Figure. Results of the systematic review.
Rambhatla PV, Lim HW, Hamzavi I. A systematic review of therapies for hidradenitis suppurativa. Arch Dermatol. Published online December 19, 2011. doi:10.1001/archdermatol.2011.1950.
eTable 1. Antibiotics
eTable 2. Biologics
eTable 3. Laser Surgery
eTable 4. Excisional Surgery
eTable 5. Miscellaneous
This supplementary material has been provided by the authors to give readers additional information about their work.
Rambhatla PV, Lim HW, Hamzavi I. A Systematic Review of Treatments for Hidradenitis Suppurativa. Arch Dermatol. 2012;148(4):439–446. doi:10.1001/archdermatol.2011.1950
Author Affiliations: Follicular Disorders Clinic, Department of Dermatology, Henry Ford Hospital, Detroit, Michigan.
Objectives To conduct a systematic review of the effectiveness of various modalities to treat hidradenitis suppurativa (HS) and to establish recommendations on its appropriate management.
Data Sources MEDLINE, Cochrane, and PubMed databases.
Study Selection English-language prospective, retrospective, and case studies describing at least 4 patients with HS.
Data Extraction Data quality and validity were addressed by multiple reviewers using independent extraction.
Data Synthesis Studies were categorized as treatments using antibiotics, biological agents, laser surgery, excisional surgery, or miscellaneous modalities. Of 62 publications included in the review, 4 studies met criteria to be assigned the highest grade for quality of evidence.
Conclusions Shown to be effective treatments for HS were a clindamycin-rifampin combination regimen, a course of infliximab, monthly Nd:YAG laser sessions, and surgical excision and primary closure with a gentamicin sulfate–collagen sponge. Most therapies used to treat HS were supported by limited or weak scientific evidence. A treatment approach is presented based on the evidence and on clinical experience at the Follicular Disorders Clinic, Department of Dermatology, Henry Ford Hospital, Detroit, Michigan. This review emphasizes the need for large randomized controlled trials to evaluate treatment options for HS.
Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent, debilitating skin follicular disease that usually manifests after puberty with painful deep-seated inflamed lesions in the apocrine gland–bearing areas of the body, most commonly the axillary, inguinal, and anogenital regions. The prevalence of HS is estimated to be 1% among the general population.1- 3 Despite this high prevalence, treatment options are limited, and few large-scale randomized controlled trials have explored the safety and efficacy of treatment for HS. Physicians often rely on clinical experience and trial-and-error individualized patient care. A comprehensive review of research studies on HS treatment in the last 20 years is presented, with the aim of providing treatment guidance to physicians.
A literature search was conducted using MEDLINE, Cochrane, and PubMed databases from January 1, 1990, to November 1, 2010, to identify relevant English-language publications. Key search terms included hidradenitis suppurativa, acne inversa, or Verneuil's disease in combination with the keyword treatment. In addition, references of relevant articles and reviews were manually searched for additional sources. Bibliographies of retrieved publications were reviewed to identify sources not obtained in our search. Two of us (P.V.R. and I.H.) independently reviewed the abstracts to identify articles that met eligibility requirements. Any disagreement was resolved using arbitration by another of us (H.W.L.).
A study was included if it involved the treatment of HS. Studies that did not exclusively deal with the treatment for HS were excluded. However, if data among patients with HS were presented separately within the study so that the information could be abstracted independent of other data, then the study was included. Editorials and studies describing 3 or fewer patients were excluded. Review articles that mentioned treatments were excluded; however, studies cited within the articles were manually searched for possible inclusion in the review. Studies were excluded if they were not published in the English language (Figure).
Studies meeting eligibility criteria were independently abstracted and reviewed by 2 of us (P.V.R. and I.H.) using predetermined inclusion and exclusion criteria. We then independently graded the strength of the clinical recommendation based on risks, benefits, and costs. Morbidity, mortality, symptom improvement, cost reduction, and quality of life were considered in grading a recommendation.
