissect a large and complex
deep-seated inflammatory nodules and ab- literature on their own. Herein, we review the
scesses, sinus tracts, and extensive scarring.1,2 literature pertaining to the clinical features, path-
Although the effect of current therapies on the ogenesis, and treatment of HS and provide an
course of HS has not been defined, early diagnosis evidence-based algorithm for its management
and aggressive control of disease is important in in the primary care setting.
theory, because the destruction of cutaneous ar-
chitecture that accompanies advanced disease is PREVALENCE AND NATURAL HISTORY
extremely challenging to treat and associated The point prevalence of HS has been estimated
with debilitating medical and psychosocial to be between 0.1% and 4.1%. Both familial
sequelae. Estimated reported delays from disease and sporadic cases have been described.
onset to diagnosis range from 7 to 12 years, sug- Although cases have been reported in children
gesting that increasing physician and patient (most often in the context of precocious adre-
awareness of HS remains an important goal.3,4 narche), the disease most often appears after
Hidradenitis suppurativa is commonly encoun- pubertydcommonly in the second and third
tered in the primary care setting and may be decades of lifedand is rare in the elderly.6
increasing in incidence.5 It is managed by general Several studies have confirmed a strong female
practitioners, dermatologists, and various surgical preponderance.5 A racial predilection has not
specialtiesda fact that underscores the impor- been firmly established.7
tance of widespread physician familiarity with The course of HS is prolonged and marked
its presentation and management. by intermittent periods of activity and remission.

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 MAYO CLINIC PROCEEDINGS

buttock, pubic region, chest, scalp, retroauric-

ARTICLE HIGHLIGHTS ular, and eyelid.20
Clinical severity is graded using the Hurley
n Important lifestyle modifications include smoking cessation,
staging system21 (Table 1) and Sartorius scoring
weight loss, and avoidance of tight-fitting clothing. system.22 Risk factors for greater disease severity
n Comprehensive treatment should include optimization of have been investigated in a handful of studies
associated comorbidities and management of pain and psycho- and include male sex; disease duration; body
logical sequelae. mass index (calculated as the weight in kilo-
grams divided by the height in meters squared);
n Evidence supports the use of medical therapies including topical
smoking-pack years; presence of axillary, peri-
and oral antibiotics, oral contraceptives, acitretin, cyclosporine, anal, or mammary lesions; personal history of
dapsone, and tumor necrosis factor inhibitors. acne; spontaneous/nonfamilial HS; and involve-
n Combining medical therapy with early surgical management ment of atypical locations (eg, ears).23,24
(deroofing, local or radical wide excision, and laser ablation) Although chronicity and recurrences are hall-
marks of HS, there is substantial variability in its
may yield better outcomes.
course. This complicates both the diagnosis of
n We recommend a maintenance regimen of topical clindamycin HS and its treatment, because heterogeneity in
and cleansing agents such as chlorhexidine gluconate solution response to treatment (eg, disease activity) may
4.0% or benzoyl peroxide for all patients. presumably be the result of undetected clinical
subtypes differentially responding to different
treatment modalities. Three clinical subtypes of
Lesions may rupture spontaneously, developing HS have been recently proposed using latent class
into intradermal or subcutaneous epithelial- analysis in a large prospective cross-sectional
lined sinus tracts.4 In the absence of proper treat- study (N¼618): (1) a classic axillary-mammary
ment, normal skin is compromised by persistent HS subtype, representing 48% of cases and char-
draining sinuses and the severe dermal scarring acterized by breast and axillary involvement and
that ensues.4 hypertrophic scarring; and 2 “atypical” subtypes:
Long-standing, poorly controlled disease can (2) a follicular HS subtype, representing 26% of
lead to a wide array of complications. Diffuse cases who were predominantly male smokers
fibrosis and scarring, especially with axillary dis- with a family history of HS and characterized by
ease, can lead to limb contractures and impaired follicular lesions, including epidermal cysts, pilo-
mobility. Complications of chronic suppuration nidal sinus, comedones, and severe acne; and (3)
include anemia, hypoalbuminemia, and amyloid- a gluteal HS subtype, representing 26% of cases,
osis; the last 2 rarely progress to renal failure.8,9 typically smokers with a lower body mass index,
Other complications include axial and peripheral and with morphology characterized by follicular
arthropathy, peripheral lymphedema, fistula for- papules, folliculitis, and gluteal involvement.25
mation, and the development of squamous cell These subtypes have yet to be associated with
carcinoma in areas of chronic inflammation; the distinct pathogenic mechanisms or differential re-
last complication has been estimated to occur at sponses to therapy, and the extent of overlap be-
a 4.6-fold increased rate compared with unaf- tween them in a clinical population has not been
fected populations.7,10-12 Psychosocial sequelae quantified. It is notable that the authors report an
of HS include decreased quality of life and earlier onset, more prolonged, and more severe
work productivity, sexual disturbances, depres- course for patients with the follicular HS subtype
sion, and social isolation.13-19 and a more prolonged but less severe course for
patients with the gluteal subtype.25
CLINICAL FEATURES
The diagnosis of HS is made on a clinical ba- METHODS
sis via recognition of the typical morphology We searched PubMed, Embase, and Google
(Figure 1), typography, and course of the Scholar, and scrutinized citation lists for reports
disease. of treatments used for HS. Given the scarcity of
Predilection sites, in order of decreasing randomized controlled trials (RCTs) for HS
frequency, include axillary, inguinal, perianal (and overall scarcity of treatment data), we also
and perineal, mammary and inframammary, reviewed data from any case reports or
n n
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HIDRADENITIS SUPPURATIVA

FIGURE 1. Morphology of hidradenitis suppurativa. Typical morphological features include inflamed

nodules, abscesses, sinus tracts, and hypertrophic fibrous (“bridged”) scarring. Adjacent pairs of comedones
(“tombstone comedones”) are characteristic of more chronic disease. A, Multiple tender erythematous
nodules. B, Abscess. C, “Tombstone” double comedones. D, Draining sinus tracts. E, Bridged, hypertrophic
scarring.

prospective and retrospective studies that were and spontaneous cases, but are overall thought
located. Search terms included hidradenitis suppu- to play an etiologic role in only a minority of cases
rativa and acne inversa. Only articles in English, of HS.27-30
published before July 2014, were included.
Two authors (A.M.C. and C.M.W.) indepen-
Immunological Factors
dently extracted data from relevant articles.
Elevated levels of several proinflammatory cyto-
kines, most notably tumor necrosis factor a
CAUSES AND MECHANISMS OF DISEASE (TNF-a), interleukin (IL)-1b, and IL-17, as
The pathogenesis of HS has not been fully eluci- well as anti-inflammatory cytokines such as IL-
dated and is likely multifactorial. Histopatholog- 10 have been identified in lesional skin.31-35
ical studies suggest that hyperkeratosis of the Over- and underexpression of antimicrobial
follicular epithelium may be the primary event. peptides and abnormalities in Toll-like receptor
Hidradenitis suppurativa likely results from the signaling have also been implicated in the path-
synergistic effect of the various factors discussed ogenesis of HS, although it is unclear whether
below. these alterations are a primary triggering event
or a secondary consequence of bacterial
Genetic Factors carriage.32,36,37 One theory posits that the initi-
A total of 35% to 40% of patients report a family ating event may be an aberrant immune
history of HS.23,24,26 Mutations in the g-secretase- response to commensal microbes, leading to
Notch signaling pathway, which is thought to the production of antimicrobial peptides and
be involved in epithelial proliferation and differ- cytokines and recruitment of an inflammatory
entiation, have been identified in both familial infiltrate. This inflammation, in turn, results in

