LETTERS 1. Ferrante FM, Myerson GE, Goldman JA: Subclavian artery thrombosis mimicking the aortic arch syndrome in systemic lupus erythernatosus. Arthritis Rheum 25:1501-1504, 1982 2 . Lessof MH, Glynn L E : The pulseless syndrome. Lancet i:799801, 1959 3 . Harris E N , Loizou S. Englert H , Derue G , Chan JK, Gharavi A E , Hughes GRV: Anticardiolipin antibodies and lupus anticoagulant (letter). Lancet ii:1099, 1984 4. Harris E N , Gharavi A E , Boey ML, Patel BM, MackworthYoung C G , Loizou S . Hughes GRV: Anticardiolipin antibodies: detection by radioirnmunoassay and association with thrombosis, in systemic lupus erythematosus. Lancet ii:1211-1214, 1983 5 . Boey ML. Colaco CB, Gharavi AE, Elkon KB, Loizou S, Hughes GRV: Thrombosis in systemic lupus erythematosus: striking association with the presence of circulating lupus anticoagulant. Br Med J 287:1021-1023, 1984 6. Harris E N , Gharavi A E , Asherson RA, Boey ML. Hughes GRV: Cerebral infarction in systemic lupus: association with anticardiolipin antibodies. Clin Exp Rheumatol 2:47-51, 1984 7. Asherson RA, Mackworth-Young CG, Harris E N , Gharavi AE, Boey M L , Hughes GRV: Multiple venous and arterial thromboseij associated with the lupus anticoagulant and antibodies to cardiolipin in the absence of S L E . Rheumatol Int 5:91-93, 1985 8 . Hughes GRV. Asherson RA: Atypical lupus with special reference to ANA negative lupus and lupus subsets, Advances in Nephrology. Edited by J P Grunfeld, MH Maxwell. Chicago, Year Book Medical Publishers, 1985, pp 333-346 9. Jinidal MK, Martin MFR, Gayner A: Gangrene developing after minor surgery in a patient with undiagnosed systemic lupus erythematosus and lupus anticoagulant. Ann Rheum Dis 42.347-349. 1983 10. Asherson RA, Harris E N , Gharavi AE, Hughes GRV: Clinical manifestations associated with the lupus anticoagulant and elevations of antibodies to cardiolipins in S L E and other conditions, Progress in Rheumatology. Vol. 11. Edited by I Machtey, Israel, Hasharon Hospital, 1984, pp 323-329 595 gm/day. After 3 months of treatment, the patient was clinically improved, but in February 1984. she developed a generalized edema and was hospitalized. At that time, laboratory investigations revealed the following: serum creatinine of 2 mgl100 ml, creatinine clearance of 46 mliminute, proteinuria at 4.5 gmi24 hours (moderately selective according t o Cameron’s index), hypoalbuminemia at 1.9 gmilOO ml, hypercholesterolemia at 3 0 mgilO0 ml. Immunologic studies revealed normal levels of C3, C4, and CH50, and tests for fluorescent antinuclear antibodies, anti-double-stranded DNA, cryoglobulins, and circulating immune complexes ( C l q and conglutinin binding tests) showed negative results. H L A identification showed that she had A29,B I ~ , B ~ ~ , C W ~ , D R ~ , D R,MT2. S,MTI A renal biopsy was performed, and under light microscopy, the sample showed normal glomeruli. Immunofluorescence analysis of the specimen gave negative results using antisera against IgG, IgM, IgA. C l q . C3, C4, and fibrinogen. Using electron microscopy, the only abnormality noted was a complete loss of the foot processes of the epithelial cells (foot process disease) (Figure I ) . Withdrawal of the tiopronin (total cumulative dose 70 gm) and institution of prednisone treatment ( I mglkgiday) completely resolved the nephrotic syndrome within 1 month. There are many similarities in the nephrotic syndrome induced by tiopronin and that induced by D-penicillamine, both drugs having a chemical structural affinity (6-1 I ) . First, the highest incidence of disease occurs during the first year of treatment, showing no correlation between mean daily dose and toxicity. Second, the glomerular injury is mediated by an immunologic mechanism, and it appears to be self-limiting upon withdrawal of the offending drug. Nephirotic syndrome induced by tiopronin: association with the HLA-DR3 antigen To the Editor: The role of tiopronin as a useful disease-remittive drug in rheumatoid arthritis (RA) has been established in clinical trials (1-3). Pasero et al (4), in a multicenter trial comparing tiopronin treatment with D-penicillamine treatment, have demonstrated comparable efficacy. In Pasero’s study, proteinuria ranging from 2-3 gmlday (but not associated with nephrotic syndrome) occurred in 4 patients in the tiopronin-treated group. We describe a patient who developed nephrotic syndrome during treatment with tiopronin, and was also found to have the HLA-DR3 antigen. In October 1983, a 60-year-old woman was diagnosed as haking definite RA. according to American Rheumatism Association criteria (5). Treatment with tiopronin was started, with gradually increasing doses, until she was taking 1 Figure 1. Electron micrograph of renal biopsy specimen from a 60year-old woman with tiopronin-induced nephrotic syndrome, showing complete loss of the foot processes of epithelial cells (original magnification x 5,000). LETTERS 596 Third, the morphologic basis of glomerulopathy consists of both membranous and minimal change glomerular lesions. The pathogenesis of tiopronin-induced nephropathy is still unclear. The renal injury may be an immune complexmediated