Ntatsaki E, Carruthers D, Chakravarty K, et al; BSR and BHPR Standards, Guidelines and Audit Working Group. BSR and BHPR guideline for the management of adults with ANCA-associated vasculitis. Rheumatology (Oxford). 2014 Dec;53(12):2306-9. doi: 10.1093/rheumatology/ket445. Epub 2014 Apr 11. PubMed PMID: 24729399.
Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013 Jan;65(1):1-11. doi: 10.1002/art.37715. PubMed PMID: 23045170.
Mukhtyar C, Guillevin L, Cid MC, et al; European Vasculitis Study Group. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis. 2009 Mar;68(3):310-7. doi: 10.1136/ard.2008.088096. Epub 2008 Apr 15. PubMed PMID: 18413444.
Definition, Etiology, PathogenesisTop
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) (EGPA) is a multisystem necrotizing granulomatous inflammation with eosinophilic infiltration of various tissues and organs. The lung is the most commonly involved organ, followed by skin. EGPA can affect any other organ in the cardiovascular, gastrointestinal, renal, and central nervous systems. In the respiratory tract, necrotizing inflammation affects predominantly small-sized and medium-sized vessels and is associated with concomitant asthma and eosinophilia. Nasal polyps as well as granulomatous and nongranulomatous extravascular inflammation (eg, nongranulomatous eosinophil-rich infiltrates of the lungs, myocardium, and gastrointestinal [GI] tract) are often observed.
Clinical Features and Natural HistoryTop
1. Signs and symptoms:
1) General symptoms: Fever, weakness, anorexia, weight loss.
2) Respiratory manifestations: Asthma (in >95% of patients; usually severe), allergic rhinitis, often nasal polyps, acute or chronic sinusitis, pleural effusion, rarely hemoptysis due to alveolar bleeding.
3) Nervous system manifestations: Mononeuritis multiplex (in ~70% of patients), symmetric polyneuropathy (~60%), central nervous system symptoms (rare).
4) Renal manifestations: Glomerulonephritis (85%).
5) Cardiovascular manifestations: Eosinophilic endocarditis and/or myocarditis, vasculitis affecting coronary arteries (may lead to myocardial infarction), and pericarditis. Symptoms of heart failure and of secondary hypertension due to renal involvement.
6) Cutaneous manifestations (40%-70%): Palpable purpura. Less frequently subcutaneous nodules, urticaria, livedo reticularis, ulcerating papules.
7) GI manifestations: Eosinophilic gastroenteritis, intestinal ischemia, necrosis, and perforation due to vasculitis, manifesting as recurrent, often severe abdominal pain, diarrhea, and GI bleeding.
8) Other manifestations (rare): Obstructive uropathy (due to urethral narrowing or prostatic granulomas), myalgia, muscle weakness, arthralgia (usually without effusion), choroiditis.
2. Natural history:
1) Prodromal phase: In patients aged 20 to 40 years, allergic rhinitis is usually observed, sometimes with polyps and asthma (usually in patients >30 years).
2) Eosinophilia phase: Symptoms of eosinophilic infiltration of tissues, for instance, in the lungs and the GI tract.
3) Vasculitis phase: Usually within 3 years from the onset of symptoms (occasionally as late as after 30 years).
Vasculitis may resolve with time, while allergic symptoms may recur. The disease may also manifest with minor or atypical symptoms. The most frequent causes of death are cardiac complications (heart failure, myocardial infarction, cardiac arrest); less commonly, hemorrhage, renal failure, GI complications (perforation or hemorrhage), and respiratory failure.
1. Laboratory tests: Eosinophilia in peripheral blood (often >1.5×109/L), elevation in the erythrocyte sedimentation rate and C-reactive protein levels, normocytic anemia, features of renal involvement (microscopic hematuria, proteinuria), a positive myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) test result (in ~60% of patients).
2. Imaging studies: Radiographs and computed tomography (CT) reveal signs of chronic sinusitis and alveolar hemorrhage.
3. Pulmonary function tests: Features characteristic of asthma.
4. Histologic examination of samples of the involved organs (usually of the respiratory tract, skin, or kidneys): Patchy necrotizing vasculitis affecting small and medium vessels, necrotizing granulomatous inflammation with extensive eosinophilic infiltrates (nongranulomatous inflammation with eosinophilic infiltrates may also be present).
Diagnostic criteria are based on the typical clinical features and histologic examination of the samples of the involved organs (if biopsy results are available). The Lanham classification criteria consist of asthma, peripheral blood eosinophilia (>1500 microL), and features of vasculitis involving ≥2 extrapulmonary organs.
Differential diagnosis should include other systemic vasculitides (will not present with peripheral blood eosinophilia), chronic severe asthma, pulmonary eosinophilias, and other causes of peripheral blood eosinophilia (see Chronic Eosinophilic Leukemia (and Other Causes of Hypereosinophilia)); in particular idiopathic eosinophilia, which is not associated with vasculitis).
The choice of treatment depends on disease extent and prognosis and requires a specialist approach. Prognosis is worse in patients aged >65 years; those with heart failure, gastrointestinal tract involvement, or creatinine levels >150 micromol/L; and those without ear, nose, and throat involvement. Patients with mild disease (none or only 1 of the above factors present) and no renal involvement may be treated with glucocorticoid monotherapy.Evidence 1Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the open-label study design and indirectness (no comparison to placebo). Ribi C, Cohen P, Pagnoux C, et al; French Vasculitis Study Group. 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. doi: 10.1002/art.23198. PubMed PMID: 18240234. Ribi C, Cohen P, Pagnoux C, et al; French Vasculitis Study Group. Treatment of polyarteritis nodosa and microscopic polyangiitis without poor-prognosis factors: A prospective randomized study of one hundred twenty-four patients. Arthritis Rheum. 2010 Apr;62(4):1186-97. doi: 10.1002/art.27340. PubMed PMID: 20131268. In more severe cases, especially with central nervous system involvement, glucocorticoid therapy can be used in combination with cyclophosphamide according to the treatment regimen used in granulomatosis with polyangiitis.Evidence 2Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). de Groot K, Adu D, Savage CO; EUVAS (European vasculitis study group). The value of pulse cyclophosphamide in ANCA-associated vasculitis: meta-analysis and critical review. Nephrol Dial Transplant. 2001 Oct;16(10):2018-27. PubMed PMID: 11572891. de Groot K, Harper L, Jayne DR, et al; EUVAS (European Vasculitis Study Group). Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med. 2009 May 19;150(10):670-80. PubMed PMID: 19451574. Walters G, Willis NS, Craig JC. Interventions for renal vasculitis in adults. Cochrane Database Syst Rev. 2008 Jul 16;(3):CD003232. doi: 10.1002/14651858.CD003232.pub2. Review. Update in: Cochrane Database Syst Rev. 2015;9:CD003232. PubMed PMID: 18646089. Harper L, Morgan MD, Walsh M, et al; EUVAS investigators. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up. Ann Rheum Dis. 2012 Jun;71(6):955-60. doi: 10.1136/annrheumdis-2011-200477. Epub 2011 Nov 29. PubMed PMID: 22128076. Five-year survival rates are ~80%. In patients with refractory or relapsing disease, the addition of mepolizumab was associated with some benefit.Evidence 3Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness and imprecision. Wechsler ME, Akuthota P, Jayne D, et al; EGPA Mepolizumab Study Team. Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2017 May 18;376(20):1921-1932. doi: 10.1056/NEJMoa1702079. PubMed PMID: 28514601; PubMed Central PMCID: PMC5548295.