Andrei Calin

Treatment of Intractable Rheumatoid Arthritis with Total Lymphoid Irradiation

Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation (total dose, 2000 rad) in an uncontrolled feasibility study, as an alternative to long-term therapy with cytotoxic drugs such as cyclophosphamide and azathioprine. During a follow-up period of five to 18 months after total lymphoid irradiation, there was a profound and sustained suppression of the absolute lymphocyte count and in vitro lymphocyte function, as well as an increase in the ratio of Leu-2 (suppressor/cytotoxic) to Leu-3 (helper) T cells in the blood. Persistent circulating suppressor cells of the mixed leukocyte response and of pokeweek mitogen-induced immunoglobulin secretion developed in most patients. In nine of the 11 patients, these changes in immune status were associated with relief of joint tenderness and swelling and with improvement in function scores. Maximum improvement occurred approximately six months after irradiation and continued for the remainder of the observation period. Few severe or chronic side effects were associated with the radiotherapy.

An Experimental Epidemic of Reiter's Syndrome Revisited: Follow-up Evidence on Genetic and Environmental Factors

The relation between a specific infective event (shigellosis), a specific disease entity (Reiters syndrome), and a specific histocompatibility antigen (HL-A B27) is documented by follow-up study of an epidemic of post-Shigella Reiters syndrome. Five of the original 10 patients have been traced, HL-A typed, and clinically assessed 13 years after the initial episode. One of the 5 has minimal disease, remains symptom-free, and is HL-A B27-negative. The remaining 4 have followed a chronic course, have persistent active disease, and are HL-A B27-positive. It is estimated that after this single episode of shigellosis, from one sixth to one third of the persons who were HL-A B27-positive developed Reiters syndrome. The prognosis for postdysenteric Reiters syndrome must be guarded, especially in the subject who is B27-positive.

The Chronicity of Symptoms and Disability in Reiter's Syndrome: An Analysis of 131 Consecutive Patients

To assess the natural history of Reiters disease, we evaluated 131 consecutive patients at a university clinic or at a community center. One hundred twenty-two patients (93%) were available for follow-up at a mean of 5.6 years. The results showed that there were no major differences between patients at the two centers; at follow-up, 101 (83%) had some disease activity, 27 (22%) had annoying symptoms, 42 (34%) had sustained disease activity, 19 (16%) had had to change jobs, and 13 (11%) were unemployable; there were no major differences between the 19 (15%) females and 112 (85%) males or between the HLA-B27-positive (83%) and -negative (17%) patients, except for increased prevalence of sacroilitis and chronic uveitis in HLA-B27-positive patients; and, at entry, only increased heel disease differentiated those destined to have a poor prognosis. Most patients with Reiters syndrome have persisting symptoms that can lead to chronic disability.

Efficacy of total lymphoid irradiation in intractable rheumatoid arthritis. A double-blind, randomized trial.

Twenty-six patients participated in a randomized, double-blind study of the efficacy of total lymphoid irradiation in the treatment of intractable rheumatoid arthritis. All 26 patients, for whom therapy with gold compounds and penicillamine had failed, would ordinarily have been considered candidates for cytotoxic or antimetabolite drug therapy. Thirteen patients randomly assigned to receive full-dose total lymphoid irradiation (2000 rad) and 11 patients assigned to receive control low-dose total lymphoid irradiation (200 rad) completed radiotherapy. Alleviation of joint disease activity was significantly greater in the high-dose group as judged by morning stiffness, joint tenderness, and functional assessment (global composite score) at 3 and 6 months after radiotherapy. The high-dose group had a marked reduction in both T-lymphocyte function and numbers, but this finding was not observed in the low-dose group. Complications seen in the high-dose but not low-dose group included transient neutropenia, thrombocytopenia, pericarditis, and pleurisy.

HLA-B27: To Type or Not to Type?

The association between the histocompatibility antigen HLA-B27 and the seronegative spondylarthritides such as ankylosing spondylitis and Reiters syndrome is dramatic. A question that arises in practice is, when should a clinician request HLA-B27 typing in the assessment of a patient with a rheumatologic complaint? Generally, diagnosis of these spondylarthropathies depends on history, clinical and radiologic examination, and, occasionally, confirmatory laboratory tests. This paper reviews the criteria for the diagnosis of the spondylarthritides, discusses the sensitivity and specificity of HLA-B27 typing in these conditions, analyzes the relation between HLA-B27 status and prognosis, and defines the role of genetic counseling. It is concluded th,t knowledge of the patients HLA-B27 status provides only minimal help to the physician. Indiscriminate typing is to be deprecated.

The treatment of intractable rheumatoid arthritis with lymphoid irradiation

Abstract Subdisphragmatic lymphoid radiation was used as an alternative to cytotoxic drug therapy to treat six patients with progressive erosive rheumatoid arthritis. All were previously unresponsive to conventional therapy. Radiation (4,000 rad) was given to subdispbragmatic lymphoid tissues in fractionated doses of 150–250 rod each. Three of the six patients demonstrated long-lasting clinical improvement with a decrease in synovitis and morning stiffness and an increase in joint function. All six patients showed a profound depression in the peripheral blood lymphocyte count which persisted for at least six months. The irradiation was well tolerated; there have been no serious complications due to radiotherapy with follow-up ranging from 13 to 36 months. The substantial efficacy in some patients and the lack of severe toxicity in all suggests that radiotherapy deserves further study as an alternative to cytotoxic drugs in the treatment of rheumatoid arthritis.

HLA-B27 in 1982: Reappraisal of a Clinical Test

Excerpt The practice of medicine may be regarded as a beneficent union of art and science, but many physicians feel uncomfortable with its metaphysical or mathematical aspects. In an article in thi...

Clinical Use of Tolmetin Sodium in Patients with Ankylosing Spondylitis: A Review

Abstract: The efficacy and safety of tolmetin sodium in the management of ankylosing spondylitis are presented in a review of published and unpublished data. In both open and controlled clinical studies, tolmetin was superior to placebo and equal to indomethacin in its capacity to relieve pain, inflammation, and other symptoms of ankylosing spondylitis (AS). Objective and subjective assessments showed that both tolmetin sodium and indomethacin provided significant therapeutic benefits to patients with AS. In AS, the two drugs showed similar adverse reaction profiles. Adverse reactions with both drugs were minimal and predominantly affected the gastrointestinal tract, in most cases these symptoms cleared spontaneously without discontinuing the drugs.