1144 LETTERS Preliminary criteria for remission in rheumatoid arthritis To the Editor: The report by the Subcommittee for Criteria of Remission in Rheumatoid Arthritis of the American Rheumatism Association (Preliminary criteria for clinical remission in rheumatoid arthritis. Arthritis Rheum 24: 1308-13 15, 1981) represents a significant effort which is to be highly commended. I appreciate the sentiment of the physician who commented from the floor at the ARA meeting in Boston that no committee could tell him how to decide whether his patient was in remission, but his comment seems to me to have completely missed the point. Unless physicians A, B, C . . . X can agree on what the term “remission” means, then it is guaranteed that we will be miscommunicating more often than not. In fact, a wide variation in concepts of remission was noted by the subcommittee in their reference to the “absolutists” and the “relativists.” There are two important points to bring out. First, the definition of remission will be of future significance only if the criteria have operational validity. In their report of a retrospective test on a sample of patients judged to be in remission by informed observers, the committee demonstrated a reasonable consistency of collective judgment in defining how individual physicians determine remission. This is an important first step, but the more critical test will be in applying the criteria in a prospective study to carefully evaluate their ability to predict the long-term consequences of abatement of the disease symptoms. Until this is accomplished, the actual validity of the criteria, either individually or collectively, cannot be fully evaluated. Second, I question whether “partial remission” is an appropriate term. It would appear that the subcommittee has proposed criteria that define remission and partial remission in terms of levels of activity of the disease process. This seems quite appropriate and, if proven to predict future course accurately, would be extremely useful. However, “partial remission” implies an assessment at a given date that describes the patient’s disease status relative to a prior observation. If patient X had had the disease for several years, had improved spontaneously or as a consequence of treatment, but had not gone into complete remission, this patient would be referred to as being in “partial remission.” However, patient Z, who recently had had onset of rheumatoid arthritis and had mild disease without progression, would be properly described as a patient with recent onset of arthritis who (still) has mildly active disease. It would be inappropriate to describe patient Z as being in “partial remission,” even though hidher level of disease activity might be the same as for patient X. Therefore, it seems more reasonable to propose that in testing their operational effectiveness, the criteria should Arthritis and Rheumatism, Vol. 25, No. 9 (September 1982) be considered as defining levels of activity which can be tested prospectively by patient followup to determine longterm outcome, both in assessing the natural history of the disease and its modification by modern treatment. John T. Sharp, MD Director, Joe and Betty Alpert Arthritis Cznter Professor of Medicine University of Colorado School of Medicine Denver, CO Tolmetin-induced thrombocytopenia To the Editor: To1metin sodium is a nonsteroidal antiinflammatory drug that has been approved for use in juvenile rheumatoid arthritis (JRA). The Pediatric Rheumatology Collaborative Study Group (1) compared tolmetin with aspirin. No serious side effects occurred in either treatment group, although abnormal liver function test results were associated with the aspirin-treated group. Specifically, there were no episodes of thrombocytopenia or significant bone marrow suppression in the tolmetin-treated group. I report here an episode of presumed tolmetin-induced thrombocytopenia in a young girl with seronegative polyarticular JRA. A 4-year-old white girl had a history of approximately 1 year of polyarticular swelling that involved her metatarsophalangeal, metacarpophalangeal, and distal interphalangeal joints, as well as her wrists, ankles, elbows, knees, and shoulders. Her back and hips were not involved. Morning stiffness decreased with activity, and her mother noted decreased range of motion associated with swelling and pain in multiple joints. Therapy had been limited to salicylates. There was no history indicative of a more diffuse connective tissue disease (rash, photosensitivity, Raynaud’s phenomenon, spiking fevers, pleurisy, eye inflammation, etc.). Physical examination results were indicative of active synovitis in multiple joints. Results of all of the following tests were normal or negative: slit-lamp examination, complete blood count (CBC), platelet count, antinuclear antibody (ANA), rheumatoid factor, and urinalysis. The highest erythrocyte sedimentation rate was 27 mm/hour. Salicylate levels were within therapeutic range while she was taking aspirin. Aspirin therapy was changed to