Whipple's disease

Did You Know?

• Treatment with penicillin, ampicillin, tetracycline, or co-trimoxazole for one to two years is used; any treatment lasting less than a year has a relapse rate around 40%.
• Whipple referred to the disease as 'intestinal lipodystrophy' in his 1907 paper.
• In 2003, doctors from Johns Hopkins Hospital and the French microbiologist Didier Raoult applied novel diagnostic methods to stored tissue samples from Whipple's original patient and demonstrated T.

Signs and symptoms

The most common symptoms are diarrhea, abdominal pain, weight loss, and joint pains. The joint pains may be due to migratory nondeforming arthritis, which can occur many years before digestive-tract symptoms develop; they tend to involve the large joints and do not damage the joint surface to the point of deformity. Fever and chills occur in a small proportion of people. In its more advanced form, malabsorption leads to wasting and enlargement of lymph nodes in the abdomen. Neurological symptoms are more common in those with severe abdominal disease. Chronic malabsorptive diarrhea causes poor absorption of fat, resulting in steatorrhea, flatulence, and abdominal distension. Protein-losing enteropathy may occur, causing depletion of albumin and peripheral edema. Hyperpigmentation of the skin occurs in almost half of patients; some also have skin nodules. Various eye problems such as uveitis may occur, typically with deteriorating vision and pain. Endocarditis has been reported in a small number of cases, sometimes without other symptoms. Of those affected, 10–40% have problems related to brain involvement; the most common are dementia, memory loss, confusion, and decreased level of consciousness. Oculomasticatory myorhythmia is highly characteristic. Weakness, poor coordination, headaches, seizures, and other neurological features are present in some cases.

Pathogenesis

Whipple's disease shares features with infections from MAC bacteria because its cause, T. whipplei, is a distant cousin of the Mycobacterium avium complex. The illness appears more often in farmers and people regularly around soil or animals, pointing to those environments as the likely source. Those with a weakened ability to break down swallowed germs inside their cells, especially macrophages, are most at risk. A key underlying issue may be poor T-lymphocyte function, specifically in the TH1 group. Susceptible individuals also have fewer circulating cells that carry CD11b, a molecule essential for telling macrophages to kill internalized T. whipplei.

Diagnosis

Whipple's disease typically presents with diarrhea, fatty stools, abdominal pain, weight loss, joint pain that moves between joints, fever, and nervous system issues. The most common signs prompting diagnosis are weight loss and diarrhea, though these may be preceded by long-lasting, unexplained, recurring episodes of non-destructive arthritis that is seronegative, often affecting large joints. In classic intestinal cases, an endoscopy of the duodenum and jejunum may show a pale yellow, shaggy lining with red, eroded patches, while small bowel X-rays can reveal thickened folds. Other findings include enlarged mesenteric lymph nodes, an overabundance of foamy macrophages in the lamina propria, and fewer lymphocytes and plasma cells. Diagnosis is confirmed through biopsy, usually via duodenal endoscopy, which shows PAS-positive macrophages containing non acid-fast, Gram-positive bacilli. Immunohistochemical staining and polymerase chain reaction assays are also used; PCR on saliva, gastric or intestinal fluid, and stool is very sensitive but not specific, since healthy people can carry the bacterium without developing the disease.

Epidemiology

Whipple’s disease is very rare, with about one new case per million people each year. Men are affected more often than women, at a ratio between two and three to one. In the United States and elsewhere, it mostly appears in people of Caucasian background, hinting at a possible genetic link. The bacterium T. whipplei is common in the environment and often lives harmlessly in the gut. For the disease to develop, some inherited or acquired immune defect is likely needed, though this defect seems specific to this bacterium since other infections are not more common. Diagnosis typically occurs in middle age, with a median of 49 years. German studies note that the average age at diagnosis has been increasing since the 1960s.