Materiały źródłowe

• #1 Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss Syndrome) – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK537099/

  Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, belongs to a group of diseases characterized by necrotizing vasculitis affecting small- and medium-sized systemic blood vessels, also known as antineutrophil cytoplasmic autoantibody (ANCA)associated vasculitis (AAV). […] The primary trigger in the pathogenesis at the cellular level appears to be an aberrant T-helper (Th)-cell pathway. […] The pathogenic role of T lymphocytes in this aberrant immune response has been supported by the presence of specific clonally expanded T-cell subpopulations and an increased frequency of related HLA alleles, such as HLA-DRB1:04 and HLA-DRB1:07. […] The pathogenesis and clinical phenotype of EGPA follow a dichotomy of either eosinophil-mediated damage or ANCA-induced endothelial injury.

• #2 Pathogenesis of Churg-Strauss syndrome: recent insights – PubMed

  https://pubmed.ncbi.nlm.nih.gov/19811306/

  Churg-Strauss syndrome (CSS) is a rare systemic necrotizing vasculitis associated with granuloma formation and severe blood and tissue eosinophilia. CSS occurs almost exclusively in patients with asthma. Its pathogenesis remains largely unknown, as triggering factors for CSS development have not been identified so far. […] On a cellular level, CSS is characterized by a strong Th2-type immune response. Th2-associated cytokines such as IL-4, IL-13 and IL-5 may precipitate the severe eosinophilia in CSS, while migration of Eos to inflammatory sites is possibly mediated by eotaxin-3. This review summarizes recent advances in the knowledge on epidemiology, clinical features, and pathogenesis of CSS.

• #3 Epidemiology, pathogenesis, and pathology of eosinophilic granulomatosis with polyangiitis – UpToDate

  https://www.uptodate.com/contents/epidemiology-pathogenesis-and-pathology-of-eosinophilic-granulomatosis-with-polyangiitis

  Eosinophilic granulomatosis with polyangiitis (EGPA), which was previously called the Churg-Strauss syndrome (CSS) or allergic granulomatosis and angiitis, is a multisystem disorder characterized most commonly by asthma, rhinitis, nasal polyps, and prominent peripheral blood and tissue eosinophilia. […] The epidemiology, pathogenesis, and pathology of EGPA will be reviewed here.

• #4 Churg-Strauss Disease: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1178795-overview

  The pathophysiology of Churg-Strauss disease (CSD), now known as eosinophilic granulomatosis with polyangiitis (EGPA), particularly the triggering circumstances, is not well understood and still under investigation. […] ANCAs in part mediate vascular endothelial injury in CSD/EGPA, as they do in polyarteritis nodosa (PAN), microscopic polyangiitis (MPA), and Wegener’s granulomatosis (WG). […] The primary trigger in pathogenesis at the cellular level seems to be an aberrant T-helper cell pathway. […] The pathogenic role of T cells in EGPA was shown to have specific clonally expanded subpopulations of T cells as well as increased frequency of related HLA alleles. […] In EGPA there is high serum level of IL-10, which leads to suppression of Th-1 cells, thus leading to relative elevation of serum Th-2.

• #5 Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome): Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/333492-overview

  The pathophysiology of EGPA is primarily attributed to a dysregulation of the cell-mediated adaptive immune system. The CD4 T-helper cells are highly up-regulatedespecially Th2 lymphocytes, but also Th17 and Th1. The T cells are most likely activated by an antigen-presenting cell presenting a foreign antigen from the respiratory system, as asthma is a major feature of EGPA, found in 96-100% of cases. […] The Th2 subset of CD4 is responsible for the secretion of interleukin-5 (IL-5), which prompts a vigorous eosinophilic response. IL-5 enhances the production, maturation, and activation of eosinophils and prolongs eosinophil survival, mainly by inhibiting apoptosis. […] The increased population of Th1 results in increased interferon-gamma production, which is responsible for the granulomatous formation in EGPA.

