Churg Straus Syndrome – renamed as eosinophilic granulomatosis with polyangiitis (EGPA) – is a specific variant of the group of diseases characterized by necrotizing vasculitis of small and medium-sized systemic blood vessels. Other subtypes within the broad group include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and polyarteritis nodosa. It is distinctive from the other diseases in the category by the coexistence of asthma, rhinosinusitis, and presence of peripheral eosinophilia.
Jacob Churg and Lotte Strauss first described the entity based on autopsy findings in a case series of 13 patients in 1951. They all had a familiar pattern of illness with severe asthma, fever, blood eosinophilia and autopsy evidence of granulomatous necrotizing vasculitis. They named the disease allergic granulomatosis and angiitis. Their classic definition and diagnosis of the disease required presence of all 3 features of:
However, as individuals presented a wide variance of these features, rarely with the presence of all 3 features, more clinically relevant diagnostic criteria became necessary.
Lanham et al. proposed a definition based on:
An unintended drawback of this diagnostic criteria was a delayed diagnosis of the disease waiting until 2 or more organ systems were involved. Early cases with a more favorable prognosis, therefore, ran into the risk of being missed.
American College of Rheumatology proposed new classification criteria in 1990 where 4 out of 6 features needed to be identified:
It rendered a 99.7% specificity and 85% sensitivity for diagnosis.
The Chapel Hill consensus conference in 1994 came up with a definition of EGPA as "eosinophil-rich and granulomatous inflammation involving respiratory tract and necrotizing vasculitis affecting small to medium-sized vessels associated with asthma and eosinophilia."
The significance of this definition was its exclusion of biopsy as a necessity for diagnosis and therefore its ability to recognize early cases with only asthma and tissue and blood eosinophilia.
There have been efforts in recent years to sub-classify clinical phenotypes of eosinophilic granulomatosis with polyangiitis based on the presence or absence of vasculitis, somewhat counterintuitive to the nomenclature itself.
Patients who are ANCA positive (reported around 40% of all EGPA patients) tend to have a vasculitic phenotype and are more common to have myalgia, migrating polyarthralgia, weight loss, mononeuritis multiplex, and renal involvement either as crescentic or necrotizing glomerulonephritis.
Conversely, patients without ANCA positivity tend to have an eosinophilic phenotype with a higher incidence of myocarditis.
Presence of ANCA alone, however, is not the absolute correlate to vasculitis. About 47% of patients in a study by Cottin et al. had vasculitis without seropositivity for ANCA, while 29% were positive for myeloperoxidase ANCA without the presence of vasculitis.
About 41% of patients in the same series by Cottin et al., did not have vasculitis but rather an eosinophilic tissue infiltrate and involvement.
They, therefore, suggested isolating and recognizing a subgroup with features of vasculitis to be defined here.
2. Surrogates of Vasculitis
4. Presence of ANCA
The rest of the patients will fall into the eosinophilic asthma phenotype. It is important to recognize that subgroup early, particularly in the presence of myocarditis with no other evidence of vasculitis. Overly depending on the presence of vasculitis to diagnose EGPA may result in missing out those eosinophilic asthma patients who may otherwise benefit from early targeted therapy.
The primary trigger in pathogenesis in cellular level seems to be an aberrant T-helper cell pathway.
Role of the Th2 Cell Lineage
There have been various theories about what prompts an abnormal Th-2 type immune response in the first place. Allergies, infections, medications have all been considered. The allergy theory has not been substantiated in spite of a high prevalence of IgE levels as studies show that hypersensitivity to currently tested allergens is present only in 30% of cases of CSS. Rolla et al. suggested a superantigen theory in CSS which activated oligoclonal expansion of certain T cell subsets. There has also been some evidence of colonization of airways with Aspergillus or Actinomyces. Several medications have also been reported including sulfonamides, difluinisides, macrolide, and diphenylhydantoin. None of them, however, has been as strong as a possible association between onset of EGPA and use of leukotriene inhibitors montelukast and zafirlukast. Bibby et al. reviewed the USFDA database from 1996 to 2003 to report 181 cases of EGPA in which a pharmacological trigger was suspected. 90% involved leukotriene receptor antagonists. Although some argue that it could merely be the unmasking of disease following ability to wean off steroids in severe asthma after initiation of leukotriene inhibitors.
The pathogenic role of T cells in the aberrant immune response of this disease has been further proven by the presence of specific clonally expanded subpopulations of T cells as well as increased frequency of related HLA alleles like HLA- DRB1 04 and HLA-DRB1 07.
There is an increased serum presence of IL-10 which mediates inhibition of Th-1 response, thus tilting the scale towards differentiation of Th2 cells. This phenomenon is particularly common in ANCA negative phenotype of EGPA.
The estimated prevalence of the disease is 10.7 to 14 per million adults worldwide. Mean age of onset as reported is between 38 to 54 years with a median of 40. However, it has been reported in extremes of age as well, from as low as 4 to as high as 74. There is no gender difference in incidence.
In contrast to certain small vessel vasculitis that has a preponderance in childhood (Henoch-Schonlein purpura, Kawasaki disease), ANCA-associated vasculitis is rare in children. Regardless of age, adult and childhood EGPA both present with highly elevated IgE and eosinophil levels. About 40% of adults have a positive ANCA while 25% of children are seropositive.
Clinically, however, childhood EGPA has a higher incidence of cardiomyopathy, pneumonic infiltrates with a rarer occurrence of mononeuritis multiplex. Higher prevalence of cardiac disease increases the mortality in childhood EGPA, just as in adult disease.
