Granulomatosis with polyangiitis

Most cases occur between ages 40-60 years.

The disease is more frequent among Caucasians, although all racial and ethnic groups can be affected.

Classic triad of organ involvement is that of sinus, respiratory tract, and kidney.

GPA because inflammation of the upper respiratory tract resulting in rhinitis, otitis, subglottic stenosis, and sinusitis.

Organ involvement can be variable, leading to delay in diagnosis due to the incongruous nature of symptoms.

Clinical manifestations are protean.

Paranasal sinuses symptoms or commonly involved in up  to 73% of patients, skin manifestations in 15-50% of patients and is mostly palpable purpura, or less commonly nodules, vesicles or ulcers resembling pyoderma gangrenosum.

Up to 70% of patients with granulomatosis with polyangiitis are chronic nasal carriers of Staphylococcus aureus, with carriers having an eight times increased risk of relapse: considered a type II hypersensitivity reaction.

Acute phase reactants are elevated, and cANCA positivity occurs and 75%-90% of cases.

Diagnostic diagnosis is confirmed with a combination of clinical picture, serpositivity for c-ANCA and biopsy results.

Patients with GPA most commonly have a cytoplasmic ANCA pattern and antibodies directed against proteinase3, located in neutrophils and monocytes.

A small number of patients have a perinucleus staining pattern P-ANCA with antibodies typically directed against myeloperoxidase.33“21

Differential diagnosis includes: Chung-Strauss syndrome, Goodpasture syndrome, and sarcoidosis.

Every patient with suspected granulomatosis with polyangoitid should have cANCA testing, evaluation for sinusitis, and histopathologic examination of biopsy specimens.

Untreated is uniformly fatal.

GPA causes necrotizing granulomatous inflammation in small blood vessels throughout the body, most commonly affecting the capillary beds of the kidneys, lungs, and skin.

Renal and pulmonary involvement can progress rapidly and the diagnosis warrants urgent management.

Rapidly progressive glomerulonephritis occurs in up to 70% the patients with GPA.

commonly affects the lower respiratory tract with lung granuloma, alveolar hemorrhage.

Associated with significantly increased risks of myocardial infarction and ischemic stroke.

Management includes oral steroids.

Dermatological lesions are usually responsive to corticosteroids, cyclophosphamide or both treatments.

With generalized disease pulmonary cavitation and pleural  disease developing over 50% of patients, and glomerulonephritis may develop in almost 80% of cases.

Ocular and orbital involvement occur between 20 and 50% of patients and muscular skeletal, neurological and cardiac disease also may occur.

Rituximab and intravenous immunoglobulin are reserved for refractory disease.

Azothioprine and methotrexatebmay be added as a steroid sparing agent.

With current therapy of immunosuppressive agents five-year survival rate is now greater than 75%-80%.

For remission induction in severe or organ/life-threatening GPA, guidelines, recommend rituximab (375 mg/m² weekly ×4 or 1000 mg ×2 two weeks apart) or cyclophosphamide (oral 2 mg/kg/day or IV 15 mg/kg every 2–3 weeks) in combination with high-dose glucocorticoids (prednisone 1 mg/kg/day, with rapid tapering).

Rituximab is preferred in relapsing disease and ANCA positivity, while cyclophosphamide is preferred in new, severe presentations, especially with advanced kidney dysfunction.

Avacopan (C5a receptor inhibitor) may be used as a glucocorticoid-sparing adjunct, particularly in patients at high risk for steroid toxicity.

For nonsevere GPA, methotrexate, mycophenolate mofetil, or azathioprine (with glucocorticoids) are alternatives, especially when organ- or life-threatening disease is absent.

Cyclophosphamide is avoided in this setting due to toxicity.

For remission maintenance recommend rituximab (preferred, especially after rituximab induction), azathioprine, methotrexate, or mycophenolate mofetil. I recommended.

Rituximab is superior to azathioprine for maintenance after rituximab induction, particularly in relapsing disease.