Arab Journal of Gastroenterology xxx (2014) xxx–xxx

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Case Report

Refractory ascites as the first presentation of systemic lupus erythematosus Abdulrahman M. Aljebreen ⇑, Sultan A. Al-Mogairen Gastroenterology Division and Rheumatology Division, Department of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia

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Article history: Received 7 November 2013 24 January 2014 Accepted 5 January 2014 Available online xxxx Keywords: Ascites Protein-losing enteropathy SLE

a b s t r a c t Serositis (peritonitis, pleuritis, and pericarditis) can be observed in approximately 13% of patients with systemic lupus erythematosus (SLE). However, peritoneal serositis presenting as painless massive ascites is extremely rare with only few cases been reported. Indeed, ascites in SLE has been reported to occur only when complicated by nephrotic syndrome, congestive cardiac failure, or portal hypertension. We describe herein a very unique case of SLE related serositis presenting with a massive refractory ascites, normal albumin, and absence of a clear autoimmune disorder or protein-losing enteropathy (PLE) at the time of her presentation, which only responded to a pulse course of corticosteroid. SLE was confirmed 2 years later. Ó 2014 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.

Introduction Serositis (peritonitis, pleuritis, and pericarditis) can be observed in approximately13% of patients with systemic lupus erythematosus (SLE) [1]. However, peritoneal serositis presenting as painless massive ascites is extremely rare with only few cases been reported [2–16]. Indeed, ascites in SLE has been said to occur only when complicated by nephrotic syndrome, congestive cardiac failure, or portal hypertension. We describe a patient who developed massive painless refractory ascites secondary to an autoimmune related serositis, who responded only to a pulse course of corticosteroid. Case report A 41-year old Saudi woman who was known to have hypothyroidism and is on replacement therapy presented to our clinic on December 2005, with 3 months history of increasing abdominal girth and mild abdominal discomfort. She denied any other gastrointestinal symptoms. She had 3 years history of Raynaud’s phenomenon of her fingers and had history of two abortions. She had no cardiac or respiratory symptoms. On physical examination, she looked well with no stigmata of chronic liver disease. She was normal on cardiac and respiratory examination. Abdominal examination revealed only massive ascites. Initial laboratory results showed normal CBC, bilirubin, albumin, liver enzymes, coagulation profile, thyroid function tests, urine analysis and kidney function tests. Abdominal ultrasound showed massive ascites with no evi⇑ Corresponding author. Address: P.O. Box 2925, Internal Medicine Department, King Khalid University Hospital, Riyadh 11461, Saudi Arabia. Tel.: +966 1 467 1215; fax: +966 1 467 1217. E-mail address: [email protected] (A.M. Aljebreen).

dence of portal vein thrombosis. Ascitic fluid showed low serum albumin ascitic gradient (SAAG) on 2 occasions (9 and 10 respectively) with 20 white blood cells (all lymphocytes), negative acid fast bacilli smear (AFB) and mycobacterium tuberculosis (TB) culture. Tests for Hepatitis B surface Antigen (HbsAg), hepatitis C virus antibody, antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA), anti-double stranded DNA antibody and anti-mitochondrial antibody (AMA) were all negative. Doppler ultrasound and magnetic resonance angiography (MRA) of abdomen showed no evidence of hepatic, portal vein or inferior vena cava thrombosis. An echocardiogram showed normal left ventricular function with no evidence of pericardial effusion. CT abdomen showed massive ascites and nodular omentum. Her tuberculin skin testing (PPD) was 15 mm. Given the low SAAG and the positive PPD skin test, she underwent laparoscopy which merely revealed nodular omentum. Multiple omental biopsies were taken and were all normal including TB culture. She underwent liver biopsy, which was normal. She was followed for 1 year on diuretics requiring frequent therapeutic ascitic tap (every 14 days). Eighteen months later to her first symptoms, she started to complain of frequent loose bowel motions, arthralgia and significant weight loss. She had normal gastroscopy with normal duodenal biopsy and normal colonoscopy with multiple colonic biopsies. Repeated CT abdomen showed the same findings, however, she had low albumin and elevated PTT for the first time of her presentation. Her mixing study showed weak lupus inhibitor and her anticardiolipin (ACA) was 97. Again, her ANA, ASMA, anti-DsDNA, anitsmith, antigliadin, antiendomisial antibodies and antisjögren A and antisjögren B were all negative. Follow up liver enzymes showed significant elevation of alkaline phosphatase and gamma glutamyl transferase (GGT) (1372 and 230, respectively) and her bone densimetry scan of the lumbar spine showed mild osteoporosis ( 2.7), which were all suggestive of osteomalacia secondary to intestinal mal-absorption. Her Tech-

