Over the last three years, there have been over twenty case reports of lymphoma in patients given low-dose methotrexate for rheumatoid arthritis. We observed the first case of cutaneous pseudolymphoma.
A 56-year-old man had been treated with methotrexate (15 mg/day) for 6 years due to rheumatoid arthritis. He developed three isolated papulonodular ulcerations on the limbs. The histology and immunohistochemical examinations demonstrated T and B lymphoplasmocyte infiltration without epidermotropism nor destruction of the annexes. Immunolabelling for anti-Epstein-Barr virus was negative. There was a IgG lambda type monoclonal hypergammaglobulinaemia, Bence-Jones proteinuria and an increase in beta 2-microglobulin. The thoracoabdominal scan, bone marrow biopsy and gallium scintigraphy were normal. There was no sign of a Gougerot-Sjögren syndrome nor of a Felty syndrome. The skin lesions and the Bence-Jones proteinuria disappeared rapidly after withdrawal of methotrexate. There has been no recurrence with a follow-up of 16 months.
The diagnosis of pseudolymphoma was retained on the basis of the clinical features, the histological and immunohistochemical evidence and especially on the clinical course after methotrexate withdrawal, i.e. spontaneous regression of the lesions within 3 weeks. A similar course has been observed in three cases of lymphocyte proliferation suggesting that this immunosuppressor would be the most probable causative agent. Lymphocyte proliferation, mainly B-cell lymphomas in haematopoietic organs occurring under methotrexate administration have occurred mainly in patients with rheumatoid arthritis. Three cases have also been described in patients with dermatomyositis, but none have been reported in patients with psoriasis. This would suggest that cofactors involved in these autoimmune diseases could also have an effect: immunodepression, potentialization due to associated treatment (corticosteroids), Epstein-Barr virus...
Data on these observations should be combined in order to analyse the question of the safety of low-dose methotrexate in these patients.