The Whipple Prodrome: A Diagnostic Challenge

Abstract

Purpose: Whipple disease is a rare infection involving multiple organ systems that causes a constellation of symptoms including weight loss, arthralgias, diarrhea, and abdominal pain. This is a case report of a patient who presented with arthralgias and weight loss, who was subsequently diagnosed with Whipple disease. History of Illness: This is a 45-year-old white male with a history of ankylosing spondylitis. He presented with 3 months of increasing arthralgias of multiple small and large joints, weight loss of 40 pounds, night sweats, and vague abdominal pain. He denied diarrhea, melena, and hematochezia. Physical exam and lab: He was a thin, otherwise healthy appearing male with normal heart and lung exam. He had mild abdominal discomfort in the epigastrium. No masses, ascites, or hepatosplenomegaly were noted. No joint deformities or neurologic deficits were noted. Chemistry, liver, and thyroid tests were normal. Hemoglobin was 8.4 with MCV of 69 and RDW of 18. Iron was 10 with saturation of 3%. CRP was 106. Diagnostic Studies: PET/CT showed mesenteric lymph nodes that were suspicious for lymphoma. EGD/Colonoscopy was performed for iron deficiency and weight loss. EGD showed nodular mucosa in duodenum. Biopsies demonstrated villous atrophy with evidence of foamy macrophages. PAS stain was positive and acid fast stain was negative, which confirmed Whipple disease. Discussion: Whipple disease is a rare systemic disorder with unknown prevalence, although data suggests it is less than 0.1%. It typically effects middle-aged white males, but can affect people of all ages. Whipple disease is caused by the gram-positive bacillus, Tropheryma whippelii. There are four cardinal manifestations that a clinician should be aware of: arthralgias, weight loss, diarrhea, and abdominal pain. Two stages of Whipple disease exist, a prodrome and steady state. The prodromal stage is marked by chronic nonspecific symptoms, arthralgias, and arthritis; and the steady state by diarrhea and weight loss. The average time between the stages is 6 years. Other less common manifestations are CNS symptoms (ophthalmoplegia, nystagmus, myclonus, dementia), cardiac disease (dyspnea, pericarditis, culture negative endocarditis), fevers, skin hyperpigmentation, and pleural effusions. Endoscopy with small bowel biopsies is the test of choice for diagnosis. Histology will show villous atrophy and foamy macrophages in the lamina propria that will stain PAS positive and acid fast negative. Initial treatment is rocephin or penicillin intravenously for two weeks, followed by a one-year course of Bactrim. For CNS and cardiac disease, initial treatment is with four weeks of intravenous therapy.