A 66-year-old man with a 4-year history of refractory diarrhea was admitted to the Department of Gastroenterology, The Third Xiangya Hospital of Central South University, with complaints of yellow-appearing diarrhea occurring 4-6 times per day. He also reported 10-kg of weight loss over the last 8 months. He denied any abdominal pain, abdominal distention, nausea, vomiting, fever, hematochezia, or melena. The patient was initially misdiagnosed with anorexia nervosa due to poor appetite and low BMI, but later revealed his reluctance to eat was secondary to his fear of developing diarrhea after food ingestion. Due to his malnourished state, a nasogastric tube was inserted under EGD guidance for enteral nutrition.
The patient was diagnosed with non-atrophic gastritis and colonic polyps a year ago and subsequently had the colonic polyps removed by high-frequency electrocoagulation 6 months later. He denied any history of medications, including anti-hypertensives, magnesium supplements, and non-steroidal anti-inflammatory drugs (NSAIDS). There was no known history of drug or food allergies. The patient had a 25-year history of smoking tobacco but had quit 3 months prior to admission. He only occasionally drank alcohol and denied any exposure to radioactive or toxic materials.
On admission, the patient's temperature as 36.5 C, with heart rate of 65 beats per minute, and respiratory rate of 20 breaths per minute. His blood pressure was 99/67 mmHg, and oxygen saturation was 98% on room air. The patient was 41 kg, 167 cm, hence BMI of 14.7. On physical exam, cardiac and respiratory examinations were unremarkable. The abdomen was soft, non-tender on palpation, and without rebound tenderness, or masses. The liver and spleen were impalpable.
The patient's white-cell count (WBC) was 3,660 per cubic millimeter (29.7% neutrophils, 54% lymphocytes, 8.5% monocytes), hemoglobin (Hgb) was 9.8 g per deciliter (g/dl), and the platelet count was 159,000 per cubic millimeter. The alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (T. Bili), blood urea nitrogen (BUN), creatinine (Cr), serum glucose level, lipid panel, thyroid stimulating hormone (TSH), C-reactive protein (CRP), and electrolyte levels were all within normal limits. Serum CEA, AFP, CA12-5, and CA19-9 were also normal. Albumin level was slightly decreased to 3.4 g per deciliter (g/dL). Fecal elastase-1 level was 165.77 mug/g. Levels of serum gastrin 17 and fecal calprotectin were normal (Table 1). The enzyme linked immunosorbent assay (ELISA) test for IgG antibodies to 90 unique food allergens (Allerquant  90G ELISA Kit, BIOMERICA) in his serum was negative.
Meanwhile, we reviewed his test results from an outside hospital. The esophagogastroduodenoscopy (EGD) and colonoscopy a year ago showed non-atrophic gastritis and colonic polyps. Fluorine 18 fluorodeoxyglucose (FDG) PET/CT showed no abnormal FDG uptake in gastrointestinal tract, pancreas, liver, spleen, gallbladder, kidneys, adrenal glands, or bladder.
The laboratory data were consistent with mild-moderate pancreatic exocrine insufficiency, given the elastase-1 level was less than 200 mug/g. The patient was treated by oryz-aspergillus enzyme and pancreatin tablet (Combizym, Daiichi-Sankyo Europe, Munich, Germany), however, his diarrhea did not improve. On the fifth day after admission, the patient spiked a fever (Tmax 39.5 C) and reported chills. He denied cough, sputum, canker sores, pollakiuria, and dysuria. Faint bibasilar rales were noted on auscultation. The white-cell count was 6,530 per cubic millimeter (56.1% neutrophils, 34.6% lymphocytes, 6.3% monocytes) and CRP 0.99 mg/dL (normal value, < 0.5). The erythrocyte sedimentation rate (ESR) was 33 mm per hour (normal range, 0-28), the procalcitonin (PCT) level was 2.25 ng per deciliter (ng/dL), and blood cultures were obtained. The patient received empiric antibiotic treatment with piperacillin-tazobactam for possible pneumonia.
