Differentials
Seronegative rheumatoid arthritis
SIGNS / SYMPTOMS
Articular pain in Whipple's disease resembles rheumatoid arthritis. Isolated articular symptoms in patients with Whipple's disease cannot be distinguished clinically from seronegative rheumatoid arthritis.
INVESTIGATIONS
Synovial membrane samples of patients with seronegative rheumatoid arthritis show inflammatory indices, which include thickening of the lining cell layer and a dense infiltrate of mononuclear cells. However, histology of duodenal or synovial biopsies of patients with seronegative rheumatoid arthritis does not show periodic acid-Schiff (PAS)-positive cells.
Sarcoidosis
SIGNS / SYMPTOMS
Lymphadenopathy of Whipple's disease resembles sarcoidosis.
However, in contrast to patients with Whipple's disease, most people with sarcoidosis have lung involvement. Common lung symptoms are dry coughing; trouble breathing or pain with breathing; wheezing; chest pain, tightness, or discomfort; and, only rarely, haemoptysis.
INVESTIGATIONS
Histology of lymph node specimens of patients with sarcoidosis shows non-caseating granulomas, with only mild necrosis and no PAS-positive cells.
Coeliac disease
SIGNS / SYMPTOMS
GI symptoms of coeliac disease and Whipple's disease are similar.
However, the intestinal symptoms of coeliac disease are ameliorated with a gluten-free diet. Coeliac disease is often accompanied by the skin disorder dermatitis herpetiformis (Duhring's disease).
INVESTIGATIONS
Positive serology for antitransglutaminase antibodies has a high sensitivity and specificity.
Small-bowel biopsies show increased intraepithelial lymphocytes (Marsh's classification), flattening and blunting of villi, crypt hyperplasia, and lymphocyte infiltration, but no PAS-positive macrophages.
Tropical sprue
SIGNS / SYMPTOMS
GI symptoms of tropical sprue and Whipple's disease are clinically indistinguishable.
INVESTIGATIONS
Histology of duodenum reveals flattened villi, inflammation of the lining, and inflammatory cell infiltrates but no PAS-positive macrophages.
Mycobacterium avium-intracellulare enteropathy
SIGNS / SYMPTOMS
GI symptoms of M avium-intracellulare (MAI) enteropathy and Whipple's disease are similar. However, MAI infection usually first presents as a persistent cough and almost exclusively affects patients with AIDS or who are otherwise severely immunosuppressed.
INVESTIGATIONS
Duodenal biopsies from M avium-positive duodenal biopsies are also PAS-positive but, contrary to Whipple's disease specimens, they also stain positive with Ziehl-Neelsen.
Crohn's disease with reactive arthritis
SIGNS / SYMPTOMS
GI symptoms of Crohn’s disease and Whipple's disease cannot be distinguished clinically, and reactive arthritis resembles joint involvement of Whipple's disease.
INVESTIGATIONS
Gut biopsies show signs of inflammation but no PAS-positive macrophages.
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