Idiopathic hypereosinophilic syndrome and disseminated intravascular coagulation

Abstract

Hypereosinophilic syndromes (HESs) are conditions characterized by persistent eosinophilia of 1.5 × 109/L or higher and manifestations of end‐organ involvement or dysfunction attributable to the eosinophilia. Immunological, infectious, and malignant disorders can be associated with HESs but can be even idiopathic. Disseminated intravascular coagulation (DIC) associated with HES is rare. We report a case of HES complicated by DIC which improved with treatment. A 45‐year‐old woman was admitted with generalized itching for 6 months and breathlessness for 1 week. She had a history of hemorrhoids for the past 6 years. She denied a history of weight loss, had no sick contacts, and had no history of addictions. Examination showed multiple purpuric spots over both hand and foot and a Grade 3/5 pansystolic murmur over the tricuspid area. There were no other bleeding manifestations. Hemoglobin was 10.0 g/dl, total leukocyte count – 19,700/μl (neutrophil – 39%, lymphocytes – 23%, eosinophils – 33%, and monocytes – 5%), platelet count – 57,000/L, and erythrocyte sedimentation rate – 8 mm in 1 h. Peripheral smear showed hemolysis, severe eosinophilia, and moderate thrombocytopenia [Figure 1a]. Direct and indirect Coombs tests were negative. Renal function tests, blood sugar, serum electrolytes, urinalysis, and chest radiograph were all normal. Liver function tests showed indirect hyperbilirubinemia. Prothrombin time and activated partial thromboplastin time (aPTT) were both prolonged. Serum lactate dehydrogenase, D‐dimer, and fibrin degradation product level were high. HIV, HbsAg, and HCV serologies were negative. Bone marrow examination showed trilineage maturation and myeloid hyperplasia with increase in eosinophils and its precursors [Figure 1b]. Workup for hypereosinophilia including stool examination for parasites, antinuclear antibody, and antineutrophil cytoplasmic antibody was negative. Cytogenetic studies for detecting FIP1L1‐PDGFRA rearrangement, CHIC2 deletion, FGFR1 rearrangement, and breakpoint cluster region‐Abelson murine leukemia were negative. Ultrasonography abdomen showed a hypoechoic lesion in the left lobe of the liver (48 mm × 38 mm). Contrast‐enhanced computed tomography of the abdomen showed an exophytic, hypodense lesion measuring 8.1 cm × 7 × cm 4.2 cm in the segment IV of the liver, and on postcontrast imaging, the lesion showed gradual centripetal filling in the arterial, portal, and delayed phases, which was suggestive of hepatic hemangioma. Echocardiogram showed thickened posterior mitral valve leaflet, moderate tricuspid and mitral regurgitation, severe pulmonary arterial hypertension, left ventricular apical and lateral wall fibrosis and right ventricular apical fibrosis, and dysfunction [Figure 2]. Contrast‐enhanced computed tomography thorax was normal. A diagnosis of DIC complicating idiopathic HES with cardiac involvement was made. She was treated with intravenous methylprednisolone 1 g daily for 3 days, which was followed by oral prednisolone (1 mg/kg body weight). Her breathlessness improved following the treatment, but the eosinophilia was persisting and thus was started on hydroxyurea 1 g daily with which the eosinophil count became normal. The etiology of the eosinophilia in HESs can be primary (myeloid), secondary (lymphocyte driven), or unknown. HES can be classified into six clinical variants: myeloproliferative HE/HES (M‐HE/M‐HES), lymphocytic variant HE/HES (L‐HE/L‐HES), overlap HES, associated HE/HES, familial HE/HES, and idiopathic HES.1 Fifty percent of HES is idiopathic even after extensive evaluation. Thromboembolism is a common complication of HES (seen in 25%) and has a high mortality (5%–10% die as a result). The actual mechanisms responsible for HES‐derived coagulopathy are not well elucidated. The four main granule proteins released by eosinophils including major basic protein, eosinophil‐derived neurotoxin, eosinophil cationic protein, and eosinophil peroxidase are thought to be responsible for the hypercoagulable state.2