- Published on
KembaraXtra-Medicine – ANCA-Associated Vasculitis
Basic Information Anti-neutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) is a group of small- to medium-vessel systemic vasculitides that includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). These conditions share overlapping clinical manifestations and treatment strategies but differ in pathology and organ involvement. They are characterized by necrotizing, pauci-immune small-vessel vasculitis, with granulomatous inflammation present in GPA but absent in MPA. Most patients present with renal and pulmonary involvement, although the skin, nervous system, and gastrointestinal tract may also be affected. A limited form of GPA may be confined to the upper respiratory tract and can often be managed less aggressively.
Synonyms ANCA-associated vasculitis, ANCA-positive vasculitis, granulomatosis with polyangiitis (GPA), Wegener granulomatosis, microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA).
ICD-10-CM Codes I77.6 arteritis unspecified; M31.3 granulomatosis with polyangiitis; M31.7 microscopic polyangiitis; M30.1 eosinophilic granulomatosis with polyangiitis.
Epidemiology and Demographics The incidence is approximately 6–12 cases per million persons per year in Western Europe and Japan, with global variation. Prevalence ranges from 94 to 160 per million. There is a slight male predominance, and incidence increases with age, peaking between 60 and 70 years.
Risk Factors and Genetics Risk factors include infections such as Staphylococcus aureus, silica and hydrocarbon exposure, cigarette smoking, pesticides, and medications including hydralazine, minocycline, propylthiouracil, levamisole-adulterated cocaine, and allopurinol. Familial disease is rare. GPA is associated with SNPs in HLA-DP, PRTN3, and SERPINA1, whereas MPA is associated with HLA-DQ polymorphisms.
Physical Findings and Clinical Presentation Patients commonly have constitutional symptoms such as fever, fatigue, weight loss, myalgia, and arthralgia. Upper respiratory tract disease is prominent in GPA and includes chronic sinusitis, otitis media, mastoiditis, nasal crusting and epistaxis, septal perforation, subglottic or tracheal stenosis, and saddle-nose deformity. Ocular involvement includes conjunctivitis, episcleritis, scleritis, uveitis, optic neuropathy, and retinal vasculitis. Ear findings include sensorineural or conductive hearing loss and otorrhea. Oral findings may include chronic ulcerative lesions and “mulberry” gingivitis. Pulmonary disease presents with dyspnea, hemoptysis, pleuritic chest pain, nodules, cavitary lesions, infiltrates, effusions, or diffuse alveolar hemorrhage. Gastrointestinal involvement, more common in MPA, includes ischemic abdominal pain, bleeding, ulceration, or perforation. Renal disease is common in GPA and MPA and manifests as hypertension, edema, reduced urine output, rapidly progressive glomerulonephritis, microscopic hematuria, red cell casts, and proteinuria. Neurologic involvement includes mononeuritis multiplex, peripheral neuropathy, pachymeningitis, headaches, and rarely central nervous system disease. Cutaneous findings include palpable purpura, necrotic ulcers, nodules, urticaria, livedo reticularis, and digital gangrene.
Etiology The etiology is immune mediated and multifactorial. ANCAs directed against proteinase 3 (PR3) or myeloperoxidase (MPO) activate neutrophils, causing endothelial injury and tissue necrosis. Genetic susceptibility and environmental triggers contribute to disease development.
Diagnosis and Differential Diagnosis
Diagnosis is based on compatible clinical features supported by laboratory testing, imaging, and histopathology when feasible. Differential diagnoses include other systemic vasculitides, granulomatous lung diseases, anti–glomerular basement membrane disease, infections, malignancy, and drug- or cocaine-induced vasculitis.
Workup Evaluation
includes detailed history and physical examination, chest imaging, renal assessment, and targeted organ evaluation. ANCA serology typically shows PR3-ANCA in GPA and MPO-ANCA in MPA, though overlap exists and up to 15% of patients may be ANCA negative. Laboratory findings include anemia, leukocytosis, thrombocytosis, elevated inflammatory markers, impaired renal function, hematuria, and proteinuria. Tissue biopsy of affected organs, particularly kidney or lung, is recommended when safe to confirm diagnosis.
Treatment Management depends on disease severity and organ involvement. Induction therapy for moderate to severe disease includes systemic glucocorticoids combined with rituximab or cyclophosphamide. Reduced-dose steroid regimens may be used. Plasma exchange may be considered in select severe cases, though overall benefit is limited. Mild or limited disease may be treated with methotrexate-based regimens. Maintenance therapy commonly includes rituximab, azathioprine, methotrexate, or mycophenolate mofetil and is generally continued for 18–24 months. EGPA may additionally be treated with anti–interleukin-5 therapy such as mepolizumab. Prophylaxis against Pneumocystis jirovecii pneumonia is recommended during intensive immunosuppression.
Disposition and Referral
With prompt treatment, remission is achieved in most patients, though relapse is common. Renal failure and pulmonary involvement are major determinants of prognosis. Referral to rheumatology is essential, with multidisciplinary involvement from nephrology, pulmonology, ENT, dermatology, and neurology as indicated.
Pearls and Considerations
The goal of therapy is rapid induction of durable remission followed by maintenance treatment. Without treatment, mortality is high, and therapy is complicated by infection risk and progressive organ damage. Support and education resources are available through organizations such as the Vasculitis Foundation.