The pathogenesis and clinical phenotype follow a dichotomy of either eosinophil-mediated damage or ANCA-induced endothelial injury.
An initial TH2-mediated immune response provokes the margination of eosinophils. Eosinophilic presence in active disease is likely a consequence of increased synthesis, enhanced extravasation as well as prolonged survival in target tissues. IL-3 and IL-5, produced by TH-2 lymphocytes are the key regulators in maturation and release of eosinophils, as well as their survival in blood. Serum levels of IL-5 correlate consistently with disease activity and go down with the initiation of immunosuppressive therapy.
Epithelial and endothelial cells, when activated by Th-2 type cytokines also secrete eosinophil-specific chemokines like eotaxin 3(CCL26), CCL17, and CCL22. They act on CCR4 receptor to facilitate recruitment of eosinophils and effector Th2 cells to the end organs–thus amplifying the immune response. Martorana et al. demonstrated serum levels of CCL26 as a reliable marker for disease activity in CSS. 
Eosinophils, in turn, release the cationic proteins like eosinophil cationic protein (ECP), eosinophil peroxidases, eosinophil-derived neurotoxins, and eosinophil granule major basic protein which is directly involved in mediating tissue damage.
Eosinophils also secrete cytokines like IL- 1, IL-3, IL-5, TGF- beta, and vascular endothelial growth factor. IL-5, in turn, plays in an active role in maturation, differentiation, and survival of eosinophils.
Histological findings in EGPA are characterized by eosinophilic infiltrates in walls of small and medium-sized blood vessels as well as extravascular tissue spaces. In EGPA with acute pulmonary exacerbations, Bronchoalveolar lavage fluid is also rich in eosinophils, similar to acute or chronic eosinophilic pneumonia. Extravascular eosinophilic granulomas are also observed, particularly in the gastrointestinal tract.
IL- 5 is not the only mediator of eosinophilic tissue infiltration, as has been evidenced by the persistence of tissue Major Basic Protein (MBP) in spite of therapy with mepolizumab causing complete downregulation of IL5 titers. IL-4 and IL-13 are two other potent cytokines of Th-2 profile immune response and may play an important role in tissue infiltration and degranulation of eosinophils.
Elevated p- ANCA levels with” antibodies in a perinuclear pattern are seen in approximately 40% of patients with EGPA. Rarely a cytoplasmic pattern with specificity for neutrophil proteinase 3 (c- ANCA) is seen.
Presence of ANCA correlates with an increased incidence of glomerulonephritis, mononeuritis, and biopsy-proven vasculitis. Alveolar hemorrhage is also found more often in this group of patients.
Infusion of MPO- ANCA in wild-type and Rag2 knockout mice resulted in severe necrotizing and crescentic glomerulonephritis . The 2 subset hypothesis in clinical phenotyping of EGPA has been further substantiated by a recent demonstration of increased frequency of HLA- DRB4 in EGPA patients with ANCA positivity. There has been some recent evidence of the role of Th17 lymphocytes in the occurrence and maintenance of vasculitis response in the disease, particularly with regards to the balance between Th17 and Treg cells.
Clinical features of the disease follow 2-pronged themes of eosinophilic tissue infiltration or small and medium vessel vasculitis.
The clinical course is characterized by 3 phases which do not necessarily always present in the same patient. They may even overlap in the natural history of an individual’s disease.
In the initial prodromal phase, nonspecific symptoms of malaise, fever, migrating polyarthralgia, weight loss is common along with a severe adult-onset form of asthma that is refractory to conventional treatment. Diffuse myalgia and polyarthralgia have been reported in 37% to 57% of CSS patients, particularly at the onset of disease. Upper respiratory symptoms are more common with chronic rhinosinusitis (47% to 93%) and nasal polyps (62% to 77%). However nasal granulomas, erosion, and crusting or epistaxis as seen in GPA are absent here.
The second phase is characterized by eosinophilic infiltrates in end organs along with peripheral eosinophilia. Patchy peripheral nodular pulmonary infiltrates, eosinophilic gastroenteritis, serosal effusion, are common.
An onset of vasculitis characterizes the third phase, and it may take anywhere between 3 to 9 years since the onset of asthma. Neurological symptoms are a hallmark of this phase.
Organ System Involvement
Respiratory and Pulmonary Manifestations
However variable the clinical manifestations may be, Asthma in the prodromal phase seems nearly ubiquitous, reported in 96% to 100% patients. The mean age of onset of asthma is 35 to 50 years, and it precedes the onset of vasculitis by 3 to 9 years.
There has been some debate about certain asthma medications like leukotriene receptor antagonists, montelukast as well as omalizumab precipitating the onset of CSS. However, others believe that they simply help steroid-dependent patients to taper off steroids, thereby unmasking the underlying vasculitides successfully.
Churg-Strauss syndrome patients tend to present with adult-onset asthma with an eosinophilic phenotype. It is accompanied by rhinitis, sinusitis and nasal polyposis more often. Chronic rhinitis is the most common extra thoracic manifestation occurring in about 75% of cases.
Asthma is progressive and often ends up being steroid-dependent asthma. Up to 75% of patients require systemic corticosteroid therapy for asthma control before a diagnosis of EGPA is achieved.
