Thrombocytopenia Associated With the use of Anti-Tumor Necrosis Factor-α Agents for Psoriasis

Biologic therapies for psoriasis work by selectively suppressing crucial components of the immune system responsible for abnormal skin inflammation. Whereas drugs such as efalizumab disrupt T lymphocyte migration and trafficking into the skin, anti-tumor necrosis-α (TNF-α) agents (infliximab, etanercept, and adalimumab) act primarily by blocking cytokine-mediated T lymphocyte activation. Over the past decade, anti-TNF-α agents have become reliable, widely used tools for the management of chronic inflammatory conditions including rheumatoid arthritis, Crohn's disease, and, most recently, psoriasis and psoriatic arthritis. Unfortunately, enthusiasm for this highly effective class of drugs must be tempered by their potential for rare but significant drug-related adverse effects including the reactivation of latent infections (eg, tuberculosis, hepatitis B, histoplasmosis), unmasking or triggering of malignancy, and neurologic disorders such as multiple sclerosis. Now, in a retrospective analysis, Brunasso and Massone report a new potential complication: the apparent development of thrombocytopenia in 4.3% of their cohort of patients with psoriasis during anti-TNF-α therapy.

Brunasso and Massone reviewed the incidence of thrombocytopenia occurring in 93 patients with psoriasis (56 men; mean age, 50.89) during the administration of 118 courses of biologic therapy (efalizumab and/or anti-TNF-α agents). Of this group, patients took efalizumab (n = 51), etanercept (n = 39), infliximab (n = 26), and adalimumab (n = 2), with 20 patients receiving more than 1 biologic agent during a mean follow-up period of 32 months. Intriguingly, thrombocytopenia did not develop in any of the patients taking efalizumab (defined as a decrease in platelet count below 50 x 10⁹/L). In contrast, clinical symptoms and/or laboratory results consistent with drug-induced thrombocytopenia developed in 4 of the 67 patients (4.3%) during anti-TNF-α therapy. All cases of thrombocytopenia were late in onset (after 9 weeks of therapy in 1 patient and 29-30 weeks in 3 patients). Furthermore, the platelet counts rebounded to normal levels in 3 of 4 patients after cessation of anti-TNF-α therapy. In 2 cases, drug-induced thrombocytopenia recurred either with re-exposure to the same agent (etanercept) or a different drug in the same class (infliximab followed by etanercept).

Based on the following observations, Brunasso and colleagues postulate that anti-TNF-α induced thrombocytopenia is an autoimmune phenomenon: (1) in 3 patients, thrombocytopenia improved after corticosteroid and/or immune globulin therapy; (2) platelet surface-associated IgG antibodies were detected in 2 patients; (3) antinuclear antibodies (clinically asymptomatic) developed in 2 patients; and (4) bone marrow examinations performed in 2 patients showed no abnormalities.