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What Is The First Signs Of Whipple’s Disease?

Whipple’s disease (WD) is a multisystemic disease of bacterial origin, Tropheryma whippelii is its causative agent.

This rare disease of which about 1000 cases have been described in the world since its description by Whipple in 1907, usually affects males (73%-95%) of the white race, with a peak of maximum incidence between 40 and 50 years.

What Is The First Signs Of Whipple’s Disease?

What Is The First Signs Of Whipple’s Disease?

The first signs of Whipple´s disease may vary depending on the patient, in most of them, the joints are affected in a first place. On the other hand, a minority of patients present gastrointestinal symptoms. Some experts have also described an unspecific clinical presentation with eating disorders, fever, cough, joints and abdominal pain.

Although the route of acquisition of Whipple’s disease is not known with certainty, there is a high index of suspicion that the main route of entry is through the digestive tract. In this sense, the lesions are located mainly in the small intestine, and more frequently at the duodenal level. However, the presence of alterations suggestive of Whipple’s disease can be found in other locations (joint fluid, cerebrospinal fluid [CSF], endocardium, etc.). A fact that reinforces the theory of acquisition through the digestive tract is the presence of bacterial DNA in water, which may explain its environmental origin and the affectation of the digestive tract. Against this hypothesis, experts find that the first signs of the disease are in the joints in 67% of patients. In addition, this condition can precede the rest of the signs of Whipple’s disease in up to ten years, while digestive manifestations are present in only 15% of patients as first symptoms.

Like many infectious diseases, the Whipple’s disease has unspecific signs and symptoms, its forms of presentation are very varied. Experts establish three stages in Whipple’s disease. The first stage is very nonspecific and presents with anorexia (eating disorder), polyarthralgia (pain in multiple joints), cough, abdominal pain, fever, etc. In a second stage, diarrhea of steatorrheic characteristics (presence of fat in stool) predominates, malabsorption with weight loss, and abdominal pain. Finally, cachexia (malnutrition, organic deterioration, and great physical weakening), neurological deterioration, lymphadenopathy (swollen lymph nodes) and cutaneous hyperpigmentation would appear.

Although fever, diarrhea, and arthralgias are often the classic triad of Whipple’s disease, the four most common symptoms of Whipple’s disease are weight loss (85% -100%), diarrhea (72%-85%), arthralgias (65%-90%) and abdominal pain (60%-72%). Other manifestations of this disease are neurological (21%-43%), cardiac (17%), lymphadenopathy (52%), hyperpigmentation of the areas exposed to sunlight (15%-47%) and respiratory, highlighting the cough, among others.

Arthralgias, which, as already mentioned, precede even in the rest of the symptoms of the disease, are usually symmetrical and migratory, with intermittent courses during which the patient may be asymptomatic. It can affect any type of joint, although the most affected are the lower limbs.

In the digestive system, the most typical manifestation is the presence of diarrhea with signs of malabsorption (72%-85%).

Other of the described alterations is the cardiovascular ones. These include pericarditis (30%-79%), endocarditis (30%-50%) and myocarditis (10%-30%). With regard to endocarditis, it occurs with negative culture, which is why whipple’s disease must be included in the list of entities to be excluded in the case of an infectious endocarditis with negative culture. Likewise, we should point out that although endocarditis due to T. whippelii appears along with gastrointestinal clinical manifestations, recently some experts have described the absence of clinical, microscopic and microbiological evidence of Whipple’s disease in the gastrointestinal tract in patients with endocarditis due to this organism. Finally, visual manifestations such as uveitis, keratitis or papilledema, and neurological manifestations, which may present with a headache, somnolence and even meningitis, have been described, although a neurological triad has been described, present in 25%-50% of patients, which consists of dementia, supranuclear ophthalmoplegia, and myoclonus.

When Should The Whipple’s Disease Be Suspected?

In addition to chronic diarrhea with malabsorption syndrome, Whipple’s disease should be taken into account in the differential diagnosis of fever of unknown origin, pericarditis, dementia, visual alterations, arthropathy, recurrent chest pain with a cough, generalized peripheral lymphadenopathy and sarcoidosis with bad evolution.


  1. American Journal of Clinical Pathology – Whipple Disease: Explore detailed information on Whipple’s disease, including clinical presentations and diagnosis. Read more

  2. National Organization for Rare Disorders (NORD) – Whipple Disease: Discover comprehensive resources on Whipple’s disease, including its symptoms and available treatments. Read more

Team PainAssist
Team PainAssist
Written, Edited or Reviewed By: Team PainAssist, Pain Assist Inc. This article does not provide medical advice. See disclaimer
Last Modified On:September 4, 2023

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