Even when other systemic manifestations of the disease are brought under control with therapy, asthma tends to remain uncontrolled, thus detrimentally affecting the quality of life. Apart from upper airway allergic manifestations and eosinophilic asthma, pulmonary manifestations of the disease can also be related to parenchymal eosinophilic infiltration as well as the vasculitic process. During the first 2 clinical phases described, transient pulmonary infiltrates and eosinophilia is common whereas, in the vasculitic phase, necrotizing vasculitis and granuloma are more common. Alveolar hemorrhage is reported more often in ANCA positive subset although its incidence is lower than in GPA patients.
Cardiac involvement may be present in 62% of cases although it is symptomatically manifest in only 26%. It is caused by both mediators released from activated eosinophils as well as vasculitis lesions in the myocardium and coronary arteries. Myocarditis, in turn, leads to post inflammatory fibrosis and restrictive cardiomyopathy followed by congestive cardiac failure. The spectrum of clinical manifestations varies from coronary artery disease, primary arrhythmias, cardiomyopathy, acute constrictive pericarditis and myocarditis, and eosinophilic pericardial effusion. The absence of ANCA and eosinophilia correlates better with cardiac disease.
Use of echocardiography and cardiac MRI have helped in detecting cardiac abnormalities even beyond an active phase of the disease like nonreversible chronic fibrosis and cardiomyopathy.
Cardiac changes are associated with a poor prognosis and high mortality if left untreated.
Eosinophilic gastroenteritis and mesenteric vasculitis often seem to coincide as far as gastrointestinal tract involvement is concerned. They result in nonspecific symptoms of abdominal pain, nausea, vomiting, and diarrhea to more severe complications like bleeding or intestinal obstruction (mediated by submucosal nodular masses). Mesenteric vasculitis predisposes to ischemic bowel, mucosal ulceration and even perforation necessitating exploratory laparotomy. Serosal involvement can cause eosinophilic ascites and peritonitis. Rare manifestations include necrotizing acalculous cholecystitis, pancreatitis and eosinophilic liver disease.
Renal involvement is seen in 25% of patients and is less common than other medium vessel vasculitides like GPA. The most common manifestation is necrotizing crescentic glomerulonephritis, although focal sclerosing disease, IgA nephropathy or eosinophilic interstitial nephritis can also be seen. The biopsy features are not pathognomonic and often indistinguishable in isolation from other vasculitis diseases, unless combined with the spectrum of eosinophilic asthma, eosinophilia or other system manifestations.
Hypertension is seen in 10% to 30% of patients with EGPA and its presence many reflect the renal involvement.
A wrist or a foot drop resulting from mononeuritis multiplex, or mixed sensorimotor peripheral neuropathy is reported. Common peroneal and internal popliteal nerves are most commonly involved. Radial and ulnar nerves in upper limbs may also be involved. Peripheral neuropathy can be present in 75% to 80% cases. 10% to 39% of neurological involvements can be in the form of CNS vasculitis causing cerebral infarctions or hemorrhages.
Cranial nerve palsies are uncommon but the involvement of cranial nerves 2, 3, 6, and 8 have been described. Ischemic optic neuritis is the most common cranial neuropathy.
Autonomic neuropathies have also been proposed to be the root cause of cardiac dysrhythmia in EGPA patients 
Apart from CNC vasculitis, most neurologic symptoms tend to reverse well to standard therapy.
Dermatological manifestations are present in half to two-thirds of patients.
Extravascular granulomas are seen in the skin as are changes consistent with leukocytoclastic vasculitis. Nonthrombocytopenic palpable purpura is the most common skin manifestation along with scalp nodules, urticarial rashes, skin infarcts, and livedo reticularis.
Among other less common organ system involvements, central retinal artery and venous occlusion, thromboembolic disease, salivary gland involvement or vasculitis involvement of breasts have also been seen.
Because of its protean manifestations, and lack of a single diagnostic test of choice, the diagnosis of EGPA is based on clinical features, more than histopathology or lab testing. With eosinophilic asthma, tThe clinician must recognize a pattern of multisystem disease and investigate for other supportive findings.
Peripheral blood eosinophilia (greater than 10% on differential white blood cell count or greater than 1500 /dl) is the best-known lab hallmark of the disease. Elevated serum IgE is also found in 75% of patients.
Rest of the laboratory abnormalities are nonspecific including elevated ESR, CRP, normocytic normochromic anemia, and extrapulmonary rheumatoid factor in 60% patients.
As mentioned before, the prevalence of ANCA positivity in EGPA is in approximately 40% of cases. The common ANCA immunofluorescence pattern is perinuclear with specificity for myeloperoxidase (MPO).
Keogh and Specks, in their retrospective study of 74 Churg-Strauss syndrome patients, reported an increased prevalence of neuropathy and central nervous system involvement in ANCA positive patients. There have been increasing efforts since then to identify clinical phenotypes correlating with ANCA positivity. Sable–Fourtassou and colleagues from the French vasculitis study group showed a higher prevalence of renal disease, microliter vasculitis, and peripheral neuropathy in the ANCA positive subgroup of their 112 Churg-Strauss Syndrome patients. Similarly, Sinico and colleagues showed a similar end-organ involvement pattern along with alveolar hemorrhage in the ANCA positive subgroup. In both studies, vasculitis was less frequent in ANCA negative patients, with a higher prevalence of cardiomyopathy and systemic manifestations like malaise, fever, among others.
CT chest shows asymmetric diffuse bilateral peripheral ground glass infiltrates along with bronchial wall thickening. It can sometimes be migratory. Bilateral bronchocentric nodular infiltrates can also occur, but unlike GPA they do not cavitate. Pleural effusion is present in 20% to 30% cases.