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 MAYO CLINIC PROCEEDINGS

pathogenesis of HS.48 However, these effects

TABLE 1. Hurley Staging System
are likely subtle or part of a multifactorial etiol-
Hurley stage Clinical features ogy, given that studies have failed to consistently
Mild (grade I) Abscesses only (single or multiple) without sinus tracts or find higher rates of androgenism in HS cohorts as
cicatrization compared with controls.49,50
Moderate (grade II) Abscesses (single or multiple) with sinus tracts or cicatrization.
Lesions are distinct and widely separated (eg, >10 cm apart)
Severe (grade III) Multiple interconnected sinus tracts or abscesses or disease
DIFFERENTIAL DIAGNOSIS AND
with nearly diffuse to diffuse coverage of an area (eg, axilla) EVALUATION
Features of the history (chronicity and postpu-
Patients should be classified according to the Hurley staging system into those with mild (grade I),
bertal onset) and physical examination (multi-
moderate (grade II), and severe (grade III) disease.
Adapted from Dermatologic Surgery,21 with permission.
ple inflamed lesions, symmetrical involvement,
intertriginous predominance, and tombstone
comedones) are usually adequate for distinguish-
hyperkeratosis of the follicular infundibulum,
ing HS from various other conditions that can
and subsequent follicular plugging, rupture,
present with a similar clinical morphology (eg,
and activation of the inflammasome by free ker-
nodular acne, developmental fistula, and epider-
atin fibers in the dermis.38
moid, dermoid, pilonidal, or bartholin cysts). In
addition, HS can be distinguished from various
Infection infectious entities (eg, abscess, carbuncles, furun-
Infection is unlikely to be a primary causative fac- cles, actinomycosis, cat scratch disease, granu-
tor. It is hypothesized that follicular occlusion loma inguinale, lymphogranuloma venereum,
serves as a nidus for bacterial colonization, which noduloulcerative syphilis, and tuberculous
may then trigger an immunological response, or abscess) via the use of bacterial, fungal, and
alternatively, that HS may be the result of an mycobacterial cultures because conventional
aberrant response to commensal bacteria.39 cultures in HS are typically sterile or grow
multiple species as opposed to a single infec-
Smoking tious agent.51,52
Several studies point to higher-than-average Furthermore, patients with HS are typi-
smoking rates (70%-90%) among patients cally afebrile, are clinically well, and have lab-
with HS and more severe disease in smokers, oratory parameters within normal limits,
but it is unclear whether this relationship is although patients with more severe disease
causal.6,26,40,41 Nicotine may lead to follicular may have leukocytosis or elevation in their
plugging via its promotion of hyperplasia of erythrocyte sedimentation rate and C-reactive
the follicular infundibulum and oversecretion protein level. Cutaneous manifestations of in-
of eccrine glands or contribute to inflammation flammatory bowel disease, and in particular
by inducing chemotaxis of neutrophils.42-45 Crohn disease, should be considered in the
setting of perianal lesions and concomitant
Obesity gastrointestinal symptoms.53
The severity and course of HS are correlated Alikhan et al54 proposed a diagnostic algo-
with body mass index.26,41 Although obesity rithm in which fulfillment of 4 criteria is sufficient
is known to affect cutaneous physiology in for a clinical diagnosis of HS: (1) Is there more
various ways, in the case of HS it is primarily than a single inflamed lesion? (2) Is the course
thought to compound the severity of disease chronic with new and recurrent lesions? (3) Are
through mechanical effects, for example, sweat the lesions bilateral? and (4) Are the lesions
retention, maceration, and enhanced mechan- located primarily in the milk line?
ical friction, and possibly also through coexist-
ing hormonal alterations.41,46,47 LIFESTYLE MODIFICATION
Androgens Weight Loss
The premenstrual onset and female predomi- A retrospective survey study of patients with
nance of HS, along with noted improvements HS who had undergone bariatric surgery
during pregnancy or with antihormonal therapy, found that a 15% or greater reduction in
suggest that androgens may play a role in the weight was associated with a 35% decrease
n n
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HIDRADENITIS SUPPURATIVA

in HS symptoms and a significant reduction in with doxycycline, amoxicillin with clavulanic

the number of involved sites (P¼.003).55 Iso- acid, clindamycin, other tetracyclines, and cip-
lated case reports attest to sustained HS remis- rofloxacin is common in the clinical setting,
sion after extreme weight loss or bariatric only combination regimens have been system-
surgery.56 Despite the lack of a strong evi- atically evaluated.52 Combination therapy with
dence base, given the other many benefits of rifampicin and clindamycin is the most well
weight loss, we strongly encourage clinicians studied regimen. Partial response rates (some
to counsel overweight or obese patients about improvement) ranging from 71% to 93%
the role of obesity in the pathogenesis of HS as have been reported for 10-week courses of
well as the possible effect of weight loss on the rifampicin 600 mg once daily and clindamycin
course of their disease. 300 mg twice daily.62-65 A total of 11% to
47% of these patients experienced com-
Smoking Cessation plete remission.63,65 A maximum therapeu-
The effect of smoking cessation on the course tic response is typically obtained within 2.5
of HS has not been systematically assessed. months (with no therapeutic benefit with
Supporting evidence is drawn from anecdotal extension), and the mean time to relapse
reports, correlational studies, and evidence is 5 months.65 Adverse effects are reported
suggesting that nicotine may play a role in the in 13% to 43% of patients, the most com-
pathogenesis of HS.57 Despite the lack of data mon being diarrhea.62-65 An alternative
to substantiate the efficacy of this intervention, regimen with broad-spectrum coverage including
we argue that the possibility of clinical improve- anaerobes exhibited marginally superior efficacy
ment, combined with the numerous established but lower tolerability: in this retrospective study,
benefits of smoking cessation to overall health, is combination therapy with rifampin 10 mg/kg
sufficient justification to make smoking cessa- once daily, moxifloxacin 400 mg once daily,
tion a priority in HS management. and metronidazole 500 mg thrice daily (6 weeks
only) was administered for up to 6 weeks
Clothing after complete remission was achieved,
In theory, avoidance of tight-fitting, restrictive followed by secondary prophylaxis with
clothing would be beneficial, given the presumed trimethoprim-sulfamethoxazole 400 mg/80 mg
role of friction in the pathogenesis of HS. There once daily or doxycycline 100 mg once daily.
are no studies to substantiate this claim, but Complete remission was achieved in 57% of pa-
this intervention can be recommended, given tients, and a partial response was documented for
the facility and low risk of implementation. the remainder. The mean time to remission was
2.4 months for patients with Hurley stage I dis-
MEDICAL MANAGEMENT ease and 3.8 months for patients with Hurley
stage II disease. The administration of secondary
Antibiotics prophylaxis did not prevent relapse in 58% of pa-
Antibiotics are a mainstay of HS treatment, tients who achieved remission. Adverse events
likely because of their both antibacterial and were common, including nausea and diarrhea
immunomodulatory properties, although evi- (64%), vaginal candidiasis (35% of female pa-
dence for their efficacy is limited. Two blinded tients), and tendinitis (14%).61 In a recent pro-
RCTs suggest that topical clindamycin 1% spective study, the most common species
twice daily may be an adequate treatment for were coagulase-negative staphylococci, fol-
mild disease, an adjunctive therapy, or a tool lowed by Staphylococcus aureus and various
to decrease inflammation before radical sur- strains of intestinal flora, including Escheri-
gery in more severe disease.58,59 Overall, sys- chia coli, Klebsiella sp, Proteus mirabilis,
temic antibiotics appear to be effective for a Enterococcus faecalis, and Pantoea agglomer-
large proportion of patients with mild to mod- ans.52 Sensitivity studies revealed that these
erate but not severe HS: in a retrospective re- species were resistant to most antibiotics
view, improvement in lesions was noted in commonly used in the clinical setting, including
79.6% and complete clearance in 26.5% of pa- tetracyclines (64%), macrolides (58%),
tients who had received various systemic anti- trimethoprim-sulfamethoxazole (54%), lincosa-
biotic regimens.60,61 Although monotherapy mides (51%), and monobactams (75%).52

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 MAYO CLINIC PROCEEDINGS

The authors recommend an initial regimen Finasteride, a 5-a-reductase inhibitor that