Two days later, the fever resolved. However, on the twelfth day, the patient had a fever again, with peak temperatures of 40.0 C. The white-cell count was 2,070 per cubic millimeter (59.6% neutrophils, 30.6% lymphocytes, 5.1% monocytes), the hemoglobin level 8.6 g/dL, and the platelet count 149,000 per cubic millimeter. Liver and renal function measurements remained normal except for a lower albumin level of 3.2 g/dL. Comprehensive metabolic panel (CMP) showed potassium of 4.31 mmol per liter (mmol/l), sodium of 111.4 mmol/l (normal range, 137-147), chloride of 79 mmol/l (normal range, 99-109), phosphorus of 0.46 mmol/l (normal range, 0.85-1.51), calcium 1.81 of mmol/l (normal range, 2.2-2.7), and magnesium of 0.63 mmol/l (normal range, 0.75-1.02). The anion gap was 9.7 mmol/l. The PCT level was 2.87 ng dL and CRP was 2.66 mg/dL (normal range, < 0.5). Urinalysis showed no protein, red cells, or white cells per high-power field. Fecal studies showed no fecal leukocytes, ova or parasites, and the fecal occult blood test (FOBT) were negative. A sputum culture, two sets of blood and stool cultures were negative, as were serologic tests for mycoplasma, chlamydia, varicella-zoster virus, adenovirus, coxsackie virus, influenza virus, epidemic hemorrhagic fever virus, mumps virus, respiratory syncytial virus, measles virus and echovirus. Testing for HIV and HCV antibody, HBsAg and clostridium difficile (C. diff) toxin were negative. The T-cell spot test for tuberculosis infection (T-SPOT.TB), and polymerase-chain-reaction (PCR) assays for epstein-barr virus and cytomegalovirus were all negative. 1,3-beta-D-glucan and galactomannan content detection were within normal range. High resolution computed tomography (HRCT) of the chest showed bilateral moderate pleural effusion and pneumonia. CT of abdomen with of contrast showed an enlarged liver without masses and a small amount of ascites.
The antimicrobial regimen was replaced with intravenous meropenem. Meanwhile, the patient began to receive 50% saline orally, 500 ml of hypertonic saline (4.5%) intravenously, and 10 ml of 2.16 g sodium glycerophosphate in 500 ml dextrose 5% in water intravenously. The level of blood sodium rose by 9 mmol/l on the first day, then by 3-5 mmol/l daily until it was normalized. The hypophosphatemia was also gradually resolved.
The fact of simultaneous pleural effusion, peritoneal effusion, and hepatomegaly raised the possibility of the diffuse serosal inflammation (e.g., SLE). So some tests for connective tissue diseases were done. The C3 level was 0.6 g per liter (g/L) (normal range, > 0.79), and the C4 level was 0.2 g/L (normal range, > 0.16). Test for ANA (nuclear granular type) was present at a titer of 1:320. Test for anti-SSA antibodies and anti-mitochondrial antibodies were positive. Anti-SSB antibodies, antineutrophil cytoplasmic antibodies (ANCA), rheumatoid factor, cyclic citrullinated peptide (CCP) antibodies and anti-dsDNA antibodies were not detected. The level of IgG4 was normal. After focused history taken for rheumatic and autoimmune diseases, a 9-year history of a persistent dry mouth was reported by the patient, so Schirmer's test was positive (Figure 1). Then biopsy of minor salivary glands was performed, showing focal lymphocytic sialadenitis (FLS). Focus score was 1 (Figure 2).
A presumptive diagnosis of primary Sjogren's Syndrome related fever and diarrhea was made. The patient's diarrhea resolved and fever subsided with initiation of glucocorticoids (methylprednisolone tablets orally, 12 mg/day). By the time he was discharged from our hospital, his bowels had been regular and the level of electrolytes returned to normal range. He felt well and gained 5.5 kg in weight at 1-month follow-up.