CT sinuses are characterized by paranasal sinus thickening along with thickening of nasal mucosa without any evidence of bony erosion (seen in granulomatosis with polyangiitis).
Airflow obstruction is present in pulmonary function test in 70% patients. Even though FEV1 may transiently improve with corticosteroid therapy, airflow obstruction in variable degrees persist in 40% patients.
Since cardiac disease portends a poor prognosis, early detection with cardiac MRI is being advocated even in the absence of clinical symptoms once the disease diagnosis is made. Any patient with suspected EGPA should undergo a thorough evaluation of cardiac performance and coronary status.
Sural nerve biopsy is the gold standard test in documenting peripheral neuropathy. Evidence of axonal degeneration is the most common finding, and necrotizing vasculitis and perineural eosinophilic infiltration can only be confirmed in half of the cases.
Skin biopsy is the most convenient to perform. Although none of the findings are exclusive to EGPA, evidence of small vessel vasculitis in an appropriate clinical setting may be enough to clinch a diagnosis. If the kidney is involved and biopsied, focal necrosis, crescentic deposits, and the paucity of immunoglobulin deposits are the characteristic findings.
Early recognition and ability to use corticosteroids and immunosuppressants have significantly changed the natural history of EGPA, improving prognosis and overall survival.
Corticosteroids help in reduction of eosinophil burden in blood and tissues and inhibit the prolongation of eosinophil survival in extravascular tissues.
While the initial dose of therapy for a non-severe disease has been 1 mg/kbw of oral prednisone, induction of remission in severe disease is often better achieved with pulse dose methylprednisolone with or without cyclophosphamide.
Two randomized controlled trials by the French vasculitis study group established a standardized regimen of treatment based on a 5-factor score. In patients without poor prognostic factors, corticosteroid alone was able to achieve remission in 93% of patients. However, relapses happened more commonly and during tapering of steroids prompting the addition of cyclophosphamide or azathioprine for maintenance. There is an overview of the treatment plan based on a study by Ribi et al. below.
Multiple studies show that maintaining remission with a high incidence of relapses is challenging. Although agents of choice have been well established, the ideal duration of treatment and which drugs to stop first are still not well standardized.
Treatment strategy for frequent relapse or severe refractory disease somewhat depends on end-organ involvement.
Plasmapheresis is effective and preferred in rapidly progressive glomerulonephritis or alveolar hemorrhage.
Intravenous immunoglobulin, on the other hand, is considered in neuropathy or cardiomyopathy refractory to conventional therapy.
Based on smaller case series and well-evidenced success with other ANCA-associated vasculitis, rituximab (anti CD 20) and tumor necrosis factor inhibitors (TNF) are considered as an alternate option.
There has also been some success with interferon-alfa (3 million IU 3 times weekly subcutaneously) for induction of remission in seven CSS patients refractory to cyclophosphamide. It down-regulates expression of IL-5 (known to have an increased titer in CSS) and IL-13, apart from modulating eosinophil activating cytokines in CSS. However, it was unable to reduce the rate of relapses after one year of follow-up.
There have also been recent reports of successful use of mepolizumab–an anti-IL-5 monoclonal antibody as well as omalizumab (recombinant humanized monoclonal anti-IVIG E antibody) in refractory EGPA. Both drugs have already been in use for moderate to severe persistent asthma with allergic phenotypes.
The challenge as evident in multiple studies is to maintain remission with a high incidence of relapses. Although agents of choice have been well established, the ideal duration of treatment, and which drugs to stop first is still not well standardized.
Treatment Strategies for Eosinophilic Granulomatosis with Polyangiitis
Induction of Remission
Without Poor Prognosis (FFS greater than 1)
With Poor Prognosis
Maintenance of Remission
Conditions that need to be considered in the differential stems from the 2 principal phenotypes of EGPA – eosinophilic lung disease and systemic small and medium vessel vasculitis.
Eosinophilic Lung Diseases
Small and Medium Vessel Vasculitis
Most of the eosinophilic lung diseases are distinguished from EGPA by lack of multisystem involvement except Idiopathic hypereosinophilic syndrome where peripheral eosinophilia more than 1500/ cubic mm is a chronic phenomenon lasting beyond 6 months. ANCA is completely absent in hypereosinophilic syndrome, and late-onset asthma is very uncommon. Recent molecular genetic testing has helped in identifying mutations specific to idiopathic hypereosinophilic syndromes, for example, FIP1-like 1-platelet-derived growth factor receptor–alpha or T-cell antigen receptor rearrangements.
As far as differentiation from other small and medium vessel vasculitides is concerned, renal involvement is much more common in granulomatosis with polyangiitis (GPA) as is evidence of cavitary lung lesions or necrotizing upper airway lesions. Septal nasal perforation often reported in GPA does not occur in EGPA.
Following timely detection and treatment, CSS has a favorable prognosis with a 5-year survival of 90%.
Relapse rate is estimated at approximately 20% to 30% and is often minor with fever, joint pain and constitutional symptoms.
Certain risk factors for relapse include:
Just as peripheral eosinophilia is a hallmark of diagnosis, there is an association between the degree of eosinophilia and extent of vasculitis disease. A sudden rise in eosinophil count also precedes a relapse of vasculitis.
They became the basis of the Five Factor Score (FFS) used to define a poor prognosis and higher mortality in EGPA. The absence of any of the five factors carries a good prognosis (RR 0.52; 95% CI, 0.42 to 0.62; P < .03) and the presence of 2 or more increases the risk of mortality (RR 1.36; 95% CI, 1.10 to 1.62; P < .001). Of the 5 factors, cardiomyopathy is an independent risk factor in CSS (hazard ratio 3.39; 95% CI, 1.6 to 7.3).
