Microscopic polyangiitis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Microscopic polyangiitis is a necrotising small-vessel vasculitis without the granulomatous respiratory inflammation that defines GPA. Kidneys are affected frequently and lungs, skin and peripheral nerves are common additional targets. MPO-ANCA is characteristic but not universal. Nasal symptoms can occur nonspecifically, yet destructive sinus, orbital mass and cavitating granulomatous nodules should prompt reconsideration of GPA, infection or malignancy.

A pulmonary-renal presentation is an emergency differential rather than a final label. Send urine microscopy, creatinine, MPO or PR3 ANCA, anti-GBM antibodies, complement, ANA or dsDNA and infection tests. CT chest defines diffuse haemorrhagic patterns and alternatives. Kidney biopsy often offers the fastest high-yield tissue, separating pauci-immune necrotising crescents from immune-complex or anti-GBM disease and quantifying chronic scar.

Severe induction parallels other AAV: rituximab or cyclophosphamide plus a carefully reduced glucocorticoid course. Avacopan may replace most oral steroid but accompanies standard induction. Plasma exchange is no longer routine solely because AAV is severe; specialists consider it in very advanced renal failure, dialysis dependence, hypoxaemic haemorrhage and anti-GBM overlap. Acute kidney support and infection treatment run concurrently.

MPO-associated disease may relapse less often than PR3-GPA but can leave greater fibrotic kidney and lung burden. Maintenance choice and length weigh relapse against infection in an older population. Direct organ assessment guides care: persistent microscopic blood after healed nephritis, stable positive MPO and breathlessness from fibrosis should not automatically trigger immunosuppression. Cardiovascular and CKD protection continues after immune remission.

Key points

MPA commonly presents with rapidly progressive glomerulonephritis, constitutional inflammation, pulmonary capillaritis, palpable purpura or mononeuritis multiplex without granulomatous ENT destruction.
Check urine and creatinine urgently in any suspected systemic vasculitis; renal disease can be clinically silent until substantial filtration is lost.
MPO-ANCA supports the diagnosis in the correct phenotype but is neither required nor sufficient, and persistent titre alone does not prove relapse.
Kidney biopsy is the reference tissue test when active sediment is present, confirming pauci-immune necrotising crescents and quantifying reversible activity versus scar.
Send anti-GBM antibodies immediately in pulmonary-renal disease because double-positive disease occurs and changes plasma-exchange decisions.
Use rituximab or cyclophosphamide with reduced-dose glucocorticoid for organ-threatening disease; avacopan can replace much oral steroid in eligible severe active MPA.
Consider plasma exchange selectively when creatinine is very high or dialysis is required, or for hypoxaemic alveolar haemorrhage, after balancing serious-infection risk.
For non-organ-threatening systemic disease, specialist immunosuppression is still needed; steroid monotherapy creates relapse and toxicity.
Maintenance uses rituximab or azathioprine after remission, with duration tailored to relapse risk, kidney recovery, age, infection and MPO phenotype.
Before calling respiratory or renal deterioration relapse, assess infection, pulmonary oedema, thrombosis, chronic scar, drug toxicity and adherence.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

MPO-associated autoimmunity

Loss of tolerance to myeloperoxidase is common, although some cases are PR3-positive or ANCA-negative; genetic associations differ from granulomatous PR3 disease.

Environmental and medicine triggers

Silica, infection, smoking-related lung injury, hydralazine, propylthiouracil and selected other medicines can initiate or mimic an MPO-ANCA vasculitic process.

Age and immune context

MPA typically presents in later adulthood, with immune ageing, renal reserve and comorbidity shaping phenotype, treatment tolerance and recovery.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Neutrophil and complement activation
MPO-ANCA activates primed neutrophils and the C5a amplification loop, damaging capillary, venular and arteriolar endothelium with few immune deposits.
2
Pauci-immune renal capillaritis
Glomerular necrosis and crescents cause blood, protein and rapid filtration loss; biopsy chronicity determines how much renal function can recover.
3
Pulmonary capillaritis
Injured alveolar capillaries leak blood into air spaces, reducing gas exchange and haemoglobin, sometimes without visible haemoptysis.
4
Non-granulomatous systemic injury
Skin, peripheral nerves, gut, eyes and heart may infarct through small-vessel inflammation, while destructive granulomatous ENT masses are not typical.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Pauci-immune nephritisRed flag

New dysmorphic haematuria, casts, proteinuria, pressure rise and creatinine progression is the dominant and sometimes silent MPA manifestation.

Alveolar haemorrhageRed flag

Falling haemoglobin, hypoxia and diffuse bilateral opacity indicates pulmonary capillary bleeding even when haemoptysis is absent.

Skin small-vessel disease

Palpable purpura, livedo, ulcer or necrosis can provide accessible biopsy but also occurs in infection and immune-complex vasculitis.

Mononeuritis multiplex

Abrupt painful asymmetric deficits across separate nerves, including wrist or foot drop, supports vasculitic nerve ischaemia.

