Long‐term infliximab for severe hidradenitis suppurativa

SIR, Hidradenitis suppurativa (HS) is considered as a disorder of the apocrine gland-bearing follicular epithelium affecting 2–4Æ1% of the population. Recent evidence supports that follicular hyperkeratosis is the initial event, leading to occlusion, occasional secondary apocrine involvement, and follicular rupture with resultant inflammation and possibly secondary infection. Early-stage treatment consists primarily of topical (clindamycin) or systemic antibiotics (tetracyclines, clindamycin, rifampicin), topical antiseptics and intralesional corticosteroids (triamcinolone acetonide). Systemic retinoids (isotretinoin, etretinate) and antiandrogen therapy (cyproterone acetate, finasteride) have also shown a positive effect on disease progression. Currently available medical treatments are, however, insufficient and their efficacy is only transient. As a result, advanced-stage severe HS requires invasive surgical removal of all the involved tissue. There are, nevertheless, postoperative recurrences. Infliximab (Remicade ; ScheringPlough, Kenilworth, NJ, U.S.A.), a monoclonal chimeric antitumour necrosis factor (TNF)-a antibody, is currently approved for the treatment of rheumatological inflammatory diseases, Crohn disease and psoriasis. Several reports support the short-term effect of this potent immunomodulating anti-inflammatory drug for the treatment of severe HS. The effectiveness of etanercept, another TNF-a antagonist, has recently been documented in a group of patients with particularly challenging disease. Based upon these pieces of evidence, we report the efficacy of infliximab as a long-term treatment for severe HS. A 48-year-old man presented with severe inguinal, scrotal and perineal HS refractory to systemic antibiotic therapy. Colonoscopy excluded Crohn disease. He had had acne conglobata during adolescence, that regressed completely following treatment with isotretinoin (total dose 105 mg kg). On examination, this patient presented multiple confluent and suppurative inflammatory nodules of the perineum and the perianal region (Fig. 1a) associated with an erythema and an induration of the scrotum and the groin. Laboratory investigations revealed a marked inflammatory syndrome [erythrocyte sedimentation rate (ESR) 94 mm in the first hour; C-reactive protein (CRP) 110 mg L; white blood count (WBC) 15Æ9 · 10 L] and magnetic resonance imaging (MRI) showed pelvic infiltration with collections and fistulae (Fig. 1b). Infliximab treatment was initiated at a dose of 5 mg kg (300 mg) at weeks 0, 2 and 6. Maintenance therapy was then given every 2 months (5 mg kg). Based upon local guidelines, rifampicin 300 mg daily for 4 months was given to the patient as tuberculosis prophylaxis, following a positive purified protein derivative test of 16 mm. Chest X-ray was normal and the patient had received bacille Calmette-Guérin vaccination during childhood. Two weeks after the first infusion, the patient reported a subjective 90% improvement of his physical condition, with reduction of pain, infiltration and erythema. Examination showed a great reduction of the inflammatory lesions and the local infiltration (Fig. 1c); MRI (Fig. 1d) confirmed these findings. Laboratory investigations revealed a regression of the inflammatory syndrome (ESR 34 mm in the first hour; CRP 14 mg L; WBC 8Æ4 · 10 L) at week 2. Low-dose methotrexate treatment (7Æ5 mg weekly) was introduced at week 12 in order to reduce the risk of development of antichimeric antibodies during long-term treatment. Recent reports establish a clear relationship between formation of human antichimeric antibodies, an increase in the incidence of infusion reactions and a reduction of the response to treatment. Immunomodulatory agents, including methotrexate, seem to have a protective role against the development of these human antichimeric antibodies or against high titres of antibodies. The patient thus received infliximab 5 mg kg every 8 weeks for 104 weeks (13 infusions) and methotrexate 7Æ5 mg weekly. The excellent response persisted during the whole maintenance therapy and had an excellent impact on the quality of life of our patient (80% improvement in Dermatology Life Quality Index score at year 2 compared with week 0 visit). Our patient developed limited herpes zoster on the anterior aspect of the right thigh (L2) at week 5 that completely regressed after valaciclovir treatment (1 g three times daily for 7 days). This minor adverse event could possibly have been related to the concomitant immunosuppression. HS is still classified as a member of the follicular occlusion tetrad, along with dissecting cellulitis of the scalp, acne conglobata and pilonidal sinus. The classical therapeutic approach is based on an understanding of the disease as either a form of acne or a local infection. The inefficiency of the classical therapeutic approaches suggests that these entities are perhaps not a good model to explain the disease pathogenesis. The astonishing efficacy of TNF-a antagonism by infliximab and etanercept in patients with no evidence of Crohn disease supports the primary importance of chronic inflammation in the pathogenesis of HS and suggests that the infectious component is only minimal. To our knowledge, we report the first case of very effective long-term treatment of severe HS. Our patient presented no resistance to therapy during the maintenance period, as observed in other rheumatological indications, and dose intensification was consequently not required. Our patient experienced only a minor adverse event: herpes zoster infection of the right thigh. Exacerbation of cutaneous infectious, especially viral infections (herpes simplex, molluscum contagiosum), has already been reported during TNF-a antagonism. No serious adverse event was observed during the whole treatment period in our patient. The role of the lowdose methotrexate therapy in the maintenance of treatment response is not certain. Concomitant immunosuppression reduces the incidence of neutralizing antichimeric antibodies during long-term treatment. Nevertheless, some of the clinical