Hidradenitis Suppurativa: A Review with a Focus on Treatment Data
Danny Barlev, MD1; Daniel B. Eisen, MD2; Ali Alikhan, MD1
1Department of Dermatology, University of Cincinnati, OH, USA
2Department of Dermatology, University of California Davis, CA, USA
Hidradenitis suppurativa (HS) is a chronic disease of the follicular unit that often leads to marked impairment of quality of life and
usually affects the axillary, perineum and inframammary regions resulting in tender subcutaneous nodules, abscesses, fibrosis and
sinus tract formation. New updates on HS underscores the role of various genes as well as the innate and adaptive immune response
in its pathogenesis. Although every patient requires an individualized approach to treatment, topical therapy and antibiotics are
mainly used for mild to moderate disease, whereas various systemic immune modulators and/or surgical approaches play a pivotal
role in moderate to severe disease. New treatments using various immune modulators, laser modalities and other novel agents
provide clinicians with better ways of managing HS.
hidradenitis suppurativa, antibiotics, biologics, immune modulators, lasers, surgery
Hidradenitis suppurativa (HS) is a chronic disease of the follicular
unit that results in significant impairments to quality of life and
increases emergency room visits and inpatient hospitalizations.1-3 It most commonly occurs in the axillary, inguinal, and anogenital
regions in post-pubertal females.3 HS may result in sinus tract
formation and severe scarring, and is difficult to treat, with many
patients never achieving complete clearance of lesions. Ongoing
research and new insights into pathogenesis and treatment will
hopefully improve the management of HS patients.
Prevalence of HS is a matter of debate, with estimates ranging
from 0.052% to 1% of the population, likely reflecting differences
in research methodology and populations studied.1,3-12 A recent
population-based study in Olmsted County, Minnesota, found an
overall annual age- and sex-adjusted incidence of 6 per 100,000,
supporting that HS is an uncommon diagnosis.7 Incidence
appears significantly higher in women, particularly in those aged
18 to 44 years. HS may occur more commonly in certain races, but
this is still unclear.13
A review of 846 Dutch patients identified that male sex, disease
duration, obesity, pack-year smoking, and lesions in axillary,
perianal, and mammary regions are significant factors for more
About one-third of HS patients report a family history of the
disease, and families with an autosomal dominant mode of
inheritance have been identified.14 There may be a strong
association between HS and Crohn’s disease - in a recent patient
questionnaire of 1,093 patients with inflammatory bowel disease,
23% of patient responded to having signs and symptoms of
HS.15 Other diseases that may occur concomitantly include acne
conglobata, dissecting cellulitis, pilonidal cysts, spondyloarthritis,
pyoderma gangrenosum, and synovitis-acne-pustulosis-
hyperostosis-osteitis (SAPHO) syndrome.4,16,17
Hypertension, metabolic syndrome, depression, anxiety,
obesity and smoking are important co-morbidities among HS
patients.1,18-20 Furthermore, smoking and obesity are not only
predictive of disease severity but are also correlated with lower
rates of disease remission.20,21
The pathogenesis of HS is complex. Although it was previously
believed to be a disorder of apocrine glands, HS is now thought
of as a disorder of follicular occlusion. Whether immune
dysregulation precedes or follows follicular occlusion remains to
be determined, but it is evident that both play a role.22-36
Of note, recent data demonstrates that many familial cases of
HS show mutations in gamma secretase, a protease that cleaves
intramembrane receptors and regulates follicular keratinization, elucidating further the role of follicular occlusion in the
Both innate and adaptive immune dysregulation has been
demonstrated via decreased expression of epithelial-derived
antimicrobial peptides (such as ribonuclease, human beta-
defensin 3 and toll like receptor 4), which may result in excessive
inflammatory response, as well as overexpression of pro-
inflammatory cytokines (e.g., interleukin (IL)-1, IL-10, tumor
necrosis factor (TNF)-alpha, IL-17, IL-22) in HS lesions.22-24,26-28,33
Additional factors that contribute to HS include bacterial biofilms,
abnormal secretion of apocrine glands, abnormal invaginations
of the epidermis leading to sinus tract formation, and deficient
numbers of sebaceous glands.35,41-44
Hyperandrogenism and/or vitamin D deficiency may be involved, although their role is unclear at this time.45,46
HS is characterized by recurrent inflammatory nodules, cysts,
abscesses and sinus tracts in apocrine gland-bearing sites such
as the axilla, groin, perianal and/or inframammary areas.47
The lesions are frequently accompanied by chronic drainage.
