Since most, if not all, patients with Whipple's disease have central nervous system infection, but only some develop clinical or radiologic evidence of the disease and that PCR analysis of the cerebrospinal fluid can be added to the diagnostic evaluation to detect those with cerebral Whipple's disease. Currently, PCR has an undefined role in monitoring disease activity with treatment. For many years Whipple's disease was considered a fatal primary metabolic disorder. Antibiotics now are the mainstay of treatment, often providing dramatic life-saving improvement of symptoms. Antibiotic regimens include penicillin with or without streptomycin, erythromycin, ampicillin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole.
Relapses are common and can occur months or even years after initial treatment.
Many of the relapses occur in the central nervous system, and thus, antibiotics should have adequate blood-brain barrier penetration. Because of the rarity of the disease, controlled and prospective evaluations of different treatment regimens will probably never be possible. Recommendations are based on case reports, retrospective reviews, and antibiotic characteristics. Treatment with trimethoprim-sulfamethoxazole for 6 to 12 months is recommended both for initial therapy and for relapses of the disease. Other antibiotic regimens reported may be associated with a higher relapse rate and are considered to be second-line agents.