CONCISE COMMUNICATIONS and diarrhea in another 2 for 2-3 weeks. No other side effects occurred, and all patients completed the trial. Clinical parameters of disease activity (purpura, arthralgias, asthenia) significantly improved in 6 patients; cutaneous ulcers did not resolve. Cryoglobulins (measured by cryocrit) were reduced to 550% of initial values in 6 of the 8 patients. Rheumatoid factor activity (by the standard latex methods) decreased in 7 patients. Hematuria resolved in 5 of 6 patients with this feature. C4 levels improved in 2 of the 8 patients. Liver enzyme values returned to normal in 3 of the 8 patients, all of whom had EMC (Table 1). In conclusion, the clinical features of purpura and arthralgias improved with improvement in the leukocytoclastic vasculitis in most of the patients. Liver enzyme values returned to normal in those with EMC. A similar effect has been demonstrated in primary biliary , alcoholic, and postnecrotic cirrhosis (6). Cryoglobulins decreased in association with a decrease in rheumatoid factor levels, features relatable to the inhibition of the secretory process of immunoglobulins by plasma cells (3). The lack of improvement in cutaneous ulcers is not an unexpected finding; equivocal responses to dextran, heparin, and penicillamine have been reported (7), and only the combination of steroids plus a cytotoxic agent may be effective. The open study and small sample size of this trial undoubtedly affect the value of our findings. Nevertheless, the results are s a c i e n t l y encouraging to warrant further controlled studies of a larger group of patients. Colchicine’s effects on both the humoral and cellular aspects of immune response underscore its potential benefit in other immunologic diseases. Fulvio Invernizzi, MD University of Milan Milan, Italy Giuseppe Monti, MD Saronno Hospital Saronno, Italy 1. Callen JP: Oral colchicine therapy is effective for chronic cuta- 2. 3. 4. 5. 6. 7. neous leukocytoclastic vasculitis (abstract). Arthritis Rheum 30 (suppl4):S106, 1987 Plotnick S, Huppert AS, Kantor G: Colchicine and leukocytoclastic vasculitis (letter). Arthritis Rheum 32: 148%1490, 1989 Antoine JC, Maurice M, Feldrnann G, Avrameas S: In vitro and in vivo effects of colchicine and vinblastine on the secretory process of antibody-producing cells. J Immunol 125:1939-1949, 1980 Mekory YA, Chowers Y, Drucker I, Klajman A: Inhibition of delayed hypersensitivity reaction by colchicine: colchicine inhibits interferon-gamma induced expression of HLA-DR on gut epithelial cell line. Clin Exp Irnmunol 78:230-232, 1989 Kuncl RW, Duncan G, Watson D, Alderson K, Rogawski MA, Peper M: Colchicine myopathy and neuropathy. N Engl J Med 316~1562-1568, 1987 Kershenobich D, Vargas F, Garcia-Tsao G, Tamayo RP, Gent M, Roykind M: Colchicine in the treatment of cirrhosis of the liver. N Engl J Med 318:170%1713, 1988 Gorevich PD, Kassab HJ, Lev0 Y, Kohn R, Meltzer M, Prose P, Franklin EC: Mixed cryoglobulinemia: clinical aspects and longterm follow-up of 40 patients. Am J Med 69:287-308, 1980 723 Treatment with anti-CD4 monoclonal antibody and acute interstitial nephritis In recent open studies using murine anti-CD4 monoclonal antibody (MAb) as a treatment for rheumatoid arthritis (RA), reported adverse reactions have included fever, chills, and rigor, which usually occurred during antibody infusion (1,2). No persistent side effects have been reported. We have treated a patient with RA using M-T151, the murine antLCD4 MAb used in the open study by Reiter et a1 (2) (kindly provided by Professor G. Riethmiiller, Munich, Germany). Acute interstitial nephritis developed in the patient 4 weeks after treatment. Although a direct causal relationship cannot be established, the temporal relationship suggested a possible link between the murine antLCD4 MAb treatment and the development of interstitial nephritis in this patient. The patient, a 69-year-old man, had seropositive, erosive RA of 37 years duration. In 1990, 36 years after the onset of RA, he reported having dry eyes and mouth, and Schirmer’s test confirmed decreased tear production (left eye 0 mm, right eye 2 