Whipple disease: symptoms, diagnosis and treatment of this rare bacterial infection

Whipple disease is a chronic, relapsing multisystem disease first described in 1907 by the American pathologist George Hoyt Whipple, according to Patient.info's professional reference, which is written by UK doctors. The cause was only identified in 1992 as infection with the bacterium Tropheryma whipplei, probably acquired as an enteric infection, since the organism is commonly found in sewage effluent and soil and is presumed to be ubiquitous.

Most people who are infected clear the bacterium or become symptom-free carriers, and only a small group go on to develop Whipple disease. It is thought that a defect in cellular immune response may predispose certain individuals. NHS hospital laboratory pages describe it as a rare condition mainly affecting middle-aged white men, in which the small intestine cannot pass nutrients into the rest of the body.

The reference says it is more common in middle-aged and older people (mean age at diagnosis 55 years), in men, in white people, and in sewage plant workers, farmers and agricultural workers. It is not related to the Whipple operation on the pancreas, which is named after a different person.

The reference says Whipple disease may cause many different problems because several organs can be involved. Joint pain that comes and goes is often the earliest symptom, sometimes for years before gut symptoms. NHS laboratory information describes classic disease as associated with intermittent joint pain or chronic digestive disorder with diarrhoea and weight loss, with endocarditis, neurological symptoms and chronic localised infections such as lymph node, eye, lung and joint infections as other common manifestations.

• Episodic joint pains (polyarthralgia), often affecting several joints.

• Abdominal pain, diarrhoea, weight loss, bloating and fatty stools from malabsorption.

• Intermittent low-grade fever and chronic cough.

• Darkening of the skin (hyperpigmentation), reported in about half of cases.

• Enlarged lymph nodes and anaemia.

• Heart involvement, such as pericarditis, myocarditis or valve problems.

• Nervous system involvement in about 10%, including headache, confusion, memory loss, eye movement problems and gait problems.

• Eye inflammation (uveitis).

See a GP for unexplained weight loss, persistent diarrhoea or other digestive symptoms, and for joint pain that keeps returning without explanation. Because Whipple disease is so rare, these symptoms are far more likely to be caused by something else, such as coeliac disease or inflammatory bowel disease, but they deserve a proper assessment.

Seek urgent help for new confusion, severe headache, difficulty walking, chest pain, severe breathlessness or collapse. These are not specific to Whipple disease, but each needs prompt medical assessment through NHS 111, 999 or A&E as appropriate.

Patient.info's reference says routine blood and malabsorption tests are non-specific and that imaging will confirm involvement of different organs but is not diagnostic. Biopsy of affected tissue, usually the duodenum, shows infiltration with periodic acid-Schiff (PAS)-positive macrophages containing clumps of the bacterium. Extra staining is recommended because other bacteria, such as Mycobacterium avium, also stain PAS-positive. Polymerase chain reaction (PCR) testing for bacterial genetic material is increasingly used and can be done on blood, cerebrospinal fluid and other tissue samples.

NHS hospital laboratories describe a Whipple's PCR test that is often sent to a reference laboratory, with EDTA whole blood or cerebrospinal fluid as the usual samples and turnaround times of around 5 days. The reference lists the conditions that need to be distinguished, including coeliac disease, sarcoidosis, reactive arthritis, Behçet's disease, intestinal lymphoma, inflammatory bowel disease and tuberculosis.

The reference says antibiotics are the main treatment, that expert microbiological advice will be needed, and that prolonged treatment for 1 to 2 years is usually advised, with a repeat PCR at the end of treatment. Symptoms of the joints and gut may improve very rapidly with treatment, but histological and microbiological remission can take several years. The disease progresses insidiously and is fatal if untreated, so completing the course matters even once you feel well.

The reference advises close follow-up for signs of recurrence, as relapse occurs in about 40%. The US National Organization for Rare Disorders likewise says the disease can be cured with antibiotics, that various types and combinations have been used, that relapses may occur during or after therapy so treatment may be extended up to a year or longer, and that a change of regimen may be needed if symptoms reappear. The choice of regimen is a matter for infectious disease or gastroenterology specialists and may differ between centres.

Treatment is long, and side effects of antibiotics, nutritional deficiencies from malabsorption and anxiety about relapse can all be part of the experience. A dietitian may help to restore weight and correct deficiencies, and your specialist team will arrange blood tests and PCR monitoring.

Keep appointments through the full course, tell the team about any return of joint pain, diarrhoea, fever, cough or neurological symptoms, and ask what to do if you are unwell between visits. Because the condition is so rare, many people find it useful to ask their team about patient information from rare-disease organisations.

On the NHS, Whipple disease is managed by gastroenterologists with microbiology or infectious disease colleagues, and PCR testing is done through reference laboratories. A private consultation could speed access to endoscopy and biopsy, but the specialised laboratory testing and prolonged antibiotic supervision still require links with NHS microbiology. Ask any provider how they would arrange long-term follow-up and monitoring.