DOI: 10.1111/j.1468-3083.2012.04668.x JEADV ORIGINAL ARTICLE Metformin for the treatment of hidradenitis suppurativa: a little help along the way R. Verdolini,† N. Clayton,‡,* A. Smith,‡ N. Alwash,† B. Mannello§ †Department of Dermatology, Princess Alexandra Hospital NHS trust, Harlow, Essex, and ‡Department of Dermatology, The Royal London Hospital, London, UK §Mannello Statistics, Via Rodi, Ancona, Italy *Correspondence: N. Clayton. E-mail: [email protected]; [email protected] Abstract Background Despite recent insights into its aetiology, hidradenitis suppurativa (HS) remains an intractable and debilitating condition for its sufferers, affecting an estimated 2% of the population. It is characterized by chronic, relapsing abscesses, with accompanying fistula formation within the apocrine glandbearing skin, such as the axillae, ano-genital areas and breasts. Standard treatments remain ineffectual and the disease often runs a chronic relapsing course associated with significant psychosocial trauma for its sufferers. Objective To evaluate the clinical efficacy of Metformin in treating cases of HS which have not responded to standard therapies. Methods Twenty-five patients were treated with Metformin over a period of 24 weeks. Clinical severity of the disease was assessed at time 0, then after 12 weeks and finally after 24 weeks. Results were evaluated using Sartorius and DLQI scores. Results Eighteen patients clinically improved with a significant average reduction in their Sartorius score of 12.7 and number of monthly work days lost reduced from 1.5 to 0.4. Dermatology life quality index (DLQI) also showed a significant improvement in 16 cases, with a drop in DLQI score of 7.6. Conclusion Metformin helps control HS with minimal side effects and good patient compliance and can represent a further agent in the spectrum of treatments available in the treatment of this disease. Received: 12 April 2012; Accepted: 4 July 2012 Conflict of Interest None declared. Funding Sources None declared. Introduction become complicated by fibrosis and formation of extensive sinus Hidradenitis suppurativa (HS) is a stubborn inflammatory disor- tracts, which can coalesce and potentially dissect into deep struc- der affecting an estimated 2% of the population. Females are sig- tures including muscle, lymph nodes, and even urethra and bow- nificantly more affected than males. els. They extrude foul smelling purulent discharge. Subsequent HS is insidious and develops typically in the second or third repair with scarring, dermal contractures and in duration of the decade in otherwise healthy individuals. It should be strongly skin follows. suspected in post pubertal adults presenting with recurrent, deep There is considerable physical pain from these disfiguring furuncular lesions in flexural sites, especially if such lesions lesions as well as the immense social embarrassment. The enor- respond poorly to antibiotic treatment. mity of its psychological impact on patients’ social, personal, work It is characterized initially by the development of deep tender and familial spheres of life has been well documented.1,2 subcutaneous nodules primarily affecting the apocrine gland Spontaneous resolution is unlikely, and progressive disability is bearing areas, including the axillae, perineum, and sub and infra- commonly experienced by sufferers. It is primarily for this reason mammary regions. that this condition is associated with a high degree of morbidity. Over time these nodules may spontaneously rupture forming Potential complications from HS include increased risk of squa- chronic, relapsing, deep-seated dermal abscesses. Eventually, these mous cell carcinoma developing in 2–4% of sufferers.3,4 Other ª 2012 The Authors JEADV 2013, 27, 1101–1108 Journal of the European Academy of Dermatology and Venereology ª 2012 European Academy of Dermatology and Venereology 1102 Verdolini et al. long term sequelae are contractures, which can affect limb mobil- cases,19–22 have however given conflicting results in other cases,23 ity, serious infections and anaemia.5 leaving immunological disregulation as a theory of uncertain sig- The aetiology of HS is still not completely understood.6 It was nificance. long thought to have an infective aetiology, being a suppurative The notable female preponderance, the association with polycistic disorder, but bacterial colonization has now been shown to be a ovarysyndrome(PCOS)andtheobservationthatHSmaydecline secondary event and even very potent antibiotic treatments remain significantly following menopause has suggested a possible hor- unsuccessful, at least in the long term. Staphylococci eradicating monal influence.24 Past studies, having observed the association of combination therapy with Clindamycin and Rifampicin may