The clinical presentation of HS is highly variable in terms of
cutaneous features, distribution, presence of complications
(fistula formation, lymphedema, scrotal elephantiasis),
extracutaneous features (arthritis, interstitial keratitis) and
associated constitutional symptoms (i.e., fever and malaise).47
HS affecting the anogenital region may be difficult to differentiate
from Crohn’s disease, especially given the strong association
between the two disorders and that they can both present clinically
as fistulas and sinuses, and histologically as granulomas.48
Since HS is a chronic inflammatory disease, anemia and
hypoproteinemia may develop. Furthermore, HS lesions can
form fistulae to the rectum, vagina, urethra, peritoneum and/
or bladder. Reactive arthritis and SAPHO syndrome has been
described in HS patients.49 Additionally, aggressive squamous
cell carcinoma may form in areas of chronic scarring and carry a
HS can be staged by either the Hurley staging system (Table 1) or
the newer Sartorius system (Table 2). The Hurley system is more
clinically applicable while the Sartorius system is used primarily
Search for biomarkers that help diagnose HS and/or correlate
its severity have been undertaken. Analogous to Sartorius
clinical staging, these tests remain largely for research use, since
diagnosis is generally achievable via clinical findings and disease
||Abscess formation, single or multiple, without
sinus tract and scarring
||One or more widely separated recurrent abscesses
with sinus tracts and scarring
||Multiple interconnected tracts and abscesses
throughout an entire area
Table 1. Hurley staging of HS
|The Sartorius Hidradenitis Suppurativa Score
|Anatomic region involved
(3 points per region)
Other inflammatory region
|Number and score of lesions
2 points for each nodule
4 points for each fistula
1 point for each scar
1 point each for "other"
|Longest distance between
2 relevant lesions
Less than 5 cm (2 points)
Less than 10 cm (4 points)
More than 10 cm (8 points)
|Lesions clearly separated by
normal skin in each region
||Yes (0 points)
No (6 points)
Table 2. The Sartorius Hidradenitis Suppurativa Score is comprised of counting involved regions, nodules and sinus tracts
Treatment of HS varies widely depending on disease severity, with
many treatments supported by weak scientific evidence. Topical,
systemic, and surgical therapies are available and are often
used in combination. The authors list their treatment ladder in
Table 3. Non-pharmacologic therapies include avoidance of tight-
fitting clothing, reassurance, smoking cessation, management of
underlying depression and anxiety, support group referral, and
Pain is a common problem expressed by HS patients and must
be addressed.56 Given the chronicity of HS, opioid dependence
is a significant concern. Nonsteroidal anti-inflammatory drugs
(NSAIDs) and acetaminophen are good initial therapies,57 while
pregabalin, gabapentin, selective serotonin reuptake inhibitors
(SSRIs) and serotonin–norepinephrine reuptake inhibitors
(SNRIs) may be considered as second-line agents.58
Both topical and systemic antibiotics have been widely used
for patients with HS. A randomized controlled study of 30
patients treated with topical clindamycin 1% solution found the
clindamycin group did significantly better than the placebo group
at 3 months.59
In another randomized trial, Jemec et al. suggested
that topical clindamycin has similar efficacy to systemic
tetracycline (500 mg twice daily for 3 months).60
Tetracyclines are often used for mild to moderate HS, although
published data (in the form of trials) regarding their efficacy
is limited. We commonly prescribe doxycycline 100 mg orally
once to twice daily for our HS patients, and may taper down
after several months based on patient response and tolerance.58
Two prospective trials that looked at combination treatment
with systemic rifampin and clindamycin suggest this treatment
might be beneficial.61,62
However, another series reported a large
proportion of patients needed to discontinue this regimen due to
gastrointestinal side effects.63
|Hidradenitis Suppurativa Treatments by Hurley Stage
|Hurley Stage I to II
||Topical, injectable and intralesional
- Topical antibiotics (e.g., clindamycin 1%)
- Intralesional corticosteroids
- Topical resorcinol
- Botulinum toxin
- Oral antibiotics (e.g., tetracycline agents, rifampin + clindamycin, dapsone)