The Birmingham Vasculitis Activity Score (BVAS) is a detailed 66 question tool to assess vasculitic organ involvement and is widely used in clinical trials.
Vasculitis Damage Index (VDI) assesses accumulated organ damage and is a very useful assessment of organ injury due to both disease itself and its treatment. It correlates well with mortality and morbidity.
Cardiac involvement is the most frequent cause of mortality in patients with poor response to therapy.
Even though the disease has a favorable prognosis with early detection and treatment, asthma often remains refractory and impacts the quality of life (3). Persistence of severe asthma symptoms often necessitates a much longer course of systemic corticosteroids compared to other small vessel vasculitides. As reported by Solans et al., there is, therefore, an expected high prevalence of corticosteroid-induced side effects including diabetes mellitus, myopathy, osteoporosis, and vertebral fractures, osteonecrosis of femoral head etc.
Moreover, almost all patients with EGPA develop long-lasting steroid refractory neuralgia and myopathy as well.
Eosinophilic granulomatosis with Polyangiitis, previously known as Churg-Strauss Syndrome is a multisystem disease of the immune system.
Poorly controlled Asthma over months with sinus and nasal symptoms, particularly when associated with high blood eosinophil count should prompt a red flag to search for this possibility.
Early initiation of treatment with steroids and other immunosuppressants usually leads to a favorable outcome and long life expectancy
Bronchial asthma, and some muscle and nerve weakness may remain lifelong
Careful periodic screening for corticosteroid-induced adverse effects become essential as the disease may require long-term treatment with high-dose steroids over months.
Compliance with the diagnostic procedures and treatment recommendations is essential and therefore regular follow up with the healthcare provider should not be ignored once the disease is diagnosed.
Churg-Strauss Syndrome or Eosinophilic Granulomatosis with Polyangiitis is thus a pleiotropic systemic vasculitis with a dual face of manifestations- based on eosinophilic damage or ANCA associated small and medium vessel injury.
The dichotomy has made it challenging to identify a gold standard for diagnosis and has also made prognosis somewhat variable. Pharmacologic treatment, irrespective of a mechanism of injury, is still tied to early recognition, and treatment with immunomodulators with use of plasma exchange or IVIG is reserved for more refractory cases.
It responds well to treatment but is also characterized by a high remission rate and a lingering persistence of difficult to control asthma and systemic manifestations affecting quality of life
In the era of cost curtailment in healthcare and broadening of first access to healthcare in independent urgent care centers (as opposed to multispecialty hospital emergency rooms), it is important to be aware of the exceptions to the Occam’s razor principle.
When an asthmatic returns for exacerbations time and again in spite of conventional therapy, it is important to recognize the pattern of recurrence or persistence. Broadening the suspicion and correlating with simple initial blood work like cell differential, ESR, CRP, and even IgE is worthwhile. Other organ involvement like cardiomyopathy, renal disease, or GI symptoms, if present, should be tied together to a common unified diagnosis like EGPA. In a patient with eosinophilic asthma and multisystem involvement, discontinuation of leukotriene receptor antagonists should also be considered due to their potential role in pathogenesis. Prompt recognition and treatment are not only rewarding to the healthcare provider but immensely impactful to the prognosis and life expectancy in diseases like EGPA.
Finally, post diagnosis and treatment, awareness of a likelihood of prolonged steroid dependence and therefore its adverse effects becomes essential. Periodic screening of glycemic status, bone density, fall prevention, and infection prevention becomes a routine care plan for the disease.
|||CHURG J,STRAUSS L, Allergic granulomatosis, allergic angiitis, and periarteritis nodosa. The American journal of pathology. 1951 Mar-Apr [PubMed PMID: 14819261]|
|||Lanham JG,Elkon KB,Pusey CD,Hughes GR, Systemic vasculitis with asthma and eosinophilia: a clinical approach to the Churg-Strauss syndrome. Medicine. 1984 Mar [PubMed PMID: 6366453]|
|||Jennette JC,Falk RJ,Andrassy K,Bacon PA,Churg J,Gross WL,Hagen EC,Hoffman GS,Hunder GG,Kallenberg CG, Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis and rheumatism. 1994 Feb [PubMed PMID: 8129773]|