The quality of evidence was assessed based on grading recommendations published in the Archives of Dermatology4 and on evidence quality guidelines for systematic reviews. Studies were classified by treatment category (surgical, medical, or miscellaneous treatments) and listed with their grade for quality of evidence, number of patients treated, treatment intervention, and results (eTables 1, 2, 3, 4, and 5). The grades for quality of evidence were the following: A (systematic review or meta-analysis, randomized controlled trial with consistent findings, or all-or-none observational study), B (systematic review or meta-analysis, lower-quality clinical trial or study with limitations and inconsistent findings, lower-quality clinical trial, cohort study, or case-control study), and C (consensus guidelines, usual practice, expert opinion, or case series). For surgical treatments, grade B was assigned only if a study reported remission rates and focused on a particular procedure or surgical site, as these are clinically relevant variables for the clinician. Grade C was assigned to surgical studies that did not meet the requirements for grade B. A treatment approach was formulated based on results of the systematic review and on clinical experience. P values are reported when available for studies assigned grade A or grade B. For articles that did not have a consistent grading scale or were based on usual practice or expert opinion, results were reported as follows: (1) favorable (support the use of the intervention), (2) no improvement (do not support the use of the intervention), or (3) indeterminate (if the study yielded variable results). This terminology allows the presentation of results in a clinically relevant manner when study authors provided anecdotal or clinical consensus data and statistical significance was not reported.
Sixty-two publications met our inclusion criteria and are addressed in this review. Assignment of grade for quality of evidence yielded 4 studies with grade A, 16 with grade B, and 42 with grade C. Most publications that were excluded were review articles, case reports, or case series with a small sample size.
Twenty-five of 62 studies reviewed were identified as medical treatments for HS. They were further classified into 2 categories, antibiotics (eTable 1) or biologics (eTable 2).
Thirty of 62 studies reviewed were identified as surgical therapies for HS. These were further classified into 2 categories, laser surgery (eTable 3) or excisional surgery (eTable 4).
Of 62 studies reviewed, 24 were in the excisional surgery category. One study was assigned grade A, 6 studies received grade B, and the others were given grade C. Because of the difficulties and ethical dilemmas encountered with designing surgical studies, most of the literature on surgical treatments of HS is centered around surgeon experience and preference among various surgical techniques. Recurrence rates and follow-up periods were included if provided by the authors; a 1-year follow-up period was considered optimal. Buimer et al35 performed the only prospective randomized controlled surgical study with grade A, in which excision was performed and followed by primary closure with or without enclosure of a resorbable gentamicin sulfate–collagen sponge, to evaluate whether the use of antibiotic sponge would reduce the incidence of postoperative infections. The use of a gentamicin-collagen sponge resulted in fewer complications and a shorter mean time until wound healing. An open study (grade B) by van der Zee et al36 explored the efficacy of a deroofing technique in which the roof of a lesion was surgically removed and the floor of the lesion was left exposed. Of 73 treated lesions, 83% showed no recurrence during a median follow-up period of 34 months, and 17% showed recurrence after a median follow-up period of 4.6 months. Postoperative bleeding in 1 patient was the only reported adverse event, and 90% of patients responded that they would recommend the procedure to other individuals with HS.
An additional 5 studies37- 41 (grade B) looked at the role of radical excision as a treatment option for HS. Bieniek et al41 described their experience with excision and multiple methods of wound closure over the last 10 years. They noted complete recovery in 59.7% of their patients during a 2-year follow-up period and suggested that the risk of recurrence is related more to the natural course of the disease and the width of the excision than to the closure technique. A statistically significant relationship was shown between the efficacy of a procedure and the number of body areas affected. Bohn and Svensson37 described their results among 138 patients who underwent radical excision and had follow-up times ranging from 3 months to 21 years. In 38 of 116 patients (32.8%) who completed a questionnaire, the disease recurred to some degree, and 14 of them required further operation. Rompel and Petres38 presented the results of 106 patients treated via radical wide excision, with a median postoperative follow-up time of 36 months and a 2.5% rate of recurrence within operated fields. Wound infection occurred in 3.7% of patients, and the overall complication rate was 17.8%, including suture dehiscence, postoperative bleeding, and hematoma. A retrospective study39 of 31 patients undergoing drainage procedures, limited regional surgery, and radical wide excisions showed 100% recurrence after drainage, 42.8% recurrence after limited excision, and 27% recurrence after radical excision (P < .05), with a mean follow-up period of 72 months. Wiltz et al40 performed a retrospective analysis of 43 patients with perianal HS who underwent wide local excision, or incision and drainage, or limited local excision; results showed that wide local excision was more successful in preventing recurrence of disease.
Of the remaining 17 studies (grade C), 8 studies42- 49 looked at surgical excision of HS, 6 studies50- 55 reported on the use of a various flaps during surgery, 1 study56 evaluated the use of grafts and flaps, and 2 studies57,58 documented the results of specific skin grafting techniques. These grade C studies showed variable results and could not be effectively compared owing to the inconsistent and sometimes anecdotal reporting of findings.
Seven of 62 studies reviewed were identified as miscellaneous treatments for HS (eTable 5). All studies received grade C for quality of evidence.