Basic Information Anti-neutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) is a group of small- to medium-vessel systemic vasculitides that includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). These conditions share overlapping clinical manifestations and treatment strategies but differ in pathology and organ involvement. They are characterized by necrotizing, pauci-immune small-vessel vasculitis, with granulomatous inflammation present in GPA but absent in MPA. Most patients present with renal and pulmonary involvement, although the skin, nervous system, and gastrointestinal tract may also be affected. A limited form of GPA may be confined to the upper respiratory tract and can often be managed less aggressively.
Synonyms ANCA-associated vasculitis, ANCA-positive vasculitis, granulomatosis with polyangiitis (GPA), Wegener granulomatosis, microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA).
ICD-10-CM Codes I77.6 arteritis unspecified; M31.3 granulomatosis with polyangiitis; M31.7 microscopic polyangiitis; M30.1 eosinophilic granulomatosis with polyangiitis.
Epidemiology and Demographics The incidence is approximately 6–12 cases per million persons per year in Western Europe and Japan, with global variation. Prevalence ranges from 94 to 160 per million. There is a slight male predominance, and incidence increases with age, peaking between 60 and 70 years.
Risk Factors and Genetics Risk factors include infections such as Staphylococcus aureus, silica and hydrocarbon exposure, cigarette smoking, pesticides, and medications including hydralazine, minocycline, propylthiouracil, levamisole-adulterated cocaine, and allopurinol. Familial disease is rare. GPA is associated with SNPs in HLA-DP, PRTN3, and SERPINA1, whereas MPA is associated with HLA-DQ polymorphisms.
Physical Findings and Clinical Presentation Patients commonly have constitutional symptoms such as fever, fatigue, weight loss, myalgia, and arthralgia. Upper respiratory tract disease is prominent in GPA and includes chronic sinusitis, otitis media, mastoiditis, nasal crusting and epistaxis, septal perforation, subglottic or tracheal stenosis, and saddle-nose deformity. Ocular involvement includes conjunctivitis, episcleritis, scleritis, uveitis, optic neuropathy, and retinal vasculitis. Ear findings include sensorineural or conductive hearing loss and otorrhea. Oral findings may include chronic ulcerative lesions and “mulberry” gingivitis. Pulmonary disease presents with dyspnea, hemoptysis, pleuritic chest pain, nodules, cavitary lesions, infiltrates, effusions, or diffuse alveolar hemorrhage. Gastrointestinal involvement, more common in MPA, includes ischemic abdominal pain, bleeding, ulceration, or perforation. Renal disease is common in GPA and MPA and manifests as hypertension, edema, reduced urine output, rapidly progressive glomerulonephritis, microscopic hematuria, red cell casts, and proteinuria. Neurologic involvement includes mononeuritis multiplex, peripheral neuropathy, pachymeningitis, headaches, and rarely central nervous system disease. Cutaneous findings include palpable purpura, necrotic ulcers, nodules, urticaria, livedo reticularis, and digital gangrene.
Etiology The etiology is immune mediated and multifactorial. ANCAs directed against proteinase 3 (PR3) or myeloperoxidase (MPO) activate neutrophils, causing endothelial injury and tissue necrosis. Genetic susceptibility and environmental triggers contribute to disease development.
Diagnosis and Differential Diagnosis
Diagnosis is based on compatible clinical features supported by laboratory testing, imaging, and histopathology when feasible. Differential diagnoses include other systemic vasculitides, granulomatous lung diseases, anti–glomerular basement membrane disease, infections, malignancy, and drug- or cocaine-induced vasculitis.
Workup Evaluation
includes detailed history and physical examination, chest imaging, renal assessment, and targeted organ evaluation. ANCA serology typically shows PR3-ANCA in GPA and MPO-ANCA in MPA, though overlap exists and up to 15% of patients may be ANCA negative. Laboratory findings include anemia, leukocytosis, thrombocytosis, elevated inflammatory markers, impaired renal function, hematuria, and proteinuria. Tissue biopsy of affected organs, particularly kidney or lung, is recommended when safe to confirm diagnosis.
Treatment Management depends on disease severity and organ involvement. Induction therapy for moderate to severe disease includes systemic glucocorticoids combined with rituximab or cyclophosphamide. Reduced-dose steroid regimens may be used. Plasma exchange may be considered in select severe cases, though overall benefit is limited. Mild or limited disease may be treated with methotrexate-based regimens. Maintenance therapy commonly includes rituximab, azathioprine, methotrexate, or mycophenolate mofetil and is generally continued for 18–24 months. EGPA may additionally be treated with anti–interleukin-5 therapy such as mepolizumab. Prophylaxis against Pneumocystis jirovecii pneumonia is recommended during intensive immunosuppression.
Disposition and Referral
With prompt treatment, remission is achieved in most patients, though relapse is common. Renal failure and pulmonary involvement are major determinants of prognosis. Referral to rheumatology is essential, with multidisciplinary involvement from nephrology, pulmonology, ENT, dermatology, and neurology as indicated.
Pearls and Considerations
The goal of therapy is rapid induction of durable remission followed by maintenance treatment. Without treatment, mortality is high, and therapy is complicated by infection risk and progressive organ damage. Support and education resources are available through organizations such as the Vasculitis Foundation.
0 Comments