of interchangeable use of amoxicillin with halts the conversion of testosterone to the
clavulanic acid and fluoroquinolones, more active 5-a-dihydrotestosterone, has
followed by clindamycin-rifampicin combi- exhibited beneficial effects in short courses
nation and finally rifampin-moxifloxacin- (6-16 weeks) and as maintenance therapy in
metronidazole. They also recommend both female and male patients of varying
tetracyclines or macrolides for maintenance ages.67,70,71 In these studies, doses ranging
therapy.52 from 5 to 15 mg once daily were administered,
which is notably much higher than the doses
Antiandrogens commonly used for the treatment of benign
In a retrospective comparison, antiandrogen prostatic hyperplasia and androgenetic alope-
therapy was found to be superior to antibiotic cia. Even so, these doses were well tolerated
therapy for HS treatment.66 Overall, a substan- and the most common adverse effects were
tial but mostly anecdotal literature points to an gynecomastia and breast tenderness.67,70,71
important role of antiandrogenic therapy in the Women of childbearing age should use contra-
treatment of mild to moderate HS. This is in ceptives, given the risk of feminization of male
part due to higher rates of polycystic ovarian fetus. Cyproterone acetate and spironolactone
syndrome (PCOS) in this patient population; exert antiandrogenic effects via binding to testos-
as such, concomitant acne, hirsutism, androge- terone receptors and inhibition of androgen
netic alopecia, or a history of irregular menses biosynthesis. Efficacy of CPA for HS has been re-
in a patient with HS should prompt measure- ported in a few studies, but it is not approved for
ment of free and total testosterone, luteinizing use in the United States. At present, no data sup-
hormone, follicle-stimulating hormone, and port the use of spironolactone specifically for HS;
dehydroepiandrosterone sulfate levels. Inter- however, given its equivalence to CPA for the
estingly, evidence suggests that antiandrogens treatment of other conditions associated with
may be effective as an adjunctive or monother- hyperandrogenism, such as hirsutism, it may
apy for HS even in the absence of clinical or be a viable alternative.72
biochemical evidence of hyperandrogenism.67 Studies suggest that rates of metabolic syn-
Optimal antiandrogen regimens for HS have drome may be disproportionately high in the
not been defined. Treatment with a combined mostly obese HS population.73,74 Insulin resis-
oral contraceptive may be especially advanta- tance is also a central pathogenic feature in
geous for female patients of childbearing age PCOS because hyperinsulinemia affects ovarian
who also require some form of birth control. androgen production.75 Metformin, a biguanide
No difference between ethinyloestradiol 50 mg/ insulin-sensitizing agent, is a first-line treatment
norgestrel 500 mg and ethinyloestradiol 50 mg/ of PCOS and type 2 diabetes; a few case reports
cyproterone acetate (CPA) 50 mg was found in and a prospective study suggest that it may also
a double-blind crossover trial in which half of be effective in subsets of patients with HS.76 In a
the patients (N¼24) exhibited clearance of prospective study (N¼25) in which metformin
or improvement in HS over a 12-month was up-titrated to doses of 1.5 mg once daily,
period.68 Combined oral contraceptive with clinical improvement was noted in 72%
third-generation progestins (including gesto- (n=18) of patients, 7 of whom had a more
dene, norgestimate, and desogestrel), which than 50% reduction in Sartorius scores by 12
are less androgenic because they bind more weeks.76
selectively to the progesterone receptor,
should be used. Combined oral contraceptive Retinoids
with drospirenone, a synthetic progestin that Despite clinical similarities between HS and acne
is an analog of the antiandrogen spironolac- vulgaris, isotretinoin has not been proved to be
tone, may be particularly beneficial. Given efficacious in the treatment of HS, even for
the high prevalence of smoking in this patient patients with a history of acne.77 A systematic re-
population, combined oral contraceptive, view of 7 studies reports an overall nonresponse
and especially drospirenone, should be pre- rate of 64% for isotretinoin administered in daily
scribed with care because of the increased doses of 0.5 to 1.2 mg/kg for 4 to 12 months.78
risk of thromboembolism.69 In contrast, evidence suggests that acitretin
n n
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HIDRADENITIS SUPPURATIVA

(a metabolite of etretinate with a shorter elimina- the efficacy of infliximab administered as the
tion half-life) may be an efficacious alternative. Re- standard induction regimen for psoriasis and
ported dosing regimens for acitretin range from Crohn disease (5 mg/kg per week at baseline,
daily doses of 0.25 to 0.88 mg/kg and for etreti- week 2, and week 6 and/or maintenance therapy
nate from 0.35 to 1.1 mg/kg for 3 to 39 months. every 4-8 weeks).81-83 Reported response rates
In a retrospective study of patients with severe HS range from 80% to 89%, with some patients
(N¼12; 8 male patients), all patients were noted exhibiting clinical improvement within 8 weeks.
to exhibit some improvement, with most of Further dose escalation and shortening of inter-
them achieving marked or complete remission dose intervals have not been shown to improve
on dosing regimens of 0.25 to 0.88 mg/kg for aci- response.81 Clinical improvement is not main-
tretin monotherapy for 5 to 12 months. This is tained after cessation of treatment in most
consistent with a response rate of 95% reported patients (62%).83 In a systematic review of 61
in a systematic review that also incorporated evi- cases, failure to respond was associated with
dence from several case reports.78 Improvement greater baseline severity and early onset of dis-
was generally observed by 2 months and ease, as well as history of surgical treatment.
continued for the first 6 months of therapy.79 The overall relapse rate was 25%, typically occur-
Long-lasting improvement, with remission pe- ring after 37 weeks of continuous treatment (6
riods ranging from 6 to 45 months, was reported doses). Relapse was more common in those
for 9 of these patients.79 Given their teratoge- receiving monotherapy and was also associated
nicity, retinoids should be avoided in women of with baseline HS severity.81
childbearing age. If administered, adequate Adalimumab is a human monoclonal anti-
contraception must be used for the duration of body, and etanercept is a fusion protein pro-
treatment and for the recommended period after duced by recombinant DNA; both inhibit
drug cessation, which is retinoid dependent. TNF-a. Adalimumab and etanercept, which
are administered subcutaneously, have been
Zinc Gluconate investigated as alternatives to infliximab. Few
One prospective study reported favorable results comparative studies exist, but a retrospective
for monotherapy with zinc gluconate 90 mg comparative study (N¼10) found that adalimu-
once daily for patients with mild to moderate mab 40 mg twice a month was less effective than
HS: 36% experienced complete remission and infliximab 5 mg/kg at weeks 0, 2, and 6.84
the remaining 63.6% partial remission.80 Doses Various regimens of adalimumab have been
were decreased as tolerated after a clinical studied. In a double-blind RCT using a loading
response was achieved. The authors estimate dose of 80 mg followed by 40 mg twice a month
that doses of 75 and 118 mg once daily would for 12 weeks, a statistically significant change in
be required to maintain disease quiescence in Sartorius scores was reported after 6 weeks, but
mild and moderate cases, respectively. Adverse not at 12 weeks after the initiation of treat-
effects were reported in 14% and were generally ment.85 In another RCT, a 16-week, high-dose
mild (diarrhea, nausea, abdominal distention, regimen (loading dose of 160 mg, followed by
and esophagitis). 80 mg 1 week later and then 40 mg per week)
was found to be superior to a low-dose regimen
Biologics (loading dose of 80 mg, followed by 40 mg twice
Biologics are an appropriate alternative for mod- a month) and placebo. The treatment effect was
erate to severe HS refractory to treatment with particularly pronounced for current smokers
oral antibiotics, retinoids, or hormonal therapy. and for those with less severe baseline disease
At present, the cost of therapy remains an and greater body mass index.86 In most cases,
important limitation, precluding their use or a clinically evident response was first noted
imposing a significant economic burden for within 4 to 6 weeks, persisting or improving
many patients. for several months. Evidence on long-term
follow-up is limited, but a prospective study re-
Tumor Necrosis Factor a Blockade ported a decrease in the efficacy of adalimumab
Infliximab is a chimeric monoclonal antibody at the 2-year mark.87
directed against TNF-a. Case reports and a One double-blind RCT and several pro-
double-blind, placebo-controlled trial attest to spective trials and case reports have

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 MAYO CLINIC PROCEEDINGS

Mild (grade 1) disease Moderate (grade 2) disease Moderate (grade 3) disease

or first-line therapy or second-line therapy or third-line therapy

Maintenance regimen Medical management Surgical management

1. Clindamycin gel 1% BID and 1. Maintenance regimen as listed 1. Deroof chronic boils and 1. Maintenance regimen as listed
2. Decolonization with chlorhexidine for mild disease and 2. Local excision (if tract for moderate disease and any
gluconate solution 4.0% QD or 2. Tetracycline (eg, doxycycline formation or scarring present) effective medical therapies and
benzoyl peroxide solution QD or 100 mg BID) or macrolide (eg, 2. Wide local excision
bleach baths 2-3 times QW Erythromycin 250-500 mg Other reported therapies:
BID) for maintenance 3. CO2 or Nd:YAG laser abiation
Other reported therapies: 3. If female patient, also consider
• Zinc gluconate 75-118 mg QD OCP with third-generation
• Botulinum toxin Progestrin Repeat as needed for new boils,
tracts, or scarring. if tracts become
interconnected, proceed to third-line
Evaluate after 3 months Evaluate after 3 months therapies.
D/C Tetracycline and add

Proceed to second-line therapies Monotherapy with TMP-SMX DS

160/800 mg BID or
Amoxicillin-clavulanate 500 mg/
125 mg BID or
Fluoroquinolones (eg, moxifloxacin
400 mg QD) ×10 weeksa

