Summary
IgG4-related disease (IgG4-RD) is a progressive, immune-mediated fibroinflammatory condition characterized by IgG4 infiltration with subsequent formation of tumor-like sclerotic masses and organ dysfunction. The most common manifestations include type 1 autoimmune pancreatitis, retroperitoneal fibrosis, sialadenitis and dacryoadenitis, and tubulointerstitial nephritis. Symptom onset is typically subacute. Findings on serology (e.g., elevated IgG4 levels) and imaging (e.g., masses, organ enlargement) are nonspecific but can help support the diagnosis. A biopsy is required for a definitive diagnosis; characteristic features include lymphoplasmacytic infiltrate with IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. Glucocorticoids are often used first line and are highly effective in inducing remission. Immunosuppressive agents (e.g., rituximab) may be used in refractory or relapsing disease. Long-term follow-up is essential due to the risk of relapse and potential organ damage if untreated.
Overview
Epidemiology [1]
Clinical features and differential diagnoses
- IgG4-RD can involve almost any organ. [1]
- The most common manifestations are listed in the table below; other IgG4-related conditions include: [1]
- IgG4-related pachymeningitis
- IgG4-related hypophysitis
- IgG4-related pulmonary disease
- IgG4-related fibrosing mediastinitis
- Up to 90% of patients with IgG4-RD have multiorgan involvement. [3]
- It can be difficult to distinguish IgG4-RD from other conditions (e.g., carcinoma, other autoimmune diseases) based on clinical features alone. [3][4]
IgG4-RD often leads to the formation of tumor-like lesions, which are frequently misdiagnosed as cancers. [1]
Diagnosis
General principles [3][6]
- Consult specialists (e.g., rheumatology, ENT, ophthalmology) for guidance on the diagnostic approach.
- Diagnosis is often incidental and based on:
- Clinical or imaging evidence of a mass or diffuse organ enlargement
- Elevated serum IgG4 level
- Characteristic biopsy findings
- Exclusion of alternative diagnoses, e.g., malignancy, infections, GPA, Sjogren syndrome
Serologic and imaging findings of IgG4-RD are nonspecific; histopathologic confirmation is required for a definitive diagnosis. [3][4]
Laboratory studies [1][3]
- ↑ Serum IgG4: nonspecific finding; normal levels do not exclude the diagnosis
- ↑ Serum IgE and eosinophilia
- Findings of specific organ involvement, e.g.:
- ↑ Lipase in pancreatitis
- ↑ Creatinine in renal disease
Serum IgG4 may also be elevated in other conditions such as infections, autoimmune disease, immune deficiency, malignancy, allergic conditions, atopy, and cystic fibrosis. [3][7]
Cross-sectional imaging [3][5]
Masses and/or organ enlargement typically have the following features:
- CT: homogeneous enhancement
- MRI: low signal intensity on T2 imaging
Biopsy [1][3]
The feasibility of biopsy depends on the affected organ; supportive findings include:
- Dense lymphoplasmacytic infiltrate with IgG4-positive plasma cells
- Storiform fibrosis: loosely organized, forming spiral patterns (highly specific finding)
- Obliterative phlebitis
- Eosinophil infiltrates
Treatment
Consult specialists (e.g., rheumatology, ENT, ophthalmology) for guidance on management. [3][4]
- Glucocorticoids, e.g., prednisone (off-label) [3]
- Other immunosuppressants (e.g., rituximab, azathioprine) may be added in refractory or relapsing disease. [1][2]
- Surgery may be indicated for obstructive masses.
- Long-term follow-up is essential due to the risk of relapse and potential organ damage if untreated.
Immunosuppressant therapy is more likely to induce remission in early (inflammatory) rather than late-stage (fibrotic) disease. [3]