tolmetin therapy (15 mg/kg given as 100 mg tolmetin 3 times per day). On a return visit approximately 4 weeks later, her mother stated that the patient had improved dramatically within 72 hours of the start of tolmetin treatment and had become progressively more physically active during the following weeks. A week before the next visit (after about 8 weeks of tolmetin therapy), bruises were noted on the legs, arms, and back. The patient had continued taking the medication and was feeling fine, with little, if any, joint pain LETTERS 1145 or stiffness. By examination, there was no lymphadenopathy or organomegaly, but she had several ecchymoses on her forearms, legs, and back, as well as active synovitis with a little tenderness to palpation. CBC results included a normal hemoglobin and white count, but a platelet count yielded 36,000 mm3 with only occasional large platelets on the smear. Results of a repeat ANA were still negative; permission for a bone marrow examination was refused. The tolmetin was stopped, and the patient was observed. Within a few days, her platelet count had risen to 43,000 mm3, and no new ecchymoses formed. Two weeks after tolmetin treatment was stopped, the platelet count was 207,000 mm3; it has remained normal. She has subsequently started taking salicylates again, and there has been no recurrence of the bruising; periodic platelet counts have remained over 200,000 mm3. Nonsteroidal antiinflammatory drugs have only rarely been associated with blood dyscrasias (2). On the package insert for tolmetin “a few cases of granulocytopenia” are listed under the adverse reactions section, but there is no mention of thrombocytopenia. The dose of tolmetin that was used for our patient was well within the dosage range recommended by the manufacturer (3), but she developed thrombocytopenia that only responded to discontinuation of tolmetin therapy. Physicians should watch for this potential complication of tolmetin when this drug is given to children. Jack M. Lockhart, MD Department of Medicine Section of Rheumatology Gundersen Clinic, Ltd La Crosse, WI Levinson JE, Baum J, Brewer E, Fink C, Hanson V , Schaller J: Comparison of tolmetin sodium and aspirin for treatment of juvenile rheumatoid arthritis. J Pediatr 91:799-804, 1977 Paulus HE, Furst DE: Aspirin and non-steroidal antiinflammatory drugs, Arthritis and Allied Conditions. Ninth edition. Edited by DJ McCarty. Philadelphia, Lea & Febiger, 1979, pp 331-354 Physicians’ Desk Reference. 35th edition. Oradell, NJ, Medical Economics Company, 1981, p 1120 Unconventional arthritis therapies To the Editor: Unfortunately, conventional drug therapy for osteoarthritis (OA), rheumatoid arthritis (RA), and ankylosing spondylitis (AS) often fails to provide satisfactory relief to patients. Frustrated by persistent symptoms and/or disease progression, many desperate patients turn to unconventional remedies (1). We have followed 6 patients during the past 5 years who traveled to certain clinics run by nonrheumatologists and returned with drugs given for their “RA.” Toxico- Figure 1. Drugs dispensed to patients as (clockwise from upper left): “indomethacin” (actually a steroid), “DMSO” (dipyrone), “naproxam” (a steroid), and a “muscle relaxant” (diazepam). logic analysis of these drugs revealed alarming results and indicated unsuspected potential hazards for patients. Patient I is a 49-year-old married, white man who had 20 years of polyarthralgias for which aspirin was prescribed; there was no relief of his symptoms. In January 1978, wheelchair-bound with severe pain, he visited a clinic in Mexicali, Mexico, where a diagnosis of “RA” allegedly was made. He was given 10 yellow capsules (every 2 hours) and 3 white and 1 green tablets (3 times a day) (Figure 1). Functional capacity returned within 4 hours. We evaluated the patient in February 1980. Results of physical examination, joint radiographs, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and fluorescent antinuclear antibody tests were all negative or normal. Toxicologic analysis of medications revealed that the yellow capsule contained a steroid, the white tablet another steroid preparation, and the green tablet diazepam (Table 1 ) . The patient was subsequently given prednisone (10 mg per day) and diazepam (2 mg, 3 times per day) in an attempt to duplicate therapy; the attempt, however, was unsuccessful. Patient 2 is a 63-year-old married, white man, who underwent fusion of his lumbosacral spine in 1963 and complained of subsequent back pain. Because of persistent pain and arthralgias he sought evaluation at a clinic in Mexicali, Mexico. There he was given a green tablet said to be “indomethacin 25 mg,” a white tablet said to be “diazepam,” and a yellow capsule “for nerves” (Figure I), the combination of which resulted in a rapid resolution of joint pain with weight gain. He requested evaluation by us in November 1979 for complaints of vague arthralgias without synovitis. He was slightly cushingoid, without synovitis, had normal joint motion, and was thought to have osteoarthritis.