|||Mahr A,Moosig F,Neumann T,Szczeklik W,Taillé C,Vaglio A,Zwerina J, Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): evolutions in classification, etiopathogenesis, assessment and management. Current opinion in rheumatology. 2014 Jan [PubMed PMID: 24257370]|
|||Cottin V,Bel E,Bottero P,Dalhoff K,Humbert M,Lazor R,Sinico RA,Sivasothy P,Wechsler ME,Groh M,Marchand-Adam S,Khouatra C,Wallaert B,Taillé C,Delaval P,Cadranel J,Bonniaud P,Prévot G,Hirschi S,Gondouin A,Dunogué B,Chatté G,Briault C,Pagnoux C,Jayne D,Guillevin L,Cordier JF, Revisiting the systemic vasculitis in eosinophilic granulomatosis with polyangiitis (Churg-Strauss): A study of 157 patients by the Groupe d'Etudes et de Recherche sur les Maladies Orphelines Pulmonaires and the European Respiratory Society Taskforce on eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Autoimmunity reviews. 2017 Jan [PubMed PMID: 27671089]|
|||Rolla G,Guida G,Heffler E, Churg-Strauss syndrome: still a clinical challenge. Expert review of clinical immunology. 2007 Nov [PubMed PMID: 20477130]|
|||Ruppert AM,Averous G,Stanciu D,Deroide N,Riehm S,Poindron V,Pauli G,Debry C,de Blay F, Development of Churg-Strauss syndrome with controlled asthma during omalizumab treatment. The Journal of allergy and clinical immunology. 2008 Jan [PubMed PMID: 18206510]|
|||Winchester DE,Jacob A,Murphy T, Omalizumab for asthma. The New England journal of medicine. 2006 Sep 21 [PubMed PMID: 16990394]|
|||Puéchal X,Rivereau P,Vinchon F, Churg-Strauss syndrome associated with omalizumab. European journal of internal medicine. 2008 Jul [PubMed PMID: 18549941]|
|||Bargagli E,Madioni C,Olivieri C,Penza F,Rottoli P, Churg-Strauss vasculitis in a patient treated with omalizumab. The Journal of asthma : official journal of the Association for the Care of Asthma. 2008 Mar [PubMed PMID: 18350402]|
|||Wechsler ME,Wong DA,Miller MK,Lawrence-Miyasaki L, Churg-strauss syndrome in patients treated with omalizumab. Chest. 2009 Aug [PubMed PMID: 19411292]|
|||Hamilos DL,Christensen J, Treatment of Churg-Strauss syndrome with high-dose intravenous immunoglobulin. The Journal of allergy and clinical immunology. 1991 Nov [PubMed PMID: 1955642]|
|||Bibby S,Healy B,Steele R,Kumareswaran K,Nelson H,Beasley R, Association between leukotriene receptor antagonist therapy and Churg-Strauss syndrome: an analysis of the FDA AERS database. Thorax. 2010 Feb [PubMed PMID: 20147592]|
|||Vaglio A,Martorana D,Maggiore U,Grasselli C,Zanetti A,Pesci A,Garini G,Manganelli P,Bottero P,Tumiati B,Sinico RA,Savi M,Buzio C,Neri TM, HLA-DRB4 as a genetic risk factor for Churg-Strauss syndrome. Arthritis and rheumatism. 2007 Sep [PubMed PMID: 17763415]|
|||Wieczorek S,Hellmich B,Gross WL,Epplen JT, Associations of Churg-Strauss syndrome with the HLA-DRB1 locus, and relationship to the genetics of antineutrophil cytoplasmic antibody-associated vasculitides: comment on the article by Vaglio et al. Arthritis and rheumatism. 2008 Jan [PubMed PMID: 18163478]|
|||Schönermarck U,Csernok E,Trabandt A,Hansen H,Gross WL, Circulating cytokines and soluble CD23, CD26 and CD30 in ANCA-associated vasculitides. Clinical and experimental rheumatology. 2000 Jul-Aug [PubMed PMID: 10949720]|
|||Harrold LR,Andrade SE,Go AS,Buist AS,Eisner M,Vollmer WM,Chan KA,Frazier EA,Weller PF,Wechsler ME,Yood RA,Davis KJ,Platt R, Incidence of Churg-Strauss syndrome in asthma drug users: a population-based perspective. The Journal of rheumatology. 2005 Jun [PubMed PMID: 15940771]|
|||Shiota Y,Matsumoto H,Kanehisa Y,Tanaka M,Kanazawa K,Hiyama J,Ono T,Marukawa M,Mashiba H, Serum interleukin-5 levels in a case with allergic granulomatous angiitis. Internal medicine (Tokyo, Japan). 1997 Oct [PubMed PMID: 9372332]|
|||Thiel J,Troilo A,Salzer U,Schleyer T,Halmschlag K,Rizzi M,Frede N,Venhoff A,Voll RE,Venhoff N, Rituximab as Induction Therapy in Eosinophilic Granulomatosis with Polyangiitis Refractory to Conventional Immunosuppressive Treatment: A 36-Month Follow-Up Analysis. The journal of allergy and clinical immunology. In practice. 2017 Nov - Dec [PubMed PMID: 28916432]|
|||Jakiela B,Sanak M,Szczeklik W,Sokolowska B,Plutecka H,Mastalerz L,Musial J,Szczeklik A, Both Th2 and Th17 responses are involved in the pathogenesis of Churg-Strauss syndrome. Clinical and experimental rheumatology. 2011 Jan-Feb [PubMed PMID: 21470488]|
|||Polzer K,Karonitsch T,Neumann T,Eger G,Haberler C,Soleiman A,Hellmich B,Csernok E,Distler J,Manger B,Redlich K,Schett G,Zwerina J, Eotaxin-3 is involved in Churg-Strauss syndrome--a serum marker closely correlating with disease activity. Rheumatology (Oxford, England). 2008 Jun [PubMed PMID: 18397958]|
