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allergic angiitis & granulomatosis of Churg-Strauss; eosinophilic granulomatosis with polyangiitis (EGPA)

Etiology: - hypersensitivity? - occurs most often in the setting of antecedent - asthma - sinusitis - allergic rhinitis Epidemiology: 1) can occur at any age; mean age of onset: 44 years 2) male:female ratio 1.3:1 3) rare [4] Pathology: 1) tissue infiltration with eosinophils 2) extravascular granulomas surrounded by eosinophils 3) granulomatous necrotizing vasculitis a) affects small & medium sized muscular arteries, capillaries, veins, venules b) necrosis, fibrinoid deposition & leukocyte infiltration c) deposition of immune complexes in blood vessel walls 4) multiple organ involvement 5) lung involvement is predominant - granulomatous inflammation of the respiratory tract 6) skin, cardiovascular system, kidney, peripheral nervous system & gastrointestinal tract commonly involved * histopathology image [10,14] Clinical manifestations: 1) fever, malaise, anorexia, weight loss 2) allergic rhinitis, nasal polyps, mucusal crusting & septal perforation (> 70%) 3) wheezing, asthma, severe asthmatic attacks 4) upper airway & sinus disease (sinusitis) precedes difficult to treat asthma [3] 5) hemoptysis 6) skin lesions in 60-70% of patients a) palpable purpura b) subcutaneous & cutaneous nodules c) papules with vesiculation [14] d) cutaneous infarcts 7) renal disease less common than polyarteritis nodosa - pauci-immune necrotizing glomerulonephritis 8) syndrome resembling Loffler's syndrome 9) mononeuritis multiplex or sensorimotor peripheral neuropathy - foot drop 10) arthralgias, myalgias 11) cardiac - endocarditis, myocarditis, arrhythmia, heart failure 12) abdominal pain, GI bleed * images [9,10,14] Laboratory: 1) no specific laboratory tests 2) complete blood count (CBC) a) most patients have leukocytosis b) eosinophils in blood (eosinophil count) - eosinophilia (> 1000/mm3 in 80%); > 1500/mm3 [4] 3) erythrocyte sedimentation rate (ESR) is generally elevated 4) serology a) elevation of serum IgE b) negative serology for Aspergillus c) rheumatoid factor may be positive d) immune complexes may be observed e) cryoglobulins may be observed f) hypergammaglobulinemia may be observed g) pANCA positive in 40-70% - anti-myeloperoxidase Ab (MPO) - positive pANCA risk factor for glomerulonephritis palpable purpura, mononeuritis multiplex, hemoptysis 5) skin biopsy - distinguish from Henoch-Schonlein purpura 6) sural nerve biopsy [3] - necrotizing vasculitis with eosinophilic granulomas 7) see ARUP consult [5] Radiology: 1) chest X-ray - migratory pulmonary infiltrates generally in upper 2/3 of lung fields (image [10]) 2) computed tomography (thorax) - negative for bronchiectasis Differential diagnosis: 1) polyarteritis nodosa - respiratory tract disease & eosinophilia are not features 2) Henoch Schonlein purpura 3) pulmonary infiltrates with eosinophilia (PIE) syndrome 4) Loffler's syndrome 5) allergic bronchopulmonary aspergillosis 6) chronic eosinophilic pneumonia 7) hypereosinophilic syndrome 8) Behcet syndrome - recurrent oral, genital ulcers, inflammatory eye disease - mononeuritis multiplex & respiratory tract disease are not features 9) cryoglobulinemic vasculitis - pulmonary involvement is rare, eosinophilia is not a feature Complications: 1) pulmonary infiltrates or nodules 2) pleural effusion 3) pulmonary angiitis 4) cardiomegaly 5) eosinophilic gastroenteritis 6) extravascular necrotizing granuloma of the skin 7) mononeuritis multiplex 8) polyarthritis Management: 1) combination therapy for induction a) glucocorticoid plus cyclophosphamide or rituximab is recommended to induce remission in severe disease [15] b) glucocorticoid plus mepolizumab or methotrexate, azathioprine of mycophenolate mofetil to induce remission in less severe disease [15] 2) high-dose glucocorticoid therapy a) increases 5 year survival to 50% b) initial: prednisone 60 to 100 mg PO QD c) slow taper with clinical improvement - flares associated with glucorticoid tapers d) eosinophil count generally declines rapidly 3) in some patients disease is mild & may remit spontaneously or with short courses of glucocorticoids 4) cyclophosphamide and alternate day prednisone therapy for patients who fail glucocorticoids or who present with fulminant multisystem disease 5) rituximab, mepolizumab or benralizumab may be of benefit [8,16] 6) use of leukotriene inhibitors associated with flares 7) prognosis a) prognosis if untreated is poor 1] 5 year survival is 25%, if untreated 2] cause of death generally pulmonary or cardiac b) 80% of patients achieve remission with treatment c) relapse occurs in 40% d) 10-year survival is 80% [3]

