A 4-year-old male patient was admitted with chronic diarrhea and abdominal distention for the last 8 months. His anthropometric measurements revealed severe chronic malnutrition (height for age was below 80%) without edema. On physical examination, the patient had abdominal distension and mild hepatomegaly. He was anemic (hemoglobin 10.9 g/dL), and had elevated liver function tests (LFT) (aspartate aminotransferase 83 U/L, alanine aminotransferase 71 U/L, gamma-glutamyl transferase 128 U/L, alkaline phosphatase 390 U/L) and hypoalbuminemia (2.7 g/dL). The viral serology for hepatotropic viruses and specific autoantibodies for autoimmune hepatitis were all negative, serum alpha-1 antitrypsin as well as serum ceruloplasmin level was within normal limits. Proteinuria and gastrointestinal loss of protein were excluded as the etiology of hypoalbuminemia. The sedimentation rate was 7 mm/h. Stool microbiologic examinations for viral, bacterial, fungal, and parasite infections were all negative. Ultrasonography demonstrated hepatomegaly and a conglomerate of mesenteric lymph nodes, measuring maximum 16 mm in diameter.
The patient underwent an upper gastrointestinal endoscopy and colonoscopy. Every part of the gastrointestinal tract, including the terminal ileum was normal. However, non-caseating granulomas were detected both in the mucosa and submucosa of the upper gastrointestinal and colonic (including ileal) biopsy samples (Fig. 1, 2). Histopathologic examination of the biopsies was not consistent with Crohn's disease (CD), but suggestive of sarcoidosis or chronic granulomatous disease (CGD). Thus, the patient was further investigated for primary immunodeficiencies. Serum immunoglobulins (Ig), IgG subclasses, and tests for neutrophil superoxide production (nitroblue tetrazolium assay - NBT) and the dihydrorodamine oxidation test (DHR) were within normal limits. Although the biopsies were not consistent with CD, anti-saccharomyces cerevisiae antibodies were tested in the patient, which were negative. The presence of uveitis or other ophthalmologic pathologies were also investigated, and this was also normal.
An indeterminate quantiferon test in this patient, coexisting with conglomerated abdominal lymph nodes, entailed a detailed examination for tuberculosis. A normal high-resolution computed tomography of the lungs and a negative gastric juice culture for acid-fast bacillus excluded mycobacterium tuberculosis infection.
Thereafter, a liver biopsy was performed, which revealed granulomas including foreign body giant cells without central necrosis in portal regions, and mild sinusoidal fibrosis in periportal spaces (Fig. 3). Granulomatous inflammation of both the gastrointestinal system and liver along with elevated serum angiotensin-converting enzyme (ACE) levels (117 U/L, N<52 U/L) were consistent with sarcoidosis. The patient was treated with 2 mg/kg/day methylprednisolone. His chronic diarrhea improved, and serum ACE levels decreased to normal (18.8 U/L) by the end of the first month of therapy. The dosage of corticosteroid was gradually reduced to 4 mg/day and the patient has been on follow-up for a year with normal LFTs and regression of hepatomegaly. Written informed consent was obtained from the patient.