|||Dallos T,Heiland GR,Strehl J,Karonitsch T,Gross WL,Moosig F,Holl-Ulrich C,Distler JH,Manger B,Schett G,Zwerina J, CCL17/thymus and activation-related chemokine in Churg-Strauss syndrome. Arthritis and rheumatism. 2010 Nov [PubMed PMID: 20669282]|
|||Zwerina J,Bach C,Martorana D,Jatzwauk M,Hegasy G,Moosig F,Bremer J,Wieczorek S,Moschen A,Tilg H,Neumann T,Spriewald BM,Schett G,Vaglio A, Eotaxin-3 in Churg-Strauss syndrome: a clinical and immunogenetic study. Rheumatology (Oxford, England). 2011 Oct [PubMed PMID: 21266446]|
|||Guillevin L,Cohen P,Gayraud M,Lhote F,Jarrousse B,Casassus P, Churg-Strauss syndrome. Clinical study and long-term follow-up of 96 patients. Medicine. 1999 Jan [PubMed PMID: 9990352]|
|||Kiene M,Csernok E,Müller A,Metzler C,Trabandt A,Gross WL, Elevated interleukin-4 and interleukin-13 production by T cell lines from patients with Churg-Strauss syndrome. Arthritis and rheumatism. 2001 Feb [PubMed PMID: 11229479]|
|||Tsukadaira A,Okubo Y,Kitano K,Horie S,Momose T,Takashi S,Suzuki J,Isobe M,Sekiguchi M, Eosinophil active cytokines and surface analysis of eosinophils in Churg-Strauss syndrome. Allergy and asthma proceedings. 1999 Jan-Feb [PubMed PMID: 10076708]|
|||Jakiela B,Szczeklik W,Sokolowska B,Mastalerz L,Sanak M,Plutecka H,Szczeklik A, Intrinsic pathway of apoptosis in peripheral blood eosinophils of Churg-Strauss syndrome. Rheumatology (Oxford, England). 2009 Oct [PubMed PMID: 19643727]|
|||Hsieh SC,Yu HS,Cheng SH,Li KJ,Lu MC,Wu CH,Tsai CY,Yu CL, Anti-myeloperoxidase antibodies enhance phagocytosis, IL-8 production, and glucose uptake of polymorphonuclear neutrophils rather than anti-proteinase 3 antibodies leading to activation-induced cell death of the neutrophils. Clinical rheumatology. 2007 Feb [PubMed PMID: 16575489]|
|||Nogueira E,Hamour S,Sawant D,Henderson S,Mansfield N,Chavele KM,Pusey CD,Salama AD, Serum IL-17 and IL-23 levels and autoantigen-specific Th17 cells are elevated in patients with ANCA-associated vasculitis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2010 Jul [PubMed PMID: 20100727]|
|||Porges AJ,Redecha PB,Kimberly WT,Csernok E,Gross WL,Kimberly RP, Anti-neutrophil cytoplasmic antibodies engage and activate human neutrophils via Fc gamma RIIa. Journal of immunology (Baltimore, Md. : 1950). 1994 Aug 1 [PubMed PMID: 8027554]|
|||Xiao H,Heeringa P,Hu P,Liu Z,Zhao M,Aratani Y,Maeda N,Falk RJ,Jennette JC, Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice. The Journal of clinical investigation. 2002 Oct [PubMed PMID: 12370273]|
|||Ewert BH,Jennette JC,Falk RJ, Anti-myeloperoxidase antibodies stimulate neutrophils to damage human endothelial cells. Kidney international. 1992 Feb [PubMed PMID: 1313124]|
|||Knockaert DC, Cardiac involvement in systemic inflammatory diseases. European heart journal. 2007 Aug [PubMed PMID: 17562669]|
|||Boggi U,Mosca M,Giulianotti PC,Naccarato AG,Bombardieri S,Mosca F, Surviving catastrophic gastrointestinal involvement due to Churg-Strauss syndrome: report of a case. Hepato-gastroenterology. 1997 Jul-Aug [PubMed PMID: 9261619]|
|||Pagnoux C,Guillevin L, Churg-Strauss syndrome: evidence for disease subtypes? Current opinion in rheumatology. 2010 Jan [PubMed PMID: 19851111]|
|||Zhang W,Zhou G,Shi Q,Zhang X,Zeng XF,Zhang FC, Clinical analysis of nervous system involvement in ANCA-associated systemic vasculitides. Clinical and experimental rheumatology. 2009 Jan-Feb [PubMed PMID: 19646349]|
|||Oiwa H,Mokuda S,Matsubara T,Funaki M,Takeda I,Yamawaki T,Kumagai K,Sugiyama E, Neurological Complications in Eosinophilic Granulomatosis with Polyangiitis (EGPA): The Roles of History and Physical Examinations in the Diagnosis of EGPA. Internal medicine (Tokyo, Japan). 2017 Nov 15 [PubMed PMID: 28924115]|
|||De Salvo G,Li Calzi C,Anastasi M,Lodato G, Branch retinal vein occlusion followed by central retinal artery occlusion in Churg-Strauss syndrome: unusual ocular manifestations in allergic granulomatous angiitis. European journal of ophthalmology. 2009 Mar-Apr [PubMed PMID: 19253257]|
|||Allenbach Y,Seror R,Pagnoux C,Teixeira L,Guilpain P,Guillevin L, High frequency of venous thromboembolic events in Churg-Strauss syndrome, Wegener's granulomatosis and microscopic polyangiitis but not polyarteritis nodosa: a systematic retrospective study on 1130 patients. Annals of the rheumatic diseases. 2009 Apr [PubMed PMID: 19015208]|
|||Chumbley LC,Harrison EG Jr,DeRemee RA, Allergic granulomatosis and angiitis (Churg-Strauss syndrome). Report and analysis of 30 cases. Mayo Clinic proceedings. 1977 Aug [PubMed PMID: 18640]|
