Epstein-Barr virus, methotrexate, and lymphoma in patients with rheumatoid arthritis and primary Sjögren's syndrome: case series.

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Rheumatol. 2001 Jan;28(1):47-53.

Epstein-Barr virus, methotrexate, and lymphoma in patients with

rheumatoid arthritis and primary Sjögren's syndrome: case series.

Dawson TM, Starkebaum G, Wood BL, Willkens RF, Gown AM.

VA Puget Sound Health Care System, Seattle Division, Washington 98108,

USA.

OBJECTIVE: Rheumatoid arthritis (RA) and primary Sjogren's syndrome (SS)

are associated with an increased risk of lymphoma. Epstein-Barr virus (EBV),

a ubiquitous herpes virus, has been linked etiologically to lymphoma in

patients with RA and primary SS. Recently, methotrexate (MTX) has also been

linked to the development of these lymphomas. We investigated the frequency

of EBV in lymphoma tissue of patients with RA and primary SS and the

association of MTX with lymphomagenesis. METHODS: Twenty-three patients with

RA and 9 with primary SS with a history of lymphoma were identified by

writing to all Arthritis Foundation member rheumatologists in Washington

State. Formalin fixed, paraffin embedded tissue blocks were then requested

from pathology laboratories. Lymph nodes from 5 RA patients without lymphoma

were also studied. In situ hybridization using a biotinylated EBER-1

oligonucleotide probe was used to detect EBV in tissue sections. Positive

and negative laboratory controls were used to ensure procedural integrity.

RESULTS: Specimens from 21 RA patients were obtained, with 2 subsequently

excluded due to specimen quality. Specimens from 6 patients with primary SS

were obtained. In situ hybridization for EBV was positive in 5/19 (26%) RA

patients and 1/6 patients with primary SS. In the nonmalignant lymph nodes

no patient showed EBV. One primary SS and 12 RA patients were known to be

taking MTX at the time of lymphoma diagnosis. Of the EBV positive RA

lymphoma patients, 4/5 were receiving MTX at the time of diagnosis. These

results show that EBV is present in lymphoma tissue of some patients with RA

and very few with primary SS. CONCLUSION: EBV is over-represented in the

lymphomas of patients with RA, but whether MTX plays a role in predisposing

patients with RA and primary SS to the development of lymphoma, perhaps by

influencing behavior of EBV, remains unclear.

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