mm, after 5 minutes). Rheumatoid factor (RF) was positive at a titer of 15,120, but antinuclear, anti-SS-AIRo, and anti-SS-B/La antibodies were negative. Labial biopsy was not performed. Renal function was normal. On the basis of these results, a provisional diagnosis of secondary Sjogren’s syndrome (SS) was made and he was treated with hypromellose eyedrops. He continued to have aggressive RA, which did not respond to conventional disease-modifying drugs including gold, D-penicillamine, sulfasalazine, phenytoin, azathioprine, and methotrexate. He also had severe erosive esophagitis and gastritis, which precluded treatment with nonsteroidal antiinflammatory drugs (NSAIDs). All second-line drugs were stopped 6 months before the patient was admitted to the hospital for MAb treatment. Treatment at the time of admission consisted of coproxamol (paracetamol and dextropropoxyphene hydrochloride), isosorbide mononitrate, and diltiazem, which he took for pain and ischemic heart disease. He was not taking diuretics. At the time of initiation of treatment with M-T151, he had synovitis of the hands, wrists, feet, and knees, with bilateral knee effusions, early morning stiffness of 60 minutes, joint pain scored at 6.7 cm on a 0-10-cm visual analog scale (VAS), and a Ritchie Articular Index (RAI) score (3) of 11 (possible range 0-63). Results of laboratory investigations were as follows: hemoglobin 9.0 gm/dl, platelet count 689 x 109/liter, erythrocyte sedimentation rate (ESR) 82 mmhour, urea 4 mmolesfliter, creatinine 98 pmoleslliter, random blood sugar 6.4 mmoleslliter, RF titer 1:5,120 (RoseWaaler), IgG 16.8 gmhiter (normal 7.2-19), IgA 5.8 gmfliter (normal 0.&5.0), IgM 1.8 gmfliter (normal 0.5-2). No paraprotein band was detected, and results of urinalysis and urine microscopy were normal. Analysis of peripheral blood lymphocyte subsets revealed the following: CD4 1.1 x 10’Aiter (normal 0.35-2.2) and CD8 0.46 x 109/liter (normal 0.2-1.44). He received M-T151 intravenously at 10 mg/day for 7 consecutive days. Chills and slight shaking were experienced during the infusion, which lasted for 30 minutes, but CONCISE COMMUNICATIONS 724 no other reaction was observed. Two weeks posttreatment there was no significant clinical improvement. He had early morning stiffness lasting 120 minutes, an RAI score of 8, and a VAS pain score of 5.5 cm. Four weeks after M-T151 treatment he was admitted to the hospital on an emergency basis because of acute renal failure. On admission, he was dehydrated and oliguric. There was no clinical evidence of vasculitis. The hemoglobin level was 8.1 gdliter, platelet count was 708 X 109/liter, and ESR was 18 mm/hour. Urine microscopy showed 88 white cells/mm3 with granular casts; no eosinophils were seen, and culture was sterile. Serum creatinine was 552 pmoles/liter, urea 21.7 mmoles/liter, and potassium 6.5 mmoleshter. Results of liver function tests were normal. Electrocardiogram showed a small P-wave and tenting of the T-wave, consistent with hyperkalemia. Findings on ultrasound of the kidneys were normal. Autoantibodies, including anti-DNA, were again negative. Serum complement levels were normal. Creatinine clearance was 6 d m i n u t e , and the 24-hour urinary protein estimation was 0.8 g d i t e r . Peripheral blood lymphocyte subset analysis showed the following: CD4 1 x 109/liter and CD8 0.34 x 10’Aiter. DTPA (diethylene triamine penta-acetic acid) scan showed perfused, functioning kidneys of equal size, but selective accumulation of tracer with increased parenchymal transit time. Renal biopsy showed interstitial nephritis with pronounced plasma cell infiltrate. His condition improved with intravenous fluid and furosemide. Over the next few days, urine output improved and his serum creatinine level continued to decrease. Three months later, the serum creatinine level had returned to 112 pmoledliter. There are many causes of acquired interstitial nephritis. Among the most common is drug-induced disease, caused especially by NSAIDs. However, our patient was not receiving such treatment, and there was no other obvious cause. Interstitial nephritis can occur