1687-1979/$ - see front matter Ó 2014 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ajg.2014.01.001

Please cite this article in press as: Aljebreen AM, Al-Mogairen SA. Refractory ascites as the first presentation of systemic lupus erythematosus. Arab J Gastroenterol (2014), http://dx.doi.org/10.1016/j.ajg.2014.01.001

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A.M. Aljebreen, S.A. Al-Mogairen / Arab Journal of Gastroenterology xxx (2014) xxx–xxx

netium-99m albumin scintigraphy revealed clear extensive loss of albumin from blood to the lumen of the large bowel, which suggests protein-losing enteropathy (PLE). Given all of the above, an autoimmune serositis with PLE was suspected at this time and she was started on steroid pulse therapy. Ten days later, her bowel motions normalized and her arthralgia resolved. She did not require ascitic paracentesis for the first time in 18 months. She was discharged on 60 mg of prednisone and 50 mg of azathioprine. Eight months later she was off cortisone, on 100 mg of azathioprine with no evidence of ascites on ultrasound. On early 2008, she came to the clinic with massive ascites and hepatosplenomegally. She had severe normochromic, normocytic anemia with elevated creatinine. She underwent a renal biopsy, which showed grade 4-lupus nephritis. She started pulse steroid and intravenous cyclophosphamide which was later shifted to oral cyclophosphamide. She responded very well with the absence of ascites and normalization of creatinine and haemoglobin. She is currently leading normal life on immunosuppressive therapy. Discussion Ascites occurs in 8–11% of patients with SLE, usually associated with nephrotic syndrome, protein-losing enteropathy, constrictive pericarditis, congestive heart failure, or Budd–Chiari syndrome [17–19]. Cirrhosis, pancreatitis, peritoneal carcinomatosis, and tuberculous peritonitis should also be excluded. Abdominal pain in patients with active lupus is often attributed to serositis; yet, patients with histologically documented serositis have minimal ascites [19]. Chronic lupus peritonitis has been reported as causing massive ascites [3–7,9–16,18]. In these patients, SLE was usually diagnosed years earlier, and disease activity did not correlate with the course of ascites. Ascitic fluid characteristics included white blood cell counts ranging from 10/mm3 to 1630/mm3 (mean 393/ mm with predominantly lymphocytes) and a SAAG < 1.1. Several patients had detectable anti-DNA antibodies and lupus erythematosus (LE) cells in the ascitic fluid [11]. Our patient presented with massive refractory painless low SAAG ascites with no signs of portal hypertension or nephrotic syndrome or any evidence of autoimmune related disease. Other causes of ascites like malignancy and hypothyroidism were ruled out. Tuberculous peritonitis must be ruled out in a high endemic area with strongly positive PPD skin test and low SAAG ascites. Tuberculous peritonitis was ruled out in our patient by having negative peritoneal fluid TB culture and normal peritoneal biopsy. Other possibilities like Budd–Chiari syndrome, constrictive pericarditis and veno-occlusive diseases were ruled out by normal imaging, liver histopathology and normal hepatic venous pressure gradient. Other possibility was esoniophilic ascites, which was ruled out by the absence of eosinophils in the ascetic fluid and normal histology of duodenal, peritoneal and omental biopsies. The previous history of Raynaud’s phenomenon and the development of PLE with hypoalbuminemia and the dramatic response to the pulse steroids suggest a diagnosis of autoimmune related chronic serositis with presumptive diagnosis of SLE which was confirmed 1 year later by renal biopsy. Chronic autoimmune related ascites with the absence of nephropathy or PLE is extremely rare with only few cases been reported mainly secondary to a flare up of SLE. Our case is the only case, which presented as painless refractory massive ascites with normal albumin, no SLE features or clear PLE and absence of antinuclear antibodies and anti-dsDNA, which dramatically responds to steroid. All of other reported cases had underlying SLE with or without a flare up. Another interesting point in our patient’s medical course, is the late development of the PLE which was confirmed by the positive

Tc-99 m albumin scintigraphy. Recently, Zheng et al. reported an analysis of 15 PLE cases in SLE patients [20]. The mean age of PLE onset was 40.1 years, 12 were females, 53.3% of patients had PLE as the initial presentation of SLE and 11 had ascites with only 6 patients presented with abdominal pain and diarrhea. Positive antinuclear antibodies were found in all patients, but the antidsDNA antibody was negative in most cases. All patients had marked hypoalbuminemia and most cases had good response to corticosteroid and immunosuppressive therapies [21]. In conclusion, this is a unique case of SLE related serositis presenting with a massive refractory ascites, normal albumin, and absence of a clear autoimmune disorder or PLE at the time of presentation which was only confirmed to have SLE 2 years after her first presentation. Autoimmune disorders should always be considered in the differential diagnosis of new onset ascites once the typical causes have been excluded.

