Last Resort

Testing should include urinalysis for proteinuria and coagulation studies to assess synthetic function of the liver. Abdominal ultrasound is indicated to confirm ascites. If present, a diagnostic paracentesis should be performed to rule out spontaneous bacterial peritonitis and determine whether the ascites is from portal hypertension, hypoalbuminemia, or peritoneal disease. If the transaminases are elevated or if the ascitic fluid is concerning for malignancy, he will need a computed tomography (CT) of the abdomen and pelvis. A protein losing enteropathy due to malignancies (gastric cancer or lymphoma), rheumatic disease (systemic lupus erythematosus [SLE]), or infiltrative disease (amyloid) is also a possibility. If the other studies are unrevealing, stool should be sent for alpha-1 antitrypsin.

Laboratory studies revealed hemoglobin 7.8 g/dL, platelets 53 k/mm³, white blood cell count (WBC) 10.6 k/mm³, alkaline phosphatase (ALP) 217 U/L, albumin 2.7 g/dL, reticulocyte count 3 k/mm³ (reference range, 30-110 k/mm³), and ferritin 1,310 ng/mL (reference range, 20-400 ng/L). Serum aminotransferase levels, bilirubin, coagulation panel, electrolytes, and creatinine were normal. Urinalysis was negative for blood, leukocytes, and protein. Diagnostic paracentesis demonstrated a serum-ascites-albumin gradient (SAAG) of two and macrophage predominance (WBC 250 U/L). Ascitic fluid cytology and culture were negative. Blood cultures, human immunodeficiency virus (HIV)-1 and 2, cytomegalovirus (CMV), and Epstein–Barr virus (EBV) serologies were negative. Viral serologies for hepatitis A, B, and C were negative. Antinuclear antibody (ANA), anti-ds DNA, antineutrophilic cytoplasmic antibody (ANCA), serum angiotensin-converting enzyme (ACE) level, and quantitative immunoglobulin levels were all within the normal range. Chest, abdomen, and pelvis CT with contrast revealed large-volume abdominal and pelvic ascites, diffuse subcutaneous edema (Figure 1), modest hepatosplenomegaly, small bilateral pleural effusions, and mediastinal, axillary, mesenteric, periportal, peripancreatic, and retroperitoneal lymphadenopathy (Figure 2).

Malignancy is highest on the differential. In the absence of evidence of a primary tumor, a lymphoma would be the most likely diagnosis. Multicentric Castleman disease (MCD), a rare lymphoproliferative disorder with a clinical picture similar to lymphoma, should be considered.

Some of the more common viral etiologies of generalized lymphadenopathy and cytopenias are unlikely because serologies for HIV, hepatitis B and C, EBV, and CMV are negative. Tuberculosis fits with the insidious nature of his presentation and remains on the differential although a low SAAG would be expected. From a rheumatologic standpoint, the lack of characteristic findings on history and physical examination and the negative ANA and anti-ds DNA results make SLE unlikely. Although elevated in the majority of untreated sarcoid patients, a normal ACE level is not sufficient to rule out this diagnosis. IgG, IgA, and IgM levels would be low if there was significant gastrointestinal protein loss and elevated in MCD. The markedly increased ferritin level, an acute-phase reactant often elevated in the setting of inflammation or malignancy, raises suspicion for adult Still’s disease (despite the lack of characteristic arthralgias and/or rash) and hemophagocytic lymphohistiocytosis (HLH).

A SAAG greater than or equal to 1.1 indicates the presence of portal hypertension. Portal hypertension most often results from cirrhosis for which this patient has no apparent clinical findings. Etiologies of noncirrhotic portal hypertension are classified as prehepatic, intrahepatic, and posthepatic. There is no clinical or radiologic evidence of portal or splenic vein thrombosis (prehepatic) or heart failure (posthepatic). Possible intrahepatic etiologies include malignancy and sarcoid. Although uncommon, patients with malignancy-related ascites may have a high SAAG without coexisting cirrhosis. This occurs if there is portal hypertension due to extensive metastases in the liver or involvement of the portal venous system. The cytology of the ascitic fluid is negative. However, cytology is <80% sensitive in the absence of peritoneal carcinomatosis.