Whipple's disease


Whipple disease is a rare bacterial infection that most often affects your joints and digestive system. Whipple disease interferes with normal digestion by impairing the breakdown of foods, and hampering your body's ability to absorb nutrients, such as fats and carbohydrates.

Whipple disease can also infect other organs, including your brain, heart and eyes.

Without proper treatment, Whipple disease can be serious or fatal. However, a course of antibiotics can treat Whipple disease.

Small intestine lining and villi


Common signs and symptoms

Digestive signs and symptoms are common in Whipple disease and may include:

  • Diarrhea
  • Stomach cramping and pain, which may worsen after meals
  • Weight loss, associated with the malabsorption of nutrients

Other frequent signs and symptoms associated with Whipple disease include:

  • Inflamed joints, particularly the ankles, knees and wrists
  • Fatigue
  • Weakness
  • Anemia

Less common signs and symptoms

In some cases, signs and symptoms of Whipple disease may include:

  • Fever
  • Cough
  • Enlarged lymph nodes
  • Skin darkening in areas exposed to the sun and in scars
  • Chest pain

Brain and nervous system (neurological) signs and symptoms may include:

  • Difficulty walking
  • Vision problems, including lack of control of eye movements
  • Confusion
  • Memory loss

Symptoms tend to develop slowly over many years in most people with this disease. In some people, symptoms such as joint pain and weight loss develop years before the digestive symptoms that lead to diagnosis.

When to see a doctor

Whipple disease is potentially life-threatening yet usually treatable. Contact your doctor if you experience unusual signs or symptoms, such as unexplained weight loss or joint pain. Your doctor can perform tests to determine the cause of your symptoms.

Even after the infection is diagnosed and you're receiving treatment, let your doctor know if your symptoms don't improve. Sometimes antibiotic therapy isn't effective because the bacteria are resistant to the particular drug you're taking. The disease can recur, so it's important to watch for symptoms that reappear.


Whipple disease is caused by a type of bacterium called Tropheryma whipplei. The bacteria affect the mucosal lining of your small intestine first, forming small sores (lesions) within the wall of the intestine. The bacteria also damage the fine, hairlike projections (villi) that line the small intestine.

Not much is known about the bacteria. Although they seem readily present in the environment, scientists don't know where they come from or how they're spread to humans. Not everyone who carries the bacteria develops the disease. Some researchers believe that people with the disease may have a genetic defect in their immune system response that makes them more likely to become sick when exposed to the bacteria.

Whipple disease is extremely uncommon, affecting fewer than 1 in 1 million people.

Risk factors

Because so little is known about the bacteria that cause Whipple disease, risk factors for the disease haven't been clearly identified. Based on available reports, it appears more likely to affect:

  • Men ages 40 to 60
  • White people in North America and Europe
  • Farmers and other people who work outdoors and have frequent contact with sewage and wastewater


The lining of your small intestine has fine, hairlike projections (villi) that help your body absorb nutrients. Whipple disease damages the villi, impairing nutrient absorption. Nutritional deficiencies are common in people with Whipple disease and can lead to fatigue, weakness, weight loss and joint pain.

Whipple disease is a progressive and potentially fatal disease. Although the infection is rare, associated deaths continue to be reported. This is due in large part to late diagnoses and delayed treatment. Death often is caused by the spread of the infection to the central nervous system, which can cause irreversible damage.


The process of diagnosing Whipple disease typically includes the following tests:

  • Physical exam. Your doctor generally begins with a physical exam. He or she will look for signs and symptoms that suggest the presence of this condition. For example, your doctor may look for stomach tenderness and skin darkening, particularly on sun-exposed parts of your body.
  • Biopsy. An important step in diagnosing Whipple disease is taking a tissue sample (biopsy), usually from the lining of the small intestine. To do this, your doctor typically performs an upper endoscopy. The procedure uses a thin, flexible tube (scope) with a light and a camera attached that passes through your mouth, throat, windpipe and stomach to your small intestine. The scope allows your doctor to view your digestive passages and take tissue samples.

    During the procedure, doctors remove tissue samples from several sites in the small intestine. A doctor examines this tissue under a microscope in a lab. He or she looks for the presence of disease-causing bacteria and their sores (lesions), and specifically for Tropheryma whipplei bacteria. If these tissue samples don't confirm the diagnosis, your doctor might take a tissue sample from an enlarged lymph node or perform other tests.

    In some cases, your doctor may ask you to swallow a capsule that holds a small camera. The camera can take images of your digestive passages for your doctor to view.

    A DNA-based test known as polymerase chain reaction, which is available at some medical centers, can detect Tropheryma whipplei bacteria in biopsy specimens or spinal fluid samples.

  • Blood tests. Your doctor may also order blood tests, such as a complete blood count. Blood tests can detect certain conditions associated with Whipple disease, particularly anemia, which is a decline in the number of red blood cells, and low concentrations of albumin, a protein in your blood.


Treatment of Whipple disease is with antibiotics, either alone or in combination, which can destroy the bacteria causing the infection.

