Eosinophilic granulomatosis with polyangiitis

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

EGPA is a rare eosinophilic and necrotising small-vessel vasculitis occurring in people with asthma and usually chronic rhinosinusitis. Its course often moves from atopic airway disease through eosinophilic blood and tissue inflammation to systemic vasculitis, but phases overlap and the order is not mandatory. Examine skin, peripheral nerves, lungs, heart and abdomen and check urine even when asthma dominates the consultation.

ANCA separates imperfect phenotypes rather than defining the disease. MPO-positive patients more often develop glomerulonephritis, purpura and neuropathy; ANCA-negative patients may have prominent eosinophilic cardiac and lung disease. Classification criteria support research but are not a diagnostic shortcut. A tissue biopsy from skin, nerve, muscle, kidney or another affected organ can demonstrate eosinophil-rich inflammation or necrotising vasculitis and exclude infection or malignancy.

Every marked eosinophilia demands an alternative-cause assessment. Travel and residence inform helminth testing and empirical Strongyloides management before steroid where appropriate. Review all new medicines, fungal sensitisation, atopy and haematological clues such as splenomegaly, abnormal film, very high B12 or tryptase. Cardiac screening is performed even without symptoms because myocarditis and fibrosis can be missed by examination and echocardiography alone.

Treatment is severity-based. High-dose glucocorticoid plus cyclophosphamide or selected rituximab induces remission in organ-threatening disease. For eligible adults with relapsing or refractory non-organ-threatening disease, NICE recommends benralizumab as add-on treatment. Mepolizumab also has a licensed EGPA regimen, but NICE terminated its appraisal without an NHS recommendation. Airway symptoms, fixed damage and active vasculitis are assessed separately during steroid taper, rehabilitation and pain care.

Key points

Suspect EGPA when adult-onset asthma and chronic rhinosinusitis accompany eosinophilia, migratory lung infiltrates, purpura, neuropathy, cardiac, renal or gastrointestinal disease.
Check the absolute eosinophil count before high-dose steroid when safe, because glucocorticoid can normalise it rapidly and obscure phenotype.
MPO-ANCA supports a vasculitic subset but most patients can be ANCA-negative; never use a negative test to dismiss eosinophilic myocarditis or neuropathy.
Exclude Strongyloides and other exposure-related parasites, ABPA, drug reaction, clonal eosinophilia and hypereosinophilic syndrome using travel, medicine, IgE, microbiology, film and molecular or marrow tests when indicated.
Obtain ECG, troponin, NT-proBNP and echocardiography at baseline; use cardiac MRI for suspected myocarditis because cardiac disease can be clinically subtle and prognostically dominant.
Organ-threatening heart, nerve, kidney, lung or gut disease needs high-dose glucocorticoid plus cyclophosphamide or selected rituximab; an anti-IL-5 biologic does not replace urgent induction.
Benralizumab 30 mg subcutaneously every four weeks is NICE-recommended for eligible adults with relapsing or refractory non-organ-threatening EGPA and can reduce steroid exposure.
Mepolizumab 300 mg every four weeks is licensed for adult EGPA, but NICE TA845 did not make an NHS recommendation; severe-asthma funding must not be assumed to cover EGPA.
Monitor asthma, sinus, eosinophil, vascular, nerve, cardiac and steroid-toxicity domains separately; worsening wheeze does not automatically mean vasculitic relapse.
Before immunosuppression address vaccines, TB and hepatitis as agent-relevant, Strongyloides risk, Pneumocystis prevention, bone health, fertility and pregnancy.

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

Atopic and eosinophilic susceptibility

Adult-onset asthma, chronic rhinosinusitis and type-2 immune activation often precede vasculitis, with IL-5 supporting eosinophil maturation and survival.

ANCA-associated subset

MPO-ANCA occurs in a minority and associates more with glomerulonephritis, neuropathy and capillaritis, while ANCA-negative disease often has cardiac and eosinophilic tissue involvement.

