Massive Serositis as the Initial Presentation of Systemic Lupus Erythematosus : A Report of Two Cases and Review of the Literature

Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous phenotypes. Although serosal inflammation is common in SLE, massive pleural ascites and large volume pleural effusions as presenting features are unusual. Unlike most cases of lupus serositis, patients with these large effusions tend to require aggressive management with high dose steroids and steroid-sparing agents [1].


Introduction
Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous phenotypes.Although serosal inflammation is common in SLE, massive pleural ascites and large volume pleural effusions as presenting features are unusual.Unlike most cases of lupus serositis, patients with these large effusions tend to require aggressive management with high dose steroids and steroid-sparing agents [1].

Methods
Two case reports of SLE presenting as serositis with large volume effusions are described.
A literature review was performed using a Pubmed search  for all reported cases of large volume ascites or pleural effusions as the presenting features of new onset SLE.The following search terms were used: SLE/Lupus serositis, ascites, pleuritis, peritonitis, pleural effusion, peritoneal effusion.Only adult cases in the English language were reviewed.

Case Reports Case 1
A 50-year-old immigrant from Central America, was admitted with rapidly increasing ascites.Medical problems included hypertension, chronic hepatitis C with cirrhosis and portal hypertension (treated with an 8 month course of PEG-IFN one year prior to admission), and end-stage renal disease (ESRD) status post cadaveric renal transplant 10 years prior but complicated by transplant rejection and new hemodialysis requirement over the last two years.
On presentation, the patient was febrile with cervical lymphadenopathy, accompanied by massive non-tender ascites with hemodynamic compromise requiring serial large-volume paracentesis (Figure 1).The serum-ascites albumin gradient (SAAG) was < 1.1, which was inconsistent with portal hypertension ascites or possible nephrotic syndrome given the end stage renal disease.Ascitic fluid WBC counts ranged from 77-675/mm 3 with a lymphocytic predominance.Peritoneal fluid bacterial, fungal,

Abstract
Large volume effusions as a manifestation of active systemic lupus erythematous (SLE) is rare, and when it does occur, it is usually associated with complications of chronic lupus disease, such as nephrotic syndrome, constrictive pericarditis, heart failure or Budd-Chiari syndrome.Massive serositis as a presenting feature of SLE is rare.We de-scribe two adult cases of new onset SLE presenting with massive ascites in the first case, and large bilateral pleural effusions in the second case.The serositis in both patients responded well to high dose steroid therapy with signifi-cant improvement in symptoms.Only a small number of case reports describing massive ascites or large pleural effusions as initial manifestations of new onset SLE have been published.A literature review of these case reports and their treatment outcomes is described.

ISSN: 2469-5726
Geraldino-Pardilla et al.J Rheum Dis Treat 2015, 1:4 400 mg daily.This resulted in hemodynamic stability, significant improvement of the ascites, rise in complement levels and lowering anti-DNA titers.The small volume ascites that remained revealed a SAAG >1.1 which was then attributed to the known portal hypertension.

Case 2
An 80-year-old patient with history of congestive heart failure (CHF) and breast cancer in remission after a left radical mastectomy, radiation and chemotherapy presented with dyspnea.On arrival the patient required emergent mechanical ventilation for respiratory failure due to massive bilateral pleural effusions and ascites.Pleural fluid analysis was exudative with negative cultures and cytology and AFB cultures were negative and there were no malignant cells.Serum HIV, rheumatoid factor and cryoglobulins were negative.Tuberculin purified protein derivative (PPD) testing was negative as well.Hepatic or portal vascular thrombosis was ruled out with patent vessels seen on Doppler, and an echocardiogram noted preserved ventricular function.Serum ANA and anti-dsDNA antibodies were 1:2560 and 12,751 IU/mL, respectively (normal dsDNA is < 25 IU/ ml).The patient was also leukopenic (WBC-2.7/mm 3 ) and had severe hypocomplementemia (C3 = 12 mg/dL, C4 = 4 mg/dL).
A diagnosis of SLE with lupus peritonitis was made and treatment initiated with intravenous methylprednisolone 500 mg/day for a week followed by prednisone 1 mg/Kg/day and hydroxychloroquine Serologies revealed a positive serum ANA (1:320), anti-ds-DNA (119), and borderline complement levels (C3 = 89, C4 = 14).Acute renal failure subsequently developed and a renal biopsy revealed Class IV/V lupus nephritis (LN).After no response to prednisone 60 mg/day, methylprednisolone 500 mg/day for 3 days was started followed by a steroid taper, hydroxychloroquine 400 mg daily and mycophenolate mofetil titrated to 2 g/day.The renal function improved over the subsequent days and the pleural and peritoneal effusions resolved.

