What are the causes and treatment options for Eosinophilic granulomatous hepatitis?

Causes of Eosinophilic Granulomatous Hepatitis

Eosinophilic granulomatous hepatitis is primarily caused by drug reactions, followed by parasitic infections, autoimmune disorders, and vasculitides, with drug-induced cases accounting for approximately 29% of all cases. 1

Drug-Induced Causes

Drug-induced granulomatous hepatitis represents a significant proportion of cases and should be considered as a primary etiology. Key characteristics include:

• Common causative medications: 1, 2

  • Antihypertensive agents
  • Antirheumatic and analgesic drugs
  • Anticonvulsant medications
  • Antimicrobial agents
  • Approximately 60 different drugs have been documented in the literature

• Pathophysiology: Drugs act as haptens by covalently binding with macromolecular proteins, triggering an immunologic reaction 1

• Histological features: 1

  • Prominent eosinophils in early granulomatous reactions
  • Plasma cells accompanying eosinophils with continued antigenic stimulation
  • Non-caseating granulomas
  • Unicellular hepatocytic degeneration and necrosis
  • Cholestasis and acute cholangitis or vasculitis may be present

Infectious Causes

Parasitic infections represent the second most common cause of eosinophilic granulomatous hepatitis: 3

• Helminthic infections:

  • Strongyloides stercoralis (most common parasitic cause)
  • Other parasitic organisms

• Echinococcal infections: 3

  • Echinococcus granulosus (cystic echinococcosis)
  • Echinococcus multilocularis (alveolar echinococcosis)

• Liver flukes: 3

  • Clonorchis sinensis
  • Opisthorchis species

Autoimmune and Vasculitic Causes

Several autoimmune conditions can cause eosinophilic granulomatous hepatitis:

• Eosinophilic Granulomatosis with Polyangiitis (EGPA): 3, 4

  • Previously known as Churg-Strauss syndrome
  • Characterized by asthma, eosinophilia, and granulomatous or vasculitic involvement of multiple organs
  • ANCA-positive in approximately 40% of cases (usually MPO-ANCA)
  • Can present with hepatic involvement including granulomatous hepatitis

• Autoimmune hepatitis with eosinophilic features: 4

  • May coexist with EGPA
  • Presents with elevated liver enzymes, positive autoantibodies (ANA, ASMA)
  • Liver biopsy shows active chronic hepatitis with eosinophilic infiltration

• Eosinophilic gastroenteritis with hepatic involvement: 5

  • Can present with hepatosplenomegaly
  • Hepatic giant cell granulomas with surrounding eosinophilia

• TINU syndrome (Tubulo-Interstitial Nephritis and Uveitis): 6

  • Can be associated with granulomatous hepatitis
  • Presents with renal failure, uveitis, and liver enzyme elevation

Other Causes

• Sarcoidosis: Accounts for approximately one-third of granulomatous hepatitis cases 1

  • Note: Eosinophils are rare to absent in sarcoidosis, which helps differentiate it from drug-induced cases

• Occupational exposures: 2

  • Silica
  • Copper sulfate
  • Beryllium compounds

• Particulate material from therapeutic or diagnostic procedures: 2

  • Starch
  • Talc
  • Suture material
  • Polyvinyl pyrrolidone
  • Silicone
  • Barium sulfate
  • Thorium dioxide

Diagnostic Approach

1. Medication review: Thoroughly evaluate all current and recent medications, as drug-induced causes are most common 1, 2

2. Travel history: Assess for potential exposure to parasitic infections, especially in returning travelers 3

3. Systemic symptoms assessment:

   • Asthma, sinusitis, and peripheral neuropathy may suggest EGPA 3, 4
   • Gastrointestinal symptoms may suggest eosinophilic gastroenteritis 5

4. Laboratory evaluation:

   • Complete blood count with differential (eosinophil count)
   • Liver function tests
   • Autoantibodies (ANA, ASMA, ANCA)
   • Parasite serology when indicated

5. Liver biopsy: Essential for definitive diagnosis 1, 2

   • Evaluate for granulomas, eosinophilic infiltration, and other histological features
   • Special stains to rule out infectious causes

Treatment Approach

Treatment should be directed at the underlying cause:

1. Drug-induced cases: Discontinuation of the offending drug is the primary treatment 2

   • Recovery typically follows drug withdrawal

2. Parasitic infections: Appropriate antiparasitic therapy 3

   • Consult with infectious disease specialists for optimal treatment

3. EGPA and autoimmune causes: 3, 4

   • Corticosteroids (prednisone) as first-line therapy
   • For EGPA with severe manifestations, consider rituximab or cyclophosphamide with high-dose glucocorticoids 7
   • For maintenance therapy in EGPA, options include rituximab, azathioprine, or methotrexate 7

4. Monitoring: Regular follow-up of liver function tests to assess response to treatment

The prognosis is generally favorable with appropriate treatment of the underlying cause, particularly in drug-induced cases where complete resolution typically occurs after drug discontinuation.