Snapshot A 60-year-old Caucasian man presents to the emergency room with his family for fever and recent onset of dementia. His MMSE score was 20 at his last appointment with his primary care provider. His past medical history includes chronic diarrhea of unknown origin and nonspecific arthritis. On physical exam, he has multiple hyperpigmented macules on his skin, as well as a new murmur. His physician is suspicious of endocarditis. Introduction Malabsorption syndrome with multi-organ involvement Caused by infection with Tropheryma whipplei gram-positive bacillus non acid-fast Actinomyces spp. family found in soil Epidemiology More commonly in older patients (40s-50s) Caucasian male > female Risk factors previous exposure to soil or animals immunodeficiency potentially predisposes to active disease (vs carrier state) Presentation Symptoms CAN (though may not present all at once) plus diarrhea Cardiac symptoms endocarditis myocarditis pericarditis Arthralgias (very common and early in disease) Neurologic symptoms dementia seizures encephalitis 20% of patients with pathognomonic signs oculomasticatory myorhythmia oculo-facial-skeletal myorhythmia weight loss emaciation chronic diarrhea oligo-arthritis Physical exam fever mesenteric lymphadenopathy gray-brown pigmentation of skin malabsorption of vitamin D → hyperPTH → increased melanocyte stimulating hormone Evaluation Endoscopic small bowel biopsy – most accurate test periodic acid-Schiff (PAS)-positive foamy macrophages intestinal lamina propria Stool PCR may reflect carrier state – not definitive CSF typically normal but should be performed Differential Diagnosis Celiac disease Crohn disease Lyme disease (arthralgias) Treatment Whipple without cardiac involvement ceftriaxone or penicillin G for 2 weeks followed by TMP-SMX for one year Whipple with endocarditis ceftriaxone or PCN G for 4 weeks followed by TMP-SMX for one year Complications Jarisch-Herxheimer reaction to antibiotics fevers rigors hypotension Immune reconstitution inflammatory syndrome (IRIS) – up to 10% high fever mimics worsening disease but is actually a result of successful therapy Prognosis Persistence after treatment common 30-50% rate of relapse Fatal if antibiotics not given