What is Whipple disease?
Whipple disease is a very rare infectious disease that affects many organ systems of the body. Less than a thousand cases have been reported worldwide and it has an annual incidence of less than one in a million. The disease is named after George Hoyt Whipple who described the first case in 1907.1
The cause of Whipple disease is the bacterium Trophyrema whipplei (T. whipplei). T. whipplei is widespread; it has been detected in soil, sewage water and faecal material. It is not known what source or role this bacteria plays in the environment.
In some studies, up to 35% of unaffected healthy individuals carry T. whipplei in their intestines. Individuals who are at higher risk of harbouring T. whipplei are sewage plant workers, farmers and agricultural workers.
Not all infected individuals have symptoms. The symptoms of Whipple disease are related to the immune system and its interaction with the bacterium. Many studies have shown that these individuals have defects in their immune system allowing T. whipplei to disseminate widely throughout the body and cause disease. 2
What are the symptoms and signs of Whipple disease?
The four classic signs of Whipple disease are:
- Arthralgia (joint pain)
- Weight loss
- Diarrhoea – due to malabsorption (inability to absorb nutrients through the gastrointestinal tract)
- Abdominal pain
However, Whipple disease can affect any organ system and has a broad spectrum of symptoms.3
|Clinical features of Whipple disease|
|Central Nervous System||
Whipple disease and the skin
Skin signs in Whipple disease are very rare. They may be due to malnutrition or to an immune reaction to the infection. 4
Malnutrition-related skin signs are due to malabsorption and diarrhoea.
- Hyperpigmentation – due to pellagra or niacin (vitamin B3) deficiency, B12 deficiency or low cortisol levels
- Petechia or purpura – due to vitamin C or vitamin K deficiency
- Secondary palmoplantar keratoderma or ichthyosis – due to cholesterol deficiency
- Oedema – due to loss of protein from the gastrointestinal tract
Inflammatory mediated skin signs are due to the immune response towards T. whipplei. They may resemble:
The skin conditions associated with Whipple disease are treated in the same way as similar skin conditions arising for other reasons. Erythema nodosum has been treated with oral prednisone with variable success.4-6
Antibiotics targeted against T. whipplei are very important and the skin lesions may settle once the bacteria has been destroyed.
The nonspecific symptoms and signs of Whipple disease together with its rarity, makes it a very difficult disease to diagnose.
Tissue biopsy is often necessary. The following tests may detect T. whipplei within the tissue:
- Polymerase chain reaction (PCR) – picks up tiny amounts of bacteria
- Periodic-Acid Schiff (PAS) – stains the bacteria pink
- Electron microscopy (EM) – high magnification reveals the bacteria
- Immunohistochemisty staining – specific antibodies stain T. whipplei.
Before the use of antibiotics, Whipple disease was invariably fatal.
Infected individuals often need high doses of antibiotics in case the brain is infected by T. whipplei. An induction regime with intravenous ceftriaxone 2g once daily is given for two weeks.
Antibiotics should be continued for up to one year to ensure complete clearance of T. whipplei. Co-trimoxazole is often used, at a dose of 960mg twice daily.