Psoriatic lesions induced by antitumour necrosis factor‐α treatment: two cases

SIR, Both subcutaneously administered soluble receptor to tumour necrosis factor (TNF)-a (etanercept) and intravenous monoclonal anti-TNF-a antibodies (infliximab) have recently been used in severe cutaneous and ⁄ or arthropathic psoriasis, with impressive clinical improvement and few side-effects. These results suggest that these drugs might soon become an established treatment for severe forms of the disease along with other new, emerging immunotherapies. However, sideeffects of these TNF-a-modulating treatments in other indications may be more puzzling than previously assumed. We report two unusual cases of cutaneous psoriatic lesions occurring in patients treated by both categories of anti-TNF-a drugs for rheumatoid arthritis (RA). Patient 1 was a 47-year-old white woman without personal or family history of psoriasis who had been treated for seronegative RA for the last 20 years with a combination of anti-inflammatory drugs, chrysotherapy, methotrexate and systemic steroids. Treatment with intravenous infliximab (200 lg every 6 weeks) was implemented, with very good clinical results on joint inflammation which allowed her to stop taking anti-inflammatory drugs. However, 2 months after the beginning of the anti-TNF-a treatment, cutaneous lesions began to appear on anterior aspects of the legs, highly suggestive of psoriasis (Fig. 1a). Histological findings were also consistent with psoriasis, with parakeratosis, hyperkeratosis, acanthosis, lack of granular layer, tortuous dilated capillaries and a lymphocytic infiltrate in the upper dermis (Fig. 1b). Topical treatment with steroids and salicylic acid resulted in limited improvement of lesions and infliximab was continued, without further extension of cutaneous lesions after a 3-month follow-up. Patient 2 was a 55-year-old white woman with no personal or family history of skin disease. She had longlasting severe and seronegative RA treated for the preceding 2 years with low-dose systemic steroid and methotrexate without significant toxicity, and began receiving subcutaneous etanercept 25 mg twice weekly, with a good clinical result on joint inflammation. Three months after starting this treatment, inflammatory and scaly lesions reminiscent of psoriasis began to appear on the palms, soles, umbilicus, ankles, wrists and buttocks. Histological features were consistent with psoriasis, with neutrophil microabscesses in the horny layer, tortuous dilated capillaries and a lymphocytic infiltrate in the upper dermis. Etanercept was not stopped because of the good response of the arthritis, and cutaneous lesions persisted at the same locations with occasional flares on the trunk as guttate psoriasis, poorly controlled by topical steroids and vitamin D associated with narrow-band ultraviolet B (311 nm) phototherapy. Repeated X-rays and biological tests failed to demonstrate the presence of any focal infection especially in the upper aerodigestive tract. In both cases typical cutaneous lesions of psoriasis occurred within 3 months after starting anti-TNF-a treatment in patients with no previous history of cutaneous lesions, whereas joint inflammation was markedly improved. The histological features were indistinguishable from psoriasis. This effect was unexpected, as anti-TNF-a drugs have repeatedly been reported to be efficient in both cutaneous and arthropathic psoriasis. To the best of our knowledge no similar lesions have been reported either in patients with RA or with Crohn’s disease, whereas injection site reactions and occasional skin rashes have been reported with the use of etanercept in RA. However, the involvement of the anti-TNF-a molecule seems likely in both cases because of the chronology of events and the lack of other triggering factors for the onset of cutaneous psoriatic lesions. The mechanisms underlying this unusual and undesirable effect are debatable but it is of interest that treatment with TNF-a has been found to be efficient in psoriasis by some authors, resulting in marked improvement of cutaneous lesions, even though more recent biological studies suggest an involvement of this cytokine in the pathomechanism of psoriasis, with high blood titres Figure 1. Patient 1. (a) Psoriatic lesions on the legs; (b) typical histological features of psoriasis. British Journal of Dermatology 2004; 150: 506–525.