Interactions

disease interactions

Related

granulomatosis with polyangiitis; Wegener's granulomatosis

General

ANCA-associated vasculitis

Properties

PATHOLOGY: granulomatosis with polyangiitis

References

  1. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1175-76, 1672-3
  2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 173, 754, 783, 845
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2022 - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. Khasnis A and Langford CA. Update on vasculitis. J Allergy Clin Immunol 2009 Jun; 123:1226. PMID: 19501230
  5. ARUP Consult: Churg-Strauss Syndrome The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/eosinophilic-granulomatosis-polyangiitis
  6. Baldini C, Talarico R, Della Rossa A, Bombardieri S. Clinical manifestations and treatment of Churg-Strauss syndrome. Rheum Dis Clin North Am. 2010 Aug;36(3):527-43. PMID: 20688248
  7. Ribi C, Cohen P, Pagnoux C et al Treatment of Churg-Strauss syndrome without poor-prognosis factors: a multicenter, prospective, randomized, open-label study of seventy-two patients. Arthritis Rheum. 2008 Feb;58(2):586-94 PMID: 18240234
  8. Mahr A, Moosig F, Neumann T et al Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): evolutions in classification, etiopathogenesis, assessment and management. Curr Opin Rheumatol. 2014 Jan;26(1):16-23 PMID: 24257370
  9. DermNet NZ (images) Churg-Strauss syndrome (allergic granulomatosis) http://www.dermnetnz.org/systemic/churg-strauss.html
  10. Farid-Moayer M, Diamond HS (images) Medscape: Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome) http://emedicine.medscape.com/article/333492-overview
  11. Divakaran S, Vaidya A, Kobzik L, Dellaripa P. All That Wheezes... N Engl J Med 2017; 377:e6. July 27, 2017 PMID: 28745993 Free full text http://www.nejm.org/doi/full/10.1056/NEJMimc1613182 - Rothaus C All That Wheezes. NEJM Resident 360. Aug 2, 2017 https://resident360.nejm.org/content_items/all-that-wheezes
  12. Noth I, Strek ME, Leff AR. Churg-Strauss syndrome. Lancet. 2003 Feb 15;361(9357):587-94. Review. PMID: 12598156
  13. Palamara K, Nagarur A, Fintelmann FJ et al Case 32-2017 - A 64-Year-Old Man with Dyspnea, Wheezing, Headache, Cough, and Night Sweats. N Engl J Med 2017; 377:1569-1578. October 19, 2017 PMID: 29045211 http://www.nejm.org/doi/full/10.1056/NEJMcpc1703513
  14. Korman AM, Chung CG Eosinophilic Granulomatosis With Polyangiitis. JAMA Dermatol. 2021;157(6):722 PMID: 33881454 https://jamanetwork.com/journals/jamadermatology/fullarticle/2778634
  15. Chung SA, Langford CA, Maz M et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol 2021 Aug; 73:1366-1383. PMID: 34235894 https://onlinelibrary.wiley.com/doi/10.1002/art.41773
  16. Wechsler ME, Nair P, Terrier B, et al. Benralizumab versus Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2024 Feb 23. PMID: 38393328