Bong et al59 reported a case series of 10 patients treated with cryotherapy; 8 patients had improvement, with a mean healing time of 25 days and no recurrence of lesions at the treated sites. Adverse events included posttreatment ulceration, infection, or both. Most patients considered cryotherapy a better treatment option than oral antibiotics, and 8 of 10 patients stated that they would consider cryotherapy again in the future.
Gold et al60 reported a case study of 4 patients who underwent 3 to 4 total treatments of short-contact 5-aminolevulinic acid–photodynamic therapy using a topical 5-aminolevulinic acid, 20%, and blue light for activation, with a 3-month follow-up period. All patients had 75% to 100% clinical improvement. Strauss et al61 reported a case series of 4 patients who had a maximum of 4 treatments of 5-aminolevulinic acid–photodynamic therapy at weekly intervals. None had significant improvement in regional HS scores observed at follow-up visits.
Finasteride (an inhibitor of 5α-reductase type 2) was prescribed in a study62 as monotherapy (5 mg/d) in 7 patients. Six patients showed significant improvement, and 3 patients demonstrated complete healing. Two patients with follow-up periods continuing longer than 1 year reported remissions lasting 8 to 18 months.
In a pilot study by Brocard et al,63 a total of 22 patients with mild to moderate HS were prescribed zinc gluconate (90 mg/d). The authors reported 8 complete remissions and 14 partial remissions; gastrointestinal symptoms were the most commonly reported adverse effect.
Boer and Jemec64 performed an open study of 12 women with stage I or stage II HS who self-treated with topical resorcinol, 15%. Patients reported a significant decrease in pain, and the mean duration of painful abscesses was decreased.
A retrospective study65 was performed of 12 patients who were treated with acitretin (mean dose, 0.59 mg/kg/d) for a mean period of 10.8 months. Nine patients saw marked or complete remission after 1 course of treatment, and 3 patients showed mild to moderate improvement of their condition. Significant adverse effects were seen in all patients, including cheilitis in all patients, as well as dermatitis, hypertrichosis at the chin, sticky skin, depression, fatigue, buzzing in the ears, and photosensitivity in others. The authors reported that half of the treated group were unwilling to undergo a second course of treatment with acitretin.
The lack of randomized controlled blinded studies in treatments of HS often presents physicians with the arduous task of determining an appropriate and efficacious course of treatment for patients. A significant limitation of the review herein is in the surgical treatments section. Owing to the descriptive nature of research in surgical treatments, it is difficult to compare different grading scales and results; as such, extensive meta-analysis is difficult.
Using this comprehensive review as an evidence-based guide, we developed the following working approach for the management of HS. In our experience, Hurley clinical staging is a convenient and useful way to classify patients with HS for disease management and follow-up care. Physical examination should be performed to recognize the extent of disease and to classify Hurley stages in HS30 as follows: stage I (abscess formation [single or multiple] without sinus tracts or cicatrization), stage II (recurrent abscesses with tract formation and cicatrization [single or multiple widely separated lesions]), or stage III (diffuse or near-diffuse involvement or multiple interconnected tracts and abscesses across the entire area). The nature of this approach is progressive. Many treatments that are suggested for milder stages may also be used in patients with more diffuse involvement based on the clinician's assessment. For example, a patient with stage II HS may be prescribed topical treatments that are suggested for stage I disease in addition to an antibiotic regimen. After obtaining an extensive medical history, family history, and social history, it is appropriate to culture HS lesions for aerobic and anaerobic bacteria, as well as to obtain nasal swabs in patients refractory to treatment.66 Appropriate laboratory studies should be considered based on the patient's clinical history. In patients suspected of having hyperandrogen states (polycystic ovarian syndrome),12 it is prudent to recommend an appointment with an endocrinologist.
