OVERVIEW
IgG4-related disease (IgG4-RD) is a chronic, progressive inflammatory disease with fibrosis that can involve multiple organs. In the past, the disease was known by different names when it involved different tissues or organs, such as Mikulicz’s disease for salivary gland involvement, autoimmune pancreatitis for pancreatic involvement, sclerosing cholangitis for biliary tract involvement, periaortic abdominal inflammation or retroperitoneal fibrosis for retroperitoneal involvement, and so on. Later, these diseases were found to have similar immunopathologic changes, with large numbers of lymphocytes and plasma cells infiltrating the lesion sites, and IgG4-secreting plasma cells being generated locally in the inflammatory response, so these diseases were collectively referred to as IgG4-related diseases. Patients often have elevated serum IgG4 levels, IgG4-positive plasma cell infiltration in affected tissues or organs, sclerosis or fibrosis at the lesion site, and obstructive phlebitis. The disease is prevalent in middle-aged and elderly men. It is often misdiagnosed as a malignant tumor because of its tendency to form mass lesions.
Etiology
The cause of the disease has not been clearly defined and may be related to factors such as genetic susceptibility, microbial infections, and abnormal autoimmune reactions.
Symptoms
The disease may involve the pancreas, bile ducts, lacrimal gland, parotid gland, periorbital area, central nervous system, thyroid gland, lungs, kidneys, retroperitoneum and periarterial tissues, skin and lymph nodes, etc. Clinical symptoms vary according to the organs involved. Involvement of the lacrimal and salivary glands may result in glandular enlargement and sclerosis; involvement of the periorbital area may result in inflammatory pseudotumor and thickening of the extraocular muscles. Involvement of other parts of the body often results in swelling in tissues or organs, which may cause local obstruction, compression symptoms, or organ atrophy. The disease is often associated with enlarged lymph nodes, and about half of the patients have a history of allergy-related conditions.
Examination
1. Laboratory examination
Eosinophils are elevated in the peripheral blood, blood sedimentation and C-reactive protein are elevated, and immunoglobulins, especially IgG4 subtype, are significantly elevated.
2. Imaging examination
It can show the manifestations and characteristics of different tissue and organ involvement. Autoimmune pancreatitis is typically characterized by diffuse enlargement of the pancreas with salami-like changes; retroperitoneal fibrosis is a soft-tissue mass encircling the arteries; sclerosing cholangitis is characterized by thickening of the wall of the extrahepatic bile ducts and irregular narrowing of the lumen with bead-like changes; central nervous system involvement may present with diffuse enlargement of the pituitary gland or hypertrophic dura mater.
3.Histopathologic examination
A large number of lymphocyte infiltration can be seen in the lesion tissue, and lymphoid follicles can be formed. Dense IgG4-positive plasma cell infiltration, accompanied by tissue fibrosis and sclerosis. Mild to moderate eosinophilic infiltration. The inflammatory cell infiltrate is encapsulated by collagen fibers, which may form matted fibrosis with occlusive phlebitis.
Diagnosis.
Diagnostic criteria:
1. diffuse or limited swelling or mass in one or more organs.
2. serum IgG4 > 135 mg/dL.
3. a ratio of infiltrating IgG4+/IgG+ plasma cells >40% in the involved tissues and >10 IgG4+ plasma cells per high magnification field of view.
The diagnosis is confirmed if 1, 2, and 3 are met; proposed if 1 and 3 are met; suspected if 1 and 2 are met.
Differential diagnosis
IgG4-related diseases should be differentiated from lymphoproliferative diseases, Langerhans cell histiocytosis, nodular disease, inflammatory myofibroblastoma, Kimura disease, chronic infections, tumors, ANCA-related vasculitis, and malignant tumors.
Treatment
Pharmacologic treatment is the mainstay. Glucocorticoids are the first line of treatment for this disease and control the abnormal immune-inflammatory response. Medium doses are usually used, and the dose can be increased for severe symptoms, and then gradually tapered off after the disease is controlled, and maintained in small doses for a long period of time. Combination therapy with traditional immunosuppressive agents helps in glucocorticoid tapering and maintenance of disease stabilization. Rituximab may be given to patients for whom glucocorticoids are contraindicated or ineffective.
Prognosis
The long-term prognosis for most patients with IgG4-related disease is favorable. Patients respond well to hormone therapy but may relapse after glucocorticoid withdrawal or tapering and therefore require regular monitoring.