Drug and exposure context

Medicines can cause eosinophilia or unmask disease during steroid withdrawal; leukotriene antagonists are not established as a direct universal cause.

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

1
Eosinophilic tissue infiltration
Activated eosinophils release cytotoxic granule proteins and lipid mediators into lung, heart, gut, skin and nerves, causing inflammation and fibrosis.
2
Necrotising small-vessel vasculitis
Neutrophil and immune pathways injure arterioles, capillaries and venules, producing purpura, mononeuritis, renal capillaritis and organ ischaemia.
3
Granulomatous airway inflammation
Eosinophil-rich granulomatous inflammation affects respiratory tissues, linking chronic sinus disease and asthma with migratory pulmonary infiltrates.
4
Relapsing airway and vasculitic domains
Asthma and sinus activity may persist independently of systemic vasculitis, so response and relapse must be measured in separate organ domains.

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

Airway-eosinophilic prodrome

Adult-onset asthma, nasal polyps, chronic sinus disease and blood eosinophilia often precede systemic vasculitis by years.

Migratory lung disease

Transient peripheral infiltrates and eosinophilic pneumonia with asthma support EGPA after infection and ABPA are evaluated.

Mononeuritis multiplexRed flag

Acute painful asymmetric sensory loss and foot or wrist drop is a classic organ-threatening vasculitic feature.

Cardiac involvementRed flag

Chest pain, arrhythmia, troponin elevation, heart failure or MRI inflammation may occur particularly in ANCA-negative eosinophilic disease.

Skin and renal vasculitis

Palpable purpura, nodules and glomerular haematuria support systemic small-vessel disease rather than isolated severe asthma.

Red flags requiring action

Chest pain, syncope, arrhythmia, troponin rise, ventricular dysfunction or unexplained dyspnoea may indicate eosinophilic myocarditis even without striking CRP.
New painful asymmetric sensory loss, foot drop or wrist drop indicates nerve infarction and should not be attributed to asthma medication.
Severe abdominal pain, bleeding or peritonism may represent mesenteric vasculitis and requires urgent imaging and surgical review.
Hypoxia with diffuse opacity, falling haemoglobin or renal active sediment suggests pulmonary-renal capillaritis rather than uncomplicated asthma.
Marked eosinophilia requires rapid review of helminths, medicines, haematological neoplasm and hypereosinophilic syndrome before immunosuppression obscures 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
FBC with absolute eosinophils and blood filmFirst step
Why
Confirm eosinophilia before steroid and identify clonal or reactive haematological clues.
Interpretation and limitations
Steroid rapidly lowers eosinophils; abnormal cells, splenomegaly or extreme persistent count needs haematology and molecular assessment.
02
MPO-ANCA and PR3-ANCA
Why
Support vasculitic phenotype and renal or nerve risk in a compatible clinical syndrome.
Interpretation and limitations
Only a minority are positive, usually MPO; a negative assay does not exclude EGPA and a positive result is not diagnostic alone.
03
ECG, troponin, NT-proBNP, echo and cardiac MRI
Why
Detect myocarditis, ventricular dysfunction, pericardial and fibrotic disease.
Interpretation and limitations
Normal echocardiography does not exclude myocarditis; MRI provides tissue characterisation and guides cardiology involvement.
04
HRCT chest and pulmonary physiology
Why
Define eosinophilic infiltrates, haemorrhage, airway disease, infection and chronic damage.
Interpretation and limitations
Migratory ground glass or consolidation is supportive but nonspecific; pair with microbiology and oxygen, FVC and gas transfer.
05
Parasite, fungal and secondary eosinophilia screen
Why
Prevent fatal steroid-amplified infection and identify treatable mimics.
Interpretation and limitations
Use travel-based Strongyloides serology or stool testing, Aspergillus tests, HIV, medicine review, IgE and clonal studies according to risk.
06
Biopsy of affected tissue
Why
Demonstrate eosinophilic inflammation or necrotising vasculitis and exclude infection, cancer or another eosinophilic disorder.
Interpretation and limitations
Choose skin, nerve-muscle, kidney or other organ for yield and safety; classical granulomas may be absent in small samples.

