Summary about Disease
Immunoglobulin G4-Related Disease (IgG4-RD) is a chronic, immune-mediated fibroinflammatory condition characterized by tumefactive lesions, often in multiple organs simultaneously, along with elevated serum IgG4 concentrations and tissue infiltration by IgG4-positive plasma cells. It can affect nearly any organ system, and its manifestations vary widely depending on the organs involved. The disease is often responsive to immunosuppressive therapy.
Symptoms
Symptoms of IgG4-RD are highly variable depending on the organ(s) affected. Some common presentations include:
Swelling/Enlargement: painless swelling of salivary glands (especially parotid and submandibular), lacrimal glands, lymph nodes, pancreas (leading to obstructive jaundice or pancreatitis), kidneys, retroperitoneum (leading to retroperitoneal fibrosis), and orbits (leading to proptosis or vision changes).
Organ Dysfunction: Organ failure due to inflammation and fibrosis.
Constitutional Symptoms: fatigue, weight loss, and fever, although these are less common.
Specific Organ Involvement:
Pancreas: Autoimmune pancreatitis (AIP), sometimes presenting with painless jaundice.
Salivary/Lacrimal Glands: Sialadenitis (Mikulicz's disease), dacryoadenitis.
Kidneys: Tubulointerstitial nephritis.
Retroperitoneum: Retroperitoneal fibrosis.
Lungs: Interstitial lung disease, inflammatory pseudotumors.
Orbits: Orbital inflammatory disease (proptosis, vision changes).
Lymph Nodes: Lymphadenopathy.
Causes
The exact cause of IgG4-RD is unknown. It is believed to be an immune-mediated disease, potentially triggered by an unknown antigen in genetically susceptible individuals. It is not directly inherited but there are likely genetic predispositions. The disease involves an abnormal immune response, leading to excessive production of IgG4 antibodies and infiltration of various tissues with IgG4-positive plasma cells, lymphocytes, and fibrosis.
Medicine Used
The primary treatment for IgG4-RD involves immunosuppression. Common medications include:
Glucocorticoids (e.g., Prednisone): Often the first-line treatment to induce remission. High doses are typically used initially, followed by a gradual taper.
B-cell Depletion Therapy (e.g., Rituximab): An anti-CD20 monoclonal antibody that targets B cells. Often used as a steroid-sparing agent or in patients who do not respond to or cannot tolerate glucocorticoids.
Immunomodulatory Drugs (e.g., Methotrexate, Azathioprine, Mycophenolate Mofetil): Used as steroid-sparing agents to maintain remission and reduce the risk of relapse.
Other therapies: Infliximab, Tocilizumab and other agents have also been explored but not fully established yet.
Surgical intervention: May be necessary to relieve obstructions or for diagnostic purposes.
Is Communicable
IgG4-RD is not communicable. It is not an infectious disease and cannot be transmitted from person to person.
Precautions
There are no specific precautions to prevent acquiring IgG4-RD, as the cause is unknown. Precautions during treatment focus on managing the side effects of immunosuppressive medications:
Infection Prevention: Because immunosuppressants increase the risk of infection, patients should take precautions to avoid exposure to illness, practice good hygiene, and receive recommended vaccinations (when appropriate and after discussion with their physician).
Regular Monitoring: Regular blood tests and imaging studies are necessary to monitor disease activity and treatment response, as well as to screen for potential side effects of medications.
Sun Protection: Some immunosuppressants increase sensitivity to the sun.
Counseling: Discuss potential side effects of medication with your doctor to understand the risks and benefits and what to watch out for.
How long does an outbreak last?
The duration of an "outbreak" or active phase of IgG4-RD is variable. Without treatment, the disease can progress over months to years, leading to organ damage and fibrosis. With treatment, the duration of active disease can be shortened significantly, and remission can be achieved. However, relapses are common, and some patients require long-term maintenance therapy. The length of remission and the frequency of relapses vary from person to person.
How is it diagnosed?
Diagnosis of IgG4-RD typically involves a combination of clinical findings, laboratory tests, and tissue biopsy:
Clinical Presentation: Consistent signs and symptoms affecting one or more organs.
Serum IgG4 Levels: Elevated serum IgG4 concentrations (though not always present and can be falsely elevated). Normal IgG4 levels do not exclude the diagnosis.
Tissue Biopsy: The gold standard for diagnosis. Biopsy of the affected organ(s) demonstrates:
Dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells.
Storiform fibrosis (a characteristic pattern of fibrosis).
Obliterative phlebitis (inflammation of blood vessels).
The number of IgG4-positive plasma cells is usually quantified, and the IgG4/IgG ratio is often calculated.
Imaging Studies: CT scans, MRI, and ultrasound can help identify affected organs and assess the extent of inflammation and fibrosis.
Exclusion of Other Conditions: Ruling out other diseases that can mimic IgG4-RD, such as malignancy, infection, and other autoimmune disorders.
Timeline of Symptoms
The timeline of symptoms in IgG4-RD is often insidious and variable:
Early Stages: Many individuals initially experience subtle and non-specific symptoms, like mild fatigue or painless swelling of glands.
Progression: Over weeks, months, or even years, symptoms can progress, leading to more noticeable organ dysfunction.
Fluctuations: Symptoms may wax and wane, making diagnosis challenging.
Late Stages: If left untreated, chronic inflammation and fibrosis can lead to irreversible organ damage.
Post-Treatment: Symptoms usually improve after initiating immunosuppressive therapy, and the timeline for improvement varies depending on the extent of organ involvement and the individual's response to treatment.
Important Considerations
Multidisciplinary Approach: Management of IgG4-RD often requires a multidisciplinary team of specialists, including rheumatologists, gastroenterologists, nephrologists, pulmonologists, ophthalmologists, and surgeons, depending on the organs involved.
Differential Diagnosis: IgG4-RD can mimic other conditions, making accurate diagnosis crucial.
Relapses: Relapses are common, even after successful initial treatment. Long-term monitoring is essential to detect and manage relapses promptly.
Organ Damage: Early diagnosis and treatment are essential to prevent irreversible organ damage from chronic inflammation and fibrosis.
IgG4 levels may not always correlate with disease activity: Monitoring the disease should depend on imaging and symptoms, not just IgG4 levels.
Clinical trials: Clinical trials are ongoing that evaluate other therapies.