Whipple disease

Whipple disease is a very rare multisystem infectious disease caused by the bacterium Tropheryma whipplei. It primarily affects middle-aged White men, with a peak age of diagnosis at 48–54 years. The clinical presentation is highly variable, but Whipple disease is nonetheless considered to have a classic prodromal phase of migrating polyarthralgias, fever, and fatigue. Patients develop gastrointestinal manifestations, such as abdominal pain, chronic diarrhea, malabsorption, and significant weight loss several years after disease onset. Important extraintestinal symptoms include neurological symptoms, cardiac symptoms, and lymphadenopathy. Diagnosis is confirmed with polymerase chain reaction (PCR) and histopathology testing of duodenal biopsies, which shows characteristic PAS-positive foamy macrophages in the lamina propria. Treatment requires a prolonged course of antibiotics, typically starting with intravenous ceftriaxone followed by a year of oral trimethoprim/sulfamethoxazole. Whipple disease can be fatal if left untreated, and late relapses can occur even after therapy.

• Very rare ^[1]
• Peak age at diagnosis: 48–54 years ^[1]
• ♂ > ♀
• Primarily affects White individuals

Epidemiological data refers to the US, unless otherwise specified.

• Prodromal phase ^[1]
  • Migrating polyarthralgias and polyarthritis
  • Back pain ^[2]
  • Fever
  • Fatigue ^[2]
• Gastrointestinal manifestations (most common symptoms) ^[1]
  • Typically occur 6–8 years after initial infection
  • Abdominal pain, chronic diarrhea, steatorrhea
  • Clinical features of malabsorption, weight loss, cachexia
  • Clinical features of anemia ^[2]
• Extraintestinal manifestations ^[1]
  • Neurological symptoms (e.g., myoclonus, ataxia, impairment of oculomotor function)
  • Cardiac symptoms (e.g., pericardial rub, murmur, clinical features of endocarditis) ^[1][2]
  • Lymphadenopathy
  • Hyperpigmentation affecting sun-exposed areas
  • Polyserositis

The typical patient with Whipple disease is a middle-aged White man presenting with arthralgia, weight loss, and diarrhea. ^[1]

Anyone who CANT appreciate the foamy, PAStoral rivers of England gets Whipped: the most important features of Whipple disease are Cardiac symptoms, Arthralgias, Neurologic symptoms, Trots (diarrhea), and foamy, PAS-positive macrophages on biopsy.

Consult infectious diseases and gastroenterology if Whipple disease is suspected or confirmed.

• Initial test: quantitative PCR ^[1]
  • Stool
  • Saliva and/or blood
• If initial PCR is positive: EGD with duodenal biopsies ^[1]
  • Endoscopic appearance: pale yellow mucosa, dilated villi, ectatic lymph vessels
  • Histopathology: PAS-positive foamy macrophages in the lamina propria
  • Immunohistochemistry: T. whipplei antigens in tissue
  • Diagnostic confirmation: PCR on biopsy samples
• Obtain PCR of CSF in all patients with confirmed Whipple disease to rule out CNS involvement, regardless of CNS symptoms. ^[1]
• Obtain biopsies with diagnostic testing of other affected sites (e.g., lymph nodes, heart valves, skin, other body fluids) if localized disease is suspected. ^[3]
• Imaging may show enlarged mesenteric nodes.

• Treatment requires a prolonged course of antibiotics to eradicate the infection and prevent relapse.
• Standard antibiotic regimen
  • Initial phase: ceftriaxone (off-label) or meropenem (off-label) for 2 weeks ^[4]
  • Maintenance phase: trimethoprim/sulfamethoxazole (off-label) for 12 months ^[4]
• Alternative antibiotic regimen: doxycycline and hydroxychloroquine for 12 months
• Monitor for immune reconstitution inflammatory syndrome.
• Follow-up duodenal biopsies at 6-month intervals are recommended, with therapy continued until biopsies are negative.
• Patients should have lifelong monitoring because late relapses are common.

Whipple disease can be fatal if left untreated. ^[1]

• Untreated Whipple disease can be fatal.
• Late relapses are common.
• Prognosis is poor in patients with symptomatic CNS involvement: 25% experience major sequelae, and the 4-year survival rate is < 75%. ^[1]