effect of lithium on granulopoiesis. Am J Med 61:29-32,

To the Editor: In patients with systemic lupus erythematosus (SLE) the occurrence of several autoantibodies, probably caused by diminished suppressor cell function, is generally observed (1,2), and a depression of cell-mediated immunity has been reported (3,4). Therefore, levamisole, an immunomodulating drug, acting by restoration of delayed hypersensitivity response of impaired T-cell function and of detective macrophage activity (5-7), was studied in 8 patients with SLE (8). The diagnosis of SLE was based on ARA criteria (9) and the presence of antinuclear antibodies (ANA) and n-DNA-antibodies (radioassay). Duration of disease varied between 5 months and 4 years. Three patients suffered from LE-nephritis, l patient showed CNS manifestations, and 4 patients had lung involvement. When treatment with levamisole was started, all patients had only moderate clinical signs of activity of disease; 4 of them, however, were active with respect to serologic parameters (ANA and/or n-DNA-antibodies and/or complement components). At this time, 2 patients had no treatment; 5 patients were on long-term treatment with low-dose corticosteroids (15 mg prednisolone

daily); additionaliy 3 of them took 100 mg azothioprine daily and one of them 50 mg cyclophosphamide daily. The immunosuppressive drugs were withdrawn 2 weeks before levamisole treatment was started. Levamisole was given in an oral dose of 150 mg daily for 3 consecutive days every week over 1 month. During the following 3 months the same dose was given every second week. The treatment had to be withdrawn in 4 patients. In 1 patient fever and skin rash (probably drug-induced) were observed 1 month after starting the treatment; another patient developed an exacerbation of her LEskin manifestation after 2 months. In 2 patients the therapy was withdrawn after two months because of external reasons. The other 4 patients have been under treatment with levamisole for more than 4 months. During the first month of treatment 5 patients developed an increase of lymphocyte stimulation with PHA, which returned to pretreatment values within the following 3 months (Table 1 ) . The only patient with initially decreased T lymphocytes reached normal values within the first month. All other patients showed normal values of T and B lymphocytes. No significant changes of serum levels of n-DNA-antibodies and titers of ANA were observed. Low Clq levels, initially observed in 4 patients, returned to normal values during levamisole treatment. The changes in C3 levels during levamisole are shown in Table 2. In the 4 patients treated up to now, the ESR and the serum a,-globulin levels decreased in 3 and increased in 1 patient. No deterioration of renal function could be seen in these patients. Three of the 4 patients who have now been

Table 1.

Table 2.

1976 3. The current status of lithium therapy: report of the APA Task Force. A m J Psychiatr 132:997-1001, 1975 4. Stossel T P Phagocytosis. N Engl J Med 290333439. 1974

Levamisole in Systemic Lupus Erythematosus



Levamisole, 450 mg

Levamisole, 450 Mg Every Week Patient

Every Second Week




194 271 369 75 10 53 93 173

106 64 123 79 45 58 157 356

43 126 166 174 22 98 235 184


171 76 nd 14 71 101



9 60 104 125


33 I29 58 nd

Lymphocyte stimulation with 0.5 pg PHA. Results are expressed as the difference in dpm of PHA-stimulated cultures-dpm in control cultures (A dpm) X 101.

Every Week Patient

Every Second Week





76 42 28 I53 I 04 I08 80 50

76 55 55 130 nd 130 108 62

93 94 80 54 108 153 62 nd


44 30 72 62 82 74 68


38 38 80 92 86 77 63




80 I10 70 56


77 60

Serum concentrations of C3 were determined by radial immunodiffusion (Behring Werke, Marburg, West Germany). Normal values: 80-140 mg%.


treated for 4 months, have initially been on maintenance therapy with low-dose prednisolone. In all of them, the concomitant prednisolone therapy could be reduced by 5 mg daily. The remaining patient on levamisole since the SLE was diagnosed did not need additional corticosteroid therapy. Because the patients had moderate clinical signs of activity, improvement was found only in the serological parameters of inflammation. The lymphocyte stimulation test and the serum levels of C l q and C3 improved in the first month only during the weekly levamisole therapy and returned to basic values during the alternate treatment every second week. These preliminary results seem to justify further trials with levamisole in SLE patients.