• #6

  https://journals.lww.com/co-rheumatology/Fulltext/2012/01000/Churg_Strauss_syndrome___update_on_pathophysiology.5.aspx?generateEpub=Article%7Cco-rheumatology:2012:01000:00005%7C10.1097/bor.0b013e32834d85ce%7C

  ChurgStrauss syndrome (CSS) has a clear clinical phenotype but its pathogenesis is not fully elucidated. Recent studies have focused on its immunogenetic aspects and cytokine and chemokine-mediated pathogenetic mechanisms, providing the rationale for the use of newer targeted therapies. […] CSS is usually considered a Th2-mediated disease, but Th1 and Th17 responses might also play a role; the reported association between CSS and HLA-DRB4 further underlines the pathogenetic relevance of CD4+ T cells which, thanks to their ability to secrete cytokines such as IL4, IL5, and IL13, promote allergic and eosinophilic reactions. Resident cells such as endothelial and epithelial cells might also amplify the immune response by producing eosinophil-attracting chemokines such as eotaxin-3 and CCL17. […] Current knowledge on CSS pathogenesis is evolving; the identification of key molecular mechanisms will pave the way for newer, more specific treatments.

• #7 Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss Syndrome) – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK537099/

  An initial TH2-mediated immune response triggers the margination of eosinophils. […] Eosinophils release proteins such as eosinophil cationic protein (ECP), eosinophil peroxidases, eosinophil-derived neurotoxins, and eosinophil granule major basic protein, which are directly involved in mediating tissue damage. […] The presence of ANCA correlates with a higher incidence of glomerulonephritis, mononeuritis, and biopsy-proven vasculitis. […] The hypothesis of two clinical subsets in EGPA has been further supported by recent findings showing an increased frequency of HLA-DRB4 in ANCA-positive EGPA patients. […] However, endothelial injury in AAV is primarily mediated by neutrophils through the generation of reactive oxygen species and proteolytic enzymes from cytoplasmic granules.

• #8 Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome): Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/333492-overview

  The secondary granules contain a variety of pre-formed proinflammatory cytokines such as major basic proteins (MBP), eosinophilic cationic proteins (ECP), eosinophilic peroxidases (EPO), and eosinophilic-derived neurotoxins (EDN). These can cause catastrophic organ damage in EGPA. […] Normally, Th17 (proinflammatory) and Treg (anti-inflammatory) co-exist in a careful balance; however, in EGPA the regulatory function of Treg is significantly decreased, leaving Th17 unchecked. This results in the continued secretion of pro-inflammatory cytokines such as IL-17 and IL-22. […] Finally, newer research highlights the involvement of the innate immune system in EGPA. Thymic stromal lymphopoietin (TSLP), an epithelial cytokine that functions as an alarmin (ie, a self-derived molecule that recruits and activates the immune system), is released in the respiratory system in response to an infectious, environmental, or inflammatory insult. TSLP can provoke a powerful immune response by directly activating the Th2 pathway.

• #9 Eosinophilic Granulomatosis with Polyangiitis, EGPA (Churg–Strauss Syndrome)

  https://www.irheuma.com/rheumatology-a-z/a-1-3-1/eosinophilic-granulomatosis-with-polyangiitis-egpa-churgstrauss-syndrome

  EGPA (formerly Churg-Strauss syndrome, allergic angiitis and granulomatosis) is a granulomatous vasculitis of small- and medium-sized vessels, frequently involving the skin, peripheral nerves, and lungs, and is associated with peripheral eosinophilia. […] Cytokines that affect eosinophils (IL-5) and eosinophil granule proteins (major basic protein, cationic protein) appear to be important in the pathogenesis of this disease. […] The characteristic laboratory abnormality is eosinophilia (1500 cells/L). Anemia, elevated ESR/CRP, elevated IgE (70%), and positive rheumatoid factor (70%) may be found. ANCAs are present in 50% to 65% of patients. These are directed primarily against MPO and give a p-ANCA pattern. Patients who are ANCA-positive are more likely to develop renal disease, alveolar hemorrhage, mononeuritis multiplex, and purpura. There is no direct correlation between the degree of eosinophilia and disease activity.

• #10 Churg-Strauss Syndrome in a Seven-year-old Boy: A Case Report

  https://rcm.mums.ac.ir/article_9087.html

  Churg-Strauss syndrome (CSS) is a type of vasculitis of small-to-medium sized vessels. This syndrome is known by a history of bronchial asthma with systemic necrotizing vasculitis and peripheral blood hypereosinophilia. It is currently called eosinophilic granulomatosis with polyangiitis (EGPA). […] The histopathologic findings of CSS are eosinophilic inflammation, extravascular granulomas, and necrotizing vasculitis affecting multiple organs. The main clinical feature of the disease is asthma happening in almost 90% of patients. […] The pathogenesis of CSS may include damage to vascular and perivascular tissues by activated eosinophils directly secreting enzymes. The severe and sustained eosinophilia observed in the blood and organs of CSS patients is caused by chemokines such as Eotaxin 3 (CCL26).

