Granulomatosis With Polyangiitis
Disease Details
Family Health Simplified
- Description
- Granulomatosis with polyangiitis (GPA) is a rare autoimmune disease characterized by inflammation of blood vessels, which can restrict blood flow and damage vital organs and tissues.
- Type
- Granulomatosis with polyangiitis is a type of autoimmune disease characterized by inflammation of the blood vessels (vasculitis). Its exact cause is unknown, and it is not typically associated with any specific type of genetic transmission. While there may be some genetic predisposition, it is generally considered to be a multifactorial condition involving both genetic and environmental factors.
- Signs And Symptoms
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Initial signs are highly variable, and diagnosis can be severely delayed due to the nonspecific nature of the symptoms. In general, irritation and inflammation of the nose is the first sign in most people. Involvement of the upper respiratory tract, such as the nose and sinuses, is seen in nearly all people with GPA. Typical signs and symptoms of nose or sinus involvement include crusting around the nose, stuffiness, nosebleeds, runny nose, and saddle-nose deformity due to a hole in the septum of the nose. Inflammation of the outer layers of the eye (scleritis and episcleritis) and conjunctivitis are the most common signs of GPA in the eye; involvement of the eyes is common and occurs in slightly more than half of people with the disease.
Kidney: rapidly progressive glomerulonephritis (75%), leading to chronic kidney disease
Upper airway, eye and ear disease:
Ears: conductive hearing loss due to auditory tube dysfunction, sensorineural hearing loss (unclear mechanism)
Oral cavity: strawberry gingivitis, underlying bone destruction with loosening of teeth, non-specific ulcerations throughout the lining of the mouth
Trachea: subglottal stenosis
Lungs: pulmonary nodules (referred to as "coin lesions"), infiltrates (often interpreted as pneumonia), cavitary lesions, bleeding in the lungs causing a person to cough up blood, and rarely bronchial stenosis.
Arthritis: Pain or swelling (60%), often initially diagnosed as rheumatoid arthritis
Skin: subcutaneous nodules (granulomas) on the elbow, purpura, various others (see cutaneous vasculitis)
Nervous system: occasionally sensory neuropathy (10%) and rarely mononeuritis multiplex
Heart, gastrointestinal tract, brain, other organs: rarely affected. - Prognosis
- Before modern treatments, the 2-year survival was under 10% and average survival five months. Death usually resulted from uremia or respiratory failure. The revised Five-factor score is associated with 5-year mortality from GPA and is based on the following criteria: age greater than 65 years, cardiac symptoms, gastrointestinal involvement, chronic kidney disease, and the absence of ears, nose, and throat symptoms.With corticosteroids and cyclophosphamide, 5-year survival is over 80%. Long-term complications are common (86%), mainly chronic kidney failure, hearing loss, and deafness. The risk of relapse is increased in people with GPA who test positive for anti-PR3 ANCA antibodies and is higher than the relapse risk for microscopic polyangiitis.Today, medication toxicity is managed more carefully and long-term remissions are possible. Some affected individuals are able to lead relatively normal lives and remain in remission for 20+ years after treatment.
- Onset
- Granulomatosis with polyangiitis (GPA) typically has an onset in adulthood, often between the ages of 40 and 65. However, it can occur at any age, including in children and older adults. The onset can be acute or insidious, with symptoms developing over days to months.
- Prevalence
- The prevalence of Granulomatosis with Polyangiitis (GPA) is approximately 3 cases per 100,000 individuals.
- Epidemiology
- The incidence is 10–20 cases per million per year. It is exceedingly rare in Japan and in African Americans.
- Intractability
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Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is a rare form of vasculitis that affects small to medium-sized blood vessels. It is a chronic disease characterized by inflammation that can damage various organs, particularly the respiratory tract and kidneys.
While GPA can be severe and potentially life-threatening if not treated, it is not considered intractable. Advances in treatment, particularly with immunosuppressive medications like cyclophosphamide, rituximab, and corticosteroids, have significantly improved outcomes. Many patients achieve remission, although the disease can relapse and require ongoing management.
Early diagnosis and appropriate medical intervention are critical for better prognosis and quality of life. - Disease Severity
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Granulomatosis with polyangiitis (GPA), previously known as Wegener's granulomatosis, is a form of vasculitis that affects small to medium-sized blood vessels, primarily in the respiratory tract and kidneys. The disease severity can range from mild to severe, often determined by the extent and organs involved.
**Mild Disease:**
- Localized to specific areas, such as the upper respiratory tract.
