Churg-Strauss syndrome pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Ali Poyan Mehr, M.D. [2]Associate Editor(s)-in-Chief: Chandrakala Yannam, MD [3]
Overview
Eosinophilic granulomatosis with polyangiitis is a medium and small vessel vasculitis, leading to necrosis and vasculitis. The pathogenesis of eosinophilic granulomatosis with polyangiitis is not fully understood. It may occur as a result of a complex interaction involving genetic and environmental factors that lead to an inflammatory response involving eosinophils, lymphocytes and giant cells. Autoimmunity has an evident role in the presence of ANCA, hypergammaglobulinemia, elevated levels of immunoglobulin E, and rheumatic factor in the pathogenesis. HLA-DRB4 is correlated with increased risk of development of vascular manifestations of the churg-strauss syndrome. On microscopic pathology, eosinophlic infiltration, necrotizing granulomas vasculitis and necrosis of small and medium-sized arteries can be seen.
Pathophysiology
Pathogenesis
- The pathogenesis of eosinophilic granulomatosis with polyangiitis is not fully understood.[1]
- Eosinophilic granulomatosis with polyangiitis is probably caused by the result of a complex interaction involving genetic and environmental factors that lead to an inflammatory response involving eosinophils, T lymphocytes, and B lymphocytes.
- The disease most commonly involves medium and small vessel resulting in necrosis and vasculitis. It involves mainly the blood vessels of the lungs, gastrointestinal system, and peripheral nerves, but also affects the heart, skin, and kidneys.
- There is insufficient data to support the role of cell-mediated and immune complex mediations, although autoimmunity has an evident role with the presence of ANCA, hypergammaglobulinemia, elevated levels of immunoglobulin E, and rheumatic factor.[2]
- Eosinophilic granulomatosis with polyangiitis may develop in steroid-dependent asthma patients after they started treatment with leukotriene receptor antagonists / leukotriene modifying agents (eg, zafirlukast, montelukast) with reduced oral steroid dosage. This complication is more likely caused by steroid withdrawal by unmasking underlying disease.[3][4]
- It has been reported in patients whose oral steroid withdrawal is facilitated by use of inhaled glucocorticosteroids, omalizumab (human Ig E antagonist, and cocaine) likely by the unmasking of the underlying disease.
Genetics
- HLA-DRB1*7, and HLA-DRB4 are associated with the development of eosinophilic granulomatosis with polyangiitis. HLA-DRB4 is correlated with increasing risk of development of vascular manifestations of the churg-strauss syndrome.[5][6]
- Single-nucleotide polymorphisms in the Interleukin-10 gene (IL10.2 haplotype) have been associated in the pathogenesis of eosinophilic granulomatosis with polyangiitis.[7]
Associated Conditions
The following conditions are associated with Eosinophilic granulomatosis with polyangiitis:[8][9][10][11]
- Well's syndrome
- AA amyloidosis
- Asthma
- Nasal polyposis and sinusitis
- Skin
- Cardiovascular:
- Pericarditis
- Myocarditis
- Sub endocardial fibrosis
- Pericardial constriction
- Heart failure
- Myocardial infarction
- Neurologic:
- Renal:
- GI Disease:
Gross Pathology
On gross pathology, the following changes are seen in patients with eosinophilic granulomatosis with polyangiitis include:[12]
- Nodular swellings that appear along the course of small arteries of various organs.
- Infarcts, hemorrhage and scarring of affected organs
- Pulmonary artery occlusion and thrombus formation
- Patchy consolidations of the lung
- Ventricular hypertrophy, and myocardial scariing.
Microscopic Pathology
On microscopic examination, following findings can be seen in eosinophilic granulomatosis with polyangiitis, include:[13][14]
- Infiltration of eosinophils with necrosis
- Necrotizing vasculitis involving small and medium-sized arteries and venules.
- Necrotizing granulomas
- Interstitial and perivascular necrotizing granulomas
- Granulomas composed of an eosinophilic center and surrounded by macrophages, histocytes, and multi nucleated giant cells peripherally.
References
- ↑ Hellmich B, Ehlers S, Csernok E, Gross WL (2003). "Update on the pathogenesis of Churg-Strauss syndrome". Clin. Exp. Rheumatol. 21 (6 Suppl 32): S69–77. PMID 14740430.
