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A6743 - Unexplained Cough, Dyspnea, and Eosinophilia: Don't Forget the Zebras
Author Block: R. Guthrie1, L. C. Moses2; 1Pulmonary and Critical Care Medicine, Virginia Commonwealth Univ Hlth Systems, Richmond, VA, United States, 2Virginia Commonwealth Univ Hlth Systems, Richmond, VA, United States.
INTRODUCTION: Hypereosinophilic syndrome (HES) is a rare condition characterized by tissue-associated eosinophilic inflammation and peripheral eosinophilia. We highlight a case of myeloproliferative HES (M-HES) to illustrate this unusual entity which is often difficult to diagnosis, and in whom a delay in diagnosis may lead to further end-organ damage.
CASE: 56 year old male with history of cardiac disease presented to pulmonary clinic for workup of severe eosinophilia, cough, dyspnea, unintentional weight loss and night sweats. He is a cigarette smoker, previously served in the military and worked as an electrician. He denied any pets or birds at home. No history of asthma or allergies. Physical was unremarkable without dermatographia or uticaria. Complete blood count (CBC) revealed leukocyte count of 14,000, hemoglobin 14.3, platelet count of 275,000, and an absolute eosinophil count of 5,100. Basic metabolic panel, hepatic panel, and urinalysis were normal. Chest CT showed multiple lung nodules, bibasilar ground glass opacities with reticular interstitial thickening. Infectious disease evaluation was negative for fungus, parasitic infection, TB and HIV. Pulmonary workup included negative radioallergosorbent testing, minimal elevation of IgE, negative tryptase, and normal pulmonary function testing. Vasculitis workup including ANCA was negative. Flow cytometry was negative. Repeat CT chest, abdomen, and pelvis revealed worsened basilar groundglass opacities, interlobular septal thickening, mild hepatomegaly and borderline enlarged spleen without lymphadenopathy. Repeat CBC revealed leukocyte count of 23,400 and eosinophil count of 12,900. He was referred for bone marrow biopsy which revealed FIP1L1-PDGFRA positive myeloproliferative neoplasm with marked eosinophilia without increase in blasts; FISH positive for 4q12 rearrangement. He was started on Imatinib with improvement in constitutional and pulmonary symptoms. CBC one month after therapy showed leukocyte count of 7,600 and eosinophil count of 100. Repeat imaging was improved.
DISCUSSION: M-HES is subcategory of HES that combines features of myeloproliferative disorders and eosinophilia. It is associated with an abnormal fusion of Fip1-like1 (FLIP1L1) and platelet-derived growth factor receptor alpha (PDGFRA) due to a deletion on chromosome 4q12 containing the CHIC2 gene; this fusion results in production of constitutively active tyrosine kinase, thus modifying hematopoietic stem cells and leading to eosinophilia. Patients with the F/P mutation have shown marked improvement with the tyrosine kinase inhibitor, imatinib. Pulmonary manifestations of HES most commonly include cough and dyspnea, with patchy ground glass opacities on imaging. While rare, HES should be entertained in the differential for eosinophilic lung disease, especially in those patients with systemic or extrapulmonary manifestations.