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Refractory generalized pustular psoriasis responsive to a combination of adalimumab and acitretin

combination of adalimumab and acitretin Editor, Generalized pustular psoriasis is a distinctive rare variant of psoriasis which may become complicated by systemic alterations. Its management causes some difficulties, despite the availability of new modes of treatment with biologic therapy. The combination of biologics with acitretin has already been described for the treatment of moderate-to-severe plaque psoriasis but not for pustular psoriasis. We report a patient with generalized pustular psoriasis resistant to systemic conventional and biologic therapy, treated successfully with adalimumab in combination with acitretin. A 21-year-old woman presented with a 14-year history of pustular eruptions arising on an erythematous skin associated with scaly erythematous plaques; this was diagnosed clinically and histologically as pustular psoriasis. The patient had suffered an icthyosiform dermatitis during early childhood but was otherwise healthy. She had initially been treated with topical agents and intermittent courses of oral acitretin (0.5–1.0 mg/kg/d) since October 1994. In January 2004, the patient developed an acute severe thrombocytopenia that led to acitretin interruption, although the causal relationship with the drug was unclear. The patient then experienced a flare in psoriasis accompanied by fever and general malaise. Over the following four years, she was treated with different drugs as monotherapy or in combination. Firstly, treatment with oral intermittent cycles of cyclosporin (3 mg/kg/d) was ineffective. Then, acitretin monotherapy was restarted (50 mg/d), but achieved only a partial improvement with no side effects. Psoralen combined with ultraviolet A (PUVA) therapy was administered with acitretin for 12 weeks for a total dose of 37.5 J/cm and achieved a partial response. During a second cycle of PUVA therapy, after two doses of 2.0 J/cm and 2.5 J/cm, the patient developed a severe generalized pustular flare of psoriasis and required hospitalization (Fig. 1). Oral methotrexate (20 mg/week) was started, but new episodes of malaise and disseminated cutaneous lesions proved this to be unsuccessful. Intravenous infusions of infliximab (6 mg/kg) were added to methotrexate. The patient presented an increase in transaminase levels, and methotrexate was substituted by acitretin. This combination facilitated a remarkable improvement in the patient’s psoriasis, achieving almost complete clearance of the lesions, but the effectiveness of the therapy decreased progressively and relapses occurred. Infliximab was then substituted by subcutaneous adalimumab (80 mg at baseline, 40 mg at week 1, and then 40 mg every two weeks), which, in combination with acitretin (50 mg/d), achieved a dramatic improvement in the skin lesions (Fig. 2). After 11 months of continuous treatment, the patient’s psoriasis remains well controlled despite the progressive reduction of the acitretin dose (to 30 mg/d). The combination of acitretin with a biologic agent represents, in some cases, a unique approach in the Figure 1 Severe pustular generalized flare requiring hospitalization