A 28-year-old male was admitted to our hospital with a-two-month history of diarrhea, abdominal pain, weight loss, fever, and fatigue. His medical history revealed 3 to 5 episodes of diarrhea each year and recurrent respiratory tract infections since the age of 14 years old. He had been succesfully treated for postprimary cavitary pulmonary tuberculosis (acid-fast bacteria in smears of sputum and sputum culture positive for Mycobacterium tuberculosis in Lowenstein media) and had been given isoniazid (300 mg/day), rifampicine (600 mg/day), ethambutol (1.5 g/day) and pyrazinamide (2 g/day) for 2 months, followed by isoniazid and rifampicine for 10 more months, until 2 months prior to his hospitalization. His condition rapidly deteriorated with the above mentioned symptoms apparent 2 months after cessation of antituberculosis therapy.
Physical examination revealed a severely malnourished male with a temperature of 39C; blood pressure 100/60 mmHg; and a heart rate of 96/min. Abdominal examination revealed increased bowel sounds and slight abdominal tenderness. Laboratory studies disclosed: hemoglobin, 14.3 g/dL; WBC, 15,600/microL; platelets, 308,000/microL; ESR, 60 mm/h; CRP, 41.4 mg/dL (normal 0-5); total protein, 5.1 g/dL; and albumin, 2.7 g/dL. Other biochemical data was normal. Urinalysis revealed 4+ proteinuria with oval fat bodies in the sediment. Creatinine clearance was 93 mL/min and proteinuria was 9 g/d. Serum immunoglobulins were as follows: IgG, 168 mg/dL (normal 800- 1700); IgM, 8.95 mg/dL (normal 50-320); IgA, 10.2 mg/dL (normal 85-450); and, IgE, 28.7 IU/mL (normal 0-100). C3 complement was 54.3 mg/dL (normal 50-90). Anti-gliadine IgA and IgG were both negative. CD4/CD8 ratio, CD3, CD56 were normal and tuberculin skin test was positive (17 mm induration). Neutrophil function tests (chemotaxis, phagocytosis, oxidative burst) were within normal limits. Chest X-ray and ECG were normal.
Cultures of blood and urine were negative. Numerous erythrocytes and leucocytes were seen in the stool specimen, but stool cultures for Salmonella, Shigella and Campylobacter were negative. Toxin A was negative in the stool. Serologies for HIV, HBV, HCV were negative. Anti-HSV, anti-EBV and anti-CMV IgM's were also negative.
Thoracic CT revealed old fibrotic scars in the upper lobes of both lungs, suggesting healed tuberculosis. Abdominopelvic CT was normal. On radiologic examination of the small bowel, there was dilatation and increased mucosal thickness of valvula conniventes. Gastroduodenoscopy was normal; multiple biopsies were obtained and duodenal aspiration was performed. Rectosigmoidoscopy was nondiagnostic. Histologic examination of esophageal, duodenal, colon (Fig. 1) and gastric (Fig. 2) biopsies revealed extensive, subepithelial, Congo red positive amyloid deposition. Disappearance of these after adding KMnO4 suggested AA amyloidosis, also confirmed by immunohistochemical staining. In addition, the four currently identified mutations of MEVF gene on exon 10, associated with familial Mediterranean fever (FMF) -which are M694V, M694I, M680I, V726A,- were negative.
Ciprofloxacine (200 mg, bid, i.v.) and metronidazole (500 mg, bid, i.v.) were commenced. The patient's clinical condition started to improve within a few days and returned to normal at 3 weeks. The antibiotics were then discontinued and the patient was discharged. Two weeks later, diarrhea with 3-4 bowel movements/day developed, and repeated diagnostic tests revealed no specific cause. Metronidazole was recommended for 3 further months during which the patient's diarrhea disappeared and he put on 18 kg but hypogammaglobulinemia and nephrotic-range proteinuria persisted. Later, colchicine 1.5 mg/day was administered to hopefully control proteinuria.
At the end of the third year of follow-up; the patient was still using colchicine and also metronidazole (500 mg, bid, p.o.) for one week every month or in the case of > 3 mushy stools/day lasting > 3 days. The control gastroscopy and rectosigmoidoscopy were normal: biopsies showed AA amyloid infiltration. Although the patient had hypogammaglobulinemia, his condition did not worsen except for recurrent upper respiratory tract infections, a recent acute attack of chronic otitis media, and chronic recurrent diarrhea. The patient's creatinine clearance was normal, but the proteinuria was still in the nephrotic range.