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EOSINOPHILIC GRANULOMATOSIS with POLYANGIITIS EGPA: Diagnosis & Treatment Approaches Characteristics

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EOSINOPHILIC GRANULOMATOSIS with POLYANGIITIS EGPA: Diagnosis & Treatment Approaches Characteristics EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS EGPA: Diagnosis & Treatment Approaches Characteristics • Moderate to severe asthma • Peripheral blood eosinophilia (> 10% eosinophils) • Pulmonary inltrates • Paranasal sinus abnormality • Mononeuropathy or polyneuropathy • Extravascular eosinophils/eosinophilic vasculitis of small- to medium-sized blood vessels • Positive ANCA STEP 1 Basic evaluation • DETAILED HISTORY AND PHYSICAL EXAM • ASK ABOUT EXPOSURES: Medications, dietary supplements, recreational drugs, toxins, workplace, travel • SEARCH FOR EXTRAPULMONARY DISEASE: Nasal/sinus, ocular, skin, cardiac, gastrointestinal, neurologic, renal, vascular Tailor according to history and physical: • IMAGING/TESTING: CXR, chest CT scan, sinus CT scan, EMG/NCV, echocardiogram or cardiac MRI • LABORATORY: CBC with dierential, ESR, CRP, ANCA( MPO/PR3), vitamin B12, electrolytes, LFTs, total protein, urinalysis Serum tryptase level, serum Ig’s (include IgE), Troponin Bone marrow aspirate and biopsy with reticulin and tryptase stains STEP Exclude major secondary causes of 2 pulmonary eosinophilia DISORDERS EVALUATIONS AND TESTS TO TO EXCLUDE CONSIDER HIV • HIV serology Drug or Primary toxin allergic • Drug and dietary supplement history reaction disorders • Allergen testing (skin testing and specic IgE testing), • Discontinuation of potential causative agents Aspergillus specic IgE's and precipitins Parasitic/ • Travel history Autoimmune helminthic • Stools for ova and parasites • Auto-antibodies (ANA & autoantibody testing for disorders pertinent rheumatologic conditions), infection • Serologies for parasitic infection (based on travel history) specialized clotting studies Nonparasitic Systemic infection • TB skin test, IGRA, M. tuberculosis cultures mastocytosis (TB, Cocci) • Coccidioides serologies, fungal cultures • c-KIT mutation analysis, serum tryptase level Myeloid • Blood immunophenotyping and molecular phenotyping neoplasms/ • (e.g. FIP1L1-PDGFRα) Solid tumors Lymphoma • Bone marrow aspirate/biopsy with cytogenetics, • CT/MR scan immunophenotyping STEP 3 Exclude other diseases associated with eosinophilia LUNG SYSTEMIC DISEASES • Asthma/eosinophilic bronchitis DISEASES • Rheumatoid arthritis • Allergic bronchopulmonary aspergillosis • Sarcoidosis • Bronchocentric granulomatosis • Sjögren syndrome • Cryptogenic organizing pneumonia • Hypereosinophilic Syndrome • Hypersensitivity pneumonitis • Idiopathic pulmonary brosis • Pulmonary Langerhans cell histiocytosis • Postradiation pneumonitis • Chronic eosinophilic pneumonia This reference aid was supported by an educational grant from GlaxoSmithKline. njhealth.org National Jewish Health 1.877.CALLNJH (1.877.225.5654) © 2019 National Jewish Health STEP Distinguish between the primary pulmonary 4 eosinophilic disorders EOSINOPHILIC ACUTE EOSINOPHILIC CHRONIC EOSINOPHILIC HYPEREOSINOPHILIC GRANULOMATOSIS WITH PNEUMONIA PNEUMONIA SYNDROME POLYANGIITIS1 Acute febrile illness; Subacute illness; eosinophilia Sustained overproduction Necrotizing vasculitis hypoxemic respiratory failure; in lung tissue and blood; of