Microscopic polyangiitis (ORPHA:727)
A rare inflammatory, necrotizing, systemic vasculitis that affects predominantly small vessels (i.e. small arteries, arterioles, capillaries, venules) in multiple organs, including the kidney, the lungs, the skin and the peripheral nerves.
Epidemiology
Microscopic polyangiitis (MPA) has a prevalence of 1/40,000 adults in France. Pediatric-onset MPA (<10 years of age) is uncommon.
Clinical description
MPA affects small vessels (more rarely medium-sized arteries) in any organ, resulting in a wide variety of non-specific symptoms. The early clinical manifestations are indicative of systemic inflammation: fever, arthralgias, myalgias, fatigue, and/or loss of appetite. As the disease progresses, 90% of patients show renal involvement with pauci-immune necrotizing and crescentic glomerulonephritis that can have a rapidly progressive course if not treated promptly. Pulmonary involvement (alveolar hemorrhage) is frequent and manifests with symptoms such as dyspnea, cough or hemoptysis. The most severe manifestation is combined pulmonary and renal disease (pulmonary-renal syndrome). Gastro-intestinal involvement can present with abdominal pain, nausea, or vomiting, and can be life-threatening in case of peritonitis, ischemia or perforation. Neurological (mainly mononeuritis multiplex), dermatologic (mainly leukocytoclastic angiitis), musculoskeletal (arthralgias, myalgias) and ocular involvement (e.g. episcleritis, retinal vasculitis, uveitis) are also observed. Cardiovascular involvement (e.g. pericarditis, cardiac insufficiency) is rare.
Etiology
MPA is an antineutrophil cytoplasmic autoantibodies (ANCA)-associated auto-immune disease with little or no immune complex deposition. Evidence indicates that ANCA can activate neutrophils and monocytes, and cause them to attack vessel walls.
Diagnostic methods
Diagnosis can be difficult and is essentially made by exclusion of other diseases. Detection of ANCA is a useful serologic marker. Generally, 60% of patients have myeloperoxidase (MPO)-ANCA, 30% proteinase 3 (PR3)-ANCA and 10% are ANCA-negative. Blood tests can reveal elevated C-reactive protein, leukocytosis, and anemia. Urine tests can show proteinuria, hematuria, and leukocyturia. Renal, pulmonary and skin biopsy can support the diagnosis. Pathologically, MPA is characterized by segmental vascular necrosis with infiltration of neutrophils and monocytes, often with leukocytoclasia and accumulation of fibrin.
Differential diagnosis
The differential diagnosis includes granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis (distinguished from MPA by the presence of necrotizing granulomatous inflammation in the absence or presence of asthma, respectively), Henoch-Schönlein purpura and cryoglobulinemic vasculitis (distinguished from MPA by IgA-dominant and cryoglobulin immune deposits, respectively), and polyarteritis nodosa.
Management and treatment
Treatment consists of two phases: induction of remission and maintenance of remission. The first-line induction therapy consists of oral or intravenous administration of high dose corticosteroids with immunosuppressive treatment (e.g. cyclophosphamide, or rituximab) in severe cases. Milder forms can be treated with glucocorticoids alone. Maintenance treatment consists of semestral infusions of rituximab. Relapses are treated with increased or reinstituted immunosuppression. In case of renal failure, dialysis and/or renal transplantation are appropriate.
Prognosis
With early diagnosis and treatment, prognosis is improved. Induction of remission occurs in 90% of patients. Optimum treatment reduces relapses (10% of patients have a relapse within 2 years of remission). Five-year patient survival has significantly improved during the last decade.

                            Last update: 
                            October 2020


                            - Expert reviewer(s): 
                            Dr Xavier PUECHAL  - Pr Benjamin TERRIER