Allergy/Immunology The role of investigating and initiating therapy for hypereosinophilia when end organ involvement is present. A 51-year-old man with past medical history of allergic rhinitis was admitted to the hospital and treated for a right sided multi-lobar pneumonia. He presented with progressively worsening dry cough, malaise and diffuse (hip, knee, elbow, hands) joint pain. He had a history of multiple episodes of sinusitis and upper respiratory tract infections in the preceding six months requiring steroids and antibiotics with varying responses. He had no history of childhood asthma or recurrent ear/nose/throat infections. He was a previous tobacco smoker with ∼ 13-pack year history, and quit smoking in 1996. His most recent travel was to Las Vegas, Colorado, and Seattle. He had also been on a cruise to Mexico 3 years prior to presentation. On admission, he had a fever of 102*F, tachycardic, normotensive, with normal oxygen saturation. Physical exam findings were relevant for decreased breath sounds on lower and middle lung fields. Complete blood count revealed eosinophil count of > 9 eosinophils x 109/L. A bronchoalveolar lavage was performed and revealed over 90% eosinophils on analysis. He had a bone marrow biopsy showing moderate hypercellularity with marked eosinophilic hyperplasia and moderate megakaryocytic hyperplasia. FISH results were negative for PDGFRA, PDGFRB and FGFR1 rearrangements and presented normal cytogenetics. JAK2 and BCR-ABL were both negative. His clinical presentation along with the above findings was consistent with a diagnosis of idiopathic hypereosinophilic syndrome. He was started on prednisone in combination with hydroxyurea. He responded well to his current regimen. However, when his treatment was tapered he had a flare with now left sided pulmonary infiltrates and respiratory symptoms. With increase of treatment, this again resolved. Idiopathic hypereosinopillic syndrome is a diagnosis of exclusion, once reactive and neoplastic causes have been excluded and it comprises the largest category. This case report highlights the importance of investigating and initiating therapy for hypereosinophilia especially when end organ involvement is present. The goal of HES treatment is to mitigate eosinophil-mediated organ damage. Furthermore, the case shows eosinophilic pulmonary infiltrates can be unilateral despite this being a systemic process. It details the work-up that precludes diagnosis of this condition, and exclusion of multiple causes. Our case further highlights the need for steroid sparing agents in long-term management of idiopathic hypereosinophilic syndrome. With increased use of next-generation sequencing, somatic mutations are being detected in an increasing number of IHES cases. Anti–IL-5 antibodies (mepolizumab and reslizumab), and anti-CD52 antibodies (alemtuzumab) have been successful in treating HES. Additional eosinophil-targeted therapies currently in preclinical trials include those targeting Siglec-8, an eosinophil-selective receptor, and CCR3, an eosinophil-specific chemokine receptor.