Hyper-IgG4 disease

Hyper-IgG4 Disease Hyper-IgG4 disease, also known as IgG4-related disease (IgG4-RD), is a chronic inflammatory condition characterized by tissue infiltration with IgG4-positive plasma cells and often elevated serum IgG4 levels. This condition can affect multiple organs and is often associated with the formation of mass-like lesions, fibrosis, and organ dysfunction.

Clinical Features

The clinical presentation of Hyper-IgG4 disease varies depending on the organs involved. Commonly affected organs include the pancreas, salivary glands, kidneys, and lymph nodes. Symptoms may include:

• Pancreatic involvement: Often presents as autoimmune pancreatitis, with symptoms such as abdominal pain, jaundice, and weight loss.
• Salivary gland involvement: Known as Mikulicz's disease, leading to swelling of the salivary and lacrimal glands.
• Renal involvement: Can cause tubulointerstitial nephritis, leading to renal dysfunction.
• Lymphadenopathy: Enlargement of lymph nodes.

For more detailed information on specific organ involvement, see Organ-specific manifestations of Hyper-IgG4 disease.

Pathophysiology

The pathogenesis of Hyper-IgG4 disease is not fully understood, but it is believed to involve an abnormal immune response. Key features include:

• IgG4-positive plasma cells: Infiltration of affected tissues by IgG4-secreting plasma cells.
• Fibrosis: Progressive fibrosis and scarring of affected tissues.
• Elevated serum IgG4: Many patients have elevated levels of IgG4 in the blood.

The role of IgG4 in the disease process is still under investigation. For more on the immunological aspects, see Immunology of Hyper-IgG4 disease.

Diagnosis

Diagnosis of Hyper-IgG4 disease is based on a combination of clinical, serological, and histopathological findings. Key diagnostic criteria include:

• Clinical presentation: Symptoms and signs consistent with organ involvement.
• Serology: Elevated serum IgG4 levels.
• Histopathology: Biopsy showing dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis.

For more on diagnostic criteria, see Diagnostic criteria for Hyper-IgG4 disease.

Treatment

The mainstay of treatment for Hyper-IgG4 disease is corticosteroids, which are effective in reducing inflammation and symptoms. Other immunosuppressive agents may be used in refractory cases. Treatment strategies include:

• Corticosteroids: Prednisone is commonly used.
• Immunosuppressants: Azathioprine, mycophenolate mofetil, or rituximab may be considered.

For more on treatment options, see Treatment of Hyper-IgG4 disease.

Prognosis

The prognosis of Hyper-IgG4 disease varies depending on the extent of organ involvement and response to treatment. Early diagnosis and treatment are crucial to prevent irreversible organ damage.

See Also

• Autoimmune diseases
• Chronic inflammatory diseases

References

1. Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med. 2012;366(6):539-551. 2. Kamisawa T, Zen Y, Pillai S, Stone JH. IgG4-related disease. Lancet. 2015;385(9976):1460-1471.

NIH genetic and rare disease info

• NIH info on Hyper-IgG4 disease

Hyper-IgG4 disease is a rare disease.