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A3395 - Hypereosinophilic Syndromes: A Game of Diagnostic Charades
Author Block: W. Kareem1, U. Chaddha1, R. G. Barbers2; 1Pulmonary and Critical Care, University of Southern California, Los Angeles, CA, United States, 2Pulmonary and Critical Care, Keck Sch of Med of USC, Los Angeles, CA, United States.
Hypereosinophilic syndromes (HES) are rare and characterized by persistent overproduction of eosinophils leading to organ damage. HES are classified by their pathogenic mechanisms. The myeloid variant is secondary to clonal chromosomal abnormalities. The most commonly seen aberration is an interstitial deletion on chromosome 4q12 resulting in the fusion of FIP1L1-PDGFRA. The fusion demonstrates constitutive tyrosine kinase activity lending itself to treatment with tyrosine kinase inhibitors. All variants lead to increased eosinophilic production and have similar clinical presentations making the precise diagnosis and resulting treatment challenging. The myeloid variant of HES can clinically masquerade as Eosinophilic Granulomatosis with Polyangiitis (EGPA) making knowledge of this entity essential to any patient presenting with signs of HES.
A 32 year male presented with a 3 day history of left sided paresthesias and 1 day history of seizure like activity, dysarthria, confusion and chest pain and shortness of breath. Physical exam was significant for decreased orientation and decreased strength and sensation of the left upper and lower extremities. Laboratory investigations patient showed a white blood cell count (WBC) of 39,300 per microliter and absolute eosinophil count of 20,000 per microliter. Troponin was elevated. All autoimmune, immunological and infectious work up including fungal, ova and parasites was negative. Magnetic resonance imaging (MRI) of the head revealed diffuse bilateral emboli. Computerized tomography angiography of the head demonstrated luminal irregularity of the small branch vessels of the intracranial arterial vasculature. Cardiac MRI suggested infiltrative disease. Cardiac catheterization did not reveal coronary anomalies. Given elevated eosinophilic and concern for intracranial involvements the patient was started on high dose steroids with a presumptive diagnosis of EGPA. Unfortunately, the patient’s (WBC) and absolute eosinophil count did not improve. Subsequent computerized tomography imaging did not show any evidence of vasculitis. A bone marrow biopsy was performed which showed hypercellular marrow with marked dysplastic eosinophilia. Fluorescence in situ hybridization (FISH) demonstrated the FIPL1-PDGFR-alpha fusion. The patient was started was started on Imatinib and within 24 hours began having resolution of his eosinophilia and concomitant clinical symptoms.
HES is a rare clinical phenomenon with numerous variants presenting with similar clinical characteristics. In patient’s with HES it is critical to perform an early bone marrow biopsy and accompanying FISH studies to elucidate if a myeloid variant and accompanying chromosomal abnormality is present. The majority of chromosomal abnormalities in HES are responsive to tyrosine kinase inhibitors and can lead to early symptom and hematological resolution.