- Hormonal therapies (e.g., oral contraceptive pills, finasteride, spironolactone)
|Surgical and physical options
- Less invasive surgical approaches
- Laser therapy (e.g., Nd:YAG, carbon dioxide)
- Photodynamic therapy
|Hurley Stage II to III
||(includes Stage I to II approaches)
- More invasive surgical approaches (e.g., wide radical excision)
- Systemic retinoids (e.g., acitretin)
- Systemic immunosuppressants
- Biological treatments (e.g., adalimumab, infliximab, ustekinumab, anakinra)
- Weight loss
- Pain control (via topical and/or oral treatments)
- Smoking cessation
- Zinc supplementation
- Antimicrobial wash (e.g., chlorhexidine, benzoyl peroxide)
Table 3. Treatment summary for HS by Hurley Stage
Dapsone is considered relatively ineffective for HS. A study of 24
patients treated with dapsone reported improvement in 9 (38%),
while 15 (62%) did not experience any improvement.64
Although data supporting their efficacy is limited, antimicrobial
cleansers such as chlorhexidine and benzoyl peroxide are often
applied daily to affected areas.43,57,65
Anti-androgens such as spironolactone and cyproterone acetate,
as well as oral contraceptives, may be considered in female
patients who have a history of hormonal abnormalities or are
not responding to conventional treatment(s).66,67
controlled trial of 18 female patients who received either daily
ethinyloestradiol 50 mg/norgestrel 500 mg or ethinyloestradiol
50 mg/cyproterone acetate 50 mg for 6 months demonstrated
improvement in 5 patients, no change in 4, and worsening in 2.66
Finasteride has been suggested as another treatment option in
HS. A series of 3 pediatric patients receiving finasteride for HS showed marked reduction in the amount and severity of flares.68 A similar trial of 7 patients showed complete healing of lesions in 3 patients and reduction in suppuration and inflammation in the remaining 4 patients.6
Tumor Necrosis Factor-Alpha (TNF-a) Inhibitors
Biologic agents are increasingly utilized in the management
of moderate to severe HS (Table 3). Among TNF-a inhibitors,
infliximab is one of the better studied medications. A randomized
double-blind, placebo-controlled trial, in which 38 subjects received infliximab (5 mg/kg) infusions at 0, 2 and 6 weeks
compared to placebo, showed that 60% of patients in the
infliximab group compared to 5.6% of patients in the placebo
group achieved 25-50% decrease in their severity scores at
A long-term study of 10 patients who received
infliximab every 8 weeks after an initial loading regimen found
2 patients (20%) had no response to treatment after five doses
and 5 (50%) patients experienced disease recurrence after a
median treatment period of 37 weeks.71
cohort trial with more frequent dosing (every 4 weeks) found that
9 of 11 patients (mean follow-up of 60.3 months) had measurable
improvement after undergoing treatment. Two patients failed
treatment at 12 and 19 months.65
Adalimumab, unlike infliximab, is self-administered by the
In a double-blind, randomized, controlled trial, 15
patients received adalimumab 80 mg subcutaneously (SC) at
baseline followed by 40 mg SC every other week for 12 weeks. A
significantly better reduction in Sartorius score was seen at 12
weeks in the treatment group compared to placebo.74
large multicenter study demonstrated that weekly dosing of
adalimumab achieved better clinical outcomes than bi-monthly
Etanercept is considered inefficacious for HS. A double-blind,
placebo-controlled study of 20 patients in which etanercept 50 mg
was administered twice weekly for 3 months, followed by open-
label etanercept 50 mg twice weekly for an additional 3 months
found no significant difference in outcomes between groups.76
Ustekinumab, an IL-12/IL-23 antibody, may also be efficacious
for moderate to severe HS. In a small prospective trial, 3 patients
received three 45 mg SC injections at 0, 1 and 4 months. At
6 months, 1 patient had remission of disease, the second patient
improved, and the third had no response.77
Most recently, 5 patients receiving anakinra, an antibody directed
against IL-1, showed mean decrease in modified Sartorius score
of 34.8 points.78
A report of the related agent, canakinumab, also
demonstrated good response.79
Cyclosporine has been used in severe HS recalcitrant to other
therapies, though data is scant and mostly case reports.80 Two case