• #11 Churg -Strauss syndrome | PPT

  https://www.slideshare.net/slideshow/churg-strauss-syndrome-249383195/249383195

  Churg-Strauss syndrome is a disorder marked by blood vessel inflammation. This condition is also known as eosinophilic granulomatosis with polyangiitis (EGPA). Eosinophilic granulomatosis with polyangiitis (EGPA) or, as it was traditionally termed, Churg-Strauss syndrome is a rare systemic necrotizing vasculitis that affects small-to-medium-sized vessels and is associated with severe asthma and blood and tissue eosinophilia. […] In 1951, Churg and Strauss first described the syndrome in 13 patients who had asthma, eosinophilia, granulomatous inflammation, necrotizing systemic vasculitis, and necrotizing glomerulonephritis. […] PATHOGENESIS Immune Dysregulation. Eosinophil infiltration. Activated Th2 cells release cytokines IL4, IL13 and IL5 IL4, IL13 and IL5 promote eotaxin3 release from endothelial and epithelial cells Eotaxin3 brings eosinophils from the blood stream into tissue. Activated eosinophils secrete granules containing eosinophil basic protein and eosinophil derived neurotoxin, damaging tissue. Activated eosinophils secrete IL25, which activates Th2. Dysregulation of the following immune cells are also implicated: Th1, Th17, IL17A, B cells. ANCA induced endothelial damage: ANCA leads to neutrophil degranulation and tissue damage.

• #12 Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome): Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/333492-overview

  The reason for the development of granulomas in EGPA remains unclear; they might form in order to isolate and contain a chronic irritant/antigen/microbe or, as suggested by Fijoek et al, they may be intended to provide protection against the harsh cytotoxic effects of eosinophils. […] The cytotoxicity of eosinophils is attributed to their pre-formed primary and secondary granules. […] The primary granules, also known as Charcot-Leyden crystals, appear as hexagonal double-pointed crystals and are highly associated with eosinophilic inflammation. […] These crystalline structures are formed from a protein called galectin-10 within eosinophils. Once tissue eosinophils are activated, they begin a process of cell death resulting in the extrusion of their intracellular crystalline contents to the extracellular milieu, prompting a powerful inflammasome reaction, a process known as extracellular trap cell death (ETosis).

• #13 ANCA-Negative Glomerulonephritis and Nonasthmatic Churg-Strauss Sndrome

  https://www.medscape.org/viewarticle/579354_2

  Churg-Strauss syndrome progresses via three successive stages: the 'prodromal phase’, involving asthma and/or allergic rhinitis, with or without sinus polyposis; the 'eosinophilic phase’, which is characterized by eosinophil infiltration into tissues such as the lungs, heart and gastrointestinal tract, with or without granulomas; and finally the 'systemic phase’, during which necrotizing vasculitis develops in the skin, kidneys and peripheral nerves.[3] […] The clinical presentation of Churg-Strauss syndrome is variable and can involve any organ system, but pulmonary involvement is the hallmark of Churg-Strauss syndrome, with asthma reported in 98% of cases and pulmonary infiltrates in 50% of patients.[3] […] ANCA, usually directed against myeloperoxidase, are found in only about 35-50% of patients with Churg-Strauss syndrome.[7,10-12] ANCA-negative patients usually present with eosinophilic tissue infiltration involving the heart and the gastrointestinal tract, whereas ANCA-positive patients tend to present with small-vessel vasculitis in the form of glomerulonephritis, pulmonary hemorrhage or mononeuritis multiplex.[11] This difference suggests that the pathogenic mechanisms of ANCA-negative and ANCA-positive Churg-Strauss syndrome are different.[7,10-12]

• #14 Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss Syndrome) | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/19543

  In EGPA, approximately 60% of patients are ANCA-negative, around 35% are MPO-positive, and about 5% are PR3-positive. […] The hypothesis of two clinical subsets in EGPA has been further supported by recent findings showing an increased frequency of HLA-DRB4 in ANCA-positive EGPA patients. […] The dichotomy of EGPA complicates the establishment of a gold standard for diagnosis and contributes to variable prognoses.

