From the Guidelines
IgG4-related disease is a chronic inflammatory condition characterized by elevated serum IgG4 levels and tissue infiltration by IgG4-positive plasma cells, leading to fibrosis and organ dysfunction. The disease affects multiple organs including the pancreas, biliary tract, salivary glands, kidneys, and lungs, with symptoms varying based on organ involvement.
Key Characteristics
- Elevated serum IgG4 levels
- Tissue infiltration by IgG4-positive plasma cells
- Fibrosis and organ dysfunction
Treatment Approach
The first-line treatment for IgG4-related disease is glucocorticoids, typically starting with prednisone at 0.6-1 mg/kg/day (usually 30-40 mg daily) for 2-4 weeks, followed by a gradual taper over 3-6 months, as recommended by the British Society of Gastroenterology and UK-PSC guidelines 1.
Maintenance Therapy
For maintenance therapy, low-dose prednisone (2.5-5 mg daily) may be continued for 1-3 years to prevent relapse. In cases of glucocorticoid resistance, relapse, or when steroid-sparing is needed, rituximab is the preferred second-line agent, administered as 1000 mg IV infusions given two weeks apart 1.
Second-Line Treatment
Other immunosuppressants like azathioprine (2 mg/kg/day), mycophenolate mofetil (1000-1500 mg twice daily), or methotrexate (15-25 mg weekly) may be used as steroid-sparing agents. The EASL clinical practice guidelines on sclerosing cholangitis also suggest considering UDCA for its anticholestatic and anti-inflammatory effects in patients with IgG4-related disease 1.
Monitoring and Management
Regular monitoring of organ function, serum IgG4 levels, and imaging studies is essential to assess treatment response. Early diagnosis and treatment are crucial to prevent irreversible fibrosis and organ damage. Patients with active IgG4-related disease should be given corticosteroids as first-line treatment, and all patients with IgG4-related disease should be considered for continued immunosuppressive therapy 1.
From the Research
Definition and Characteristics of IgG4 Disease
- IgG4-related disease is a fibroinflammatory condition characterized by lymphoplasmocytic infiltration with predominance of IgG4+ plasma cells, fibrosis, and in most cases elevated IgG4 serum levels 2
- It can affect any organ and result in varying clinical manifestations, with multiple organs compromised in most cases, averaging 3.5 compromised organs 2
- The disease presents predominantly in male patients aged between 50 and 70 years on average, with orbital, glandular, and lymph-node compromise being the most frequent 2
Clinical Presentations and Diagnosis
- Common presentations include major salivary and lacrimal gland enlargement, orbital disease, autoimmune pancreatitis, retroperitoneal fibrosis, and tubulointerstitial nephritis 3
- The main histopathological features are a dense, polyclonal, lymphoplasmacytic infiltrate rich in IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis 3
- Diagnosis should be based on specific histopathological findings, typical laboratory and radiological aspects, and an appropriate clinical context 3
Treatment Options and Outcomes
- Glucocorticoids are the cornerstone of treatment, but there is a high percentage of relapse, and their long-term use is associated with toxic effects 2, 4, 5
- Rituximab has been shown to be effective in inducing remission in steroid-resistant disease or as a steroid-sparing agent for relapsing disease, with a high response rate of 90% in monotherapy 2, 4, 6
- Immunosuppressants, such as cyclophosphamide and mycophenolate mofetil, and targeted immunomodulators, such as abatacept and dupilimab, are being investigated as potential treatment options 5, 6
- Combination therapy with glucocorticoids and immunosuppressive agents may be more effective and better tolerated than glucocorticoids alone 6