- Symptoms may include sinusitis, nosebleeds, or ear infections.
- Typically not immediately life-threatening but requires medical attention to prevent progression.
**Moderate Disease:**
- More widespread involvement, including lungs and kidneys.
- Symptoms may include coughing (sometimes with blood), shortness of breath, and kidney issues like hematuria (blood in urine).
- More aggressive treatment likely needed to prevent irreversible organ damage.
**Severe Disease:**
- Extensive organ involvement, potentially including the kidneys, lungs, and other vital organs.
- Symptoms could include severe respiratory compromise, rapidly progressing glomerulonephritis (kidney inflammation), and systemic symptoms like fever and significant weight loss.
- Requires urgent and intensive medical treatment to prevent life-threatening complications. - Healthcare Professionals
- Disease Ontology ID - DOID:12132
- Pathophysiology
- Classic microscopic features of GPA include inflammation of blood vessels associated with poorly formed granulomas, necrosis, and many giant cells. Bacterial colonization with Staphylococcus aureus has been hypothesized as an initiating factor of the autoimmunity seen in people with GPA. Several genes involved in the immune system including PTPN22, CTLA4, and human leukocyte antigen genes may influence the risk of developing GPA.It is now widely presumed that the anti-neutrophil cytoplasmic antibodies (ANCAs) are responsible for the inflammation in GPA. The typical ANCAs in GPA are those that react with proteinase 3, an enzyme prevalent in neutrophil granulocytes. In vitro studies have found that ANCAs can activate neutrophils, increase their adherence to endothelium, and induce their degranulation that can damage endothelial cells. In theory, this phenomenon could cause extensive damage to the vessel wall, in particular of arterioles.
- Carrier Status
- Granulomatosis with polyangiitis (GPA) is not a condition associated with a carrier status. It is an autoimmune disease characterized by inflammation of the blood vessels, leading to organ damage. Carriers typically refer to individuals who possess one copy of a gene mutation that can cause a genetic disorder if two copies are present; this concept does not apply to GPA.
- Mechanism
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Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is an autoimmune disease characterized by inflammation of blood vessels (vasculitis), which can lead to damage in various organ systems, most commonly the respiratory tract and kidneys.
### Mechanism
1. **Immune System Dysfunction**: The immune system mistakenly targets small to medium-sized blood vessels, causing inflammation.
2. **Granuloma Formation**: The inflammation often results in granuloma formation, which are masses of immune cells.
3. **Tissue Damage**: This ongoing inflammation and granuloma formation can lead to necrosis and scarring, damaging affected organs.
### Molecular Mechanisms
1. **Antineutrophil Cytoplasmic Antibodies (ANCAs)**:
- A key feature of GPA is the presence of ANCAs, especially PR3-ANCA (proteinase-3 ANCA).
- ANCAs are autoantibodies directed against certain proteins in the cytoplasm of neutrophils.
2. **Neutrophil Activation**:
- PR3-ANCAs bind to PR3 on neutrophils, causing their activation.
- Activated neutrophils adhere to endothelial cells, migrate into tissues, and release enzymes and reactive oxygen species, leading to inflammation.
3. **Endothelial Damage**:
- Activated neutrophils induce direct damage to the endothelial cells lining the blood vessels.
4. **Immune Complex Formation**:
- Deposition of immune complexes in vessel walls further stimulates an inflammatory response.
5. **Cytokine Production**:
- Pro-inflammatory cytokines like TNF-α and IL-1β are upregulated, perpetuating the inflammatory cycle.
6. **T-Cell Involvement**:
- Abnormal T-cell responses may also play a role in sustaining the inflammatory process and granuloma formation.
These molecular interactions collectively contribute to the pathogenesis of granulomatosis with polyangiitis, leading to the clinical manifestations observed in the disease. - Treatment
- GPA treatment depends on its severity and whether it has caused organ damage.
- Compassionate Use Treatment
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Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is a rare autoimmune disease characterized by inflammation of blood vessels. Standard treatments include glucocorticoids and immunosuppressive agents such as cyclophosphamide or rituximab. For compassionate use or experimental treatments, the options include:
1. **Biologic Therapies**:
- **Mepolizumab**: An anti-IL-5 monoclonal antibody, which has shown promise in some small studies.
- **Abatacept**: A T-cell costimulation modulator that has been explored in clinical trials for GPA.
2. **Adjunctive Therapies**:
- **Intravenous Immunoglobulin (IVIG)**: Used in severe or refractory cases.
