Eosinophilia Clinical Manifestations Quiz

Approach to the Patient with Suspected Hypereosinophilic Syndrome

• Hypereosinophilic syndromes (HES) are a heterogeneous group of rare disorders.
• Clinical manifestations range from fatigue to life-threatening endomyocardial fibrosis and thromboembolic events.
• Eosinophilia, defined as an absolute eosinophil count (AEC) >0.45 x 10⁹/L, is relatively common, occurring in 1% to 2% of the general population.
• Hypereosinophilia (HE; AEC ≥ 1.5 x 10⁹/L) is rare, with an estimated incidence of 0.315 to 6.3 per 100,000 in the United States.

Disorders Associated with Marked Eosinophilia

• Atopic disorders: Asthma, atopic dermatitis, chronic rhinosinusitis, and others.
• Drug hypersensitivity: Various drug reactions, eosinophilia-myalgia syndrome.
• Infection and infestation: Helminth infections (especially tissue invasive), fungal infections, viral infections (HIV, COVID-19), ectoparasite infestations, and others.
• Autoimmune and immunodysregulatory disorders: Inflammatory bowel disease, sarcoidosis, IgG4-related disease, and others.

Classification of Hypereosinophilic Syndromes

• Myeloid HE/HES: Suspected or proven eosinophilic myloid neoplasm including those associated with rearrangements of PDGFRA and other recurrent molecular abnormalities.
• Lymphocytic variant HE/HES: Presence of a clonal or phenotypically aberrant T-cell population that produces cytokines that drive the eosinophilia.
• Overlap HES: Single-organ-restricted eosinophilic disorders and clinically defined eosinophilic syndromes overlapping with idiopathic HES, eosinophilic gastrointestinal disorders, and eosinophilic granulomatosis with polyangiitis.
• Associated HE/HES: Occurs in the context of a defined disorder such as helminth infection, neoplasm, immunodeficiency, or hypersensitivity reaction.
• Familial HE/HES: Occurrence in more than one family member, excluding associated HE/HES.
• Idiopathic HE/HES: Unknown cause and exclusion of other subtypes.

Clinical Manifestations

• Constitutional symptoms such as fatigue, muscle aches, fevers, pruritus, angioedema, diarrhea, and cough.
• Cardiac diseases are a major cause of mortality in HES, possibly involving endomyocardial fibrosis, pericarditis, myocarditis, and intramural thrombus formation.
• CNS involvement can lead to mononeuritis multiplex, paraparesis, encephalopathy, and dementia.
• Pulmonary involvement can manifest as pulmonary infiltrates, fibrosis, or pleural disease with effusions.
• Gastrointestinal issues such as diarrhea, gastritis, colitis, hepatitis, and Budd-Chiari syndrome are possible.
• Skin manifestations such as pruritus, angioedema, papules, or plaques.
• Kidney and bone involvement is rare.
• Tissue damage in eosinophilia is believed to be secondary to eosinophil degranulation & release of mediators (e.g., eosinophil cationic protein, major basic protein).

Myeloproliferative variant HES

• Characterized by male predominance.
• Associated with organ damage, elevated serum tryptase, splenomegaly, anemia, thrombocytopenia, bone marrow myeloproliferation, and reticulin fibrosis.
• Unresponsive to steroid therapy.
• Often associated with an interstitial deletion on chromosome 4q12, causing a FIP1L1-PDGFRA fusion gene leading to a tyrosine kinase with enhanced activity and sensitivity to low-dose imatinib therapy.

Lymphocytic variant HES (LHES)

• Characterized by a large CD2⁺ CD3⁻ CD4⁺ T-cell population that produces interleukin (IL)-4 and IL-5 in response to stimulation.
• Equally frequent in males and females.
• Often presents with dermatologic manifestations.
• Any organ system is potentially involved.
• Some asymptomatic patients have clonal aberrant T-cell populations indistinguishable from those with symptomatic LHES.
• Serum IgM, IgE, and serum and thymus and activation-regulated chemokine levels are elevated.
• Diagnosis is based on identification of a clonal and/or aberrant T-cell population.

Diagnostic Workup and Testing

• Essential tests for all suspected hypereosinophilia cases, including a detailed history and physical exam to rule out other causes & to identify any potential travel or environmental exposures.
• Initial tests include complete blood counts (CBC with differential), routine chemistries (including liver function tests), and quantitative serum immunoglobulin levels.
• Further tests may include serum tryptase and B12 levels, & T- and B-cell receptor rearrangement studies.
• Flow cytometry is important for lymphocyte phenotyping.
• Serum troponin, ECG, and echocardiogram are useful.
• Consideration for chest/abdomen/pelvis CT scans.
• Possible tissue biopsy.
• Consideration of bone marrow aspirate and biopsy.
• Pulmonary function tests are needed in patients with suspected pulmonary involvement.

Approach to therapy and clinical case examples

• Secondary causes (e.g., helminthic infection) need specific therapies.
• Corticosteroids are the first-line treatment for acute severe HES, but additional therapies might be required if the initial response isn't adequate.
• Conventional second-line therapies include hydroxyurea and interferon α.
• Eosinophil-targeting biologics (e.g. mepolizumab, reslizumab) may be used, but their use in acute settings is controversial.
• Prednisone is a primary treatment in acute and severe cases, and for life-threatening situations.

Test your knowledge on the clinical manifestations associated with eosinophilia and its implications in various diseases. This quiz covers key concepts regarding cardiac disease mortality, gastrointestinal symptoms, and the relationship of eosinophils with tissue damage. Perfect for students and professionals in medicine and immunology.