- ↑ Tsurikisawa N, Saito H, Tsuburai T, Oshikata C, Ono E, Mitomi H, Akiyama K (September 2008). "Differences in regulatory T cells between Churg-Strauss syndrome and chronic eosinophilic pneumonia with asthma". J. Allergy Clin. Immunol. 122 (3): 610–6. doi:10.1016/j.jaci.2008.05.040. PMID 18586318.
- ↑ Wechsler ME, Garpestad E, Flier SR, Kocher O, Weiland DA, Polito AJ, Klinek MM, Bigby TD, Wong GA, Helmers RA, Drazen JM (February 1998). "Pulmonary infiltrates, eosinophilia, and cardiomyopathy following corticosteroid withdrawal in patients with asthma receiving zafirlukast". JAMA. 279 (6): 455–7. PMID 9466639.
- ↑ Tuggey JM, Hosker HS (September 2000). "Churg-Strauss syndrome associated with montelukast therapy". Thorax. 55 (9): 805–6. PMC 1745850. PMID 10950903.
- ↑ 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 (September 2007). "HLA-DRB4 as a genetic risk factor for Churg-Strauss syndrome". Arthritis Rheum. 56 (9): 3159–66. doi:10.1002/art.22834. PMID 17763415.
- ↑ Bottero P, Motta F, Bonini M, Vecchio F, Ierna F, Cuppari I, Sinico RA (2014). "Can HLA-DRB4 Help to Identify Asthmatic Patients at Risk of Churg-Strauss Syndrome?". ISRN Rheumatol. 2014: 843804. doi:10.1155/2014/843804. PMC 3963189. PMID 24734195.
- ↑ Wieczorek S, Hellmich B, Arning L, Moosig F, Lamprecht P, Gross WL, Epplen JT (June 2008). "Functionally relevant variations of the interleukin-10 gene associated with antineutrophil cytoplasmic antibody-negative Churg-Strauss syndrome, but not with Wegener's granulomatosis". Arthritis Rheum. 58 (6): 1839–48. doi:10.1002/art.23496. PMID 18512809.
- ↑ Lee SH, Roh MR, Jee H, Chung KY, Jung JY (2011). "Wells' syndrome associated with churg-strauss syndrome". Ann Dermatol. 23 (4): 497–500. doi:10.5021/ad.2011.23.4.497. PMC 3229945. PMID 22148019.
- ↑ Maamar M, Tazi-Mezalek Z, Harmouche H, El Hamany Z, Adnaoui M, Aouni M (2012). "Churg-Strauss syndrome associated with AA amyloidosis: a case report". Pan Afr Med J. 12: 30. PMC 3415051. PMID 22891088.
- ↑ Neumann T, Manger B, Schmid M, Kroegel C, Hansch A, Kaiser WA, Reinhardt D, Wolf G, Hein G, Mall G, Schett G, Zwerina J (July 2009). "Cardiac involvement in Churg-Strauss syndrome: impact of endomyocarditis". Medicine (Baltimore). 88 (4): 236–43. doi:10.1097/MD.0b013e3181af35a5. PMID 19593229.
- ↑ Chumbley LC, Harrison EG, DeRemee RA (August 1977). "Allergic granulomatosis and angiitis (Churg-Strauss syndrome). Report and analysis of 30 cases". Mayo Clin. Proc. 52 (8): 477–84. PMID 18640.
- ↑ CHURG J, STRAUSS L (1951). "Allergic granulomatosis, allergic angiitis, and periarteritis nodosa". Am J Pathol. 27 (2): 277–301. PMC 1937314. PMID 14819261.
- ↑ Churg A (December 2001). "Recent advances in the diagnosis of Churg-Strauss syndrome". Mod. Pathol. 14 (12): 1284–93. doi:10.1038/modpathol.3880475. PMID 11743052.
- ↑ Katzenstein AL (November 2000). "Diagnostic features and differential diagnosis of Churg-Strauss syndrome in the lung. A review". Am. J. Clin. Pathol. 114 (5): 767–72. doi:10.1309/F3FW-J8EB-X913-G1RJ. PMID 11068552.