reports suggest that prednisone may be used in those patients
who have concomitant pyoderma gangrenosum or arthritis.81,82 Methotrexate is of limited value in the management of HS.83
In our experience, intralesional triamcinolone at concentrations
ranging from 5 mg/cc to 10 mg/cc can help with acutely inflamed
nodules and cysts, as well as with scar formation. It is important to
be confident that these are not injected into infectious abscesses
prior to administration.58
Isotretinoin has demonstrated mixed results for the management
of HS. In a retrospective trial of 68 patients, only 48 actually
completed the trial (29.4% dropped out due to side effects and/
or lack of efficacy). Sixteen patients (23.5%) had clearance
of lesions, 14 patients (20.6%) had marked improvement,
11 (16.2%) patients improved, and 7 (10.3%) experienced
no change in their disease.84
A later retrospective report with
88 patients found that only 14 patients (16.1%) noted
improvement, 67 patients (77%) had no change, and 6 patients
(6.9%) experienced disease worsening.85
Many providers feel acitretin is more effective than isotretinoin
in the treatment of HS, probably based upon initially favorable
reports. Boer et al. found in their retrospective trial of 12 patients
that 10 had marked improvement or complete disease resolution
and the remaining 2 improved from baseline. However, Mutasiak
et al. reported less favorable results in a prospective trial of 17
patients. Eight patients exhibited a 50% reduction in HS severity
index. However, 8 patients (47%) dropped out of the study due to
lack of efficacy or adverse effects.86
Alitretinoin has a similar pharmacologic mechanism to acitretin,
but a much shorter half-life and, thus, may carry a lower
teratogenic risk. In one trial, 14 female patients of childbearing
age received alitretinoin (10 mg daily) for 24 weeks with
significant improvement in Sartorius and Dermatology Life
Quality Index (DLQI) scores recorded in 78.5% of cases.87
Surgery is frequently performed to control moderate and severe
HS. The type of surgery depends on the severity and location
of the disease and can be limited or extensive.88 In one trial, 73
patients underwent a deroofing procedure (in which the roof of
a lesion is surgically removed and the floor of the lesion is left
exposed to heal by second intention) and were followed for a
median of 34 months; 83% of patients showed no recurrence.89
A study comparing recurrence rates of HS after incision and
drainage (limited excision and wide radical excision) found that
all cases recurred (median time = 3 months), 42.8% recurred in
the local excision (median time = 11 months), and 27% recurred
in the wide excision group (median time = 20 months).90
Alharabi et al. conducted a retrospective analysis of 50 operative
procedures for 32 patients who underwent wide surgical excision.
Twenty six patients (81.25%) showed no recurrence after
Lasers and Lights
Various laser and light treatments, alone or in combination
with surgery and/or systemic therapy, have been suggested in
the management of HS. Photodynamic therapy (PDT) has been
reported several times. The range of results have been described
as good92-94 to mediocre95,96
in terms of efficacy. In general,
evidence regarding PDT for HS is of such limited or poor quality
that meaningful conclusions are not ascertainable.
Bath psoralen + ultraviolet A (PUVA) was undertaken in a
retrospective trial with 13 patients receiving bath PUVA twice
weekly. Five patients had clearance or near clearance of their
lesions, 4 patients had moderate clearance, and 4 had minimal
to no response. Among the 5 patients in which clearance or near
clearance was documented, the response was sustained for at
least a 3-month follow-up period.97
Long-pulsed neodymium:yttrium-aluminum-garnet laser
(Nd:YAG) has demonstrated promising results in a randomized
trial. Mahmoud et al. enrolled 22 subjects who received monthly
Nd:YAG laser sessions for 4 months and reported a 72.7% mean
improvement on the laser-treated side compared to 22.9% on the
A subsequent trial of 19 patients showed a mean
31.6% reduction in Lesion Area and Severity Index (LASI) over all
anatomic sites 2 months following treatment.99
Intense pulse light has also been used. In a prospective trial, 18
patients were randomized to treatment on one side of the axillae,
groin, or inframammary region two times per week for 4 weeks.
