Whipple's disease

Whipple's Disease: A Bacterial Infection That Hides for Years

Whipple's disease is an extremely rare infection, affecting approximately 1 in a million people annually. It is caused by a bacterium called Tropheryma whipplei. This bacterium is ubiquitous in our environment, and many of us carry it without falling ill. However, in a small minority, likely due to a minor flaw in the immune system, it establishes itself in the gut and slowly spreads to joints, the brain, heart, and skin.

The disease was first described in 1907 by pathologist George Whipple, but the bacterium was only identified in the 1990s. Until then, diagnosis could only be made post-mortem.

What Are the Symptoms?

Whipple's disease develops insidiously, often over several years. The classic presentation has four elements, but they rarely appear simultaneously:

• Weight loss and chronic diarrhoea. The diarrhoea is typically fatty, pale, and foul-smelling because nutrients are not absorbed in the small intestine.
• Migratory joint pain. Swelling in one knee for a few days, then an elbow, then an ankle. This can mimic arthritis and often appears many years before gastrointestinal symptoms.
• Abdominal pain and bloating.
• Fatigue and pallor due to anaemia.

When the disease has been present for a long time, it can affect:

• The brain: memory problems, confusion, unusual eye movements, dementia-like symptoms.
• The heart: inflammation of the heart valves.
• The skin: dark patches, particularly on the face.
• Lymph nodes: enlarged nodes in the neck or abdominal cavity.

Men are affected four to five times more often than women, and the diagnosis is most commonly made between 40 and 60 years of age.

What Happens in the Gut?

The bacterium lives inside the white blood cells (macrophages) in the lining of the small intestine. It doesn't kill them but fills them so much that they accumulate and block the delicate architecture of finger-like projections (villi) that normally absorb nutrients from the gut. As a result, fats, vitamins, proteins, and sugars are not properly absorbed. This explains the weight loss, diarrhoea, and pallor associated with anaemia.

How Is the Diagnosis Made?

The only definitive way to diagnose Whipple's disease is by taking tissue samples from the small intestine during a gastroscopy. Under the microscope, the characteristic swollen macrophages are seen, which stain red with a special stain called PAS. These "PAS-positive macrophages" are the diagnostic hallmark.

The diagnosis is confirmed with a PCR test, which detects the bacterium's DNA in the tissue. PCR is also used on cerebrospinal fluid if the doctor suspects brain involvement, which has implications for the duration of treatment.

Treatment

Whipple's disease was fatal before antibiotics became available. Today, it can be treated, but the treatment is long and demanding:

1. Intravenous antibiotics for two weeks (typically ceftriaxone).
2. Oral antibiotics for a year or more, most often sulfamethoxazole-trimethoprim (Bactrim).

If the brain is affected, medications that can cross the blood-brain barrier are chosen, and treatment may extend even longer.

Treatment is effective for most, and diarrhoea and weight loss often subside within a few weeks. However, the disease can recur, even after many years of remission, and patients require lifelong follow-up with control biopsies and PCR.

When Should You Consider Whipple's Disease?

Naturally, one should not fear Whipple's disease with every bout of diarrhoea. However, the combination of migratory joint pain over years + unexplained weight loss and chronic diarrhoea should prompt any doctor to consider the possibility, especially in a man aged 40-60. Many patients have been diagnosed with arthritis or IBS for years before the correct diagnosis was finally made.

Frequently Asked Questions

Is Whipple's disease contagious? The bacterium is found in many places in nature, and most people have been exposed to it without becoming ill. It does not spread directly from person to person in the way we typically understand contagious diseases.

Can I make a full recovery? Yes, the vast majority become symptom-free with treatment. However, the disease can recur, so lifelong follow-up is necessary.

Why does it take so long to get a diagnosis? Because the disease is extremely rare and its symptoms resemble many other conditions. Many only have a biopsy checked for Whipple's once more common diagnoses have been ruled out.

Should my relatives also be tested? No. The risk of other family members developing the disease is not significantly higher than in the general population.

Sources

1. Marth T, Moos V, Müller C, Biagi F, Schneider T. Tropheryma whipplei infection and Whipple's disease. Lancet Infect Dis. 2016;16(3):e13-22. PubMed
2. Schneider T, Moos V, Loddenkemper C, et al. Whipple's disease: new aspects of pathogenesis and treatment. Lancet Infect Dis. 2008;8(3):179-90. PubMed
3. Sundhed.dk. Whipple's disease (doctor's handbook).
4. Lagier JC, Fenollar F, Lepidi H, Giorgi R, Million M, Raoult D. Treatment of classic Whipple's disease: from in vitro results to clinical outcome. J Antimicrob Chemother. 2014;69(1):219-27. PubMed

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This article provides general information and does not replace a medical consultation. Please contact your own doctor if you experience symptoms.