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

Parasitic and fungal infection

Strongyloides and other helminths, allergic bronchopulmonary aspergillosis and fungal disease cause eosinophilia and lung change and may disseminate after steroid.

Drug reaction

DRESS, antibiotics, anticonvulsants and other medicines can cause eosinophilia, rash, liver, renal and lung injury with a different temporal pattern.

Hypereosinophilic or clonal disease

Myeloid neoplasm, FIP1L1-PDGFRA disease and idiopathic hypereosinophilic syndrome can injure heart and organs without the characteristic asthma-vasculitis phenotype.

GPA, MPA and eosinophilic asthma

Destructive granulomatous ENT disease suggests GPA, pulmonary-renal MPO disease without asthma suggests MPA, and isolated eosinophilic asthma lacks systemic vasculitis.

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

01First-line confirmationDefine eosinophilic, vasculitic and secondary causesFirst stepFirst lineAsthma or sinus disease accompanies eosinophilia and systemic organ features.

1Record the pre-steroid eosinophil count, travel, medicines, atopy, asthma trajectory and skin, nerve, heart, lung, renal and gut findings.
2Send ANCA, urine, renal, cardiac and lung tests and a phenotype-directed parasite, fungal and clonal-eosinophilia screen.
3Biopsy the safest active site and begin urgent treatment before pathology only when myocarditis, neuropathy or another organ is threatened.

02Organ-threatening inductionCombine high-dose treatment earlyCardiac, neurological, renal, alveolar-haemorrhage or gastrointestinal vasculitis threatens function or life.

1Give intravenous methylprednisolone for critical disease then oral prednisolone with a documented reduced taper and infection protection.
2Add intravenous cyclophosphamide or rituximab selected by organ, ANCA, fertility, prior exposure, infection and specialist guidance.
3Measure heart, nerve, kidney, lung or gut response directly and provide rehabilitation and thrombosis or critical-care support.

03NICE-recommended add-onUse IL-5-receptor steroid sparingAdult EGPA relapses or remains refractory without current organ-threatening or life-threatening disease.

1Confirm the symptoms represent active EGPA rather than infection, fixed airway disease, damage, poor inhaler technique or another eosinophilic disorder.
2Optimise asthma and nasal treatment and offer benralizumab 30 mg subcutaneously every four weeks when NICE TA1096 criteria are met.
3Taper glucocorticoid against separate airway and systemic outcomes and reassess promptly if nerve, heart, kidney, lung or abdominal signs emerge.

04Apparent relapseSeparate airway activity from vasculitisWheeze, eosinophils, pain or systemic symptoms worsen during taper.

1Review adherence, inhaler technique, infection, allergen, steroid exposure and objective eosinophil, nerve, urine, cardiac and imaging changes.
2EscalationTreat asthma exacerbation and systemic vasculitis according to their own severity rather than automatically escalating all immunosuppression.
3Re-biopsy or obtain cardiac or neurological studies when mechanism remains uncertain and consequences are high.

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

Rapid suppression of eosinophilic and vasculitic inflammation while definitive steroid-sparing treatment becomes effective.

Prednisolone

For active systemic EGPA use 0.5–1 mg/kg orally once daily, with intravenous methylprednisolone 500 mg–1 g daily for three days in critical organ disease, followed by a planned taper.

Assess infection and Strongyloides risk, glucose, pressure, mood, eyes and bone and provide Pneumocystis prophylaxis when total immune risk indicates. Never stop prolonged therapy abruptly.

NICE-recommended IL-5-receptor biologic for non-organ-threatening relapsing or refractory EGPA, reducing eosinophilic activity and oral glucocorticoid exposure.

Benralizumab

For adult relapsing or refractory EGPA use 30 mg subcutaneously once every four weeks as add-on treatment under NICE TA1096 and specialist supervision.