Repeat PRN flares

Evaluate after 3 months
D/C above and add
Clindamycin 300 mg BID and
rifampicin 500 mg QD × 10 weeks

Repeat PRN flares

Evaluate after 3 months
D/C above and add

Rifampicin 800 mg QD, moxifloxacin

400 mg QD,
metronidazole 500 mg
Q6-8H ×10 weeks

Repeat PRN flares

Evaluate after 3 months
D/C above and add

For male or female patients not of

childbearing age:
Acitretin 0.25-0.89 mg/kg × 3-39
months or
If effective, continue anti-
For all: may consider dapsone TNF as maintenance for at
5-200 mg QD as maintenance or least 4-8 monthsc
cyclosporine 1-3 mg/kg BID ×
4-15 months
Infliximab 5 mg/kg QW at week Evaluate after 3 months
Complete course or continue
1, 2, 6 or
with maintenance (if dapsone)

Evaluate after 3 months Adalimumab 160 mg QW at week

1, 80 mg QW at week 2, 40 mg
D/C above and add QW at week 3b Proceed to third-line therapies

n n
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HIDRADENITIS SUPPURATIVA

investigated varying regimens of etanercept, monoclonal antibody directed against IL-12

with mixed results.88-91 Dosing regimens vary- and IL-23, which is approved for the treatment
ing from 25 to 100 mg once a week for 3 of moderate to severe plaque psoriasis.95-97
months to over 1 year have been tested. A sys-
tematic review reports a moderate to signifi- Other Immunosuppressive Agents
cant (>50%) response in 56% of patients.78 Other agents investigated for use in HS include
Follow-up in most studies is insufficient to methotrexate, colchicine, cyclosporine, and
assess potential for inducing long-term remis- dapsone. Of these, only the last 2 have reported
sion. The incidence of adverse effects is compara- efficacy in a few case reports. Dapsone mono-
ble to that seen for other patient populations therapy at doses ranging from 5 to 200 mg
using TNF inhibitors (7.6%). Although short- once daily produced clinical improvement and
term studies do not suggest an increased risk of was well tolerated in 38% to 100% of patients
malignant neoplasms, TNF inhibitors should be (overall 56%), most of whom had mild disease.
used with caution in this population, given the Clinical improvement was typically evident
increased incidence of malignancy.92,93 within 2 to 12 weeks and sustained only during
active treatment.78,98-100 Because dapsone is
nonteratogenic and typically well tolerated, it
IL-1 Blockade may be a favorable option in women of child-
Anakinra is a recombinant receptor antagonist bearing age. Before the initiation of the treat-
that competitively inhibits the biological activ- ment, a glucose-6-phosphate dehydrogenase
ity of the proinflammatory cytokines IL-1a level should be checked owing to the risk of he-
and IL-1b. Its efficacy in HS has been reported molysis. Reports of successful use of cyclo-
in an open label study, in which all (N¼5) pa- sporine have been published for a handful of
tients who completed an 8-week course of patients. Dosing schedules range from 2 to 6
anakinra 100 mg once daily reported signifi- mg/kg once daily for periods of 4 to 15 months.
cant decreases in their Sartorius scores.94 All patients in this small subset experienced
The efficacy of anakinra remains to be evalu- moderate to significant clinical improve-
ated in an RCT. ment.101-103 There are a small number of
case reports attesting to transient improve-
IL-12 and IL-23 Blockade ments in HS when oral cortiocosteroids are
A few case reports attest to the efficacy of uste- used alone or in combination with other
kinumab (overall response rate of 75%), a agents; overall, the evidence does not point

FIGURE 2. Treatment algorithm. Therapies for our algorithm were selected on the basis of established clinical efficacy, tolerability, and
potential for adverse effects. In general, we recommend an aggressive treatment approach and early surgical intervention to prevent
irreversible long-term sequelae. The appropriate initial regimen should be initiated on the basis of the assessment of disease severity at
presentation (Figure 1). Serial evaluation every 3 months should be performed; if disease control is adequate or significant improvement
is noted, the existing regimen should be continued to its completion (when appropriate). For patients demonstrating inadequate disease
control, we recommend progression through first-, second-, and third-line therapies in the order listed. More rapid progression through
the algorithm (eg, early surgical intervention) may be indicated for patients with high-risk features. Other experimental therapies not
listed (eg, anakinra) may be attempted for disease that is refractory to these agents. Maintenance therapy should be continued even
when more aggressive medical or surgical therapies are initiated. aThe recommended treatment times in our algorithm are based on the
average time to maximal response in clinical studies. There are no studies that systematically assess the safety and efficacy of the long-
term antibiotic treatment. For patients with more severe disease, clinicians may opt to continue oral antibiotic treatment for a longer
period of time. We recommend continued use of topical antibiotics in all patients as part of a maintenance regimen. b,cImmunogenicity is
a known complication of biological therapy and is associated with a progressive decrease in treatment efficacy. Combination therapy
with methotrexate (although MTX has not been shown to be effective in hidradenitis suppurativa119) has been shown to reduce the
immunogenicity of tumor necrosis factor inhibitors in the treatment of rheumatoid arthritis, Crohn disease, and spondyloarthritis, and
as such, could be considered.120 At present, there is no evidence to suggest whether abrupt discontinuation of antie
tumor necrosis factor therapy or gradual tapering of doses produces a more sustained treatment response. In most studies, treatment is
discontinued without a taper. BID ¼ twice daily; D/C ¼ discontinue; DS ¼ double strength; MTX ¼ methotrexate; Nd:YAG ¼
neodymium-doped yttrium aluminum garnet; OCP ¼ oral contraceptive; PRN ¼ pro re nata, as needed; QD ¼ once daily; QW ¼ every
week; Q6-8H ¼ every 6 to 8 hours; TMP/SMX ¼ trimethoprim-sulfamethoxazole; TNF ¼ tumor necrosis factor.

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 MAYO CLINIC PROCEEDINGS

to a clear role of routine use of oral or intrave- defect and laxity of the surrounding skin.116
nous corticosteroids in the short- or long- Several authors have suggested that the risk of
term management of HS.102,104,105 recurrence is more dependent on the breadth of
surgical excision and extent and duration of the
Neurotoxins disease rather than on the type of closure,
The efficacy of botulinum toxin in the treat- suggesting that early surgical intervention after
ment of HS has not been systematically failure of noninvasive therapies may be an impor-
assessed, but scattered case reports attest to tant goal in treatment.116-119 Overall, most pa-
its efficacy, with reported induced remissions tients (w91.3%) experience partial or complete
lasting up to 10 months.106,107 recovery with these techniques.

SURGICAL APPROACHES MANAGEMENT OF PAIN

Pain is a prominent feature of HS, thought to
Laser Surgery result from both sequelae of ongoing inflamma-
In a prospective, randomized, within-patient, tion and the associated depression. No studies
controlled trial, treatment with 4 monthly ses- have evaluated the efficacy of different pain con-
sions of neodymium-doped yttrium aluminum trol regimens in HS. Scheinfeld120 proposed a
garnet laser, along with topical benzoyl peroxide combination of both oral and topical agents,
and clindamycin, was found to be superior to including lidocaine 5% ointment, diclofenac
that with topical benzoyl peroxide and clindamy- 1% gel, and ice packs, as well as nonsteroidal
cin for moderate to severe HS.108 These findings anti-inflammatory drugs, atypical anticonvul-
are supported by another prospective RCT in sants such as gabapentin and pregabalin, and
which an overall 65.3% decrease in HS severity serotonin-norepinephrine reuptake inhibitors
was reported for anatomic sites treated with 3 such as duloxetine.120
monthly sessions of neodymium-doped yttrium
aluminum garnet laser.109 The efficacy of carbon MANAGEMENT OF PSYCHOSOCIAL
dioxide laser excision with marsupialization or SEQUELAE
healing via primary or secondary intention is re- No optimal strategy for managing the psychoso-
ported by several case series, with recurrence cial sequelae of HS has been defined, but patient
rates at surgical sites or immediately adjacent interviews suggest that referral to patient sup-
areas ranging from 1% to 22%.110-114 Studies port groups or forums, such as those found at
comparing the efficacy of these 2 techniques are the Hidradenitis Suppurativa Foundation web-
lacking. site (www.hs-foundation.org), may assist in
coping.14 Patients with symptoms of depression
Excisional Surgery or experiencing impairments in social, work, or
Surgery is an important part of the therapeutic sexual functioning should be referred for
armamentarium for HS. Conservative surgical counseling.
options for milder cases include incision and
drainage of boils and deroofing of chronic TREATMENT ALGORITHM
lesions and associated sinus tracts115; the latter We propose an algorithm for treating HS on the
has proved to be superior to incision and basis of our interpretation of the available clinical
drainage in terms of recurrence rates.115 evidence (Figure 2).121,122 Our algorithm pro-
Severe HS is treated via limited local or radical vides physicians with a layout of sequential ther-
wide excision followed by primary closure, heal- apies, including reasonable time frames for which
ing by secondary intention, flap advancement a clinical response can be expected for each
(skin, myocutaneous, and fasciocutaneous), or regimen based on estimates from the literature.
grafting. Optimal surgical techniques remain a We recommend a global baseline assessment
source of controversy, and discussion of the (Table 2) and stratification of patients based on
merits and pitfalls of these reconstructive tech- Hurley stages (Table 1 and Figure 1). Baseline
niques is beyond the scope of this review. How- and subsequent photographs are highly recom-
ever, evidence suggests that the selection of a mended for monitoring clinical progression.
wound closure method should be guided by The initiation of targeted HS therapies should
consideration of the size and location of the be paired with optimization of control of
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HIDRADENITIS SUPPURATIVA