Absence of granulomatous ENT disease

Prominent glomerulonephritis and capillaritis without destructive upper-airway masses makes MPA more likely than GPA, but phenotype can overlap.

Red flags requiring action

Haemoptysis is not required for alveolar haemorrhage; new hypoxia, diffuse opacity and unexplained anaemia is sufficient for emergency assessment.
Oliguria, potassium rise, acidosis, fluid overload or rapidly changing creatinine requires urgent nephrology and dialysis assessment.
Painful asymmetric weakness or foot drop indicates nerve infarction and needs prompt induction before deficit becomes fixed.
Mesenteric pain, myocardial injury, scleritis or severe skin necrosis indicates life- or organ-threatening vasculitis.
Infection can mimic relapse and MPO-ANCA may remain positive in remission, so treatment must follow direct organ evidence.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Urinalysis, microscopy, protein and serial renal functionFirst step
Why
Detect capillary injury and define AKI severity and dialysis complications.
Interpretation and limitations
Glomerular blood and casts support active nephritis; chronic haematuria can persist, so trend with eGFR and biopsy when decisions are high stakes.
02
MPO-ANCA, PR3-ANCA and anti-GBM
Why
Support AAV phenotype and identify urgent double-positive pulmonary-renal disease.
Interpretation and limitations
MPO is common but not pathognomonic; anti-GBM positivity changes treatment and titres alone do not define AAV relapse.
03
Kidney biopsy
Why
Confirm pauci-immune necrotising crescentic glomerulonephritis and grade activity and chronicity.
Interpretation and limitations
Biopsy is the reference renal tissue assessment and prevents immune escalation when scar dominates or deposits identify another mechanism.
04
HRCT and respiratory sampling
Why
Assess alveolar haemorrhage, infection, oedema, embolism and chronic interstitial injury.
Interpretation and limitations
Ground glass is nonspecific; bronchoscopy with progressively bloody lavage can support haemorrhage when safe and microbiology is essential during immunosuppression.
05
FBC, film, CRP or ESR, complement and autoimmune screen
Why
Measure anaemia, inflammation, TMA and immune-complex alternatives.
Interpretation and limitations
Normal complement supports but does not prove pauci-immune disease; schistocytes redirect toward TMA and high CRP cannot separate infection.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Anti-GBM disease

Pulmonary haemorrhage with rapidly progressive glomerulonephritis may be anti-GBM disease or double-positive disease requiring urgent antibody testing and a different plasma-exchange strategy.

Immune-complex glomerulonephritis

Lupus, cryoglobulinaemia, IgA and infection-related disease often show complement or immunofluorescence deposits that distinguish them from pauci-immune MPA.

Infection and drug-induced vasculitis

Endocarditis, viral disease and hydralazine or propylthiouracil exposure can cause systemic inflammation, glomerulonephritis and multiple autoantibodies.

GPA and eosinophilic disease

Destructive granulomatous ENT lesions favour GPA, while asthma, marked eosinophilia and eosinophilic tissue disease favour EGPA.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01First-line pulmonary-renal work-upConfirm mechanism while stabilisingFirst stepFirst lineActive urine, renal decline or alveolar haemorrhage raises MPA or another pulmonary-renal syndrome.

1Admit according to physiology, treat oxygen, potassium, fluid and sepsis, and send cultures before antimicrobial therapy when safe.
2Obtain MPO or PR3, anti-GBM, complement and immune-complex tests and arrange urgent kidney biopsy; sample lungs when infection or haemorrhage remains uncertain.
3Begin organ-saving induction before final pathology only when delay is more dangerous than diagnostic uncertainty.

02Organ-threatening inductionSuppress capillaritis with reduced steroid exposureActive nephritis, haemorrhage, neuropathy or another organ is threatened.

1Use intravenous methylprednisolone for the most critical disease, followed by reduced oral taper or avacopan in eligible severe active MPA.
2Give rituximab or age- and kidney-adjusted intravenous cyclophosphamide, with Pneumocystis, gastric, bone and fertility safeguards.
3Consider plasma exchange only after renal, respiratory and rheumatology review of eGFR, dialysis, hypoxaemia, anti-GBM overlap and infection risk.

03MaintenanceBalance relapse against infectionInduction achieves remission and direct organ measures stabilise.

1Choose fixed-interval rituximab or azathioprine and a treatment duration reflecting MPO relapse risk, prior severity, CKD and infection.
2Taper glucocorticoid, monitor immunoglobulin, blood, liver and renal safety and maintain vaccination and cardiovascular or kidney protection.
3Document residual urine, neuropathy, fibrosis and dialysis status so chronic damage is not later mistaken for relapse.

04New deteriorationRecheck infection, fluid and scarRenal, respiratory or systemic findings worsen during follow-up.