Conflicts of interest The authors declared that there was no conflict of interest. References [1] Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, et al. Morbidity and mortality in systemic lupus erythematosus during a 5-year period. A multicenter prospective study of 1000 patients. European Working Party on Systemic Lupus Erythematosus Medicine (Baltimore) 1999;78(3):167–75. [2] Bitran J, McShane D, Ellman MH. Arthritis rounds: ascites as the major manifestation of systemic lupus erythematosus. Arthritis Rheumatol J 1976;19(4):782–5. [3] Jones PE, Rawcliffe P, White N, Segal AW. Painless ascites in systemic lupus erythematosus. Br Med J 1977;1(6075):1513. [4] Schocket AL, Lain D, Kohler PF, Steigerwald J. Immune complex vasculitis as a cause of ascites and pleural effusions in systemic lupus erythematosus. J Rheumatol 1978;5(1):33–8. [5] Okamoto T, Okano Y, Kawagoe M, Hara M. Two cases of ascites due to lupus peritonitis. Ryumachi 1981;21(Suppl):189–94. [6] Miller MH, Urowitz MB, Gladman DD, Tozman EC. Chronic adhesive lupus serositis as a complication of systemic lupus erythematosus. Refractory chest pain and small-bowel obstruction. Arch Intern Med 1984;144(9):1863–4. [7] Ferreiro JE, Reiter WM, Saldana MJ. Systemic lupus erythematosus presenting as chronic serositis with no demonstrable antinuclear antibodies. Am J Med 1984;76(6):1100–5. [8] Mier A, Weir W. Ascites in systemic lupus erythematosus. Ann Rheum Dis 1985;44(11):778–9. [9] Wilkins Jr KW, Hoffman GS. Massive ascites in systemic lupus erythematosus. J Rheumatol 1985;12(3):571–4. [10] Averbuch M, Levo Y. Longstanding intractable ascites as the initial and predominant manifestation of systemic lupus erythematosus. J Rheumatol 1986;13(2):442–3. [11] Schousboe JT, Koch AE, Chang RW. Chronic lupus peritonitis with ascites: review of the literature with a case report. Semin Arthritis Rheum 1988;18(2):121–6. [12] Ishiguro N, Tomino Y, Fujito K, Nakayama S, Koide H. A case of massive ascites due to lupus peritonitis with a dramatic response to steroid pulse therapy. Jpn J Med 1989;28(5):608–11. [13] Kaklamanis P, Vayopoulos G, Stamatelos G, Dadinas G, Tsokos GC. Chronic lupus peritonitis with ascites. Ann Rheum Dis 1991;50(3):176–7. [14] Provenzano G, Rinaldi F, Le Moli S, Pagliaro L. Chronic lupus peritonitis responsive to treatment with cyclophosphamide. Br J Rheumatol 1993;32(12):1116. [15] Corbella X, Mitjavila F, Campoy E, Saez A, Moga I, Vidaller A. Chronic ascites in late onset systemic lupus erythematosus with antiphospholipid antibodies. J Rheumatol 1994;21(6):1141–3. [16] Ito H, Nanamiya W, Kuroda N, Inoue M, Sasaoka A, Chijiwa T, et al. Chronic lupus peritonitis with massive ascites at elderly onset: case report and review of the literature. Intern Med 2002;41(11):1056–61. [17] Mills JA. Systemic lupus erythematosus. N Engl J Med 1994;330(26):1871–9. [18] Weinstein PJ, Noyer CM. Rapid onset of massive ascites as the initial presentation of systemic lupus erythematosus. Am J Gastroenterol 2000;95(1):302–3. [19] Pollak VE, Grove WJ, Kark RM, Muehrcke RC, Pirani CL, Steck IE. Systemic lupus erythematosus simulating acute surgical condition of the abdomen. N Engl J Med 1958;259(6):258–66. [20] Zheng WJ, Tian XP, Li L, Jing HL, Li F, Zeng XF, et al. Protein-losing enteropathy in systemic lupus erythematosus: analysis of the clinical features of fifteen patients. J Clin Rheumatol 2007;13(6):313–6.

Please cite this article in press as: Aljebreen AM, Al-Mogairen SA. Refractory ascites as the first presentation of systemic lupus erythematosus. Arab J Gastroenterol (2014), http://dx.doi.org/10.1016/j.ajg.2014.01.001