Aging Begins at 30

A Rare Disease (Whipple's) With Lessons To Be Learned

Ian Maclean Smith, M.D.
Emeritus Professor
Department of Internal Medicine
University of Iowa Hospitals and Clinics
Creation Date: February 2003
Last Revision Date: February 2003
Peer Review Status: Internally Peer Reviewed

Originally Whipple's disease was a rare disease of middle-aged white men (eight times more than in women) with nutrient malabsorption, weight loss, fatty stool diarrhea, abdominal pain, intermittent arthritis, anemia, enlarged lymph glands and sometimes skin pigmentation. There was a progressive downhill course. It is now being diagnosed earlier. Its frequency remains uncertain but is still uncommon. There is malabsorption of fats (a lipodystrophy) and of nutrients that need fat for absorption, including vitamin K.

First an incurable disease of the intestine, it is now known to be a treatable generalized infection. The long-suspected causative bacterium has been isolated and is called Tropheryma whipplei. (Nourishment barrier in Greek.) It is a gram-positive branching bacterium. It was grown (1999) in human cells and calf serum in 18 days instead of hours with most other bacteria. This has led to new strategies for diagnosis, treatment and epidemiology. Possibly the infection is associated with a subtle defective immune response. Levels of immune globulin M and interleukin 12 (a chemical messenger) are low.

Electron microscopy and polymerase chain reaction are being used to understand the body and community distribution of the disease. Its source is still a mystery but it has been found in sewage and human saliva, dental plaque and feces. It can sometimes be isolated from people without Whipple's disease.

An extensive literature search by Marth and Raoult from Wiesbaden and Marseille is in the Lancet of January 18th 2003. About 55% of known cases are in Central European white people and 38% in North Americans. Many are farmers or outdoor workers. Cases can occur in a family. A quarter has the same tissue marker, HLA B27.

Arthritis may be present for ten years and weight loss (up to 20% of the previous weight) for 4 years before diagnosis. Rarely the disease shows without intestinal problems perhaps as an endocarditis or memory disorder or dementia so many specialty doctors must be alert to Whipple's disease.

Feathery threadlike intestinal absorptive villi change to club-shaped poorly functional absorpters. The lymphatics or lacteals blocked with fat deposits are seen on electron microscopy on small bowel endoscopic biopsies. The diagnosis is now by specific organismal serum antibody. The T. whipplei genome sequence has just been published (Lancet Feb. 22nd 2003.)

Untreated the disease can be fatal. The treatment is based on known relapse rates after a year's treatment. Trimethoprimsulfamethoxazole has a 4%, and penicillin-streptomycin a 12% relapse rate. Other treatments relapsed more often. Malnourished patients need folate, vitamin B 12, vitamin K, iron and other supplements. With brain-related signs the treatment must pass into the brain. Patients with a good response are followed by repeat serological tests or biopsies.

The reviewers summarize future perspectives. The reservoir should be identified, risk factors and environmental exacerbaters controlled, milder cases identified, immunological host factors better understood, organism identified more easily, antibiotic sensitivity tests developed, and better PCR methods developed. Dr. Whipple would be proud.

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See related Patient Topics Digestive Diseases--General, Digestive System, Genetics/Birth Defects, Infections, Infectious Diseases--General, Rare Diseases or Symptoms and Manifestations.

See related Provider Topics Digestive Diseases--General, Digestive System, Genetics/Birth Defects, Infections, Infectious Diseases--General or Symptoms and Manifestations.

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