HS with irregular menstruation, hirsutism, premenstrual HS flares sometimes be effective,7,8 but improvement is temporary and and acne vulgaris, suspected high total testosterone concentrations recurrences common after discontinuation of the treatment. and higher free androgen index as possible factors.25 Although The peculiarity of distribution within the apocrine glands led it some studies have argued against Hyperandrogenism as a possible to be considered a disease of the apocrine glands. However, histo- cause, as androgen levels were found normal in a significant pathology studies have confirmed it to be mostly a disorder of the proportion of HS patients,26,27 more recent studies seem to have pilosebaceous unit with the central aspect of this pathological pro- definitely confirmed a hormonal influence, with a statistically sig- cess being follicular structural abnormality and consequent inflam- nificant association with obesity, hyper-androgenism, and PCOS mation with apocrine sweat gland involvement remaining a (calculated as 38% of analyzed cases). Gene mapping of familial secondary aspect.9–12 A genetic predisposition leading to a specific cases seem to have identified a genetic link13 and further studies alteration of the terminal follicular epithelium with a possible dila- suggested a hormonal influence on gene expression. tation and distortion of the upper infundibular tract seems to be In terms of treatment, an effective standalone therapy for HS the initial causative factor.13 Thiswouldleadtotheocclusionof has not yet been established. Traditional treatments have included the affected hair follicles with subsequent bacterial infection, pus- retinoids, antibiotics (including eradication treatment with tula formation, fistulization and scarring. Clyndamycin and Rifampicin,7,8) and Dapsone, both systemic and This represents a sequence of events similar in certain aspects to topical.28–30 Clinical and histological similarities of HS to acne vul- acne vulgaris. It has therefore been strongly suggested that the garis have led to treatment attempts with Isotretinoin. This medi- name of ‘acne inversa’ is a more accurate representation of its cation, which is very effective for acne, is, however, almost pathology.14 redundant for HS. There is only anecdotal evidence substantiating Complementing the sequence of events described above is the any successful outcomes with its use. Acitretin has been more recent observation of the alteration of sebaceous gland tissue mass successful, however, its use is restricted to male patients (who are in HS sufferers. Recent studies raised suspicion of the possibility of less commonly affected than females), and females of non-child the primary involvement of sebaceous glands in the aetiology of bearing age (not frequently sufferers of this condition).31,32 HS, with a generalized reduction of Sebaceous gland tissue mass As a result of the possible hormonal influence, there have been being demonstrated in perilesional tissue. Sebaceous glands con- several trials conducted using anti-androgen therapies, such as tribute to the local homeostasis of the skin with their antibacterial, cyproterone acetate33and finestride,34 with some documented antifriction, endocrine and inflammation modulatory functions improvement in disease activity. and it has been speculated that a reduction in their volume or pos- Anecdotal reports of improvements obtained with other various sibly loss of one or more of their specific functions may represent treatment options have also been published over the years: radia- one of the primary changes leading to the cascade of events that tion therapy,35,36 Botulinum toxin,37 anti TNF-a antagonists19 and lead to HS.15 PDT,38,39 have been used with variable success. A further theory about HS having an immunological aetiology Carbon dioxide laser therapy has been successfully used to with an upregulation of toll-like receptors has also been sug- ablate tissue, producing results similar to standard surgery at its gested and immunological disregulation might represent another endpoint.40 co-factor.16,17 In particular an exaggerated expression of Toll-like Early definitive surgical intervention has been regarded as one receptor 2 has been found in the macrophages and dendritic cells of the most effective treatments for intractable HS. Surgical infiltrating the dermis in HS affected areas. Toll-like receptor 2 is removal of the entire follicular sweat gland apparatus with gener- known to have a pivotal role in the innate immune response, and ous excision margins is currently being advocated as the gold stan- its overexpression had been suspected to represent a possible con- dard.4,41,42 tributory factor in the pathogenesis of HS.18 Also neutrophilic cells However poor surgical