Whipple's disease characteristically occurs in middle-aged men, who present with weight loss, fever, abdominal pain, arthralgias and intestinal symptoms of diarrhea and malabsorption. Small bowel biopsy characteristically demonstrates PAS-positive macrophages and bacilliform bodies plus an enteropathy with villous atrophy (Figure 22A, B). Treatment improves the fever and joint symptoms within a few days; the diarrhea and malabsorption disappear within two to four weeks. Because some patients with Whipple's disease may develop CNS involvement with the recently identified organism, trimethoprim- sulfamethoxazole antibiotics are recommended; treatment is continued for one year. Relapses may occur up to one or two years later and require repeat therapy.