J. SMOLEN 0. SCHERAK J . MENZEL M. KOJER G. KOLARZ 2nd Medical Clinic Garnisongasse I3 Institute of Immunology Borschkegasse 8a University of Vienna 1090 Vienna, Austria REFERENCES 1. Hughes GRV: The diagnosis of systemic lupus erythema-

tosus. Br J Haematol 25:409, 1973 2. Report of Symposium. Ann Rheum Dis 35:466, 1976 3. Paty JG, Sienknecht CW, Townes AS, et al: Impaired cellmediated immunity in systemic lupus erythematosus (SLE). Am J Med 59:769, 1975 4. Lockshin HD, Eisenhauer AC, Kohn R, et al: Cell mediated immunity in rheumatic diseases. Arthritis Rheum 18:245, 1975 5. Editorial: levamisole. Lancet l / l 5 l , 1975 6. Brugmans J, Schuermans V, De Cock W, et al: Restoration of host defense mechanisms in man. Life Sci 13: 1499, 1973 7. Sampson D, Lui A: The effect of levamisole in cell mediated immunity and suppressor cell function. Cancer Res 36:952, 1976 8. Scherak 0, Smolen J, Menzel J, et al: Levamisole in systemic lupus erythematosus. XIV International Congress of Rheumatology, San Francisco, 1977 9. Cohen AS, Canoso JJ: Criteria for the classification of systemic lupus erythematosus-status 1972. Arthritis Rheum 15540, 1972

Rheumatoid Factors in the Serum of Gouty Patients To the Editor: We are flattered that Drs. Eisman and Fan took the time to refute our unpublished data ( 1 ). They refer to a statement by one of us during a lecture at the University of Southern California that “the incidence of positive tests for rheumatoid factor appears to be approximately 30% in patients with chronic tophaceous gout.” We have referred to this observation previously and suggested that it may result from the denaturation of immunoglobulin G (IgG) adsorbed to microcrystalline sodium urate (2,3). Other studies suggest a similar relationship. The ARA Gout Diagnostic Criteria Committee found that 10% of subjects with gout in a multicenter study had positive rheumatoid factor ( R F ) (4,5). Howell et al. demonstrated a high frequency of IgG antiglobulins approximating 40% in gouty patients (6). Neither study distinguished between tophaceous and nontophaceous patients. Our interests in the occurrence of R F in gout originally arose with the observation of a patient with polyarthritis involving the MCP, PIP, wrist, elbow, and knee joints. There were enlarged olecranon bursae and nodules on the extensor surfaces of the forearm. The patient complained of morning stiffness but related an episodic history of acute arthritis. Both sheep cell and latex tests for R F were positive. Monosodium urate crystals were found in the fluid of several involved joints, and excisional biopsy of the “nodule” revealed the typical histopathology of a tophus (including crystals). Colchicine produced an excellent therapeutic response. Subsequently, all patients with tophaceous gout were tested for R F by either the sensitized sheep cell agglutination (SSCA) or latex fixation (Hyland Laboratories, Costa Mesa, California) methods. Whenever possible, sera from unselected patients with acute crystal proven gouty arthritis were tested similarly. Nine of 30 patients (30%) with chronic tophaceous gout were R F positive, compared with 10% (3/29) of those with acute arthritis only. None of these patients was found to have co-existent rheumatoid arthritis by either radiographic or clinical criteria. As expected, the average age of the non-tophaceous group was lower than the tophaceous group (51 vs 60 years). The average age of the R F positive tophaceous gouty patients . was 54.5 years (range: 43-60), compared with 62 years (range: 50-83) for the R F negative tophaceous gouty patients, an observation that suggests that age per se is not the reason

Levamisole in systemic lupus erythematosus.

I558 effect of lithium on granulopoiesis. Am J Med 61:29-32, To the Editor: In patients with systemic lupus erythematosus (SLE) the occurrence of se...
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