• #15 Churg-Strauss Disease: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1178795-overview

  Serum level of IL-5 highly correlates with disease progression and activity. […] Histological findings in EGPA are characterized by eosinophilic infiltrates in walls of small- and medium-sized blood vessels as well as extravascular tissue spaces. […] Different cytokines and chemokines are involved in the associated immune response in EGPA. […] Other cytokines participate in the autoimmune process that is seen in the development of EGPA. […] Elevated perinuclear ANCA (p-ANCA) with myeloperoxidase (MPO)+ is the most common finding in terms of ANCA, yet less than 50% are positive. […] 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. […] Some reports have suggested that Th17 cells are associated with vasculitis, as occurs in giant cell arteritis, Henoch-Schnlein purpura, ANCA-associated vasculitis, granulomatosis polyangiitis or Wegeners granulomatosis, and EGPA.

• #16 ANCA-Negative Glomerulonephritis and Nonasthmatic Churg-Strauss Sndrome

  https://www.medscape.org/viewarticle/579354_2

  In the ANCA-negative subset of patients, the pathogenesis of Churg-Strauss syndrome is thought to be mediated by cytotoxic products of eosinophils.[3,7,12] […] However, the finding of glomerulonephritis, a typical manifestation of ANCA-positive Churg-Strauss syndrome, questions the concept that the pathogenesis of the ANCA-negative disease differs from that of the ANCA-positive disease.

• #17 Evidence-Based Guideline for the diagnosis and management of eosinophilic granulomatosis with polyangiitis | Nature Reviews Rheumatology

  https://www.nature.com/articles/s41584-023-00958-w

  Eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome) is a rare small-vessel vasculitis that occurs in patients with asthma and eosinophilia and is histologically characterized by tissue eosinophilia, necrotizing vasculitis and eosinophil-rich granulomatous inflammation. […] The pathogenesis of EGPA is driven by genetic and environmental factors. Genetic studies have highlighted associations between HLA-DQ and MPO-ANCA-positive EGPA, whereas ANCA-negative EGPA is mainly associated with genetic variants involved in mucosal responses and eosinophil biology, such as GPA33 and IL5. Several other variants linked to asthma and eosinophil counts in the general population are associated with the whole EGPA spectrum. […] Several cell types participate in the immunopathogenesis of the disease. Eosinophils are clearly central and are likely to mediate tissue damage, a concept supported by the evidence that targeting IL-5 (for example, using mepolizumab), a survival factor for eosinophils, is an effective therapy for EGPA.

• #18 Research Shows Genetic Links in ANCA-Associated Vasculitis – Page 2 of 3 – The Rheumatologist

  https://www.the-rheumatologist.org/article/research-shows-genetic-links-in-anca-associated-vasculitis/2/

  Dr. Smith transitioned to a discussion of unpublished genetic data on the rare disease eosinophilic granulomatosis with polyangiitis (EGPA), also known as the ChurgStrauss syndrome. […] The implicated genes suggest asthma results from a breakdown in the communication of epithelial damage to the adaptive immune system as well as the activation of airway inflammation. […] Dr. Smith has now documented 11 EGPA SNP associations that support the hypothesis that EGPA is a polygenic disease. […] Ten of the 11 EGPA loci are associated with eosinophil count, which suggests a unifying hypothesis in which eosinophil count drives the EGPA prodrome. […] Genetic variants associated with long-term outcomes, however, are likely to be distinct from those that drive the susceptibility to disease, and therefore future research efforts will focus on genetics role on treatment response, which should make it possible to identify new therapies that target GWAS-identified pathways.

• #19 Analysis of Innate and Adaptive Immune Responses in Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss) – ACR Meeting Abstracts

  https://acrabstracts.org/abstract/analysis-of-innate-and-adaptive-immune-responses-in-eosinophilic-granulomatosis-with-polyangiitis-churg-strauss/

  Eosinophilic granulomatosis with polyangiitis (EGPA, formerly called Churg-Strauss syndrome) belongs to ANCA-associated vasculitis and is characterized by late onset asthma, blood and tissue eosinophilia and systemic symptoms. […] In the present study, we analyzed the implication of innate and adaptive immunity in EGPA through a systematic phenotyping of T and B cells, type 2 innate lymphoid cell (ILC2) as well as cytokine profile in active and remission EGPA. […] EGPA patients are characterized by a Th2 polarization of T cell response and a trend for Th9 and Th17 polarization in peripheral blood, an activation of B cells and a dramatic decrease of blood ILC2 during active disease. This decrease could be explained by a recruitment of these cells within involved tissues. Increase of IL-25, TSLP and TARC as well as Th2-related cytokines in serum could illustrate the cross-talk between innate and adaptive immunity in this disease, in which ILC2 could play a central role.

