CASE REPORT Cytomegalovirus Colitis Following Immunosuppressive Therapy for Lupus Peritonitis and Lupus Nephritis Naro OHASHI, Taisuke ISOZAKI, Kentaro SHIRAKAWA,Naoki Ikegaya, Tatsuo YAMAMOTO*and Akira HlSHIDA* Abstract agents. Here, we report a patient with CMVcolitis, which developed after immunosuppressivetherapy for severe lupus Wereport a womanwith lupus nephritis complicated nephritis and lupus peritonitis. CMVcolitis was diagnosed with lupus peritonitis and cytomegalovirus (CMV)colitis. by colonoscopy and CMVantigenemia assay, and was suc- Diagnosis of lupus peritonitis was made by abdominal cessfully treated by ganciclovir. computed tomography scan, colonoscopy, and ascitic fluid analysis. Steroid and cyclophosphamide therapy re- sulted in the improvement of severe lupus nephritis and Case Report peritonitis. Thereafter, she developed multiple colonic ul- A 30-year-old womanwas admitted to our hospital for the cers as diagnosed by colonoscopy and positive CMV fifth time because of diarrhea, abdominal pain, nausea, vom- antigenemia assay. Treatment with ganciclovir resulted iting, and hypocomplementemia on October 28,1999. She in the disappearance of colonic lesions. The low cluster of was first hospitalized in September 1996 for fever, lympha- differentiation (CD)4+ lymphocyte count (41/mm3) sug- denopathy, and hepatosplenomegaly. Although a definitive gested that the cell-mediated immunity of this patient diagnosis was not made, the symptoms subsided after treat- was comparableto that seen in patients with acquired ment with prednisolone (PSL). On her second admission in immunodeficiency syndrome (AIDS). November1996, insulin-dependent diabetes mellitus was di- (Internal Medicine 42: 362-366, 2003) agnosed; she has been treated with insulin since that time. On her third admission in November 1997, she was suffering Key words: systemic lupus erythematosus, CMVantigene- from central nervous system disturbances, nephrotic syn- mia, colonoscopy, CD4, ganciclovir, compro- drome, and joint pain; test results for antinuclear antibody mised host (ANA) and antiphospholipid antibody were positive, and SLEwas diagnosed. A renal biopsy was performed and the diagnosis of lupus nephritis (World Health Organization class Vb) was established. The patient was treated with ster- Introduction oid pulse therapy followed by oral PSL and mizoribine. This resulted in the disappearance of peripheral edema and im- Lupus peritonitis is a comparatively rare but important provement of laboratory test results. She was discharged in gastrointestinal complication of systemic lupus erythemato- May1998 on maintenance PSL (20 mg/day). However, ta- sus (SLE); it can be diagnosed by analysis of ascitic fluid pering of PSL to 15 mg/day was associated with increased (1). Treatment of lupus peritonitis usually requires strong proteinuria and worsening of hypocomplementemia.She was immunosuppressive therapy (2). Cytomegalovirus (CMV) admitted for the fourth time in January 1999. Steroid pulse infection is a frequent and sometimes life-threatening com- therapy followed by oral PSL treatment resulted in improve- plication in immune compromised patients such as those ment of serum complement levels. However, her proteinuria with acquired immunodeficiency syndrome (AIDS) (3). was unchanged. She was discharged from the hospital in Patients with lupus peritonitis are prone to develop CMV March 1999 on a PSL dose of 25 mg/day. Although PSL was disease after aggressive treatment with immunosuppressive tapered slowly, when PSL was reduced to 10 mg/day, gastro- From the Division of Nephrology, Seirei Hamamatsu General Hospital, Hamamatsu and *the First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu Received for publication December 1 1, 2000; Accepted for publication January 20, 2003 Reprint requests should be addressed to Dr. Naro Ohashi, the First Department of Medicine, Hamamatsu University School of Medicine 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3 192 362 Internal Medicine Vol. 42, No. 4 (April 2003) Lupus Nephritis/peritonitis, CMVColitis Table 1. Laboratory Findings on Admission H em ato lo gy Im m u n olo gical ex a m in ation W B C 4 , 95 0 / m m3 CRP 1. 5 mg/ dl R B C 4 8 6x l O 7 m n r I mmu ne Com ple x 6.9 ug /ml P lt 4 1.9x lO7 m m 3 Antinuclear antibody 40x Hb 14.2 g/dl A nti-D NA an tibod y <2 IU/m l H t 3 9.S Anti-Sm antibody (-) CI-Lo 13 U/ml Bl ood Ch em ist ry C3 23 mg/dl T.P. 5.2 g/dl C4 3 mg/dl Albumin 2.6 g/dl Im muno globu lin G 99 3 mg /dl T. Bil. 0.3 mg/dl Im muno globu lin A 29 5 mg /dl AS T 1 6 U /Z Im mun oglo bul in M 41 mg/ dl AL T 7 U/ Z LD H 45 1 U/Z U rin a ly sis BU N 20 mg /d l P ro tein (3+ ) Cr 1.1 mg/dl S u gar (1+ ) Na 136 mEq /l O ccult b lo od (1+ ) Figure 1. Axial computed tomography image of the K 3.3 mEq/Z Protein/day 4.52 g/day abdomen on October 30, 1999, showing marked colonic C 1 100 roE q /Z C reatin in e clearan ce 63.8 //day wall thickening and massive ascites. T. Choi. 200 mg/dl N-acetylglucosaminidase 9.5 U// T.G. 354 mg/dl B2 microglobulin 1,210 ag/l Blood sugar 101 mg/dl A computed tomography scan of the abdomen showed Hb A ,C 9. 