The influence of HS on a patient's emotional and psychological state has been shown to significantly affect quality of life and must be addressed by clinicians. Psychosocial factors often affect patient compliance and follow-up care and should be considered by physicians in the decision-making process when developing a therapeutic relationship with a patient and in establishing a workable treatment plan. Matusiak et al67 showed a statistically significant correlation between the Dermatology Life Quality Index and disease activity (R = 0.67, P < .001). This significant effect of HS on patient well-being may necessitate extensive counseling in a dermatology clinic setting and may warrant referral to a psychiatrist for additional support when deemed necessary. It is important to stress lifestyle changes, including smoking cessation.1,68,69
Topical clindamycin, 1%, lotion or solution can be used for Hurley stage I mild HS.13 It is appropriate to consider performing monthly therapy with Nd:YAG laser on the lesions.34 Carbon dioxide laser treatment is another viable option, showing some efficacy in clinical studies,2,3,31- 33 that should be offered to patients. Oral isotretinoin is not an effective option supported by the scientific literature and should not be initiated in this subgroup of patients.9,10 Although case series11,62 involving few patients have reported some efficacy with the use of dapsone or finasteride, no large trials support their use. Zinc gluconate (90 mg) once daily can be offered as an adjunctive treatment to patients, following appropriate counseling about potential gastrointestinal adverse effects.63 For Hurley stage II, clindamycin (300 mg) in combination with rifampin (300 mg) twice daily may be initiated for 10 weeks.5,6,8 This regimen must be started in conjunction with a comprehensive patient discussion about potential likely adverse effects, including diarrhea, which may be severe enough to lead to termination of this treatment regimen. Another efficacious option to consider is treatment with Nd:YAG laser for a minimum of 3 to 4 monthly sessions.34 If the patient is unable to tolerate these treatment regimens or if the disease continues to be refractory to treatment, focus can be shifted to the use of biological agents. Infliximab should be the first-line treatment given the favorable outcomes demonstrated by a randomized double-blind trial20 and by several case series. One small clinical trial28 and a case series27 evaluating adalimumab showed inconsistent results and provided insufficient evidence to recommend treatment for all patients with HS at this time. An ongoing open-label phase 2 study70 is under way to determine the safety and efficacy of adalimumab in moderate to severe HS. Efalizumab has been shown in a small case series29 to be an ineffective treatment modality; it was withdrawn from the US market in 2009 owing to its adverse effects. Cryotherapy59 and photodynamic therapy60,61 have shown variable results in the literature thus far; they should not be routinely recommended.
At the level of Hurley stage III HS, a trial of the aforementioned medical treatments that are used for Hurley stage I and stage II disease can be recommended before discussion of surgical options. Although the literature discusses external beam radiation treatment for refractory HS,71 no strong evidence-based data support this treatment option. In refractory HS or extremely severe cases, it is appropriate to refer patients to a plastic surgeon or reconstructive urologist (for perianal or vulvar disease) to discuss surgical options.
A multidisciplinary approach using both medical and surgical treatment modalities may be required for successful treatment of HS. Surgical treatments were included in this review to present clinicians with the most comprehensive data available. We recognize that suggestions for surgical procedures and specific techniques may be beyond the scope of recommendations made by dermatologists. However, it is vital that dermatologists should know when it is appropriate to consider a surgical consultation for a patient with HS.
Although progress has been made in the last 20 years of research, most treatment options for HS are largely based on trial-and-error patient care and physician clinical experience. Until additional randomized controlled studies of existing and novel treatments are performed, the evidence-based treatment approach offered in this review will aid clinicians in managing the treatment of HS.
Correspondence: Iltefat Hamzavi, MD, Follicular Disorders Clinic, Department of Dermatology, Henry Ford Hospital, 3031 W Grand Blvd, Ste 800, Detroit, MI 48202 (Ihamzav1@hfhs.org).
Accepted for Publication: September 27, 2011.
Published Online: December 19, 2011. doi:10.1001/archdermatol.2011.1950
Author Contributions:Study concept and design: Rambhatla and Hamzavi. Acquisition of data: Rambhatla and Hamzavi. Analysis and interpretation of data: Rambhatla, Lim, and Hamzavi. Drafting of the manuscript: Rambhatla, Lim, and Hamzavi. Critical revision of the manuscript for important intellectual content: Rambhatla, Lim, and Hamzavi. Statistical analysis: Rambhatla and Hamzavi. Obtained funding: Rambhatla, Lim, and Hamzavi. Administrative, technical, and material support: Rambhatla, Lim, and Hamzavi. Study supervision: Rambhatla, Lim, and Hamzavi.
Financial Disclosure: Dr Lim serves as a consultant for La Roche-Posay/L’Oreal, Orfagen, and Dow Pharmaceutical Sciences. Dr Hamzavi serves as a consultant for Kythera; he has worked as an investigator with Abbott, Johnson & Johnson, Centocor, Dow Pharmaceutical Sciences, Cipher, and Pfizer.
Funding/Support: The Department of Dermatology at Henry Ford Hospital received a research grant on photobiology from Johnson & Johnson.
Role of the Sponsor: The sponsor had no role in the design or conduct of the study; in the collection, analysis, or interpretation of the data; or in the preparation, review, or approval of the manuscript.