Hypereosinophilic Syndrome Presenting with Unusual Triad of Immune Thrombocytopenic Purpura, Cerebral Venous Sinus Thrombosis, and Eosinophilic Pneumonia: A Case Report

DISCUSSION

Hypereosinophilic syndromes are a group of rare disorders characterized by the persistent overproduction of eosinophils. This excessive eosinophil count results in organ dysfunction due to tissue infiltration.⁴ HES can be classified into three categories: primary (myeloproliferative), secondary (T-cell lymphocytic), or idiopathic.³ The evaluation for primary HES in our patient showed negative results for the FIP1L1-PDGFRA (F/P) fusion gene, PDGFRB mutation, JAK2 V617F mutation, and BCR-ABL mutation. Workup for secondary eosinophilia (infections, inflammation, allergy, and neoplasm) was also negative. Since our patient did not have an identifiable cause, she was labeled as idiopathic HES. Steroids play a major role as the first-line treatment for idiopathic HES and other F/P-negative HES (F/P-positive HES should be treated with imatinib). The initial recommended dose of prednisone for HES treatment typically ranges from 0.5 to 1 mg/kg. However, in cases of severe disease characterized by persistently elevated eosinophil counts and progressive organ dysfunction, higher doses may be necessary. Therapy should be adjusted daily, with incremental increases based on the severity of eosinophilia and the patient’s overall clinical condition. This tailored approach ensures that treatment intensity matches disease activity, optimizing patient outcomes while managing potential side effects. In our case, the patient was started on an injection of methylprednisolone 60 mg/day. Eosinophil count decreased significantly to <5% within 2 days and continued to remain within the normal range throughout the course of the treatment (Fig. 2).

In cases of HES, the condition often manifests in at least two organ systems, as observed in our patient’s presentation involving pulmonary, thrombotic, thrombocytopenic, and dermatologic manifestations. It’s notable that thrombocytopenia is more commonly encountered than thrombocytosis in individuals with HES, with rates of 31 and 16%, respectively. However, it’s worth emphasizing that severe thrombocytopenia, defined as platelet counts below 20 × 10/μL, is a rare occurrence in these patients, underscoring the complexity and variable clinical spectrum of the disease.⁴ No specific variants of HES are specifically associated with thrombocytopenia. Understanding the mechanism behind thrombocytopenia in HES remains incomplete, initially attributed to diminished marrow megakaryocytosis. However, in our patient’s case, a bone marrow biopsy unveiled normocellular marrow, characterized by significant eosinophilia (21%) and adequate megakaryocytes without signs of myelofibrosis. These findings challenge previous assumptions, suggesting a more nuanced interplay between eosinophils and platelet dynamics in HES-related thrombocytopenia. Another workup for thrombocytopenia (ADAMTS13, disseminated intravascular coagulation profile, sepsis, antiphospholipid antibody profile, vasculitis, and connective tissue disorder) was all negative. Diagnosis of ITP was made, and the patient was initiated on IVIG at a dose of 2 gm/kg over 2 days. Platelets increased to >1 lakh (Fig. 3) after two doses of IVIG. There are no cases of Idiopathic HES with ITP reported in the literature to the best of our literature search. Two case reports of secondary HES with ITP secondary to Helicobacter pylori infection were reported, and in both patient’s platelet count recovered and eosinophil count normalized after H. pylori treatment without the need for any further treatment.⁵ In our patient, a workup for secondary ITP was negative and the patient responded to IVIG treatment.

Hypereosinophilic syndrome is a prothrombotic state associated with thrombotic complications.⁵ Eosinophils contribute to thrombosis by releasing tissue factors and creating a procoagulant phospholipid surface, facilitating thrombin generation. Moreover, their secretion of eosinophilic granular proteins, particularly cationic proteins, triggers factor XII activation, promoting internal coagulation pathways. Additionally, eosinophil-derived major basic protein and eosinophil peroxidase play roles in platelet activation, further exacerbating the prothrombotic state. The direct cytotoxic effect of eosinophils by endothelial damage and recruitment of inflammatory mediators may also contribute to a procoagulant state. Approximately, 25% of patients with HES experience thromboembolic complications, primarily affecting venous systems such as DVT and thromboses in the pulmonary, hepatic, portal, and cutaneous veins. These thromboembolic events are serious, with 5–10% of affected patients succumbing to these complications. Consequently, managing and preventing thromboembolic risks is crucial for improving the prognosis and survival rates of individuals with HES.⁵ CVST is very rare and so far, nine reports of HES with CVST have been reported in the literature of which nearly 50% of patients died.⁶ Thrombosis presents a significant risk for patients with HES, emphasizing the urgent need for effective strategies to prevent and manage thromboembolism in these cases. Currently, there are no specific guidelines for treating thromboembolic events in HES patients, and the decision to use anticoagulation therapy remains controversial. However, anticoagulation should be considered for those at high-risk, including patients with intracardiac thrombosis, DVT, recurrent thromboembolic events, or CSVT. Severe thrombocytopenia (<20 × 103/μL) in our patient initially prevented us from initiating therapeutic anticoagulation. However, the diagnosis of ITP and treatment with IVIG helped us in the timely initiation of therapeutic anticoagulation, which improved the outcome in our patient. Therefore, when a patient with HES presents with thrombocytopenia, ITP should be considered a potential diagnosis. Given the complexity of HES and its associated conditions, a thorough evaluation for ITP is crucial to ensure accurate diagnosis and appropriate management.