membranous nephropathy similar to the D-penicillamine-induced lesions. The antigenic role of tiopronin has been demonstrated by Stratta e t al (9), who have shown a positive result on immune complex elution testing after incubation of kidney sections with tiopronin. According to Lupo et al(8), in tiopronin-induced minimal change nephropathy, a sensitization mechanism similar to that described in minimal change nephropathy associated with exposure to allergens may occur. In patients with HLA-DR3, Speerstra et a1 (12) showed that there is an increased risk of nephrotic syndrome during treatment with D-penicillamine. Our observation suggests a similar immunogenetic susceptibility for the renal damage induced by tiopronin; however, further studies will be necessary to prove whether this association is statistically significant. Carlo Salvarani, M D PierLuigi Macchioni, M D Fulvia Rossi, MD Ido Iori, MD Giordano Filippi, M D Hospital of Reggio Emilia Reggio Emilia, Italy I . Pasero G , Ciompi ML: Thiopronine therapy in rheumatoid arthritis (letter). Arthritis Rheum 222303404, 1979 2. Pasero G, Pellegrini P, Ciompi ML, Colamussi V, Barbieri P, Mazzoni MR: La tiopronine, nouveau traitement de fond de la polyarthrite rhumatoi’de: Ctude ouverte de 158 cas. Rev Rhum Ma1 Osteoartic 47: 163-168, 1980 3. Amor B, Mery C, de Gery A: La tiopronine: nouvel antirhumatismal i action lente dans la polyarthrite rhumatoide. Rev Rhum Ma1 Osteoartic 47: 157-162, 1980 4. Pasero G, Pellegrini P, Ambanelli U , Ciompi ML, Colamussi V , Ferraccioli G , Barbieri P, Mazzoni MR, Menegale G , Trippi D: Controlled multicenter trial of tiopronin and D-penicillamine for rheumatoid arthritis. Arthritis Rheum 25:923-929, 1982 5. Ropes MW, Bennett GA, Cobb S , Jacox R, Jessar RA: 1958 revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis 9:175-176, 1958 6. Bacon PA, Tribe CR, Mackenzie JC, Verrier-Jones J, Cumming RH, Amer B: Penicillamine nephropathy in rheumatoid arthritis. Q J Med 45:661-684, 1976 7. Falck HM, Tornroth T, Koch B, Wegelius 0: Fatal renal vasculitis and minimal change glomerulonephritis complicating treatment with penicillamine. Acta Med Scand 205: 133-138, I979 8. Lupo A, Faraggiana T, Loschiavo C, Parolini C, Maschio G: Nephrotic syndrome during 2-mercapto-propionyl-glycine (thiola) therapy. Nephron 28:96-99, 1981 9. Stratta P, Coratelli P, Camussi G , Passavanti G , Segoloni GP, Coppo R, Amerio A, Vercellone A: Sindrome nefrosica durante trattamento con 2-mercaptopropionilglicina. Minerva Nefrol 25:87-92, 1978 10. Fruttero B, Dall’Aglio PP, Bruno M, Rossi E, Pozzo L, Ferrari C, Linari F, Migone L: Sindrome nefrosica indotta dalla 2mercapto-propionil-glicina. Symposium on Metabolic, Physiochemical and Therapeutical Aspects of Urolithiasis. Edited by F Linari, M Brund, B Fruttero, M Marancella. Milan, Italy, Wichtig, 1983, pp 131-135 11. kzzoni G , Pavanello L, Dussini N , Chiandetti L, Zacchello G: Nephrotic syndrome during treatment with alpha-mercaptopropionylglycine. J Urol 122:381-382, 1979 12. Speerstra F, Reekers P, Van de Putte LBA, Vandenbroucke JP, Rasker JJ, de Rooij DJRAM: HLA-DR antigens and proteinuria induced by aurothioglucose and D-penicillaminein patients with rheumatoid arthritis. J Rheumatol 10:948-953, 1983 Idiopathic thrombocytopenic purpura with high-titer, speckled pattern antinuclear antibodies: possible marker for systemic lupus erythematosus To the Editor: Idiopathic thrombocytopenic purpura (ITP) has been associated, in a small number of patients, with the subsequent development of systemic lupus erythematosus (SLE) ( I , 2 ) . Several histologic features resembling those described in S L E have been found in the spleens of some ITP patients (3), supporting the concept that an ITP-like syndrome can be the initial manifestation of S L E . Since S L E is a chronic and potentially fatal disease, it is of prognostic importance to identify ITP patients who are at risk of developing SLE. In this report we provide evidence suggesting that ITP patients presenting with high-titer, speckled pattern, antinuclear antibodies (ANA) appear to be at risk of developing SLE. Between 1976 and 1983, we studied 18 patients in whom the diagnosis of ITP was made. All patients presented with easy bruising, petechiae and/or bleeding, and platelet counts ranging from 5,000-15,000/mm3. None of the patients had ingested drugs known to induce thrombocytopenia, nor did they have evidence of any other underlying disease. All patients were female, with a mean age of 29 years (range 1038). Patients were followed for a mean of 3.4 years (range 10 months-7 years). At the time of diagnosis of ITP, all patients had serum drawn for rheumatoid factor (latex fixation), complement levels (C3 and C4), antibodies to double-stranded DNA, and ANA determinations. In those sera exhibiting speckled pattern ANA, the presence or absence of antibodies directed against the nuclear antigens R N P and/or Sm was determined (4). The diagnosis of S L E was established using the American Rheumatism Association preliminary criteria (5). Presence of 4 or more criteria was required before the diagnosis of S L E was made.