|||Keogh KA,Specks U, Churg-Strauss syndrome: clinical presentation, antineutrophil cytoplasmic antibodies, and leukotriene receptor antagonists. The American journal of medicine. 2003 Sep [PubMed PMID: 12967693]|
|||Yılmaz İ,Tutar N,Şimşek ZÖ,Oymak FS,Gülmez İ, Clinical and Serological Features of Eosinophilic and Vasculitic Phases of Eosinophilic Granulomatosis with Poliangiitis: a Case Series of 15 Patients. Turkish thoracic journal. 2017 Jul [PubMed PMID: 29404165]|
|||Guillevin L,Pagnoux C,Karras A,Khouatra C,Aumaître O,Cohen P,Maurier F,Decaux O,Ninet J,Gobert P,Quémeneur T,Blanchard-Delaunay C,Godmer P,Puéchal X,Carron PL,Hatron PY,Limal N,Hamidou M,Ducret M,Daugas E,Papo T,Bonnotte B,Mahr A,Ravaud P,Mouthon L, Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. The New England journal of medicine. 2014 Nov 6 [PubMed PMID: 25372085]|
|||Sinico RA,Di Toma L,Maggiore U,Bottero P,Radice A,Tosoni C,Grasselli C,Pavone L,Gregorini G,Monti S,Frassi M,Vecchio F,Corace C,Venegoni E,Buzio C, Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in Churg-Strauss syndrome. Arthritis and rheumatism. 2005 Sep [PubMed PMID: 16142760]|
|||Vaglio A,Strehl JD,Manger B,Maritati F,Alberici F,Beyer C,Rech J,Sinico RA,Bonatti F,Battistelli L,Distler JH,Schett G,Zwerina J, IgG4 immune response in Churg-Strauss syndrome. Annals of the rheumatic diseases. 2012 Mar [PubMed PMID: 22121132]|
|||Cottin V,Khouatra C,Dubost R,Glérant JC,Cordier JF, Persistent airflow obstruction in asthma of patients with Churg-Strauss syndrome and long-term follow-up. Allergy. 2009 Apr [PubMed PMID: 19154547]|
|||Ribi C,Cohen P,Pagnoux C,Mahr A,Arène JP,Lauque D,Puéchal X,Letellier P,Delaval P,Cordier JF,Guillevin L, Treatment of Churg-Strauss syndrome without poor-prognosis factors: a multicenter, prospective, randomized, open-label study of seventy-two patients. Arthritis and rheumatism. 2008 Feb [PubMed PMID: 18240234]|
|||Guillevin L,Cohen P,Mahr A,Arène JP,Mouthon L,Puéchal X,Pertuiset E,Gilson B,Hamidou M,Lanoux P,Bruet A,Ruivard M,Vanhille P,Cordier JF, Treatment of polyarteritis nodosa and microscopic polyangiitis with poor prognosis factors: a prospective trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in sixty-five patients. Arthritis and rheumatism. 2003 Feb 15 [PubMed PMID: 12579599]|
|||Hellmich B,Gross WL, Recent progress in the pharmacotherapy of Churg-Strauss syndrome. Expert opinion on pharmacotherapy. 2004 Jan [PubMed PMID: 14680433]|
|||Roccatello D,Baldovino S,Alpa M,Rossi D,Napoli F,Naretto C,Cavallo R,Giachino O, Effects of anti-CD20 monoclonal antibody as a rescue treatment for ANCA-associated idiopathic systemic vasculitis with or without overt renal involvement. Clinical and experimental rheumatology. 2008 May-Jun [PubMed PMID: 18799057]|
|||Pabst S,Tiyerili V,Grohé C, Apparent response to anti-IgE therapy in two patients with refractory [PubMed PMID: 18663073]|
|||Kahn JE,Grandpeix-Guyodo C,Marroun I,Catherinot E,Mellot F,Roufosse F,Blétry O, Sustained response to mepolizumab in refractory Churg-Strauss syndrome. The Journal of allergy and clinical immunology. 2010 Jan [PubMed PMID: 20109753]|
|||Mukhtyar C,Flossmann O,Hellmich B,Bacon P,Cid M,Cohen-Tervaert JW,Gross WL,Guillevin L,Jayne D,Mahr A,Merkel PA,Raspe H,Scott D,Witter J,Yazici H,Luqmani RA, Outcomes from studies of antineutrophil cytoplasm antibody associated vasculitis: a systematic review by the European League Against Rheumatism systemic vasculitis task force. Annals of the rheumatic diseases. 2008 Jul [PubMed PMID: 17911225]|
|||Cohen P,Pagnoux C,Mahr A,Arène JP,Mouthon L,Le Guern V,André MH,Gayraud M,Jayne D,Blöckmans D,Cordier JF,Guillevin L, Churg-Strauss syndrome with poor-prognosis factors: A prospective multicenter trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in forty-eight patients. Arthritis and rheumatism. 2007 May 15 [PubMed PMID: 17471546]|
|||Gayraud M,Guillevin L,le Toumelin P,Cohen P,Lhote F,Casassus P,Jarrousse B, Long-term followup of polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome: analysis of four prospective trials including 278 patients. Arthritis and rheumatism. 2001 Mar [PubMed PMID: 11263782]|
|||Exley AR,Bacon PA,Luqmani RA,Kitas GD,Carruthers DM,Moots R, Examination of disease severity in systemic vasculitis from the novel perspective of damage using the vasculitis damage index (VDI). British journal of rheumatology. 1998 Jan [PubMed PMID: 9487252]|
|||Nguyen Y,Guillevin L, Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss). Seminars in respiratory and critical care medicine. 2018 Aug [PubMed PMID: 30404114]|
|||Arbach O,Metzler C,Gause A, [Churg-Strauss syndrome: outcome and long-term follow-up of 32 patients]. Zeitschrift fur Rheumatologie. 2004 Aug [PubMed PMID: 15338259]|