Discussion
Hypereosinophilic Syndrome (HES) is defined by an abnormal overproduction and deposition of eosinophils in the blood or peripheral organs leading eosinophil - mediated organ damage or dysfunction.4 HES has been further divided based on etiology into primary (stem cell, myeloid or eosinophilic malignancy), secondary (parasitic infections, solid tumors, T cell lymphoma), or idiopathic.3 According to various sources idiopathic HES is an extremely rare disease and its incidence ranges from 0.04 to 0.17 per 100,000 persons and the prevalence ranges from 0.15 to 0.89 cases per 100,000 persons.5 Due to advances in diagnostic techniques, causes of eosinophilia can be identified in a proportion of cases that in the past would have been classified as idiopathic. However, due to the unavailability of services in Nepal, some of the investigations of the indexed case were sent to India for further evaluation. The hypereosinophilic syndrome reports male predominance, with a male-to-female ratio of 9:1.5 HES is commonly diagnosed in patients aged 20-50 years, with a peak incidence in the fourth decade. This study also exemplified that 38 years-old male case presented with rare clinical manifestations of hypereosinophilic syndrome.
The most common cause of eosinophilia in the United States is an allergic reaction or allergic disease.6 Worldwide, the most common cause of eosinophilia is parasitosis.7Several mechanisms have been proposed for the pathogenesis of hypereosinophilic syndrome, including the overproduction of eosinophilopoietic cytokines, their enhanced activity, and defects in the normal suppressive regulation of eosinophilopoiesis.8 Eosinophils amplify the inflammatory cascade by secreting chemoattractants that recruit more eosinophils.9 Organ damage-induced HES is due to the eosinophilic infiltration of the tissues accompanied by the mediator (major basic protein, eosinophil peroxidase, eosinophil-derived neurotoxin, and eosinophil cationic protein) release from the eosinophil granules.9 The case presented in this study was suspected of the parasitic infestation and later further investigations reported that the cause could be eosinophilic leukemia. A similar case of hypereosinophilic syndrome case was presented with features of dilated cardiomyopathy as a dilemma to approach and treatment, as our case with the presentation of bilateral hydro pneumothorax as presentation.10
HES is a heterogeneous disease process with multiple manifestations that may occur simultaneously or individually.4 The presentation can be sudden and dramatic, with cardiac, neurologic, or thrombotic complications, but, more often, the onset is insidious. HES can involve any organ system but commonly involves the respiratory tract, skin, central nervous system, and cardiac.4Many patients experience fever and night sweats. Some sources identify anorexia and weight loss as common presenting manifestations. Cardiac involvement is the leading cause of mortality and common symptoms of cardiac involvement include chest pain, dyspnea, or orthopnea. A chronic, persistent cough, usually nonproductive, is the most common respiratory symptom reported in hypereosinophilic syndrome. Rhinitis or angioedema is sometimes a presenting feature. Dyspnea may occur in cardiac or respiratory involvement. Embolic or thrombotic strokes or transient ischemic episodes may occur and are often the initial manifestations. Some patients with HES experience encephalopathy caused by CNS dysfunction. Peripheral neuropathies account for about 50% of all neurologic symptoms in HES.
Arthralgia, myalgia, pruritus, diarrhea, and fatigue are relatively common manifestations of HES but are non-specific. However, the case in this study demonstrated some of the abovementioned clinical such as shortness of breath, dry cough, and chest pain.
The decision to use a drug for the treatment of HES depends partly on the presence or absence of organ involvement.4 So, the initial evaluation of the patient with eosinophilia should include tests that facilitate the assessment of target organ damage. In asymptomatic patients’ treatment is postponed till a diagnostic workup is completed and a specific diagnosis is made. Early initiation of therapy is reasonable in clonal eosinophilia associated with imatinib mesylate—sensitive molecular markers (eg, FIP1L1-PDGFRA, PDGFRB rearrangement, BCR-ABL ). In idiopathic HES no evidence to support early drug treatment. Periodic follow-up with monitoring of complications is reasonable (no evidence to support this).2 Symptomatic patients with clonal HES imatinib mesylate are the first drug to be considered in the presence ofFIP1L1- PDGFRA or PDGFRA/PDGFRB translocations. For induction of remission and maintenance 100mg/d of Imatinib mesylate is recommended. In the case of rare mutant FIP1L1-PDGFRA, imatinib-resistant, other tyrosine kinase inhibitors or interferon-alpha is sensitive for induction of remission. In refractory cases, allogeneic hematopoietic cell transplant needs to be considered.8 The case in this study firstly was treated with oral antiparasitic medications and steroids, later he underwent anti-tubercular therapy.
In 2018 RN Das et al reported the first case in Nepal of idiopathic HES presented with fatal eosinophilic cardiomyopathy and dysphagia.11 They reported the case of a farmer presenting with symptoms of persistent fever, cough, dyspnea, and refractory heart failure for 7 months with peripheral eosinophilia. They found no cause for eosinophilia despite a thorough evaluation.12 In 1971, similarly Rickles et al reviewed 16 cases of hypereosinophilic syndrome, most of which were doubtful eosinophilic leukemia.13 In 2009, a multicenter study conducted by Princess U Ogbogu in 161 patients with eosinophilia found FIP1L1-PDGFRA test positive in 18 patients. 11
The strength of this case study is that this has reported a rare case, and this has been reported in a tertiary care hospital in Nepal. This case report has been presented with several limitations. This case report reported only one case; thus, several such case studies would help to provide us with comprehensive information. Due to the limitations in the equipment and other resources, timely diagnosis has been one of the major challenges. Many investigations were sent to India due to unavailability in Nepal. So, the studies highlighting the challenges might contribute to disseminating the information and filling up the gap.