Whipple’s disease

Introduction

Whipple’s disease is a rare, chronic, systemic infection caused by the gram-positive intracellular bacterium Tropheryma whipplei. It most commonly affects the gastrointestinal (GI) system but can also involve the joints, central nervous system (CNS), cardiovascular system, lymphatic system, and skin. It is a potentially fatal condition if left untreated, but long-term antibiotic therapy can lead to a good prognosis.

Peak Incidence

• Most common in males over the age of 40.

Pathophysiology

• Tropheryma whipplei infects macrophages, leading to accumulation of PAS-positive foamy macrophages in the lamina propria of the small intestine.
• This disrupts nutrient absorption, resulting in malabsorption and systemic symptoms.
• The infection can disseminate via the lymphatic and blood systems to other organs, including the CNS and heart.

Symptoms

Gastrointestinal

• Chronic diarrhoea.
• Steatorrhoea (fatty stools).
• Abdominal pain.
• Weight loss.

Extraintestinal

• Fever.
• Lymphadenopathy.
• Articular:
  • Migratory arthralgia.
  • Enteropathic arthritis.
• Cardiac:
  • Valvular insufficiencies, which may lead to heart failure.
  • Pericarditis (less common).
• Neurological (less common but serious):
  • Ataxia (loss of coordination).
  • Myoclonus (involuntary muscle jerking).
  • Seizures.
  • Dementia or cognitive decline.
  • Ocular symptoms such as ophthalmoplegia or impaired oculomotor function.

Signs

Gastrointestinal

• Cachexia.
• Abdominal tenderness.
• Abdominal distension (due to inflammation and malabsorption).

Musculoskeletal

• Joint tenderness.
• Visible signs of arthritis.

Dermatological

• Hyperpigmentation, especially in sun-exposed areas.

Lymphatic

• Generalised lymphadenopathy.

Neurological (if involved)

• Ataxia.
• Myoclonus.
• Ophthalmoplegia.
• Cognitive changes or confusion.

Diagnosis

Definitive Testing

• Small bowel (jejunal) biopsy:
  • Reveals PAS-positive foamy macrophages in the lamina propria.
  • May also show villous atrophy and crypt hyperplasia.

Blood Tests

• FBC – Normocytic, normochromic anaemia.
• Urea and electrolytes (U&Es):
  • Hypokalaemia due to diarrhoea.
  • Elevated urea:creatinine ratio suggesting dehydration.
• Albumin – Often low due to malabsorption (hypoalbuminaemia).

Additional Tests

• Polymerase Chain Reaction (PCR):
  • Detects Tropheryma whipplei DNA in tissue or blood samples.
• If neurological symptoms are present:
  • Lumbar puncture – CSF analysis to assess CNS involvement.
  • MRI brain – May show white matter changes, cerebral atrophy, or enhancing lesions.

Complications

• Severe malnutrition due to prolonged malabsorption.
• Electrolyte disturbances.
• Heart failure due to valvular involvement.
• Progressive neurological deterioration – seizures, dementia, or ataxia.
• Relapse if inadequately treated.

Management

Antibiotic Therapy

• Induction phase:
  • Intravenous penicillin (or ceftriaxone) for 2 weeks.
• Maintenance phase:
  • Oral co-trimoxazole (trimethoprim-sulfamethoxazole) for 12 months to prevent relapse.

Supportive Therapy

• Correction of electrolyte imbalances.
• Nutritional support, including repletion of fat-soluble vitamins (A, D, E, K).
• Management of cardiac or neurological complications as needed.

Follow-up

• Monitor for resolution of GI symptoms.

• Assess improvement in cardiac and neurological signs.

• Regular follow-up to detect relapse, especially in CNS-involved cases.