associated comorbidities (eg, diabetes mellitus

TABLE 2. Baseline Disease Assessmenta,b
and PCOS), initiation of aggressive therapies to
address modifiable risk factors, and referral for Supplementary
Variable Evaluation criteria recommendations
management of psychological sequelae. In the
event of treatment failure, we encourage rapid Baseline Disease severity (see Figure 1) See Figure 2
disease Obtain a baseline photograph
progression to the next set of treatments, and
assessment Obtain laboratory parameters
for patients with high-risk features, the clinician
(CBC count, ESR, and CRP
may consider bypassing initial treatments that level)
are unlikely to work and may result in further High-risk Male sex Consider a more aggressive
disease progression in the interim. A multidisci- features approach through the
Duration >15 y
plinary approach is preferred, with close collabo- therapeutic algorithm
Smoking >15 pack-year history
ration with dermatologists and surgeons to
prevent progression to advanced disease and its Possible high-risk features:
attendant complications. Presence of follicular lesions
Previous or current severe acne
AREAS OF CONTROVERSY AND Atypical typology
UNCERTAINTY Axillary or perianal disease

Effect of Early vs Late Intervention Lifestyle factors Smoking Consider referral to dietician
The basis for recommending early aggressive Obesity or support services for
Clothing weight loss and smoking
therapeutic intervention remains hypothetical
cessation
because the natural history of HS is still poorly
Comorbidities Diabetes mellitus Optimize disease control and
understood. Although it is hypothesized that un- Polycystic ovarian syndrome consider administering
treated or poorly controlled disease is accompa- metformin
nied by a gradual destruction of cutaneous Psychological Assess functional capacity and Support group referral highly
architecture that leads to progression and irre- well-being quality of life recommended for all
versible sequelae, there is a need for additional Screen for depression and patients
studies to further elucidate the natural history anxiety Consider referral to psychiatry
of HS as well as predictors of persistent or Pain control Assess frequency and severity Administer topical analgesics
more severe disease. In particular, longitudinal of pain and effect on quality Supplements with NSAIDs or
studies comparing outcomes between patients of life other oral therapy, if
necessary
with early and late intervention or between pa-
tients with more and less aggressive therapeutic a
CBC ¼ complete blood cell; CRP ¼ C-reactive protein; ESR ¼ erythrocyte sedimentation rate;
approaches are needed. NSAID ¼ nonsteroidal anti-inflammatory drugs.
b
Baseline screening of patients should include assessment of the 6 domains listed above. The
presence of high-risk features may justify a more aggressive approach with a more rapid pro-
Cancer Risk gression through the treatment algorithm in the event of treatment failures. Optimization of
To date, only one retrospective study has comorbidities and lifestyle modification are crucial components of treatment and should be
assessed the risk of malignancy in patients with discussed at length with patients, with secondary referral to specialists as deemed necessary. Given
the tremendous effect of HS on quality of life, evaluating and addressing psychosocial well-being
HS, suggesting that HS is associated with an over-
and pain control are other critical components of the treatment.
all 50% increased risk of developing any cancer.7
Additional studies are needed to delineate risk
factors for cancer development in diverse popula- acne, and HS syndrome; synovitis, acne, pus-
tions of patients with HS as well as optimal tulosis, hyperostosis, and osteitis syndrome;
screening regimens. pachyonychia congenita; Adamantiades-Behcet
disease; and keratitis-ichthyosis-deafness syn-
Hidradenitis Suppurativa as a Systemic drome, in addition to obesity and metabolic
Disease syndrome.123,124 These associations beg the
Isolated case reports have noted associations question of whether HS is a systemic disease.
between HS and various conditions, including Although the data linking HS with obesity and
inflammatory bowel disease; spondyloarthrop- metabolic syndrome are well-founded, more
athy; pyoderma gangrenosum; pseudoan- rigorous controlled studies are required to assess
giomatous stromal hyperplasia syndrome; the veracity of associations between HS and these
pyogenic arthritis, pyoderma gangrenosum, various other conditions. A recent review

