Successful treatment of massive ascites due to lupus peritonitis with hydroxychloroquine in old- onset lupus erythematosus

Systemic lupus erythematous (SLE) is an auto-immune disease with multiple organ involvements that occurs mainly in young women. Literature data suggest that serositis is more frequent in late-onset SLE. However, peritoneal serositis with massive ascites is an extremely rare manifestation. We report a case of old-onset lupus peritonitis treated successfully by Hydroxychloroquine. A 77-year-old Tunisian woman was hospitalized because of massive painful ascites. Her family history did not include any autoimmune disease. She was explored 4 years prior to admission for exudative pleuritis of the right lung without any established diagnosis. Physical examination showed only massive ascites. Laboratory investigations showed leucopenia: 3100/mm3, lymphopenia: 840/mm3 and trace protein (0.03g/24h). Ascitic fluid contained 170 cells mm3 (67% lymphocytes), 46 g/L protein, but no malignant cells. The main etiologies of exudative ascites were excluded. She had markedly elevated anti-nuclear antibody (ANA) titer of 1/1600 and a significantly elevated titer of antibody to double-stranded DNA (83 IU/mL) with hypo-complementemia (C3 levl was at 67 mg/dL). Antibody against the Smith antigen was also positive. Relying on these findings, the patient was diagnosed with SLE and treated with Hydroxychloroquine 200 mg daily in combination with diuretics. One month later, there was no detectable ascitic fluid and no pleural effusions. Five months later she remained free from symptoms while continuing to take chloroquine. This case was characterized by old age of onset of SLE, the extremely rare initial presentation with lupus peritonitis and massive painful ascites with dramatic response to only hydroxychloroquine treatment.


Introduction
Systemic lupus erythematous (SLE) is an auto-immune disease with multiple organ involvements that occurs mainly in young women.
However, the elderly onset of SLE is rarely reported. This later age at onset has a strong modifying effect on the clinical presentation [1]. For instance, literature data suggest that pulmonary involvement and serositis are more frequent in late-onset SLE [2].
However, peritoneal serositis with massive ascites (known as lupus peritonitis) is an extremely rare manifestation [3]. Here, we report a 77-year-old woman with SLE whose disease manifested first as massive ascites treated successfully with Hydroxychloroquine.

Patient and observation
A 77-year-old Tunisian woman was hospitalized because of massive painful ascites. Her family history did not include any autoimmune disease. She denied a history of hepatitis, jaundice or alcohol use.
She had a history of diabetes, hypertension treated by glinide and calcium blocker. She was explored 4 years prior to admission for exudative pleuritis of the right lung without any established diagnosis after multiple explorations including thoracoscopy with biopsies. On admission, blood pressure was 150/70 mmHg, her rate was 80 /mn and body temperature was 37°C.

Discussion
Systemic lupus erythematosus is an autoimmune disorder characterized by involvement of various organs. Inflammation of serous membranes including pericardium, pleura is relatively common (12 %) and was admitted by American College of Rheumatology as one of the 11 criteria of SLE [4]. The incidences of pleuritis and pericarditis were reported to be higher in the elderly patients with SLE compared to younger patients [1]. Ascites may present with or without pain, and may be due to lupus peritonitis. In post mortem study, peritoneal involvement has been found in tow thirds of patients [5]. While, peritoneal serositis with ascites in clinical practice is extremely rare [6]. Diagnosing lupus peritonitis as initial symptoms of SLE remains a challenging task. Lupus peritonitis may have similar symptoms as those of acute abdominal conditions such as acute cholecystitis, acute pancreatitis, bleeding peptic ulcer, intestinal obstruction, peritonitis or rapid onset of massive ascites. It Page number not for citation purposes 3 can also manifest in a chronic way as long lasting painless ascites, chronic pancreatitis or mild abdominal pain [7].
The mechanism of ascites in SLE may be multifactorial. nephritic syndrome, protein losing enteropathy, malnutrition and congestive heart failure [9]. Peritonel histology showed chronic inflammation and small vasculitis, the degree of inflammation in the peritoneum may be different between acute and chronic lupus [10].
In the case reported here, the patient had a massive painful ascites of acute-onset in a case of elderly onset lupus erythematosus. Her initial SLE manifestation may be pleuritis 4 years before. In this age, the presenting manifestations in these patients are commonly atypical and the diagnosis in this age group is usually tardy [1]. A literature search with Pubmed revealed only three elderly cases with lupus peritonitis were reported previously [8,10,11] Table 1.
Proteinuria was seen in two patients, pleuretis was noted in all cases that presented chest X-ray including the present case.
Pericarditis was fond in two cases. Steroid administration was performed in all patients. Two patients died despite treatment with high dose of prednisolone, Recently, Ito et al reported only three death from 16 cases reported, two from three death are elderly aged more than 70 years. They suggest that lupus peritonitis at elderly onset shows a poor prognosis than in the younger patients [10]. Some data showed a greater disease activity score and greater damage in late-onset patients, this hypothesis was supported by a higher mean of SLEDAI score and greater mortality [12]. More recently in updated pooled analysis data in the literature, Chen et al reported that old-onset SLE presented less skin and renal damages as well as autoantibodies, but lung damage was more severe [13].
The cause of death in elderly SLE patient may be multifactorial: Comorbidities concomitant therapies, infections, cardiovascular disorders and malignancies. In our case, the activity of SLE was low, SLEDAI was 7. The patient had a history of diabetes mellitus and her blood glucose still fluctuated. Considering her age and serious comorbidities, we initiate hydroxychloroquine, the massive ascites responded dramatically to this therapy. In old-onset SLE, the use of antimalarial agents such as hydroxychloroquine is an important aspect of SLE treatment when skin changes and arthritis are manifested, unless contraindicated. Willis et al confirmed in multiethnic multi-center cohort that Hydroxychloroquine therapy resulted in significant clinical improvement in SLE patients with reductions in IFN-a levels [14], Other treatments mostly include corticosteroids and immunosuppressive agents, depending on which organs are involved. Ito and associates in a recent review of chronic lupus peritonitis, reported that all patients treated by steroids, but only 13/16 reached remissions, In 40 % additional immunosuppressant agents were associated to manage incomplete remission and recurrence ascites [10]. In our knowledge this the first case treated only by using hydroxychloroquine and diuretics.
This suggests that inflammation of the peritoneum may be mild in the elderly.

Conclusion
This case we report is one of four cases at the onset age of SLE over 60 years, which presented with lupus peritonitis as initial symptom with a dramatic response with hydroxychloroquine.
Systemic lupus erythematous rarely presents with massive ascites.
Other causes of ascites should be excluded. Treatment is based on the use of diuretics, high dose of steroids, and in non-responding cases immunosuppressive drugs. Antimalarial agents might be effective in severe ascites if no acute life-threatening organ damage exists.