803 LETTERS Sickle cell anemia, complement, and systemic lupus erythematosus To the Editor: We read with interest the letter of Drs. Karthikeyan, Wallace, and Blum (1) which reported an additional case of the concurrence of systemic lupus erythematosus (SLE)and sickle cell anemia (SCA) in the same patient. Dr. Karthikeyan et a1 are justified in their statement that the complement factor B protein concentration in their patient was not significantly reduced, but we would like to point out that this does not necessarily exclude a reduction in the functional concentration of factor B in serum. We have recently shown (2) that the factor B concentration measured hemolytically in a large group of patients with SCA was reduced, whereas as noted in previous studies (3,4) factor B concentration assayed immunochemically was normal; the concentration of hemolytically active factor B was shown to be inversely related to its in vivo fractional catabolic rate (2). Reduced hemolytic factor B concentration has also been demonstrated in B thalassemia major (another chronic hemolytic anemia) by means of a functional assay similar to the one we used (5). It has also been shown that, unlike the classic pathway of complement activation, the alternate pathway is functionally aected by small changes in the concentration of its component and control proteins (6). Activation of the alternate pathway in vivo would thus be expected to produce relatively small changes in the concentration of factor B, which is consumed during the reaction sequence. Thus, in order to exclude an alternate pathway defect, it seems necessary to screen patients with SCA with functional alternate pathway assays. In interpreting the results, it should be borne in mind that relatively small changes in factor B concentration may have functional significance. Both autologous immune complex nephritis (7) and poststreptococcal nephritis (8) have been reported in patients with sickle cell anemia. In the latter study patients with SCA were noted to be grossly over represented in a hospital population of adult patients with poststreptococcal nephritis; this suggested that they may be unduly susceptible to this form of nephritis. The case reports of the concurrence of SLE and SCA provide an additional stimulus for a prospective study of the prevaArthritis and Rheumatism, Vol. 22, No.7 (July 1979) lence of the serologic and clinical features in immune complex diseases in a large group of patients with sickle cell anemia; such a study is in progress in our unit. WENDELL A. WILSON,MD, MRCP KARELDE CEULAER, MD ANTHONYG. MORGAN, MD, MRCP Department of Medicine University of the West Indies Kingston 7 Jamaica REFERENCES 1. Karthikeyan G, Wallace SL, Blum L: SLE and sickle cell disease. Arthritis Rheum 21:862-863, 1978 2. Wilson WA, Thomas El, Sissons J G P Activation of the complement system in asymptomatic patients with sickle cell anemia. Clin Exp Immunol 1979, in press 3. Koethe SM, Casper JT, Rodey GE: Alternative complement pathway activity in sera from patients with sickle cell disease. Clin Exp Immunol23:56-60,1976 4. Strauss RG, Asbrock T, Foristal J, et a1 Alternate pathway of complement in sickle cell disease. Pediatr Res 11:285289,1977 5. Auderset MJ, Casali P, Lambert PH: Decreased factor B activity in B thalassaemia major (abstract). Pathol Biol 25:391, 1977 6. Nydegger UW, Fearon DT, Austen KF: The modulation of the alternative pathway of complement in C2 deficient human serum by changes in the concentration of component and control proteins. J Immunol 1201404-1408, 1978 7. Pardo V, Strauss J, Kramer H, Ozawa T, McIntosh RM: Nephropathy associated with sickle cell anemia: an autologous immune complex nephritis. J Med 59:650-659, 1975 8. Nicholson G D Post streptococcal glomerulonephritis in adult Jamaicans with and without sickle cell anaemia. West Indian Med J 26:78-84, 1977 Thiopronine therapy in rheumatoid arthritis To the Editor: In recent years D-penicillamine proved to be an effective drug for “specific” therapy of rheumatoid arthritis, although its use is often complicated by untoward reactions (1). Thiopronine (a-mercaptopropio- LETTERS Table 1. Results of thiopronine therapy in rheumatoid