Contents

Search

hypereosinophilic syndrome

Etiology: - secondary eosinphilia (see eosinophilia) - helminth infection (most common cause of eosinophilia) [2] - connective tissue disorder - neoplasm - allergy - primary myeloproliferative neoplasm [2] - activations of PDGFR-alpha or PDGFR-beta [2] Epidemiology: 1) rare 2) most patients are in the 3rd or 4th decade of life 3) male:female ratio is 7:1 Pathology: 1) absence of obvious reason for eosinophilia 2) sustained overproduction of eosinophils in the bone marrow 3) eosinophil tissue infiltration including skin, lung, GI tract, liver, heart, spleen & lymph nodes 4) end organ damage resulting from eosinophilia - skin, lung, GI tract & heart 5) lung involvement in 40% of patients a) pulmonary infiltrates b) pulmonary fibrosis may develop in chronic cases 6) endocardial disease, restrictive cardiomyopathy Genetics: 1) fusion of FIP1L1 & PDGFRA (FIP1L1-PDGFRA), due to an interstitial chromosomal deletion del(4)(q12q12) 2) constitutive activation of PDGFR-alpha or PDGFR-beta Clinical manifestations: 1) fever 2) night sweats 3) GI: anorexia, diarrhea, weight loss 4) lung: cough, progressive dyspnea, pulmonary crackles 5) skin & mucous membranes: - pruritus, erythroderma, aphthous ulcers [2] 6) heart: - restrictive cardiomyopathy [2] - jugular venous distension (JVD), S4 heart sound, systolic murmur, peripheral edema 8) hepatosplenomegaly 9) often asymptomatic - eosinophilia is often an incidental finding Diagnostic criteria: - eosinophilia (>1500 cells per cubic millimeter) persisting for 6 months - absence of secondary causes of eosinophilia - end-organ involvement Laboratory: 1) complete blood count (CBC) with differential a) leukocytosis generally > 10,000/mm3 b) eosinophilia > 1500/mm3 (30-70%) for > 6 months duration c) 10-30% of cases may lack eosinophilia 2) peripheral smear: 1) normal appearing eosinophils 2) no blasts 3) bronchoalveolar lavage (BAL) - cell count may show > 70% eosinophils 4) molecular diagnostic testing - chromosomal deletion del(4)(q12q12) - PDGFRA gene mutation - helminth DNA 5) examination of the stool for helminth infection - ova & parasites Special laboratory: - electrocardiogram: low QRS voltage (case presentation [2]) - echocardiogram: (case presentation [2]) - mitral regurgitation - restrictive left ventricular filling - increased echogenicity of endocardium Radiology: - chest X-ray - interstitial nodular infiltrates Differential diagnosis: eosinophilic leukemia Complications: 1) pulmonary fibrosis may develop in chronic cases 2) cardiac complications a) endomyocardial fibrosis b) restrictive cardiomyopathy 3) thromboembolism a) mural thrombus formation b) arterial thromboembolism - embolic stroke c) deep vein thrombosis 4) cerebrovascular lesions 5) peripheral neuropathy 6) often fatal disease Management: 1) supportive 2) eosinophilia & clinical course may remain stable for years 3) glucocorticoids 1st line [2] - lytic effect on peripheral & tissue eosinophils [2] - may exacerbate Strongyloides infection [2] 4) second line therapy a) tyrosine kinase inhibitor - imatinib effective with PDGF receptor alpha (or beta ?) aberrations [2] b) interferon c) cyclosporine d) chemotherapy 5) warfarin for cardiac thrombus 6) endomyocardectomy (palliative) [2]

General

pulmonary infiltrates with eosinophilia (PIE) syndrome

Database Correlations

OMIM 607685

References

  1. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 755
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2009, 2015, 2018, 2022. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  3. Tefferi A, Gotlib J, Pardanani A Hypereosinophilic syndrome and clonal eosinophilia: point-of- care diagnostic algorithm and treatment update. Mayo Clin Proc. 2010 Feb;85(2):158-64 PMID: 20053713
  4. Klion AD. How I treat hypereosinophilic syndromes. Blood. 2015 Aug 27;126(9):1069-77. Review. PMID: 25964669 Free PMC Article