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 MAYO CLINIC PROCEEDINGS

suggested that these associations must be investi- 5. Vazquez BG, Alikhan A, Weaver AL, Wetter DA, Davis MD.
Incidence of hidradenitis suppurativa and associated factors: a
gated further but may point to a common genetic population-based study of Olmsted County, Minnesota.
or environmental trigger or shared inflammatory J Invest Dermatol. 2013;133(1):97-103.
pathway.123 If this is the case, additional studies 6. Revuz JE, Canoui-Poitrine F, Wolkenstein P, et al. Prevalence
and factors associated with hidradenitis suppurativa: results
may prove that certain treatment strategies are from two case-control studies. J Am Acad Dermatol. 2008;
more efficacious for patients with different over- 59(4):596-601.
lap syndromes. 7. Lapins J, Ye W, Nyrén O, Emtestam L. Incidence of cancer
among patients with hidradenitis suppurativa. Arch Dermatol.
2001;137(6):730-734.
CONCLUSION 8. Tennant F Jr, Bergeron JR, Stone OJ, Mullins JF. Anemia asso-
A growing literature has led to an increased un- ciated with hidradenitis suppurativa. Arch Dermatol. 1968;
98(2):138-140.
derstanding of HS, but many questions remain. 9. Moschella SL. Hidradenitis suppurativa: complications resulting
The pathogenesis remains poorly understood; in death. JAMA. 1966;198(1):201-203.
current research suggests an interplay between 10. Maclean GM, Coleman DJ. Three fatal cases of squamous cell
carcinoma arising in chronic perineal hidradenitis suppurativa.
multiple genetic, immunological, behavioral, Ann R Coll Surg Engl. 2007;89(7):709-712.
and endocrine factors. Likewise, although the 11. Vasey FB, Fenske NA, Clement GB, Bridgeford PH,
therapeutic armamentarium of HS includes Germain BF, Espinoza LR. Immunological studies of the
arthritis of acne conglobata and hidradenitis suppurativa. Clin
various treatments, a large number of these treat- Exp Rheumatol. 1984;2(4):309-311.
ments have not been systematically assessed in 12. Hurley HJ. Apocrine Glands. New York: McGraw Hill; 1979.
randomized placebo-controlled trials. In addi- 13. Matusiak L, Bieniek A, Szepietowski JC. Psychophysical aspects
of hidradenitis suppurativa. Acta Derm Venereol. 2010;90(3):
tion, there are few comparative studies of efficacy 264-268.
of treatments in different pharmaceutical classes. 14. Esmann S, Jemec GB. Psychosocial impact of hidradenitis sup-
At present, the sum of the evidence seems to sug- purativa: a qualitative study. Acta Derm Venereol. 2011;91(3):
328-332.
gest that a multimodal approach may be most 15. Onderdijk AJ, van der Zee HH, Esmann S, et al. Depression in
effective for most patients, incorporating both patients with hidradenitis suppurativa. J Eur Acad Dermatol
medical and surgical treatments in addition to Venereol. 2013;27(4):473-478.
16. Kurek A, Peters EM, Chanwangpong A, Sabat R, Sterry W,
lifestyle modification. Future studies should Schneider-Burrus S. Profound disturbances of sexual health
also attempt to determine whether certain pheno- in patients with acne inversa. J Am Acad Dermatol. 2012;
typic factors are associated with differential re- 67(3):422-428, 428.e1.
17. Kurek A, Johanne Peters EM, Sabat R, Sterry W, Schneider-
sponses to certain treatments. These data will Burrus S. Depression is a frequent co-morbidity in patients
tremendously advance the evidence base for the with acne inversa. J Dtsch Dermatol Ges. 2013;11(8):
treatment of HS and hopefully lead to minimal 743-749.
18. Jemec GB, Heidenheim M, Nielsen NH. Hidradenitis suppura-
homogeneity in treatment practices and optimal tivadcharacteristics and consequences. Clin Exp Dermatol.
outcomes for patients struggling with this debili- 1996;21(6):419-423.
tating and difficult-to-treat disease. 19. Matusiak Ł, Bieniek A, Szepietowski JC. Hidradenitis suppura-
tiva markedly decreases quality of life and professional activity.
J Am Acad Dermatol. 2010;62(4):706-708, 708.e1.
Abbreviations and Acronyms: CPA = cyproterone ace- 20. Slade DE, Powell BW, Mortimer PS. Hidradenitis suppurativa:
tate; HS = hidradenitis suppurativa; IL = interleukin; PCOS = pathogenesis and management. Br J Plast Surg. 2003;56(5):
451-461.
polycystic ovarian syndrome; RCT = randomized controlled
21. Hurley HJ. Axillary hyperhidrosis, apocrine bromhidrosis,
trial; TNF = tumor necrosis factor
hidradenitis suppurativa, and familial benign pemphigus: surgi-
cal approach. In: Roenigk RK, Roenigk HH, eds. Dermatologic
Correspondence: Address to Kieron S. Leslie, MBBS, FRCP,
Surgery. New York: Marcel Dekker; 1989:729-739.
Department of Dermatology, University of California, San 22. Sartorius K, Lapins J, Emtestam L, Jemec GB. Suggestions for
Francisco, 1001 Potrero, Bldg 90, Ward 92, San Francisco, uniform outcome variables when reporting treatment ef-
CA 94110 ([email protected]). fects in hidradenitis suppurativa. Br J Dermatol. 2003;
149(1):211-213.
23. Schrader AM, Deckers IE, van der Zee HH, Boer J, Prens EP.
REFERENCES Hidradenitis suppurativa: a retrospective study of 846 Dutch
1. Jansen T, Plewig G. Acne inversa. Int J Dermatol. 1998;37(2): patients to identify factors associated with disease severity.
96-100. J Am Acad Dermatol. 2014;71(3):460-467.
2. Brown TJ, Rosen T, Orengo IF. Hidradenitis suppurativa. South 24. Canoui-Poitrine F, Revuz JE, Wolkenstein P, et al. Clinical char-
Med J. 1998;91(12):1107-1114. acteristics of a series of 302 French patients with hidradenitis
3. Mebazaa A, Ben Hadid R, Cheikh Rouhou R, et al. Hidradenitis suppurativa, with an analysis of factors associated with disease
suppurativa: a disease with male predominance in Tunisia. Acta severity. J Am Acad Dermatol. 2009;61(1):51-57.
Dermatovenerol Alp Pannonica Adriat. 2009;18(4):165-172. 25. Canoui-Poitrine F, Le Thuaut A, Revuz JE, et al. Identification
4. Poli F, Jemec GB, Revuz J. Clinical presentation. In: Jemec G, of three hidradenitis suppurativa phenotypes: latent class anal-
Revuz BE, Leyden JJ, eds. Hidradenitis Suppurativa. Heidelberg: ysis of a cross-sectional study. J Invest Dermatol. 2013;133(6):
Springer; 2006:11-24. 1506-1511.

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www.mayoclinicproceedings.org
HIDRADENITIS SUPPURATIVA

26. Sartorius K, Emtestam L, Jemec GB, Lapins J. Objective scoring 47. Yosipovitch G, DeVore A, Dawn A. Obesity and the skin: skin
of hidradenitis suppurativa reflecting the role of tobacco physiology and skin manifestations of obesity. J Am Acad Der-
smoking and obesity. Br J Dermatol. 2009;161(4):831-839. matol. 2007;56(6):901-916, quiz 917-20.
27. Pan Y, Lin MH, Tian X, et al. Gamma-secretase functions 48. Barth JH, Layton AM, Cunliffe WJ. Endocrine factors in pre-
through Notch signaling to maintain skin appendages but is and postmenopausal women with hidradenitis suppurativa.
not required for their patterning or initial morphogenesis. Br J Dermatol. 1996;134(6):1057-1059.
