1 / 12

Hypereosinophilic Syndromes

Hypereosinophilic Syndromes. Eosinophils – The Basics. Produced in the bone marrow Function to combat parasitic infections, ectoparasites, certain viral infections, and amplify responses of mast cells in atopy

lynsey
Download Presentation

Hypereosinophilic Syndromes

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Hypereosinophilic Syndromes

  2. Eosinophils – The Basics • Produced in the bone marrow • Function to combat parasitic infections, ectoparasites, certain viral infections, and amplify responses of mast cells in atopy • This is largely accomplished by generating ribonucleases, oxidative species = apoptosis, and inducing degranulation of basophils and mast cells • Eosinophils are attracted to tissues by certain chemokines (RANTES, CCL11/24) and leukotrienes • They require IL-5 (Eosinophil growth factor, secreted by T-cells) for proliferation and to prevent apoptosis • They are VERY sensitive to steroids

  3. Eosinophils – The Basics • These granules are full of: • Major Basic Protein = toxic to helminths and epithelial cells • Ribonuclease A (aka Eosinophil Cationic Protein) • Eosinophil Peroxidase = generation of hypobromite used to combat Helminths and TB • Proteases that are involved in tissue remodeling

  4. Hypereosinophilic Syndromes • Represents a heterogenous group of uncommon disorders marked by blood or tissue eosinophilia • Known causes of secondary or reactive eosinophilia must be ruled out • Range from benign idiopathic eosinophilia to eosinophilic leukemia • Pretty rare, 50 total documented cases between 1971 – 1982 • Previously defined by Chusid et al in 1975 by the following: • Greater than or equal to 1500 eosinophils/mm3 for at least 6 months • Lack of evidence for secondary etiologies of hypereosinophilia • Presumptive signs and symptoms of organ involvement

  5. Hypereosinophilic Syndromes • Secondary (reactive) causes of eosinophilia

  6. Hypereosinophilic Syndromes • Main DDx include: • Systemic mastocytosis • Occult malignancy, solid (adenocarcinoma) or liquid (leukemia/lymphoma) • Churg Strauss • Atopy • Parasitic infections • Chronic TB • Other granulomatous disease such as sarcoid and IBD • Endocrine causes such as hypoadrenalism • Morbidity and mortality associated with these syndromes = usually due to cardiac and neuropathic complications • These represent medical emergencies that require emergent treatment with corticosteroids

  7. Hypereosinophilic Syndromes • Primary cardiac complications include cardiogenic shock or heart failure due to • Loeffler’s endocarditis = a restrictive cardiomyopathy from eosinophilic infiltration leading to fibrotic thickening • Endomyocardial fibrosis (aka Davies Disease, seen in the tropics) • Other clinical manifestations include: • Skin and mucosal ulcerations • Thromboembolic disease • Splenomegaly • Pleural effusions and/or pulmonary fibrosis

  8. Hypereosinophilic Syndromes • More recent analyses differentiate the spectra of hypereosinophilic diseases as the following varients: • FIP1L1/PDG positive, aka myeloproliferative variant HES • Lymphocyte variant HES = significant eosinophilopoiesis • Familial HES • Associated HES (from reactive eosinophilia) • Overlap HES

  9. Clinical Approach • CBC with diff, serum tryptase, strongyloides antibody, peripheral lymphocyte clonal studies • Bone marrow biopsy with FISH/Flow, ANA, SPEP • TTE, CT chest and abdomen

  10. Treatment • Corticosteroids 1mg/kg/day with good success • Imatinib therapy if the FIP1L1/PDG fusion protein is present • Anti-IL-5 therapy with mepolizumab

  11. References • Klion, A. How I treat hypereosinophilic syndromes. Blood, 2009;114(18):3736-3741 • Chusid, DC et al. The hypereosinophilic syndrome. Medicine. 1975;54(1):1-27 • Cools, J et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. New England Journal of Medicine. 2003;348(13):1201-1214

  12. Gratuitous photos

More Related