arthritis Grip strength ESR mm/hr Ritchie index Lee index Steroid dose Result No. of patients Before After Before After Before After Before After Before After Good Moderate Null 6 13 3 33 45 23 11 158 32 30 I15 240 128 140 8.5 13.6 14.6 1.5 6.7 14.6 5.0 6.2 5.6 0 4.3 6.3 2.0 5.0 5.0 0 2.3 4.0 141 nylglycine), already utilized as a penicillamine-like agent in the treatment of cystinuria (2), is reputed to be devoid of major side effects. We have initiated a preliminary long-term open trial with thiopronine in outpatients with active, definite rheumatoid arthritis (ESR >20 mm/hour, Ritchie’s index >5). Patients admitted to the trial were all on steroidal (6-methyl-prednisolone), as well as nonsteroidal (indomethacin or diclofenac), antiinflammatory drugs, but had stopped any other therapy (gold, antimalarials, immunosuppressors)for at least 6 months. According to recommended dose regimen for penicillamine (3), we have initially administered 250 mg/day of thiopronine, increasing 250 mg/day every 15 days, up to a maximum daily dose of 1 gm. Patients were examined at least every 2 months for the following parameters: ESR, grip strength, Ritchie’s index, Lee’s index, and reduced need for antiinflammatory agents. Thirty-two patients have now been on treatment for 4 to 14 months. A preliminary evaluation of the trial in the patients in which the drug was not discontinued is summarized in Table 1. Six patients obtained good clinical remission and stopped any antiinflammatory agent. In a further patient with palindromic rheumatism, episodes of transient monarthritis did not recur. In one of these patients an initial steroid cataract reversed under thiopronine treatment; incidentally, thiopronine has been reported to be effective in inhibiting senile cataract (4). Thirteen patients obtained an appreciable clinical remission and reduced the requirement of antiinflammatory agents. Three patients remained unmodified. Untoward reactions occurred in 13 patients and in 9 the drug had to be discontinued: 4 patients complained of ageusia, 2 of stomatitis, 2 of skin rash, 1 of nausea and vomiting; finally 2 had transient proteinuria and 2 developed a nephrotic syndrome while on treatment. All symptoms reversed after withdrawal of the drug; in the two with nephrotic syndrome the clinical picture returned to normal in 2 to 3 weeks after discontinuation of thiopronine and high-dose steroid treat- ment. The patients with ageusia restarted the treatment after a transient withdrawal or dose reduction. No one had hemocytopenia. On the basis of this very preliminary experience, thiopronine seems to be of value in the “specific” therapy of rheumatoid arthritis. Recent evidence indicates that this drug is effective in the pertussis vaccine edema (5), a promising experimental model for screening of penicillamine-like agents (6). Surprisingly, incidence of side effects was more than expected and these were similar to those described with penicillamine. A more extensive assessment of thiopronine seemed therefore justified, and a multicenter long-term controlled trial of this drug compared with penicillamine is now in progress. G. PASERO M. L. ClOMPl Service of Rheumatology University of Pisa Via Roma 2 56100 Pisa, Italy REFERENCES I. Jaffe IA: D-penicillamine. Bull Rheum. Dis 28:948-952, 1977 2. King SJ Jr.: Treatment of cystinuria with a-mercaptopropionylglycine: a preliminary report with some notes on column chromatography of mercaptans. Proc SOCExp Biol Med 129:927-932, 1968 3. Day AT, Golding JR, Lee PN, Buttenvorth AD: Penicillamine in rheumatoid disease: a long-term study. Br Med J 1:180-183, 1974 4. Imaizumi K, Atsumi K, Ogawa K: Thiola tablet, a senile cataract inhibitor. Ophthalmology (Tokyo) 12:468-470, 1970 5 . Arrigoni-Martelli E, Bramm E: Immunopharmacological investigations on sulfhydryl compounds: comparative study of D-penicillamine, 5-mercapto-pyridoxine and amercaptopropionylglycine. (Personal communication) 6. Arrigoni-Martelli E, Bramm E, Huskisson EC, Willoughby DA, Dieppe PA: Pertussis vaccine oedema: an experimental model for the action of penicillamine-like drugs. Agents Action 6:613-617, 1976
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