• #20 Evidence-Based Guideline for the diagnosis and management of eosinophilic granulomatosis with polyangiitis | Nature Reviews Rheumatology

  https://www.nature.com/articles/s41584-023-00958-w

  The pathogenic relevance of B cells is also underlined by the good response to B cell-depleting agents (such as rituximab) in a substantial proportion of patients. […] In the past few years, considerable advances have been made in EGPA research, particularly in the differential diagnosis and in understanding of pathogenesis and clinical sub-phenotypes; additionally, new treatment options are available and long-term follow-up studies have enabled the definition of disease prognosis based on clinical presentation.

• #21 Eosinophilic granulomatosis with polyangiitis – Wikipedia

  https://en.wikipedia.org/wiki/Eosinophilic_granulomatosis_with_polyangiitis

  Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as allergic granulomatosis, is an extremely rare autoimmune condition that causes inflammation of small and medium-sized blood vessels (vasculitis) in persons with a history of airway allergic hypersensitivity (atopy). […] The second stage is characterized by an abnormally high level of eosinophils (a type of white blood cell) in the blood and tissues as a result of abnormal eosinophil proliferation, impaired eosinophil apoptosis, and increased toxicity due to eosinophil metabolic products. […] The damage done to the blood vessels can be explained by the overabundance of eosinophils that are produced and flowing throughout the vasculature of the body; eosinophil production, while essential for assisting inflammatory responses to infections and diseases, can lead to tissue damage when it is done in excess. […] While the pathogenic mechanisms are not fully understood, this finding suggests a role of B cells the precursors of ANCA-producing plasma cells in the pathogenesis of EGPA.

• #22 Churg-Strauss Disease: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1178795-overview

  Unlike most noninfectious vasculitides, EGPA is fairly distinctive in its pathology, owing to the abundance of eosinophils in the inflammatory perivenular exudate. […] The inflammatory arteriopathy evolves into granulomatous fibrinoid necrosis of the vascular media. […] The characteristic vasculopathy of EGPA is predominantly an arteriopathy, tending to affect small- and medium-sized arteries much more than arterioles, veins, or capillaries.

• #23 Churg-Strauss syndrome – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/churg-strauss-syndrome/symptoms-causes/syc-20353760

  Churg-Strauss syndrome is a disorder marked by blood vessel inflammation. This inflammation can restrict blood flow to organs and tissues, sometimes permanently damaging them. […] The cause of Churg-Strauss syndrome is largely unknown. It’s likely that a combination of genes and environmental factors, such as allergens or certain medications, triggers an overactive immune system response. Instead of protecting against invading bacteria and viruses, the immune system targets healthy tissue, causing widespread inflammation. […] Churg-Strauss syndrome can affect many organs, including the lungs, sinuses, skin, gastrointestinal system, kidneys, muscles, joints and heart. Without treatment, the disease can be fatal.

• #24 Eosinophilic Granulomatosis with Polyangiitis – Vasculitis Foundation

  https://vasculitisfoundation.org/education/vasculitis-types/eosinophilic-granulomatosis-with-polyangiitis/

  Eosinophilic granulomatosis with polyangiitis (EGPA), formerly called Churg-Strauss syndrome, is a form of vasculitis, a family of rare diseases characterized by inflammation of the blood vessels, which can restrict blood flow and damage vital organs and tissues. […] EGPA is known as an ANCA-associated vasculitis, referring to a blood protein (anti-neutrophil cytoplasmic antibody) that attacks the body’s own cells and tissues. […] The cause of EGPA is not fully understood. Researchers believe an infection may set the inflammatory process in motion. Environmental factors such as inhaled allergens, or certain medications or vaccinations, may also play a role in starting EGPA or in its return. Family history and genetics may also cause it.

• #25 Jornal Brasileiro de Pneumologia – Asthma and Churg-Strauss syndrome

  https://jornaldepneumologia.com.br/details/1149/en-US/asthma-and-churg-strauss-syndrome;

  The pathogenesis of CSS has not been fully clarified, but it likely involves auto-immune mechanisms in which leukocytes and endothelial cells play a role. […] Recently, an alteration in the CD95 ligand-mediated apoptosis of lymphocytes and eosinophils was observed. […] In addition, an increase in the serum levels of cationic eosinophilic proteins and soluble thrombomodulin, which are responsible for endothelial cell lesions, has been reported. […] An increase in the level of soluble IL-2 receptor suggests T-cell activation. […] It has also been suggested that CSS is induced by drugs such as zafirlukast, montelukast, zileuton, fluticasone, salmeterol, macrolide antibiotics, estrogens, cocaine, paroxetine and carbamazepine. […] These drugs might act through pseudoallergic/hypersensitivity or idiosyncratic mechanisms.