Dev Cell. 2004;7(5):731-743. 49. Jemec GB. The symptomatology of hidradenitis suppurativa in
28. Pink AE, Simpson MA, Desai N, Trembath RC, Barker JN. g- women. Br J Dermatol. 1988;119(3):345-350.
Secretase mutations in hidradenitis suppurativa: new insights 50. Mortimer PS, Dawber RP, Gales MA, Moore RA. Mediation of
into disease pathogenesis. J Invest Dermatol. 2013;133(3): hidradenitis suppurativa by androgens. Br Med J (Clin Res Ed).
601-607. 1986;292(6515):245-248.
29. Pink AE, Simpson MA, Desai N, et al. Mutations in the g-sec- 51. Jemec GB, Faber M, Gutschik E, Wendelboe P. The bacteriology
retase genes NCSTN, PSENEN, and PSEN1 underlie rare of hidradenitis suppurativa. Dermatology. 1996;193(3):203-206.
forms of hidradenitis suppurativa (acne inversa). J Invest Der- 52. Matusiak Ł, Bieniek A, Szepietowski JC. Bacteriology of hidra-
matol. 2012;132(10):2459-2461. denitis suppurativadwhich antibiotics are the treatment of
30. Wang B, Yang W, Wen W, et al. Gamma-secretase gene mu- choice? Acta Derm Venereol. 2014;94(6):699-702.
tations in familial acne inversa. Science. 2010;330(6007):1065. 53. Huang BL, Chandra S, Shih DQ. Skin Manifestations of inflam-
31. van der Zee HH, de Ruiter L, van den Broecke DG, Dik WA, matory bowel disease. Front Physiol. 2012;3:13.
Laman JD, Prens EP. Elevated levels of tumour necrosis factor 54. Alikhan A, Lynch PJ, Eisen DB. Hidradenitis suppurativa: a
(TNF)-a, interleukin (IL)-1b and IL-10 in hidradenitis suppura- comprehensive review. J Am Acad Dermatol. 2009;60(4):
tiva skin: a rationale for targeting TNF-a and IL-1b. Br J Derma- 539-561, quiz 562-563.
tol. 2011;164(6):1292-1298. 55. Kromann CB, Ibler KS, Kristiansen VB, Jemec GB. The influ-
32. Wolk K, Warszawska K, Hoeflich C, et al. Deficiency of IL-22 ence of body weight on the prevalence and severity of hidra-
contributes to a chronic inflammatory disease: pathogenetic denitis suppurativa. Acta Derm Venereol. 2014;94(5):553-557.
mechanisms in acne inversa. J Immunol. 2011;186(2):1228-1239. 56. Thomas CL, Gordon KD, Mortimer PS. Rapid resolution of
33. van der Zee HH, Laman JD, de Ruiter L, Dik WA, Prens EP. hidradenitis suppurativa after bariatric surgical intervention.
Adalimumab (antitumour necrosis factor-a) treatment of Clin Exp Dermatol. 2014;39(3):315-317, quiz 317-318.
hidradenitis suppurativa ameliorates skin inflammation: an in 57. Simonart T. Hidradenitis suppurativa and smoking. J Am Acad
situ and ex vivo study. Br J Dermatol. 2012;166(2):298-305. Dermatol. 2010;62(1):149-150.
34. Schlapbach C, Hänni T, Yawalkar N, Hunger RE. Expression of 58. Clemmensen OJ. Topical treatment of hidradenitis suppura-
the IL-23/Th17 pathway in lesions of hidradenitis suppurativa. tiva with clindamycin. Int J Dermatol. 1983;22(5):325-328.
J Am Acad Dermatol. 2011;65(4):790-798. 59. Jemec GB, Wendelboe P. Topical clindamycin versus systemic
35. Dréno B, Khammari A, Brocard A, et al. Hidradenitis suppura- tetracycline in the treatment of hidradenitis suppurativa. J Am
tiva: the role of deficient cutaneous innate immunity. Arch Der- Acad Dermatol. 1998;39(6):971-974.
matol. 2012;148(2):182-186. 60. Kohorst JJ, Hagen C, Baum CL, Davis MD. Treatment experi-
36. Hofmann SC, Saborowski V, Lange S, Kern WV, Bruckner- ence in a local population with hidradenitis suppurativa.
Tuderman L, Rieg S. Expression of innate defense antimicro- J Drugs Dermatol. 2014;13(7):827-831.
bial peptides in hidradenitis suppurativa. J Am Acad Dermatol. 61. Join-Lambert O, Coignard H, Jais JP, et al. Efficacy of rifampin-
2012;66(6):966-974. moxifloxacin-metronidazole combination therapy in hidrade-
37. Schlapbach C, Yawalkar N, Hunger RE. Human beta-defensin- nitis suppurativa. Dermatology. 2011;222(1):49-58.
2 and psoriasin are overexpressed in lesions of acne inversa. 62. Mendonça CO, Griffiths CE. Clindamycin and rifampicin com-
J Am Acad Dermatol. 2009;61(1):58-65. bination therapy for hidradenitis suppurativa. Br J Dermatol.
38. van der Zee HH, Laman JD, Boer J, Prens EP. Hidradenitis sup- 2006;154(5):977-978.
purativa: viewpoint on clinical phenotyping, pathogenesis and 63. Gener G, Canoui-Poitrine F, Revuz JE, et al. Combination
novel treatments. Exp Dermatol. 2012;21(10):735-739. therapy with clindamycin and rifampicin for hidradenitis sup-
39. Yazdanyar S, Jemec GB. Hidradenitis suppurativa: a review of purativa: a series of 116 consecutive patients. Dermatology.
cause and treatment. Curr Opin Infect Dis. 2011;24(2):118-123. 2009;219(2):148-154.
40. König A, Lehmann C, Rompel R, Happle R. Cigarette smoking 64. Bettoli V, Zauli S, Borghi A, et al. Oral clindamycin and rifam-
as a triggering factor of hidradenitis suppurativa. Dermatology. picin in the treatment of hidradenitis suppurativa-acne inversa:
1999;198(3):261-264. a prospective study on 23 patients. J Eur Acad Dermatol Vene-
41. Kromann CB, Deckers IE, Esmann S, Boer J, Prens EP, reol. 2014;28(1):125-126.
Jemec GB. Risk-factors, clinical course and long-term prog- 65. van der Zee HH, Boer J, Prens EP, Jemec GB. The effect of
nosis in hidradenitis suppurativa: a cross-sectional study. Br J combined treatment with oral clindamycin and oral rifampicin
Dermatol. 2014;171(4):819-824. in patients with hidradenitis suppurativa. Dermatology. 2009;
42. Parks RW, Parks TG. Pathogenesis, clinical features and man- 219(2):143-147.
agement of hidradenitis suppurativa. Ann R Coll Surg Engl. 66. Kraft JN, Searles GE. Hidradenitis suppurativa in 64 female pa-
1997;79(2):83-89. tients: retrospective study comparing oral antibiotics and anti-
43. Kurzen H, Kurokawa I, Jemec GB, et al. What causes hidrade- androgen therapy. J Cutan Med Surg. 2007;11(4):125-131.
nitis suppurativa? Exp Dermatol. 2008;17(5):455-456, discus- 67. Joseph MA, Jayaseelan E, Ganapathi B, Stephen J. Hidradenitis
sion 457-472. suppurativa treated with finasteride. J Dermatolog Treat. 2005;
44. Hana A, Booken D, Henrich C, et al. Functional significance of 16(2):75-78.
non-neuronal acetylcholine in skin epithelia. Life Sci. 2007; 68. Mortimer PS, Dawber RP, Gales MA, Moore RA. A double-
80(24-25):2214-2220. blind controlled cross-over trial of cyproterone acetate in fe-
45. Lapins J, Asman B, Gustafsson A, Bergström K, Emtestam L. males with hidradenitis suppurativa. Br J Dermatol. 1986;
Neutrophil-related host response in hidradenitis suppurativa: 115(3):263-268.
a pilot study in patients with inactive disease. Acta Derm Vene- 69. Jick SS, Hernandez RK. Risk of non-fatal venous thromboem-
reol. 2001;81(2):96-99. bolism in women using oral contraceptives containing drospir-
46. Edlich RF, Silloway KA, Rodeheaver GT, Cooper PH. Epidemi- enone compared with women using oral contraceptives
ology, pathology, and treatment of axillary hidradenitis suppu- containing levonorgestrel: case-control study using United
rativa. J Emerg Med. 1986;4(5):369-378. States claims data. BMJ. 2011;342:d2151.