0 % marked wall thickness of the small intestine and the entire colon (Fig. 1), and colonoscopy revealed edematous wall thickening at the same lesion. Analysis of ascitic fluid T.P.: total protein, T. Bil: total bilirubin, AST: aspartate aminotransferase, ALT: alanine aminotransferase, LDH:lac- showed the exudative ascitic fluid, that is to say, total pro- tate dehydrogenase, BUN: blood urea nitrogen, Cr: serum tein, 2.1 g/dl (ascitic fluid/serum protein ratio, 0.53) and lac- creatinine, T. Choi.: total cholesterol, T.G.: triglyceride, tate dehydrogenase (LDH), 443 U// (ascitic fluid/serum LDH HbAiC: glycosolated hemoglobin, CRP: C-reactive protein, ratio, 0.92). Low complement levels (CH50, 0 U/ml; C3, 6 CH5o: complement activity. mg/dl; C4, 2 mg/dl) and slightly elevated IC levels (3.4 jug/ml) were also seen in the ascitic fluid. Although ANA was not examined, anti-DNA antibody was slightly elevated intestinal symptoms such as diarrhea, abdominal pain, nau- for the ascitic fluid (5 IU/ml). Cytologic examination of the sea and vomiting, and hypocomplementemia progressed. She fluid showed the presence of erythrocytes (1+) and mononu- was admitted to our hospital for the fifth time in October clear leukocytes (2+) but no malignant cells; results of a bac- 1999. terial culture werenegative. Basedon the abovefindings, a On admission, blood pressure was 118/68 mmHg,pulse diagnosis of lupus peritonitis was made(1). Accordingly, the rate was 120 beats/min with a regular rhythm, and tempera- patient received steroid pulse therapy (M-PSL 500 mg/day, ture was 37. 1°C. Physical examination showed pretibial pit- drip intravenous) for 3 consecutive days followed by oral ad- ting edema. The lower abdomen was distended due to ministration of PSL 40 mg/day. However, the gastrointesti- ascites. The abdomenwas tender, but there was no rebound nal symptoms did not improve. Consequently, the dose of tenderness or muscle guarding. Anemia, jaundice, cyanosis, oral PSL was increased to 60 mg/day. Three weeks of such and skin lesions were not detected. Results of a neurologic therapy resulted in improvement of the gastrointestinal examination were negative. symptoms and a marked fall in proteinuria to 0.3 g/day. The Results of laboratory tests indicated nephrotic syndrome same dose of oral PSL was continued for 6 weeks, and then and hypocomplementemia (Table 1) with total protein of 5.2 tapered gradually to 40 mg/day over 2 weeks, based on nor- g/dl, albumin 2.6 g/dl, blood urea nitrogen 20 mg/dl, serum malization of serum complement levels (CH5o, 49 U/ml; C3, creatinine 1.1 mg/dl, and urinary protein excretion of 4.52 47 mg/dl; C4, 20 mg/dl) (Fig. 2). Continuation of PSL at 40 g/day. ANAwas 40x (homologous), but anti-DNA antibody mg/day for 1 week, however, showed a decreasing tendency was negative. Amarked decrease in complementlevels was of complement levels (CH50, 33 U/ml; C3, 33 mg/dl; C4, 12 noted (complement activity [CH50], 13 U/ml; C3, 23 mg/dl; mg/dl). Therefore, intravenous (IV) cyclophosphamide C4, 3 mg/dl). Serum immune complex (IC) levels were ele- (CPA) pulse therapy ( 500 mg/day, drip intravenous) was ad- vated (6.9 fig/ml). The blood cell count was normal with ministered (Fig. 2) (4). This treatment resulted in the com- white blood cell count, 4,950/mm3; red blood cell count, plete disappearance of subjective gastrointestinal symptoms 486xlO4/mm3, lymphocyte count, 822 /mm3 ; hematocrit, and ascites, and prevented further falls in serum complement 39.9%; and platelet count, 41.9xlO7mm3. Results of plain levels. CT scan of the abdomen showed no colonic wall chest X-ray film and electrocardiogram were normal. thickness. Internal Medicine Vol. 42, No. 4 (April 2003) 363 Ohashi et al Oct 28, 1999 July 13, 2000 admission discharge July1999 Aug Sep Oct Nov Dec Jan2000 Feb Mar Apr May Jun Jul : psl ^ y/////M&&^^V///// '6O'^^ 4»j^^^^^i20 y////j42Z6P^& M-PSL500mgX3days XX 500 750 CPA (mg) ±^ ± GCV(mg)(div) Oj HO å å ! GCV(mg)(p.o.) M W[ isnnN^^a CH50 (U/ml) \ a ^^#-#^ flV CMV Ag. Figure 2. Clinical course after the present admission. PSL: prednisolone, M-PSL: methylprednisolone, CPA: cyclophosphamide, GCV:ganciclovir, CMVAg: cytomegalovirus antigenemia. A follow-up colonoscopy, performed on January 17, 2000, showed multiple colon ulcers (Fig.