Background: Whipple disease (WD) is an exceedingly rare disease. Despite its rarity, there has been a longstanding allure with this disease. The classic form manifests with arthralgia, weight loss, abdominal pain, and diarrhea. However, the infection may involve other organs causing a great diversity of symptoms. Case Presentation: We report a case of a patient presenting to the emergency room with weight loss, abdominal pain and diarrhea. Duodenal biopsies revealed periodic acid Schiff-positive macrophages and Tropheryma whipplei was detected on a cervical lymph node. Diagnosis of WD was established. The patient also had multifocal secondary amyloidosis. We started the patient on a standardized antibiotic regimen for 1 year. Clinical improvement was seen early during the treatment. Conclusion: This case is an example of the protean nature of WD. To the authors’ knowledge, this is the first case report on WD with multifocal secondary amyloidosis affecting several digestive organs.

Keywords: Whipple disease, Tropheryma whipplei, PAS-positive macrophages, secondary amyloidosis, case report