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 MAYO CLINIC PROCEEDINGS

70. Farrell AM, Randall VA, Vafaee T, Dawber RP. Finasteride as a open-label phase II prospective trial. Exp Dermatol. 2010;
therapy for hidradenitis suppurativa. Br J Dermatol. 1999; 19(6):538-540.
141(6):1138-1139. 90. Cusack C, Buckley C. Etanercept: effective in the management
71. Randhawa HK, Hamilton J, Pope E. Finasteride for the treat- of hidradenitis suppurativa. Br J Dermatol. 2006;154(4):726-
ment of hidradenitis suppurativa in children and adolescents. 729.
JAMA Dermatol. 2013;149(6):732-735. 91. Adams DR, Yankura JA, Fogelberg AC, Anderson BE. Treat-
72. O’Brien RC, Cooper ME, Murray RM, Seeman E, ment of hidradenitis suppurativa with etanercept injection.
Thomas AK, Jerums G. Comparison of sequential cyprot- Arch Dermatol. 2010;146(5):501-504.
erone acetate/estrogen versus spironolactone/oral contra- 92. Williams CJ, Peyrin-Biroulet L, Ford AC. Systematic review
ceptive in the treatment of hirsutism. J Clin Endocrinol with meta-analysis: malignancies with anti-tumour necrosis
Metab. 1991;72(5):1008-1013. factor-a therapy in inflammatory bowel disease. Aliment Phar-
73. Sabat R, Chanwangpong A, Schneider-Burrus S, et al. macol Ther. 2014;39(5):447-458.
Increased prevalence of metabolic syndrome in patients 93. Ramiro S, Gaujoux-Viala C, Nam JL, et al. Safety of synthetic
with acne inversa. PLoS One. 2012;7(2):e31810. and biological DMARDs: a systematic literature review
74. Gold DA, Reeder VJ, Mahan MG, Hamzavi IH. The prevalence informing the 2013 update of the EULAR recommendations
of metabolic syndrome in patients with hidradenitis suppura- for management of rheumatoid arthritis. Ann Rheum Dis. 2014;
tiva. J Am Acad Dermatol. 2014;70(4):699-703. 73(3):529-535.
75. Pugeat M, Ducluzeau PH. Insulin resistance, polycystic ovary 94. Leslie KS, Tripathi SV, Nguyen TV, Pauli M, Rosenblum MD.
syndrome and metformin. Drugs. 1999;58(suppl 1):41-46, dis- An open-label study of anakinra for the treatment of moder-
cussion 75-82. ate to severe hidradenitis suppurativa. J Am Acad Dermatol.
76. Verdolini R, Clayton N, Smith A, Alwash N, Mannello B. Met- 2014;70(2):243-251.
formin for the treatment of hidradenitis suppurativa: a little 95. Sharon VR, Garcia MS, Bagheri S, et al. Management of recal-
help along the way. J Eur Acad Dermatol Venereol. 2013; citrant hidradenitis suppurativa with ustekinumab. Acta Derm
27(9):1101-1108. Venereol. 2012;92(3):320-321.
77. Soria A, Canoui-Poitrine F, Wolkenstein P, et al. Absence of 96. Gulliver WP, Jemec GB, Baker KA. Experience with ustekinu-
efficacy of oral isotretinoin in hidradenitis suppurativa: a retro- mab for the treatment of moderate to severe hidradenitis
spective study based on patients’ outcome assessment. suppurativa. J Eur Acad Dermatol Venereol. 2012;26(7):911-
Dermatology. 2009;218(2):134-135. 914.
78. Blok JL, van Hattem S, Jonkman MF, Horváth B. Systemic ther- 97. Santos-Pérez MI, García-Rodicio S, Del Olmo-Revuelto MA,
apy with immunosuppressive agents and retinoids in hidrade- Pozo-Román T. Ustekinumab for hidradenitis suppurativa: a
nitis suppurativa: a systematic review. Br J Dermatol. 2013; case report. Actas Dermosifiliogr. 2014;105(7):720-722.
168(2):243-252. 98. Hofer T, Itin PH. Acne inversa: a dapsone-sensitive dermatosis
79. Boer J, Nazary M. Long-term results of acitretin therapy for [in German]. Hautarzt. 2001;52(10, pt 2):989-992.
hidradenitis suppurativa. Is acne inversa also a misnomer? Br 99. Yazdanyar S, Boer J, Ingvarsson G, Szepietowski JC, Jemec GB.
J Dermatol. 2011;164(1):170-175. Dapsone therapy for hidradenitis suppurativa: a series of 24
80. Brocard A, Knol AC, Khammari A, Dréno B. Hidradenitis sup- patients. Dermatology. 2011;222(4):342-346.
purativa and zinc: a new therapeutic approach. Dermatology. 100. Kaur MR, Lewis HM. Hidradenitis suppurativa treated with
2007;214(4):325-327. dapsone: a case series of five patients. J Dermatolog Treat.
81. Paradela S, Rodríguez-Lojo R, Fernández-Torres R, Arévalo P, 2006;17(4):211-213.
Fonseca E. Long-term efficacy of infliximab in hidradenitis sup- 101. Buckley DA, Rogers S. Cyclosporin-responsive hidradenitis
purativa. J Dermatolog Treat. 2012;23(4):278-283. suppurativa. J R Soc Med. 1995;88(5):289P-290P.
82. Grant A, Gonzalez T, Montgomery MO, Cardenas V, 102. Rose RF, Goodfield MJ, Clark SM. Treatment of recalcitrant
Kerdel FA. Infliximab therapy for patients with moderate to hidradenitis suppurativa with oral ciclosporin. Clin Exp Derma-
severe hidradenitis suppurativa: a randomized, double-blind, tol. 2006;31(1):154-155.
placebo-controlled crossover trial. J Am Acad Dermatol. 103. Gupta AK, Ellis CN, Nickoloff BJ, et al. Oral cyclosporine in the
2010;62(2):205-217. treatment of inflammatory and noninflammatory dermatoses:
83. Haslund P, Lee RA, Jemec GB. Treatment of hidradenitis sup- a clinical and immunopathologic analysis. Arch Dermatol. 1990;
purativa with tumour necrosis factor-alpha inhibitors. Acta 126(3):339-350.
Derm Venereol. 2009;89(6):595-600. 104. Marquardt AL, Hackshaw KV. Reactive arthritis associated with
84. van Rappard DC, Leenarts MF, Meijerink-van ’t Oost L, hidradenitis suppurativa. J Natl Med Assoc. 2009;101(4):367-
Mekkes JR. Comparing treatment outcome of infliximab and 369.
adalimumab in patients with severe hidradenitis suppurativa. 105. Fearfield LA, Staughton RC. Severe vulval apocrine acne suc-
J Dermatolog Treat. 2012;23(4):284-289. cessfully treated with prednisolone and isotretinoin. Clin Exp
85. Miller I, Lynggaard CD, Lophaven S, Zachariae C, Dufour DN, Dermatol. 1999;24(3):189-192.
Jemec GB. A double-blind placebo-controlled randomized 106. O’Reilly DJ, Pleat JM, Richards AM. Treatment of hidradenitis
trial of adalimumab in the treatment of hidradenitis suppura- suppurativa with botulinum toxin A. Plast Reconstr Surg. 2005;
tiva. Br J Dermatol. 2011;165(2):391-398. 116(5):1575-1576.
86. Kimball AB, Kerdel F, Adams D, et al. Adalimumab for the treat- 107. Feito-Rodríguez M, Sendagorta-Cudós E, Herranz-Pinto P, de
ment of moderate to severe Hidradenitis suppurativa: a parallel Lucas-Laguna R. Prepubertal hidradenitis suppurativa success-
randomized trial. Ann Intern Med. 2012;157(12):846-855. fully treated with botulinum toxin A. Dermatol Surg. 2009;
87. Arenbergerova M, Gkalpakiotis S, Arenberger P. Effective 35(8):1300-1302.
long-term control of refractory hidradenitis suppurativa with 108. Mahmoud BH, Tierney E, Hexsel CL, Pui J, Ozog DM,
adalimumab after failure of conventional therapy. Int J Derma- Hamzavi IH. Prospective controlled clinical and histopatholog-
tol. 2010;49(12):1445-1449. ic study of hidradenitis suppurativa treated with the long-
88. Giamarellos-Bourboulis EJ, Pelekanou E, Antonopoulou A, pulsed neodymium:yttrium-aluminium-garnet laser. J Am
et al. An open-label phase II study of the safety and efficacy Acad Dermatol. 2010;62(4):637-645.
of etanercept for the therapy of hidradenitis suppurativa. Br 109. Tierney E, Mahmoud BH, Hexsel C, Ozog D, Hamzavi I. Ran-
J Dermatol. 2008;158(3):567-572. domized control trial for the treatment of hidradenitis suppu-
89. Pelekanou A, Kanni T, Savva A, et al. Long-term efficacy rativa with a neodymium-doped yttrium aluminium garnet
of etanercept in hidradenitis suppurativa: results from an laser. Dermatol Surg. 2009;35(8):1188-1198.

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110. Hazen PG, Hazen BP. Hidradenitis suppurativa: successful 118. Rompel R, Petres J. Long-term results of wide surgical excision
treatment using carbon dioxide laser excision and marsupiali- in 106 patients with hidradenitis suppurativa. Dermatol Surg.
zation. Dermatol Surg. 2010;36(2):208-213. 2000;26(7):638-643.
111. Lapins J, Sartorius K, Emtestam L. Scanner-assisted carbon di- 119. Büyükaşik O, Hasdemir AO, Kahramansoy N, Çöl C, Erkol H.
oxide laser surgery: a retrospective follow-up study of pa- Surgical approach to extensive hidradenitis suppurativa. Der-
tients with hidradenitis suppurativa. J Am Acad Dermatol. matol Surg. 2011;37(6):835-842.
2002;47(2):280-285. 120. Scheinfeld N. Treatment of hidradenitis suppurativa associated
112. Lapins J, Marcusson JA, Emtestam L. Surgical treatment of pain with nonsteroidal anti-inflammatory drugs, acetamino-
chronic hidradenitis suppurativa: CO2 laser stripping-secondary phen, celecoxib, gabapentin, pegabalin, duloxetine, and venla-
intention technique. Br J Dermatol. 1994;131(4):551-556. faxine. Dermatol Online J. 2013;19(11):20616.
113. Madan V, Hindle E, Hussain W, August PJ. Outcomes of treat- 121. Jemec GB. Methotrexate is of limited value in the treatment
ment of nine cases of recalcitrant severe hidradenitis suppurativa of hidradenitis suppurativa. Clin Exp Dermatol. 2002;27(6):
with carbon dioxide laser. Br J Dermatol. 2008;159(6):1309-1314. 528-529.
114. Finley EM, Ratz JL. Treatment of hidradenitis suppurativa with 122. Jani M, Barton A, Warren RB, Griffiths CE, Chinoy H. The role
carbon dioxide laser excision and second-intention healing. of DMARDs in reducing the immunogenicity of TNF inhibi-
J Am Acad Dermatol. 1996;34(3):465-469. tors in chronic inflammatory diseases. Rheumatology (Oxford).
115. van der Zee HH, Prens EP, Boer J. Deroofing: a tissue-saving 2014;53(2):213-222.
surgical technique for the treatment of mild to moderate 123. Dessinioti C, Katsambas A, Antoniou C. Hidradenitis suppura-
hidradenitis suppurativa lesions. J Am Acad Dermatol. 2010; tiva (acne inversa) as a systemic disease. Clin Dermatol. 2014;
63(3):475-480. 32(3):397-408.
116. Bieniek A, Matusiak L, Okulewicz-Gojlik D, Szepietowski JC. 124. Yadav S, Singh S, Edakkanambeth Varayil J, et al. Hidrade-
Surgical treatment of hidradenitis suppurativa: experiences nitis suppurativa in patients with inflammatory bowel
and recommendations. Dermatol Surg. 2010;36(12):1998-2004. disease: a population-based cohort study in Olmsted
117. Tanaka A, Hatoko M, Tada H, Kuwahara M, Mashiba K, County, Minnesota [published online ahead of print May
Yurugi S. Experience with surgical treatment of hidradenitis 5, 2015]. Clin Gastroenterol Hepatol. doi:10.1016/j.cgh.
suppurativa. Ann Plast Surg. 2001;47(6):636-642. 2015.04.173.

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