I. OVERVIEW. A group of disorders in which inflammation and necrosis of blood vessels lead to organ dysfunction due to the development of thrombosis or hemorrhage. Mimics of vasculitis include subacute bacterial endocarditis, atrial myxoma, antiphospholipid syndrome, and cholesterol embolism.

1. Characterized by granulomatous inflammation of the upper and lower respiratory tract, segmental necrotizing glomerulonephritis, and small vessel inflammation of other organ systems.

2. Reasons for intensive care unit (ICU) admission for GPA and all of the vasculitides include respiratory failure due to alveolar hemorrhage, rapidly progressive renal failure, and infections, including those due to immunosuppressive treatment of disease. Stridor due to subglottic stenosis can occur in GPA.

1. There is no known etiologic agent for GPA.

2. Antineutrophilic cytoplasmic antibodies (ANCA) are present in >90% of cases of GPA. C-ANCA (with specificity to PR3 antigen) seen in 90% and P-ANCA (with specificity to myeloperoxidase [MPO]) seen in a minority of cases.

1. Clinical presentation typically includes sinusitis, rhinitis, epistaxis, otitis media, and hearing loss.

2. Lower respiratory tract is involved frequently, with cough, dyspnea, hemoptysis, and progressive respiratory failure due to alveolar hemorrhage. Pulmonary infiltrates may be diffuse, patchy, nodular, or cavitary. Lung biopsy may be necessary to confirm diagnosis and eliminate the possibility of mycobacterial or fungal disease.

3. Renal involvement may be rapidly progressive leading to dialysis. Rarely, ANCA-associated vasculitis coexists with antiglomerular basement antibodies (anti-glomerular basement membrane [GBM]). Diagnosis is confirmed based on clinical findings, presence of ANCA, and tissue biopsy
of affected organs, including the kidney, lung, eye, nerve, or skin. In some cases, tissue biopsy may not be necessary when the clinical suspicion for disease is high, and the ANCA pattern unequivocally supports the diagnosis.

1. In the setting of severe disease (respiratory failure, alveolar hemorrhage, and progressive renal failure), therapy should include cyclophosphamide (CYC) or rituximab (375 mg/m² weekly for 4 weeks or 1 g twice separated by 2 weeks) and high-dose corticosteroids. Intravenous (IV) methylprednisolone in doses of 1,000 mg/day for 3 days may be considered.

2. Oral dosing of CYC is 2 mg/kg but, in renal failure, it is as follows: 1.5 mg/kg/d if creatinine clearance (CrCl) is 50 to 99; 1.2 mg/kg/d if CrCl is 25 to 49; 1.0 mg/kg/d if CrCl is 15 to 24; and 0.8 mg/kg/d if CrCl is <15 or dialysis.

3. In the setting of critical illness and potential variability of gastrointestinal (GI) absorption, IV CYC (0.5 g/m² to 1 g/m²) may be indicated. Appropriate IV hydration pre- and post-CYC infusion and addition of MESNA are important.

4. Pneumocystis pneumonia (PCP) prophylaxis should be offered.

5. Plasmapheresis and IV immunoglobulin (Ig) may be useful during pregnancy or in severe or refractory GPA and severe alveolar hemorrhage with or without anti-GBM antibodies.

6. The presence of worsening pulmonary infiltrates in those treated with CYC and steroids raises the suspicion of fungal infections and PCP, warranting early bronchoscopy or biopsy and early consideration for antifungal and PCP therapy.

7. Other agents such as mycophenolate mofetil, azathioprine, or methotrexate may be used in less severe cases or in refractory cases.

1. Small- and medium-vessel necrotizing vasculitis presenting with pauciimmune segmental necrotizing glomerulonephritis and pulmonary capillaritis with alveolar hemorrhage.

2. ANCA (P-ANCA with MPO specificity) is positive in 70% of cases.

3. Clinical presentation can overlap with GPA, though pathologically there is lack of granulomas.

B. Diagnosis.

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