What drugs are associated with eosinophilic granulomatosis in the liver?

From the Guidelines

Drugs such as minocycline, nitrofurantoin, and infliximab have been associated with eosinophilic granulomas in the liver, as they can trigger an autoimmune response leading to liver injury. The liver injury can be severe and impact the patient's quality of life and mortality. When considering the management of patients with liver injury, it is essential to consider the potential role of medications, as discontinuation of the offending drug can lead to resolution of the condition. Some of the key drugs associated with liver injury include:

• Minocycline, which has been linked to autoimmune hepatitis 1
• Nitrofurantoin, which has also been associated with autoimmune hepatitis 1
• Infliximab, a biologic agent that can trigger an autoimmune response in the liver 1 These medications can cause a range of liver injuries, from mild elevations in liver enzymes to severe autoimmune hepatitis. In patients with unexplained liver abnormalities, healthcare providers should maintain a high index of suspicion for drug-induced liver injury and consider discontinuation of potential offending medications. The diagnosis of drug-induced liver injury can be challenging, but a thorough medical history, laboratory tests, and liver biopsy can help establish the diagnosis. Management of drug-induced liver injury typically involves discontinuation of the suspected drug, and in severe cases, corticosteroids may be necessary to reduce inflammation and prevent long-term liver damage. It is crucial to prioritize the patient's morbidity, mortality, and quality of life when managing drug-induced liver injury, and healthcare providers should be aware of the potential risks associated with certain medications.

From the FDA Drug Label

Gastrointestinal:Hepatitis (including cholestatic jaundice and hepatic necrosis), elevation of serum transaminase and bilirubin, pseudomembranous enterocolitis, pancreatitis, stomatitis, glossitis, nausea, emesis, abdominal pain, diarrhea, anorexia Respiratory:Cough, shortness of breath and pulmonary infiltrates, acute eosinophilic pneumonia, acute and delayed lung injury, interstitial lung disease, acute respiratory failure Hematologic:Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, neutropenia, hemolytic anemia, megaloblastic anemia, hypoprothrombinemia, methemoglobinemia, eosinophilia, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura Allergic Reactions:Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, allergic myocarditis, erythema multiforme, exfoliative dermatitis, angioedema, drug fever, chills, Henoch-Schoenlein purpura, serum sickness-like syndrome, generalized allergic reactions, generalized skin eruptions, photosensitivity, conjunctival and scleral injection, pruritus, urticaria, rash, periarteritis nodosa, systemic lupus erythematosus, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized erythematous pustulosis (AGEP), and acute febrile neutrophilic dermatosis (AFND)

The sulfonamides are associated with eosinophilic granulomas in the liver, as part of a broader category of drug reaction with eosinophilia and systemic symptoms (DRESS), which can involve the liver, among other organs. Key points to consider include:

• Hepatitis (including cholestatic jaundice and hepatic necrosis)
• Eosinophilia
• Drug reaction with eosinophilia and systemic symptoms (DRESS) 2

From the Research

Drugs Associated with Eosinophilic Granulomas in Liver

• Eosinophilic granulomas in the liver can be caused by various drugs, including:
  • Aromatic anticonvulsants such as carbamazepine, phenytoin, and phenobarbitone 3
  • Sulfa drugs like sulfonamides, sulfasalazine, and dapsone 3
  • Acetylsalicylic acid (aspirin) 4
• These drugs can induce eosinophilia, which is a diagnosis of exclusion 4
• Granulomatous diseases of the liver, including those caused by drugs, can present with a range of symptoms and can be diagnosed through liver biopsy and other tests 5, 6

Diagnosis and Management

• The diagnosis of drug-induced eosinophilia and granulomas in the liver involves excluding other causes of eosinophilia and granulomatous disease 4, 7
• Management of drug-induced eosinophilia and granulomas in the liver typically involves discontinuing the offending drug and treating any resulting inflammation or organ damage 3, 7
• In some cases, treatment with corticosteroids or other immunosuppressive agents may be necessary to manage symptoms and prevent further organ damage 7