Due to the heterogeneous manifestations of the disease and severity varying from mild to end-organ damage, comprehensive history taking and diligent physical examination is extremely important, and sometimes enough, for diagnosis.[4] Skin, pulmonary, and gastrointestinal organ systems are commonly involved. Constitutional symptoms like low-grade fevers, night sweats, fatigue, weight loss can occur in multiple conditions, including myeloproliferative and lymphoid neoplasms, Churg Strauss syndrome, DRESS syndrome.

Skin rashes, pruritus can be seen in cutaneous T cell lymphoma, eczema. Dyspnea, cough, wheezing can be seen in multiple conditions, including bronchopulmonary aspergillosis, Loeffler's syndrome, hay fever, asthma, reactive pulmonary eosinophilia, Churg strass syndrome. Detailed travel history, work environment, drug history, close contacts with HIV, syphilis helps identify infections, parasitic infestations, and drug adverse reactions.[8][9] Physical examination should be complete, including a skin assessment, lung auscultation to look for rhonchi, wheezes, abdomen exam to look for splenomegaly.

Secondary causes of eosinophilia should be ruled out first. The evaluation for primary eosinophilia should begin with screening peripheral blood for FIP1L1- PDGFRA gene fusion. Diagnostic testing should start with peripheral smear. Cytogenetic testing and FISH analysis can be performed on peripheral blood as well.[4][8]

Concurrent cytophilias or cytopenias, if present, can help for diagnosis. In that case, bone marrow biopsy, along with karyotype and genetic screen of chromosomes, may be required.[5][10] 

B12 level and tryptase level, along with cytogenetic/immunophenotypic testing and marrow findings, help diagnose chronic mastocytosis, acute/chronic myeloid leukemia, myelodysplastic syndrome, MDS/MPN overlap. When skin rashes are present, skin biopsy helps to diagnose cutaneous disorders like pemphigoid, eczema, mycosis fungoides, Sezary syndrome. Imaging of the chest helps diagnose aspergillosis, Loeffler syndrome, Churg Strauss syndrome. Ultrasound abdomen helps to evaluate for splenomegaly. Stool testing helps to assess for parasitic infections.

Management depends on the underlying cause. The goal of the therapy is to mitigate end-organ damage from eosinophilia.[10] In mild cases without any symptoms or signs of organ involvement, a conservative approach can be undertaken. In emergency conditions with hemodynamic instability or organ failure, treatment with IV steroids is important.[8] 

For some conditions like drug and food allergies or infections, treatment can be simple, like withdrawing the offending agent or treating with antibiotics. But in some conditions, due to the varying clinical manifestations and multi-systemic involvement, a multidisciplinary approach involving hematologist, pulmonologist, infectious diseases, might be necessary. In steroid-resistant cases of hypereosinophilic syndrome and chronic eosinophilic leukemia, hydroxyurea and interferon-alpha have demonstrated efficacy.

In aggressive forms of the disease, second-line cytotoxic agents and stem cell transplants have proven some benefit. Antibody use against interleukin-5 (IL-5) (mepolizumab), the IL-5 receptor (benralizumab), and CD52 (alemtuzumab), as well as other targets on eosinophils, continues to be an active area of investigation.[10][9] Timely intervention is vital to reduce morbidity and mortality.

Diagnoses can be narrowed down based on the predominant system involved. For example, when manifested with pulmonary symptoms: asthma, bronchopulmonary aspergillosis, with hay fever: skin involvement: Mycosis fungoides, Sezary syndrome, eczema, bullous pemphigoid.

Prognosis can be varying from mild disease to fatal outcome, depending on multiple factors like cause of the eosinophilia, presence of organ damage, the subtype of eosinophilia, and timeline of intervention.

As eosinophils can produce proinflammatory cytokines and contain proteolytic enzymes that can damage host cell wall, tissue damage can occur if not treated appropriately. Based on the etiology, the outcome can be fatal and cause severe end-organ damage.

When multiple symptoms are not explainable or when there is an exacerbation of underlying condition without any risk factors, patients need to seek prompt medical attention. They need to give their physician a detailed history, including their living conditions, travel, and medications.

When there is no obvious cause found, pathologists should recommend further hematology testing like FISH analysis and cytogenetics. When there is a multi-systemic involvement, early intervention with a multidisciplinary approach helps.[8]