eMedicine Specialties > Gastroenterology > Intestine

Whipple Disease

Author: Ingram M Roberts, MD, MBA, Associate Clinical Professor of Medicine, University of Connecticut School of Medicine; Program Director of Internal Medicine Residency, Vice Chairman, Department of Medicine, St Vincent's Medical Center
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Updated: Aug 14, 2008

Introduction

Background

Whipple disease is a systemic disease most likely caused by a gram-positive bacterium, Tropheryma whippelii.^1,2 Although the first descriptions of the disorder described a malabsorption syndrome with small intestine involvement, the disease also affects the joints, CNS, and cardiovascular system. Because fewer than 1000 reported cases have been described, clinical experience with this disorder is sparse.

Pathophysiology

The clinical manifestations of the disease are believed to be caused by infiltration of the various body tissues by T whippelii. The patient's immune system reacts by incorporating the organisms into tissue macrophages.

These macrophages can be easily observed infiltrating the tissues using conventional light microscopy. The macrophages are easily observed when periodic acid-Schiff stain is used for the histologic sections. However, positive periodic acid-Schiff–stained macrophages infiltrating body tissues are not pathognomonic for Whipple disease. These microphages also can be detected in infection due to Mycobacterium avium intracellulare, cryptococcosis, or other parasitic organisms (usually observed in patients who are immunosuppressed with HIV disease).^3,4 Stains for fungal organisms and acid-fast bacilli are helpful in ruling out Whipple disease.

Diagnostic electron microscopy reveals coccobacillary bodies that represent the T whippelii organism. This is diagnostic because a positive polymerase chain reaction (PCR) for T whippelii will be present in the affected tissue.^5,6,7

The malabsorption observed in the small bowel that is associated with this condition is believed to be secondary to the disruption of normal villous function due to infiltration of the lamina propria of the small bowel. Patients with arthralgias have been found to have the organism in the synovial tissues.⁸ The organisms have been detected in the heart valves of patients with cardiac Whipple disease^9,10 and in the CNS of patients with neurologic disease.¹¹ Rarely, the organism can be detected in the lungs of affected patients.¹² In short, although Whipple disease represents a systemic condition, only a few organ systems of the body are affected overtly.

Frequency

International

Whipple disease is extremely rare worldwide; only several hundred clinical cases have been reported, mostly from North America and western Europe. The disease appears to be associated with the human leukocyte antigen B27 (HLA-B27) haplotype.¹³ The incidence has been estimated to be less than 1 per 1,000,000.¹⁴

Mortality/Morbidity

Untreated patients have a poor prognosis. The disease is almost universally fatal after 1 year in patients who do not receive the correct diagnosis and therapy.^15,16,17

Race

Whipple disease is most common in white males and rarely is described in females.

Sex

Whipple disease is more predominant in males than in females, roughly 8-9:1.

Age

Whipple disease is usually observed in middle-aged and elderly persons (older than 40 y).

Clinical

History

• The classic presentation of Whipple disease is that of a wasting illness characterized by arthralgias, arthritis, fever, and diarrhea.
• Lymphadenopathy may be present.
• If Whipple disease affects the small intestine, steatorrhea often is present.
• Approximately 90% of patients with Whipple disease present with weight loss, and 70% of patients with Whipple disease complain of either diarrhea or arthralgias.
• Occult GI bleeding can be found in 80% of patients of Whipple disease, but frank hematochezia is uncommon.
• Cardiac involvement occurs in approximately 30% of cases.

Physical

• Swelling of the joints may occur, but frankly deforming arthritis is quite rare.¹⁸ Sacroileitis, pancarpal narrowing, and cervical epiphyseal fusion has been described in selected patients.
• Patients with Whipple disease may have any of the physical findings associated with malabsorption. These findings are nonspecific but include the following:  
  • Cachexia
  • Distended abdomen
  • Glossitis
  • Perlèche (angular cheilitis)
  • Chvostek or Trousseau sign (secondary to hypocalcemia)
  • Gingivitis and parafollicular hemorrhages (secondary to vitamin C deficiency)
  • Night blindness (secondary to vitamin A deficiency)
  • Visible peristalsis with borborygmi
  • Hyperpigmentation around the orbital and malar areas of the face (occasionally)
• When the CNS is involved, patients may demonstrate signs of frontal release (as seen with dementia), meningoencephalitis, or ataxia and clonus (if the cerebellum is affected).¹⁹ One review noted that supranuclear ophthalmoplegia and cerebellar ataxia were two of the most common neurologic findings.²⁰

Causes

• The disease is believed to be due to a disordered host response to the bacterium T whippelii. Interestingly, patients with HIV infection do not acquire the disease.
• Of interest are data that suggest that T whippelii DNA may be found in patients who are asymptomatic.²¹ The study revealed its presence in saliva in 35% of a sample of 40 healthy patients.²² This suggests that Whipple disease is a manifestation of an abnormal host response to a microorganism that may occur frequently in humans (perhaps in a similar manner to that observed with Helicobacter pylori).
• To date, Koch's postulates have not been fulfilled completely (infection of an animal model and isolation of the organism from the animal). However, T whippelii bacteria have been grown successfully in HEL (a human fibroblast line) cells.² The production of immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies has been shown. The organism has been cultured from affected CSF and vitreous humor of patients with Whipple disease.

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