There was significant reduction in Sartorius score of 55% after
completion of treatment compared to 10% on the untreated side.
Patients maintained a 33% reduction in their Sartorius score
compared to 3% on the untreated side at 12 months.100
Lastly, several studies show that carbon dioxide (CO2) laser
ablation is an efficacious treatment in HS.101-103
In a trial by
Hazen et al., all (61) patients who underwent CO2 laser ablation
followed by marsupialization had clearance of treated areas. Of
note, 17 patients (28%) experienced postsurgical hypertrophic
granulation tissue appearing approximately 5 weeks after
Cryoinsufflation, a modified spray cryotherapy performed by
injecting liquid nitrogen through a needle directly into HS tracts,
has been recently described. Results are restricted to a single
One case report of a patient with moderate HS who underwent
four treatments of 50 units of botulinum toxin type A (100 units dissolved in 4 mL of 0.9% sodium chloride solution) injected to
each axilla (administered over 3 years) achieved lesion clearance
following the second treatment (6 months) with maintenance of
remission 1 year after completion of treatment.106
||Author and Trial Design
Miller et al. (2011),
||Adalimumab 80 mg SC at
baseline followed by 40 mg
||Reduction in Sartorius score of 10.7
points at 6 weeks and 11.3 points at
12 weeks was seen in the treatment
group compared to 7.5 points and
5.8 points in the placebo group,
|Kimball et al. (2012),
phase 2, parallel,
trial consisting of
a blinded 16-week
period (period 1) and
||Adalimumab, 40 mg/wk;
adalimumab, 40 mg EOW;
or placebo. All patients
40 mg EOW, at the
beginning of period 2
but switched to weekly
dosing if the response was
suboptimal at weeks 28
||At week 16, 3.9% of patients
receiving placebo (2 of 51), 9.6%
of patients receiving adalimumab
EOW (5 of 52), and 17.6% of
patients treated weekly (9 of 51)
achieved minimal or mild HS-PGA
score by week 16
||Paradela et al. (2012),
||Infliximab 5mg/kg every
8 weeks after initial
standard loading dose
||2 patients (20%) had no response
to treatment after 5 doses; 5 (50%)
patients experienced disease
|Grant et al. (2010),
infusions at 0, 2 and 6
||60% of patients in the infliximab
group compared to 5.6% of patients
in the placebo group achieved
25%-50% decrease in in their
|Moriarty et al. (2014),
||Infliximab 5mg/kg infusion
every 4 weeks after initial
standard loading dose
||9 patients had measurable
improvement after undergoing
treatment; 2 had treatment failure at
12 and 19 months
||Ustekinumab 45 mg SC
injections at 0, 1 and
||1 patient had remission of disease,
the second patient improved, and
the third had no response
||Adams et al. (2010),
||Etanercept 50 mg SC was
administered twice weekly
for 3 months, followed by
50 mg SC, twice weekly for
an additional 3 months
||No statistically significant difference
among PGA, patient global
assessment, and DLQI at 12 or
24 weeks between treatment and
||Anakinra 100 mg SC daily
||Mean decrease in modified
Sartorius score of 34.8 points
Table 4. Summary of trials for biologics used in HS|
N = number of patients, SC = subcutaneous, DLQI = dermatologic quality of life Index, PGA = physician global assessment,
EOW = every other week dosing
A study of 22 patients with mild to moderate HS receiving zinc
gluconate (90 mg/day) for at least 6 months (with a mean follow-
up of 23.7 months) demonstrated a positive response in all
patients with complete remission in 8 and partial remission in 14
Eighteen of 25 (72%) patients who received metformin (500 mg
daily to 500 mg three times daily) had a mean reduction in their
Sartorius sore of 12.7 at 24 weeks of treatment. Seven patients
had no response.108
HS is associated with significant morbidity and health care costs.
Many treatments are available to meet the needs of these patients,
though more data is warranted to determine optimal management
algorithms. Care needs to be individualized to each patient's
situation and preferences, with a strong emphasis on improving
quality of life and management of related comorbidities.
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In this issue:
- Hidradenitis Suppurativa: A Review with a Focus on Treatment Data
- Ivermectin 1% Cream for Rosacea
- Update on Drugs and Drug News - July-August 2015