Methotrexate for chronic unresponsive urticaria

By Dr. Mascaró

Chronic urticaria can be a very severe and disabling condition in some patients. These patients are usually unresponsive to most standard therapies and represent a therapeutic challenge for dermatologist. A few reports in the past showed that methotrexate could be an option in these patients.  In a recent publication in the British Journal of Dermatology a group of investigators from England enrolled 16 patients with steroid-dependent chronic urticaria. The disease had been present for a mean of 48·5 months , and all had failed first-line therapies with second-generation H1 antihistamines, sedating antihistamines as well as  H2antihistamines. Other second and third line treatments such as doxepin, montelukast, colchicine, hydroxychloroquine, sulfasalazine, dapsone , intravenous immunoglobulins, azathioprine , or ciclosporin had also been been uneffective. All patients had become steroid-dependent either to control flares or maintain remission. Twelve of the 16 patients responded to methotrexate (with doses ranging from 5 mg to 25 mg weekly) , and seven were able to reduce oral steroids and 2 could even stop them.

This study is very interesting as chronic urticaria is a very freqüent  disease. Many patient do not respond readily to traditional therapies with antihistamines, and therefore there is a need for new treatments. The present study shows positive results in steroid-dependent patients, and so it would be predictable that results can be even better in patients with cronic urticaria that are not steroid-dependent.

Methotrexate: a useful steroid-sparing agent in recalcitrant chronic urticaria

Perez A, Woods A, and Grattan CEH

Br J Dermatol 2010; 162: 191-194

Background. Reports of methotrexate for chronic urticaria are anecdotal.

Objectives To assess the effectiveness of methotrexate in steroid-dependent chronic urticaria, its impact on steroid reduction and any differences in response between patients with and without functional autoantibodies.

Methods A retrospective case-note review of 16 patients with steroid-dependent chronic urticaria treated with methotrexate was carried out. Ten patients had chronic ordinary/spontaneous urticaria (CU), including three with associated delayed-pressure urticaria; four patients had normocomplementaemic urticarial vasculitis (UV); and two patients had idiopathic angio-oedema without weals. Median disease duration before methotrexate was 48·5 months (range 12–164). All were unresponsive to antihistamines and second-line agents, except prednisolone. Eleven were assessed for autoimmune urticaria with the basophil histamine release assay (n = 5), autologous serum skin test (n = 5) or both (n = 1). Response to methotrexate was scored: no benefit; some benefit (fewer weals and symptomatic improvement but no steroid reduction); considerable benefit (improvement with steroid reduction); or clear (no symptoms, off steroids but on antihistamines).

Results Twelve of 16 patients (eight CU, three UV, one idiopathic angio-oedema) responded. Three showed some benefit, seven considerable benefit and two cleared. Four of eight responders and three out of three nonresponders showed evidence of functional autoantibodies. The dose to achieve a steroid-sparing effect was 10–15 mg weekly (cumulative dose range 15–600 mg, median 135 mg). Methotrexate was well tolerated.

Conclusions Methotrexate may be a useful treatment for steroid-dependent chronic urticaria. Functional autoantibodies do not correlate with response. The beneficial effects of methotrexate may be anti-inflammatory and immunosuppressive. It may therefore benefit chronic urticaria independently of the pathogenic mechanism, whether autoimmune or not.

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