in primary SS (4), but renal manifestations are uncommon in secondary SS. In a review by Tu et a1 (9,patients with interstitial nephritis had primary SS with only minor arthritis. Interstitial nephritis is a histologic diagnosis and, because renal biopsy is not performed routinely in patients with RA and secondary SS who have normal renal function, it is possible that mild subclinical interstitial nephritis may occur in secondary SS. Our patient experienced chills and rigor during treatment, which has been attributed to cytokine release by the antiCD4 MAb (6). The latter may have led to an exacerbation of preexisting subclinical interstitial nephritis related to secondary SS. Other possible pathogenic mechanisms by which anti-CD4 MAb could induce interstitial nephritis include formation of immune complexes (7). Although it is impossible to know the exact role of anti-CD4 monoclonal antibodies in this patient’s acute renal failure, the possibility of a link, either causal or by exacerbation of a preexisting subclinical condition, cannot be excluded. When anti-CD4 MAb is used as an experimental treatment, investigators should be vigilant in monitoring possible side effects. E. H. S. Choy, MB, BCh, MRCP G. H. Kingsley, BSc (Hons), MB, MRCP G. S. Panayi, ScD, MD, FRCP United Medical and Dental Schools Guy’s Hospital London, UK 1. Horneff G, Bunnester GR, Emmrich F, Kalden JR: Treatment of 2. 3. 4. 5. 6. 7 rheumatoid arthritis with an anti-CD4 monoclonal antibody. Arthritis Rheum 34: 129-140, 1991 Reiter C, Kakavand B, Rieber EP, Schattenkirchner M, Riethmiiller G, Kruger K: Treatment of rheumatoid arthritis with monoclonal CD4 antibody M-T151: clinical results. and immunopharmacologic effects in an open study including repeated administration. Arthritis Rheum 34525-536, 1991 Ritchie DM, Boyle JA, McInnes JM, Jasani MK, Dalakos TG, Grieveson P, Buchanan WW: Clinical studies with an articular index for the assessment of joint tenderness in patients with rheumatoid arthritis. Q J Med 37:393-406, 1968 Tala1 N, Zisman E, Schur PH: Renal tubular acidosis, glomerulonephritis and immunologic factors in Sjogren’s syndrome. Arthritis Rheum 11:774-786, 1968 Tu WH, Shearn MA, Lee JC, Hopper J Jr: Interstitial nephritis in Sjogren’s syndrome. Ann Intern Med 69: 1163-1170, 1968 Horneff G, Krause A, Emmrich F, Kalden JR, Burmester GR: Elevated levels of circulating tumor necrosis factor-alpha, interferon-gamma and interleukin-2 in systemic reaction induced by anti-CM therapy in patients with rheumatoid arthritis. Cytokine 3:266-267, 1991 Williams RC Jr: Immune Complexes in Clinical and Experimental Medicine. Cambridge, Harvard University Press, 1980 The watermelon stomach in scleroderma Gastric antral vascular ectasia, or “watermelon stomach,” is a rare cause of chronic gastrointestinal bleeding, with characteristic endoscopic and histologic features. This unusual disorder has rarely been reported in association with scleroderma. The patient described here is a 46-year-old woman with a 4-year history of scleroderma. In April 1992, she was evaluated by her primary care physician and was found to be anemic (hemoglobin value 7.0 gm/dl). Esophagogastroduodenoscopy (EGD) (performed elsewhere) showed gastric ulceration, with no evidence of active bleeding. Treatment was initiated with omeprazole (Prilosec; Merck, West Point, PA), 20 mg/day, and hemotransfusion. During the subsequent 4 months, she continued to require 2 units of blood every 3 weeks. Further investigations, including colonoscopy, radiographic barium study of the upper gastrointestinal tract with small bowel follow-through, radionuclide scan for sites of bleeding, and mesenteric angiography, revealed no active gastrointestinal bleeding. At that time, she was referred to us for further evaluation. The patient was a nonsmoker, did not drink alcohol, and did not take nonsteroidal antiinflammatory drugs. Pertinent review of systems revealed only occasional melena and infrequent blood-tinged stools over the preceding 4 months. She was taking omeprazole, 20 mglday, and fluoxetine (Prozac; Dista, Indianapolis, IN), 20 mglday ,for depression.