• #26 Jornal Brasileiro de Pneumologia – Asthma and Churg-Strauss syndrome

  https://jornaldepneumologia.com.br/details/1149/en-US/asthma-and-churg-strauss-syndrome;

  It should be stated that the aforementioned drugs do not have a common chemical structure, thereby making it difficult to provide a single explanation of the pathogenesis of CSS. […] It has not yet been established whether using corticosteroids to treat asthma masks CSS symptoms and postpones the onset of vasculitis, or whether the condition would be aggressive independent of the use of corticosteroids. […] There is considerable discussion regarding the pathophysiological aspects of CSS and the need for controlled prospective studies in order to increase knowledge of the drugs related to its onset. […] Sex hormones could be considered potential determinants of asthma severity. […] Additional studies are needed in order to learn more about the pathological mechanisms involved in the interaction between asthma and sex hormones.

• #27 Eosinophilic Granulomatosis Polyangiitis (EGPA) – EyeWiki

  https://eyewiki.org/Eosinophilic_Granulomatosis_Polyangiitis_(EGPA)

  The precise pathogenesis of EGPA remains ill-defined but is likely similar to other inflammatory autoimmune diseases including AAV. There may be a connection to environmental factors (e.g., allergen, infection, vaccination, and medication exposure) as well as a genetic predisposition. […] Leukotriene receptor antagonist medications used to treat asthma have been suggested to increase the incidence of EGPA. However, it has also been suggested that this may be a mere association based on leukotriene receptor antagonist use in conjunction with tapering of glucocorticoid that caused resurfacing of EGPA. […] In terms of genetic predisposition, the genome-wide association study (GWAS) on EGPA conducted by Lyons et al. in 2018 revealed different genetic associations between MPO-ANCA positive and MPO-ANCA negative EGPA that served to explain differing clinical symptoms and organ manifestation of the disease associated to EGPA ANCA status.

• #28 Churg-Strauss Syndrome or Eosinophilic Granulomatosis with Polyangiitis

  https://www.mdpi.com/2673-351X/1/1/24

  Eosinophilic granulomatosis with polyangiitis (Churg-Strauss, EGPA) is a systemic small-to-medium-sized vasculitis associated with asthma and eosinophilia. Histologically EGPA presents tissue eosinophilia, necrotizing vasculitis, and granulomatous inflammation with eosinophil tissue infiltration. […] The pathogenesis of EGPA is multifactorial. The disease can be triggered by exposure to a variety of allergens and drugs, but a genetic background has also been described, particularly an association with HLA-DRB4. Th2 response is of special importance in the upregulation of different interleukins such as IL-4, IL-13, and IL-5. Th1 and Th17 responses are also of significance. Activated eosinophils have a prolonged survival and probably cause tissue damage by releasing eosinophil granule proteins, while their tissue recruitment can be regulated by chemokines such as eotaxin-3 and CCL17. […] The response of T and B cells along with the activation of eosinophils play an important role in the pathogenesis and ANCAs are the hallmark for the complications of vasculitic disease.

• #29 Update on the pathogenesis of Churg-Strauss syndrome.

  https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W198085912

  Churg-Strauss syndrome (CSS) is a rare form of systemic vasculitis occurring in patients with asthma. The cause of CSS is unknown, and yet little data are available regarding its pathogenesis. The presence of a marked tissue- and blood-eosinophilia, as well as secretory products of eosinophils in blood and tissues, implicates a pathogenetic role of eosinophil granulocytes. Prolonged survival of eosinophils due to inhibition of CD95-mediated apoptosis by soluble CD95 seems to contribute to eosinophilia in CSS. Although the mechanisms involved in eosinophil-activation in CSS have not been elucidated, recent data suggest a possible role of T lymphocytes secreting eosinophil-activating cytokines. […] This review describes the current insights into the pathogenesis of CSS in the light of its putative nature as a type 2 granulomatous disease. Recent clinical, experimental and epidemiologic data regarding the possible role of inflammatory cells and their secretory products, anti neutrophil cytoplasm antibodies (ANCA), epidemiologic factors and anti-asthma treatments are summarized.

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