Treatment is long-term, generally lasting a year or two, with the aim of destroying the bacteria. But symptom relief generally comes much quicker, often within the first week or two. Most people with no brain or nervous system complications recover completely after a full course of antibiotics.

When choosing antibiotics, doctors often select those that wipe out infections in the small intestine and also cross a layer of tissue around your brain (the blood-brain barrier). This is done to eliminate bacteria that may have entered your brain and central nervous system.

Because of the lengthy use of antibiotics, your doctor will need to monitor your condition for development of resistance to the drugs. If you relapse during treatment, your doctor may change your antibiotics.

Treatment for standard cases

In most cases, Whipple disease therapy begins with two to four weeks of ceftriaxone or penicillin given through a vein in your arm. Following that initial therapy, you'll likely take an oral course of sulfamethoxazole-trimethoprim (Bactrim, Septra) for one to two years.

Possible side effects of ceftriaxone and sulfamethoxazole-trimethoprim include allergic reactions, mild diarrhea, or nausea and vomiting.

Other medications that have been suggested as an alternative in some cases include oral doxycycline (Vibramycin, Doryx, others) combined with the antimalarial drug hydroxychloroquine (Plaquenil), which you'll likely need to take for one to two years.

Possible side effects of doxycycline include loss of appetite, nausea, vomiting and sensitivity to sunlight. Hydroxychloroquine may cause loss of appetite, diarrhea, headache, stomach cramps and dizziness.

Symptom relief

Your symptoms should improve within one to two weeks of starting antibiotic treatment and go away entirely within about one month.

But even though symptoms improve quickly, further lab tests may reveal the presence of the bacteria for two or more years after you begin taking antibiotics. Follow-up testing will help your doctor determine when you can stop taking antibiotics. Regular monitoring can also detect development of resistance to a particular drug, often indicated by a lack of improvement in symptoms.

Even after successful treatment, Whipple disease can recur. Doctors usually advise regular checkups. If you've experienced a recurrence, you'll need to repeat antibiotic therapy.

Taking supplements

Because of the nutrient-absorption difficulties associated with Whipple disease, your doctor may recommend taking vitamin and mineral supplements to ensure adequate nutrition. Your body may require additional vitamin D, folic acid, calcium, iron and magnesium.

Preparing for your appointment

If you have signs and symptoms common to Whipple disease, make an appointment with your doctor. Whipple disease is rare, and the signs and symptoms can indicate other, more common disorders, so it can be hard to diagnose. As a result, it's often diagnosed in its later stages. However, an early diagnosis reduces the risk of serious health effects associated with not treating the condition.

If your doctor is uncertain about the diagnosis, he or she may refer you to a doctor who specializes in digestive diseases or to another specialist depending on the symptoms you're having.

Here's some information to help you get ready for your appointment, and know what to expect from your doctor.

Information to gather in advance

  • Write down your symptoms, including when you first noticed them and how they may have changed or worsened over time.
  • Write down your key medical information, including other conditions with which you've been diagnosed and the names of all medications, vitamins and supplements you're taking.
  • Write down key personal information, including any recent changes or stressors in your life. These factors can be connected to digestive signs and symptoms.
  • Take a family member or friend along, if possible. Someone who accompanies you may remember something that you missed or forgot.
  • Write down questions to ask your doctor. Creating your list of questions in advance can help you make the most of your time with your doctor.

For signs and symptoms common to Whipple disease, some basic questions to ask your doctor include:

  • What is the most likely cause of my condition?
  • Are there any other possible causes for my condition?
  • What diagnostic tests do I need?
  • What treatment approach do you recommend?
  • I have other medical conditions. How do I manage them together?
  • How soon do you expect my symptoms to improve with treatment?
  • For how long will I need to take medications?
  • Am I at risk of complications from this condition?
  • Am I at risk of a recurrence?
  • How often will you need to see me for monitoring?
  • Do I need to change my diet?
  • Should I take any nutritional supplements?
  • Are there any lifestyle changes I can make to help reduce or manage my symptoms?

Don't hesitate to ask any other questions you have.

What to expect from your doctor

A doctor who sees you for possible Whipple disease is likely to ask a number of questions, such as:

  • What are your symptoms, and when did you notice them?
  • Have your symptoms gotten worse over time?
  • Are your symptoms typically worse after a meal?
  • Have you lost weight without trying?
  • Do your joints hurt?
  • Do you feel weak or fatigued?
  • Do you have difficulty breathing or a cough?
  • Have you developed confusion or memory problems?
  • Have you noticed problems with your eyes or vision?
  • Has anyone close to you had similar signs or symptoms recently?
  • Have you been diagnosed with any other medical conditions, including food allergies?
  • Do you have any family history of bowel disorders or colon cancer?
  • What medications do you take, including prescription and over-the-counter medications, vitamins, herbs, and supplements?
  • Are you allergic to any medications?

Content From Mayo Clinic Updated: 11/07/2022
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