eosinophils; marked of small- to medium- diuse pulmonary inltrates; bilateral pulmonary inltrates peripheral blood eosinophilia; sized blood vessels; KEY BAL uid eosinophils > 25%; may be peripheral in location tissue eosinophilia; end- asthma; eosinophil-rich FEATURES1 previously healthy person organ damage; includes granulomatous inammation myeloproliferative, of respiratory tract; lymphocytic, familial, and involves multiple organs idiopathic variants Acute Indolent Indolent Indolent Onset (days) (weeks/months) (months/years) (months/years) Pulmonary inltrates Diuse Peripheral Patchy Patchy Fulminant respiratory failure Frequently Occurs Rarely Occurs Rarely Occurs Rarely Occurs Asthma/allergy history Rarely Occurs Commonly Occurs Rarely Occurs Frequently Occurs Smoking history Commonly Occurs Rarely Occurs Rarely Occurs Rarely Occurs Vasculitis Rarely Occurs Rarely Occurs Rarely Occurs Frequently Occurs ANCA Rarely Occurs Rarely Occurs Rarely Occurs Commonly Occurs Cardiac involvement Rarely Occurs Occasionally Occurs Frequently Occurs Commonly Occurs Neurologic involvement Rarely Occurs Occasionally Occurs Frequently Occurs Frequently Occurs Requirement for therapies Rarely Occurs Rarely Occurs Frequently Occurs Commonly Occurs other than corticosteroids STEP 5 Comparison of ANCA-associated vasculitides Small to medium vessel necrotizing vasculitides with dierentiating features GPA EGPA MPA Almost Always ANCA positive Sometimes ANCA positive Almost always ANCA positive C-ANCA and PR3 specicity p-ANCA and MPO specicity p-ANCA and MPO specicity Unlikely to exhibit asthma Asthma common Unlikely to exhibit blood eosinophilia Unlikely to exhibit blood eosinophilia Always exhibits blood eosinophilia Glomerulonephritis common Glomerulonephritis common Glomerulonephritis less common STEP 6 Treatment CHRONIC: Unresponsive to steroids alone Unable to refer ACUTE: Frequent exacerbation/relapses despite steroid Corticosteroids, 1-2 mg/kg CNS Try Add-on RX - mepolizumab (300 mg/monthly)2 EGPA Rx Cardiac OFFLABEL methotrexate (MZX) OFFLABEL Add cyclophosphamide for severe systemic OFFLABEL azathioprine (AZA) involvement OFFLABEL mycophenolate mofetil (MMF) Treat asthma/sinus disease CLINICAL BENEFIT USING Remission (BVAS 0 and ≤ 4 mg/day GC) AND/OR MEPOLIZUMAB FOR THE ≥50% reduction in OCS dose AND/OR TREATMENT OF EGPA3 Relapse-free [78% Mepolizumab vs 32% Placebo] • Eosinophilic granulomatosis with polyangiitis (EGPA) was previously called Churg-Strauss syndrome. • BAL, transbronchial or open-lung biopsy may be necessary, depending on clinical and radiographic ndings. • Additional testing may be needed to evaluate for extrapulmonary disease. Abbreviations: BAL, bronchoalveolar lavage; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; ANCA, antineutrophil cytoplasmic antibody; Ig, immunoglobulin; LFT, liver function test; TB, tuberculosis; IGRA, interferon gamma release assay; RT-PCR, reverse transcriptase-polymerase chain reaction; References: 1 Wechsler ME. Pulmonary eosinophilic syndromes. Immunol Allergy Clin N Am. 2007;27:477-492.3 2 Wechsler, ME, et al. Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2017 May 18;376(20):1921-1932 3 Steinfeld J, et al. Evaluation of clinical benet from treatment with mepolizumab for patients with eosinophilic granulomatosis with polyangiitis. J Allergy Clin Immunol 2019 Jun;143(6):2170-2177.
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