Discussion
Although serositis is found in 63% of SLE patients on autopsy, [2] massive ascites and large pleural effusions are uncommon in the lifetime of lupus disease, and are even more rare as the initial manifestation [2][3][4].Pleural effusions occur in up to 50% of patients with SLE, but it is the presenting feature in only 1-5% of patients, with effusions usually small to moderate in size [5].Unlike pleural involvement, the true prevalence of lupus peritonitis is unknown but presumably low, although probably overlooked despite several cases being published since Metzger's initial case report in 1974 [6].
Large effusions are usually attributed to a complication from CHF, constrictive pericarditis, nephrotic syndrome, portal hypertension, Budd-Chiari, peritoneal carcinomatosis, infectious peritonitis or pneumonia.One of these etiologies is usually cited as the cause for the 8-11% of SLE patients that develop ascites during the lifetime of their disease [7,8].It is nonetheless important to consider active SLE in the differential, as was the situation in the two cases described that had SLE-related massive ascites and/or large pleural effusions as the initial presentation of SLE.Our patients met the 1997 American College of Rheumatology classification criteria for SLE [9], given positive anti-ANA and anti-ds-DNA antibodies, serositis, as well as leukopenia in case No.1, and lupus nephritis in case No.2.For case No.1, although portal hypertension was present, the low SAAG in the absence of infection, malignancy, or acute portal thrombosis was inconsistent with portal hypertension ascites and suggested peritonitis of unknown etiology.Given the positive serum ANA and ds-DNA antibodies, low complement levels, and a significant clinical response to steroids, SLE remains the most likely diagnosis.Unfortunately, the etiology of the ESRD in this patient could not be determined since the renal biopsy had been performed many years prior in Central America.It is also debatable whether the discontinuation of the immunosuppressants, which the patient had in the past taken following the renal transplant, now unmasked the SLE, or whether the treatment with PEG-IFN, on the other hand, resulted in a drug-induced lupus-like illness.In the second case, although the patient had a history of a prior CHF episode, the echocardiogram and right heart catheterization were normal, arguing against CHF as the cause for the large effusions.
Serositis results from fluid and protein leak due to increased permeability of the microvascular circulation that occurs with inflammation of the pleural and peritoneal microvessels.The presumed vasculitis is caused by immune-complex deposition and complement activation, described since the 1970s and noted in biopsies of the pleural and peritoneal vessels [2,[10][11][12].Bitran et al. revealed granular depositions of IgG and complement along the mesothelial layer and blood vessels in SLE patients with serositis [13].In massive ascites, marked serosal exudate in conjunction with a reduced peritoneal absorptive capacity facilitate rapid fluid accumulation.

Conclusion
Since Dubois stated in 1964 that lupus serositis does not cause significant effusions [19], case reports have been published suggesting that massive lupus serositis does occur and can be the main initial manifestation of the disease.Our case reports and review of the literature emphasize how appropriate evaluation and aggressive immunosuppressive therapy is often required to assure a positive outcome in these cases.

Table 1 :
Case reports of ascites as the presenting feature of SLE.

Table 2 :
Case reports ofmassive pleural effusions as the presenting feature of SLE.Year Old; M: Male; F: Female; NR: Not Reported; Pos: Positive; DCR: Decreased Serum Complement Levels (taken from the original publication, actual serum level not reported).