Microscopic Polyangiitis

An antineutrophil cytoplasmic antibody associated small vessel vasculitis characterised by pauci immune necrotising inflammation of small vessels without the granulomatous features or the upper respiratory tract predilection typical of granulomatosis with polyangiitis, with renal and pulmonary involvement dominating the clinical picture.

Pathophysiology

Antineutrophil cytoplasmic antibodies, predominantly directed against myeloperoxidase, activate neutrophils and cause endothelial injury affecting capillaries, venules and small arterioles, producing necrotising vasculitis without significant immune complex deposition and without the granulomatous inflammation that distinguishes granulomatosis with polyangiitis. The kidneys and lungs, richly supplied by small vessels, bear the brunt of clinical disease.

Rapidly progressive glomerulonephritis is the dominant and most consequential manifestation, often presenting with an acute rise in creatinine, haematuria and proteinuria, frequently discovered only once significant renal impairment has already developed given the tendency for silent progression.

Pulmonary involvement includes diffuse alveolar haemorrhage, presenting with haemoptysis, breathlessness and a falling haemoglobin, representing a life threatening emergency requiring immediate recognition and treatment, and pulmonary fibrosis is an increasingly recognised association, sometimes preceding overt vasculitis by years.

Constitutional symptoms (fever, weight loss, fatigue, arthralgia) are common and often precede organ specific manifestations.

Cutaneous involvement with palpable purpura, peripheral neuropathy (mononeuritis multiplex), and gastrointestinal involvement occur as in the other small vessel vasculitides, while the upper respiratory tract involvement characteristic of granulomatosis with polyangiitis (nasal crusting, septal perforation, subglottic stenosis) is notably absent or minimal in microscopic polyangiitis.

The combined renal pulmonary syndrome of glomerulonephritis with alveolar haemorrhage, when present, requires urgent recognition and treatment given the rapidity with which both organ systems can deteriorate.

Antineutrophil cytoplasmic antibody testing is positive in the majority, typically with a perinuclear staining pattern and myeloperoxidase specificity, distinguishing the serological profile from the proteinase 3 predominance more typical of granulomatosis with polyangiitis, though overlap occurs and serology alone does not define the clinical phenotype.

Renal biopsy, where feasible, shows pauci immune crescentic glomerulonephritis with minimal immune deposition on immunofluorescence, and is valuable both for confirming the diagnosis and for providing prognostic information regarding the proportion of active versus chronic irreversible changes.

Chest imaging assesses for alveolar haemorrhage, ground glass change and, in longer standing disease, pulmonary fibrosis.

Full blood count (anaemia from chronic disease or acute blood loss with alveolar haemorrhage), inflammatory markers, renal function and urinalysis with microscopy for red cell casts complete the essential diagnostic workup, alongside exclusion of infection and other vasculitis mimics before committing to immunosuppression.

Induction of remission follows the same principles as the other severe antineutrophil cytoplasmic antibody associated vasculitides, using high dose corticosteroids combined with rituximab or cyclophosphamide, with plasma exchange reserved for the most severe presentations, particularly diffuse alveolar haemorrhage or severe renal impairment with a high creatinine at presentation.

Maintenance therapy with rituximab, azathioprine or methotrexate follows successful induction, continued for an extended period given the substantial relapse risk shared across this group of conditions.

Long term monitoring of renal function, given that a proportion of patients progress to chronic kidney disease or end stage renal failure despite treatment, together with surveillance for relapse and treatment related toxicity, underpins ongoing specialist nephrology and rheumatology follow up.