It has not been studied as induction for active organ-threatening or life-threatening EGPA. Treat helminth infection first where possible, monitor hypersensitivity and taper glucocorticoid gradually. Prefer avoidance in pregnancy; use only when maternal benefit outweighs fetal risk, and individualise breast-feeding.

Potent induction for myocarditis, severe neuropathy, renal, pulmonary-haemorrhage or gastrointestinal vasculitis.

Intravenous cyclophosphamide

For severe organ-threatening EGPA, one specialist approach gives 15 mg/kg intravenously at baseline, week two and week four, followed by pulses every three weeks; age, renal function and cytopenia determine reductions.

Monitor FBC, infection, urine and cumulative exposure and provide bladder and antiemetic support. Address fertility preservation, pregnancy avoidance and malignancy risk.

Specialist alternative for severe or relapsing vasculitic EGPA, particularly MPO-positive disease or when cyclophosphamide is unsuitable.

Rituximab

Specialists may use 1,000 mg intravenously on days 1 and 15 or 375 mg/m² weekly for four doses; both regimens are off-label for the EGPA indication.

Exclude infection and screen hepatitis B and TB; check immunoglobulins, vaccinate before treatment when feasible, and watch for infusion reactions, delayed neutropenia and low IgG. Plan pregnancy with the specialist team and seek neonatal B-cell and live-vaccine advice after later gestational use.

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

Cardiac failure and arrhythmia

Eosinophilic myocarditis, coronary arteritis, pericarditis and fibrosis can cause ventricular failure, thrombosis, arrhythmia and sudden death.

Permanent neuropathy

Vasa-nervorum infarction causes painful mononeuritis multiplex and fixed foot or wrist drop despite later control of inflammation.

Pulmonary and gastrointestinal injury

Asthma, eosinophilic pneumonia, haemorrhage, mesenteric ischaemia, perforation and bleeding can threaten respiration, tissue perfusion and bowel viability.

Treatment and eosinophil-rebound harm

Infection, osteoporosis and metabolic steroid toxicity coexist with relapse when glucocorticoid is tapered without adequate disease control.

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

Track asthma control, oral steroid, exacerbations and spirometry separately from eosinophil count and vasculitic organ activity.
Repeat ECG, troponin, NT-proBNP, echocardiography or cardiac MRI according to baseline involvement and new symptoms.
Document nerve pain, sensory maps, power and function with neurophysiology or rehabilitation follow-up after mononeuritis.
Check FBC with eosinophils, renal, liver, urine and agent-specific immunoglobulin, infection and vaccine safety.
Review Strongyloides and travel risk before each major steroid escalation and investigate infection during new lung opacity.
Address bone, glucose, pressure, fertility, pregnancy, neuropathic pain, falls and work throughout long-term treatment.

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

ANCA-negative is still vasculitis

Many cardiac and eosinophilic EGPA cases lack ANCA, so direct organ and tissue evidence matters more than seronegativity.

Asthma and vasculitis decouple

Wheeze may persist after systemic remission, and life-threatening myocarditis can occur when airway symptoms seem modest.

Capture eosinophils before steroid

One high-dose glucocorticoid dose can rapidly erase a diagnostic blood clue, though emergency treatment must never be delayed.

Cardiac MRI adds tissue information

Echocardiography can be normal despite myocarditis or fibrosis; MRI detects oedema and scar that changes prognosis and treatment.

Commissioning follows indication

Benralizumab now has positive NICE EGPA guidance, whereas the terminated mepolizumab appraisal did not create routine NHS EGPA funding despite a licence.

11Common pitfallsFrequent interpretation and management errors.

01
Excluding EGPA because ANCA is negative.
02
Starting high-dose steroid for eosinophilia without considering Strongyloides exposure and clonal disease.
03
Treating new foot drop as lumbar radiculopathy without mapping separate painful nerve deficits.
04
Omitting baseline cardiac assessment because there is no chest pain.
05
Using an asthma biologic schedule or commissioning route without checking the EGPA indication.
06
Calling every wheeze systemic relapse and accumulating glucocorticoid without objective organ assessment.