1Repeat urine microscopy, eGFR, haemoglobin, oxygen, imaging, cultures, medicine and volume assessment before using ANCA as an activity marker.
2Use biopsy or bronchoscopy when active vasculitis versus infection, oedema, fibrosis or chronic nephron loss remains unresolved.
3Reinduce confirmed organ-threatening relapse and revise maintenance and infection prophylaxis.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Standard remission induction for severe MPA and an effective scheduled maintenance treatment; BSR permits individualised 500–1,000 mg maintenance every four to six months.

Rituximab

For licensed adult induction, give 375 mg/m² intravenously on four consecutive weekly occasions. The two-dose 1,000 mg schedule on days 1 and 15 is a common specialist off-label alternative. Licensed maintenance is 500 mg twice, fourteen days apart, followed by 500 mg six-monthly for at least two years; after rituximab induction, the first maintenance course is no earlier than week 16.

Exclude active infection and screen hepatitis B and TB; measure immunoglobulins, plan vaccination, and follow infusion reactions, delayed neutropenia and recurrent infection. Discuss pregnancy in advance; after later gestational use, assess the neonate's B cells and seek specialist advice before live vaccines.

Alternative severe-disease induction when rituximab is unsuitable or the clinical context favours cyclophosphamide.

Cyclophosphamide intravenous pulses

Administer 15 mg/kg intravenously at induction, two weeks later and again at week four; subsequent pulses are three-weekly for the planned course, with reductions for age, renal impairment or leukopenia.

Monitor FBC, urine and infection, provide antiemesis and bladder protection and discuss fertility preservation, teratogenicity, bladder injury and cumulative malignancy risk.

Complement C5a-receptor blockade substitutes for much oral glucocorticoid exposure but does not replace definitive induction.

Avacopan

Use 30 mg orally twice daily with food alongside rituximab or cyclophosphamide in eligible severe active MPA under NICE commissioning; clinical product data extend to 52 weeks.

Check liver tests and hepatitis B, review infection, avoid strong CYP3A4 inducers and grapefruit, and stop for significant liver injury or angioedema. It is not recommended in pregnancy or without contraception when pregnancy is possible; individualise breast-feeding.

Conventional maintenance alternative when fixed-interval rituximab is unsuitable or reproductive considerations favour it.

Azathioprine

After remission, start 25–50 mg orally daily following TPMT assessment and increase toward 1.5–2 mg/kg/day under blood and liver monitoring.

Monitor FBC, liver and renal function, infection and pancreatitis; allopurinol or febuxostat requires expert avoidance or major dose adjustment. Doses up to 2 mg/kg/day are pregnancy-compatible under BSR guidance.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Chronic kidney failure

Necrotising crescentic nephritis can leave dialysis dependence, CKD, hypertension and cardiovascular risk even after immune remission.

Respiratory failure

Alveolar haemorrhage, infection, fibrosis and fluid overload can each produce hypoxia and may coexist during induction.

Permanent neuropathy and tissue loss

Nerve infarction, skin necrosis, mesenteric or cardiac ischaemia can cause fixed motor, sensory and organ disability.

Immunosuppression harm

Opportunistic infection, hypogammaglobulinaemia, cytopenia, gonadal toxicity, cancer, diabetes, osteoporosis and adrenal suppression require active prevention and structured surveillance.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

During induction follow oxygen, haemoglobin, urine output, creatinine, potassium, urinalysis, protein, FBC and liver tests at severity-appropriate frequency.
After remission measure eGFR, pressure, urine and protein and manage CKD cardiovascular, anaemia, bone and vaccination risk.
Follow immunoglobulins and infection burden during rituximab and cumulative cyclophosphamide exposure, fertility and urinary malignancy risk.
Assess fixed neuropathy, respiratory fibrosis and dialysis status separately from immune activity and provide rehabilitation.
Do not use MPO titre as a standalone reason to intensify treatment; respond to new objective organ change.
Revisit pregnancy, contraception and compatible maintenance before every teratogenic or long-persistence treatment.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

MPA lacks granulomatous destruction

Upper-airway symptoms do not exclude MPA, but a destructive nasal or orbital mass shifts probability toward GPA, infection or cancer.

Blood may stay microscopic

Persistent urinary red cells after remission can reflect damaged glomeruli; rising creatinine, casts and biopsy clarify renewed activity.

MPO is not an activity meter

Antibody can persist through remission, while serious relapse can occur without a dramatic titre rise.

Ground glass has competitors

Haemorrhage, infection, oedema and organising injury look similar and demand physiological and microbiological correlation.

Older age changes the balance

Lower relapse tendency in some MPO disease must be weighed against higher infection, CKD and cytotoxic-treatment risk.

11Common pitfallsFrequent interpretation and management errors.

01
Calling pulmonary-renal disease MPA before sending anti-GBM antibodies and cultures.
02
Waiting for haemoptysis before recognising diffuse alveolar haemorrhage.
03
Treating persistent MPO positivity without objective organ activity.
04
Assuming every new ground-glass opacity is relapse during rituximab treatment.
05
Giving unadjusted cyclophosphamide pulses in older adults with renal impairment.
06
Equating dialysis at presentation with irreversible renal failure before biopsy chronicity and recovery trajectory are known.