- **Plasma Exchange (Plasmapheresis)**: Considered for rapidly progressive disease, particularly with renal involvement.
3. **Other Experimental Agents**:
- **Avacopan**: A C5a receptor inhibitor that has been evaluated in clinical trials and may reduce the need for glucocorticoids.
These treatments are still under investigation and access might be limited to clinical trial settings or specific compassionate use programs. Always consult healthcare professionals for the most current and applicable treatment options. - Lifestyle Recommendations
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For individuals with Granulomatosis with Polyangiitis, key lifestyle recommendations include:
1. **Medication Adherence**: Consistently take prescribed medications to manage symptoms and prevent flare-ups.
2. **Regular Monitoring**: Maintain regular appointments with healthcare providers for monitoring disease progression and treatment efficacy.
3. **Healthy Diet**: Consume a balanced diet rich in fruits, vegetables, lean proteins, and whole grains to support overall health and immune function.
4. **Exercise**: Engage in moderate physical activity to improve cardiovascular health and maintain muscle strength, while avoiding overly strenuous activities that may exacerbate symptoms.
5. **Smoking Cessation**: Avoid smoking, as it can worsen respiratory symptoms and overall health.
6. **Stress Management**: Practice stress-relief techniques such as mindfulness, yoga, or meditation to help manage emotional and physical stress.
7. **Vaccinations**: Stay up-to-date with vaccinations, especially flu and pneumonia vaccines, as respiratory infections can be particularly harmful.
8. **Avoid Infections**: Practice good hygiene and avoid close contact with individuals who have contagious illnesses to reduce the risk of infections.
9. **Rest**: Ensure adequate rest and sleep to help the body recover and manage fatigue associated with the disease.
10. **Support System**: Engage with support groups or counseling to help cope with the psychological impact of living with a chronic illness. - Medication
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Granulomatosis with polyangiitis (GPA) is typically treated with a combination of medications to control inflammation and suppress the immune system. Common medications include:
1. **Corticosteroids (e.g., prednisone)**: Used to reduce inflammation.
2. **Immunosuppressive drugs**:
- **Cyclophosphamide** or **Methotrexate**: For severe cases to induce remission.
- **Azathioprine** or **Mycophenolate mofetil**: Often used for maintenance therapy once remission is achieved.
3. **Rituximab**: A biologic therapy that targets B-cells, effective for both inducing and maintaining remission.
4. **Trimethoprim-sulfamethoxazole**: Sometimes used for prophylaxis against infections, particularly Pneumocystis pneumonia.
Management often requires a tailored approach based on disease severity and patient response to treatment. Regular monitoring and follow-up with healthcare providers are crucial. - Repurposable Drugs
- There are no widely recognized repurposable drugs officially designated for Granulomatosis with Polyangiitis (GPA). Current standard treatments primarily include immunosuppressants such as cyclophosphamide, rituximab, methotrexate, and corticosteroids.
- Metabolites
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Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is a rare autoimmune disease characterized by inflammation of the blood vessels (vasculitis), which can restrict blood flow and damage vital organs and tissues. Currently, no specific metabolites are uniquely linked to GPA. The diagnosis and monitoring of GPA rely on clinical evaluation, imaging, and laboratory tests, such as blood tests for antineutrophil cytoplasmic antibodies (ANCAs).
Regarding "nan," if it refers to "not a number," it may be indicative of data not being available or applicable in a specific context, such as a lab result that is outside the measurable range. If "nan" is an abbreviation for something specific in another context (such as "nanotechnology"), there are no established treatments for GPA directly involving nanotechnology. Standard treatments typically include immunosuppressive medications like cyclophosphamide, rituximab, and corticosteroids. - Nutraceuticals
- There is currently no strong evidence to support the use of nutraceuticals in treating or managing granulomatosis with polyangiitis (GPA), also known as Wegener's granulomatosis. GPA is an ANCA-associated vasculitis that requires immunosuppressive therapy, typically involving medications such as corticosteroids, cyclophosphamide, or rituximab. Always consult with a healthcare provider for personalized treatment options.
- Peptides
- Granulomatosis with polyangiitis (GPA) is an autoimmune disease characterized by inflammation of small to medium-sized blood vessels. The role of peptides in GPA involves their potential use in therapeutic strategies or as biomarkers for disease activity, but this area is still under research. Utilizing nanoparticles (nan) in GPA treatment or diagnosis is also an emerging field, focusing on targeted drug delivery systems and improved imaging techniques to enhance specificity and reduce side effects.