Makindo Medical Notes

🧬 Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder where IgG4-positive plasma cells infiltrate multiple organs. ⚠️ If untreated, it can progress to fibrosis and irreversible organ dysfunction. It is often misdiagnosed due to its ability to mimic malignancy, infection, or other autoimmune conditions.

📖 About IgG4-Related Disease

• A multi-organ fibroinflammatory condition first described in 2001 in patients with autoimmune pancreatitis.
• Characterized by swelling of affected organs, dense lymphoplasmacytic infiltrates, storiform fibrosis, and raised IgG4 plasma cells.
• Most common in middle-aged to elderly men, but can affect any age group.

🧪 Aetiology & Pathogenesis

• Exact cause remains unclear – thought to involve dysregulated immune response with overproduction of IgG4 subclass antibodies.
• IgG4 itself may not be directly pathogenic but serves as a marker of immune dysregulation.
• Chronic inflammation → progressive fibrosis → irreversible organ damage if not treated early.

🩺 Clinical Features

• 📌 Pancreas: Autoimmune pancreatitis (classically presenting with painless jaundice).
• 📌 Salivary/Lacrimal glands: Painless enlargement (mimics Sjögren’s syndrome).
• 📌 Retroperitoneum: Retroperitoneal fibrosis causing ureteric obstruction.
• 📌 Cardiac involvement: Coronary artery stenosis, pericardial thickening.
• 📌 CNS: Chronic subdural collections, hypertrophic pachymeningitis.
• 📌 Lymphadenopathy and skin lesions (papules, nodules).
• Often associated with other autoimmune disease history.

🔍 Investigations

• Serum IgG4: Elevated in ~70% of cases (>135 mg/dL supports diagnosis, but not always elevated).
• Biopsy: Gold standard. Shows dense lymphoplasmacytic infiltrate, storiform fibrosis, and IgG4+ plasma cells (>40% of total IgG cells).
• Imaging: FDG-PET or MRI helps map extent of disease and monitor treatment response.
• Exclude mimics: Malignancy, infection, and other autoimmune disorders must be ruled out.

⚕️ Management

• 💊 Corticosteroids: First-line therapy. 90% show rapid response (clinical + radiological improvement).
• 🛡️ Immunosuppressants: For relapsing/refractory disease – azathioprine, methotrexate, or mycophenolate. Evidence is limited.
• 🎯 Biologics: Rituximab (anti-CD20) effective in resistant or relapsing cases.
• 📈 Monitoring: Track serum IgG4 levels, imaging, and clinical symptoms to guide long-term therapy.

🌟 Key Clinical Pearl

IgG4-RD is sometimes called a "great mimicker" 🕵️ – it can resemble cancer, infection, or other autoimmune diseases. Always confirm with histology before committing to long-term immunosuppression. Early recognition and treatment are vital to prevent irreversible fibrosis.

📚 References

• NIH: Immunoglobulin G4-related Disease
• Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med. 2012;366:539-51.