Hidradenitis suppurativa is a debilitating and mutilating disease and its pathogenesis is still poorly understood. It involves the development of recurrent, painful nodules in intertriginous areas that become inflamed, form abscesses that may rupture, and develop chronic fistula tracts. The cause of hidradenitis suppurativa (HS) is thought to be multifactorial and may begin with follicular occlusion and rupture, leading to a cascade of inflammatory responses in susceptible individuals. The disease has been associated with high body mass index, smoking and genetic predisposition. There is a known association between HS and the metabolic syndrome, an association that remains after controlling for body mass index. HS predominantly affects women and ethnic minorities and the prevalence is thought to be as high as 2%, although embarrassment and lack of awareness may lead to an underestimate of the true burden of disease.
Although HS is a fairly common disease, relatively little is understood about its pathogenesis. Immune dysregulation is thought to play a role in disease development. Increased levels of interleukin (IL)-12, IL-17, IL-23, tumor necrosis factor α, IL-10 and IL-1β were found to be expressed in lesional skin of HS patients. Recent studies have also identified elevated levels of IL-17 in the serum of patients with HS.
HS is associated with a significant impact on patient quality of life. Patients suffer from both the physical and psychological impact of disease. Many therapies have been used to treat HS, from topical antibiotics to oral retinoids to radical surgeries, but all have limited efficacy. Despite efforts to control disease, many patients live with chronic wounds and disability. The decision about appropriate therapy for HS, especially in the early stages, is mainly based on expert opinion, anecdotal evidence, and small studies. Topical and systemic antimicrobial treatments are often used as first line therapies, although studies have repeatedly shown that the abscesses of HS are sterile or contain only normal flora. The mechanism of improvement with antimicrobials may be through alterations in the local microbiome. Significant improvement in disease has been seen with dual therapy with twice daily use of 300mg rifampicin and 300mg clindamycin, neither of which have an FDA indication for use in HS. Doxycycline is used frequently in HS, but little evidence supports this. Despite success with the above therapies, the risk of antimicrobial resistance is real, and is increased with frequent and prolonged use of these medications in HS. Teratogenic effects, gastrointestinal upset, and photosensitivity with use of tetracyclines, risk for clostridium difficile colitis with clindamycin, and antimicrobial resistance with rifampicin highlight a need for safer and effective therapeutic options for the treatment of early HS.
For more advanced disease (Hurley stage II and III), the tumor necrosis factor inhibitor adalimumab is the only FDA approved biologic treatment for HS. It has shown promise in severe disease, but only \~50% of patients achieved a clinical response at 12 weeks, and this clinical response declined over time. Additionally, newer biologic therapies have been used in small numbers of patients with HS with variable results. Importantly, the cost of these medications is considerable.
Hydroxychloroquine, initially developed as an antimalarial, has been used successfully for over 70 years in the treatment of autoimmune disease. Its mechanism of action is still poorly understood, but it has been shown to have many varied immunomodulatory properties. Evidence suggests that hydroxychloroquine has an effect on inflammatory disease through decreasing levels of TNFα and Th-17 cytokines (including IL-6, IL-17, and IL-22). Additionally, studies have shown a beneficial effect of hydroxychloroquine on lipid metabolism and glucose. Patients with rheumatoid arthritis (which similarly to HS has an independent association with cardiovascular disease) who were treated with hydroxychloroquine had an overall decreased incidence of cardiovascular events. Hydroxychloroquine has a relatively benign safety profile, with retinopathy being the most concerning long term side effect. The retinopathy caused by hydroxychloroquine is reversible if identified early, and standard protocols for the use of this medication include yearly ophthalmologic examination.
Patients with HS suffer daily from the physical and psychological effects of their disease. Despite insufficient data about disease progression and prognosis, early intervention with safe and effective therapies is our goal. Hydroxychloroquine has never been used to treat HS, but the good safety profile, based on many years of usage in other autoimmune diseases, and known ability to modify many of the aberrant metabolic and inflammatory components of HS make it an ideal candidate therapy for this debilitating disease.
Research activities:
1. Treatment with hydroxychloroquine 200mg twice daily. Treatment length will be 6 months. Patients will be allowed to continue or initiate use of topical therapies during the study.
2. Telephone call to assess toxicity after 1 month of treatment
3. Assessment of hidradenitis suppurativa disease activity using Sartorius scoring at baseline, and after 3 and 6 months of treatment
4. Collection of patient serum at baseline and after 6 months of treatment
5. Quality of life questionnaire at baseline, 3 and 6 months
6. Follow up telephone call at \~9 and 12 months (3 and 6 months after therapy completion) to assess for toxicity
7. Baseline ophthalmologic exam for patients on hydroxychloroquine will be conducted within the first year of treatment
