Sustained improvement of intractable rheumatoid arthritis after total lymphoid irradiation

Abstract

Total lymphoid irradiation (TLI) was administered to 11 patients who had intractable rheumatoid arthritis that was unresponsive to conventional medical therapy, including aspirin, multiple nonsteroidal antiin‐flammatory drugs, gold salts, and D‐penicillamine. Total lymphoid irradiation was given as an alternative to cytotoxic drugs such as azathioprine and cyclophosphamide. After radiotherapy, 9 of the 11 patients showed a marked improvement in clinical disease activity as measured by morning stiffness, joint tenderness, joint swelling, and overall functional abilities. The mean improvement of disease activity in all patients ranged from 40–70 percent and has persisted throughout a 13–28 month followup period. This improvement permitted the mean daily steroid dose to be reduced by 54%. Complications included severe fatigue and other constitutional symptoms during radiotherapy, development of Felty's syndrome in 1 patient, and an exacerbation of rheumatoid lung disease in another. After therapy, all patients exhibited a profound T lymphocytopenia, and a reversal in their T suppressor/cytotoxic cell to helper cell ratio. The proliferative responses of peripheral blood mononu‐clear cells to phytohemagglutinin, concanavalin A, and allogeneic leukocytes (mixed leukocyte reaction) were markedly reduced, as was in vitro immunoglobulin synthesis after stimulation with pokeweed mitogen. Alterations in T cell numbers and function persisted during the entire followup period, except that the mixed leukocyte reaction showed a tendency to return to normal values.

Lymphoid irradiation in intractable rheumatoid arthritis. A double‐blind, randomized study comparing 750‐rad treatment with 2,000‐rad treatment

“…A detailed analysis of changes in humoral immunity following lymphoid irradiation is the basis of a separate report (28). The quantitative and qualitative immunologic changes noted are similar, but not identical to those reported following 2,000-rad TLI (10,12,14) and 3,000-rad TLI (11,13). The reduction in PB helper (Leu-3a+) : suppressor (Leu-2a+) ratios was less marked than that previously reported (10-14).…”

“…Although there was a decrease in CRP levels of up to 76% in 10 patients, there was no significant change overall in either group. Short-term toxicity has been reported in previous studies of TLI in patients with intractable RA (10)(11)(12)(13)(14). Although transient, it was severe enough to prevent 18-20% of patients in these other studies from completing therapy (10,ll).…”

“…Infection occurred only in patients receiving 2,000 rads, and repeated joint aspirations in 17 patients and joint replacement surgery in 3 patients were free of complications. Delayed bacterial sepsis, which was fatal in 2 previously described patients, has been reported 12-39 months following 3,000-rad TLI (13), but not following 2,000-rad TLI (12). Possible explanations for this include the total dose of radiation used, a predisposition to bacterial infection in RA patients (25), and functional hyposplenism secondary to splenic irradiation (13).…”

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“…This conclusion is supported by data obtained during a 13-28-month followup period of patients with intractable RA who were treated with a 2,000-rad, 2-portal TLI regimen (29). However, because of the morbidity and mortality encountered in the 3,000-rad open trial, TLI protocols in non-neoplastic autoimmune diseases still should be considered experimental.…”

Dissection of the mechanisms of immune injury in rheumatoid arthritis, using total lymphoid irradiation

“…Second, immunohistologic examination of the synovium in RA has shown a prominent infiltrate of lymphocytes; the majority of these are T cells, which appear to be activated (9-12). Third, several therapies, the principal action of which appears to be confined to T lymphocytes, have been reported to be effective in RA; these include thoracic duct drainage (13), cyclosporin A (14), and total lymphoid irradiation (TLI) (15)(16)(17)(18). However, it is not clear whether synovial T lymphocytes are responding to an antigenic stimulus within the joint or whether they infiltrate the synovium as a consequence of the inflammatory process that is already active at this site.…”