From the Guidelines
IgG4 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, and should be treated with corticosteroids as first-line treatment. The disease affects multiple organs, including the pancreas, biliary tract, salivary glands, and retroperitoneum, with symptoms varying based on the affected organs 1. Key features of IgG4 disease include:
- Elevated serum IgG4 levels
- Tissue infiltration by IgG4-positive plasma cells
- Fibrosis and organ dysfunction
- Response to corticosteroid treatment, with a common regimen being oral prednisolone 40 mg daily for 2–4 weeks, subsequently reduced by 5 mg every week over approximately 8–12 weeks 1. For maintenance therapy, consideration should be given to continued immunosuppressive therapy, particularly in patients with multiorgan involvement 1. In cases of relapse or steroid resistance, immunosuppressants such as azathioprine or rituximab may be considered 1. Regular monitoring of organ function, serum IgG4 levels, and inflammatory markers is essential during treatment to assess response and adjust therapy as needed. Given the complexity of management, it is advisable for patients with possible IgG4 disease to be referred to specialists or centers with experience of the disease to establish the diagnosis, plan management, and recruit into trials 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 many cases, averaging 3.5 compromised organs per patient 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 of IgG4-related disease 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, excluding other conditions such as malignancies and vasculitis 4.
Treatment Options and Outcomes
- Glucocorticoids are the cornerstone of treatment for IgG4-related disease, but there is a high percentage of relapse, and long-term administration can have adverse effects 2, 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 around 90% 2, 5.
- Other treatment options include immunosuppressive agents such as cyclophosphamide and mycophenolate mofetil, which can be used in combination with glucocorticoids to reduce doses and improve tolerance 5.
- New drugs such as abatacept and dupilimab are under investigation, showing promising results 5.