eosinophils

**Morphology & Development** - Granulocyte of the myeloid lineage; bilobed nucleus with large, bright red-orange cytoplasmic granules on H&E/Wright stain (acidophilic, from affinity for eosin). - Normal: ~1–4% of WBCs (absolute count <500/µL). Eosinophilia: >500/µL. Hypereosinophilic syndrome: >1500/µL for ≥6 months with end-organ damage. - Maturation and survival depend on IL-5 (key), plus IL-3 and GM-CSF. Produced by Th2 cells, ILC2s, and mast cells. Eotaxin (CCL11) recruits them to tissue through CCR3.

**Granule Contents & Function** - Major basic protein (MBP): toxic to helminths and respiratory epithelium. It is the main granule protein. - Eosinophil cationic protein, eosinophil peroxidase, and eosinophil-derived neurotoxin. - Charcot-Leyden crystals: crystallized lysophospholipase/galectin-10 from eosinophil membranes. They are seen in the sputum of asthma patients. - Helminth killing occurs by antibody-dependent cellular cytotoxicity (ADCC). IgE (and IgG) coat the parasite, and eosinophils bind through Fc receptors (FcεRI), then degranulate. - Also modulate allergic reactions: they release histaminase and arylsulfatase, which dampen mast cell mediators. They also release leukotrienes and PAF, which can amplify inflammation.

**Causes of Eosinophilia (mnemonic NAACP)** - **N**eoplasia: Hodgkin lymphoma, CML, T-cell lymphoma, and eosinophilic leukemia (FIP1L1-PDGFRA fusion, imatinib-responsive). - **A**sthma/Allergy: atopic diseases, allergic rhinitis, eczema, allergic bronchopulmonary aspergillosis (ABPA), and eosinophilic esophagitis. - **A**ddison disease (adrenal insufficiency): loss of cortisol means loss of its eosinopenic effect. - **C**ollagen vascular disease: eosinophilic granulomatosis with polyangiitis (EGPA/Churg-Strauss, associated with asthma and p-ANCA). - **P**arasites: tissue-invasive helminths (Strongyloides, Ascaris, hookworm, Toxocara, Schistosoma, Trichinella, filaria). Protozoa and cestodes with no tissue phase usually do not cause eosinophilia. - Others: drug reactions (DRESS, interstitial nephritis), acute interstitial nephritis (urine eosinophils are neither sensitive nor specific), and eosinophilic pneumonia.

**Eosinopenia** - Caused by corticosteroids, Cushing syndrome, and acute stress or infection (endogenous cortisol and epinephrine). Corticosteroids cause demargination of neutrophils but decrease eosinophils and lymphocytes.

**Clinical Pearls** - Eosinophilic esophagitis: dysphagia and food impaction in young atopic patients. Endoscopy shows rings or furrows, and biopsy shows >15 eos/hpf. It is treated with PPIs, swallowed topical steroids, and diet elimination. - Asthma: eosinophilic airway inflammation. Targeted therapies include anti-IL-5 (mepolizumab, reslizumab), anti-IL-5Rα (benralizumab), anti-IgE (omalizumab), and anti-IL-4Rα (dupilumab). - Loeffler syndrome: transient pulmonary infiltrates with eosinophilia during larval migration (Ascaris, Strongyloides, hookworm). - Acute interstitial nephritis: drug-induced (penicillins, NSAIDs, PPIs, diuretics) with fever, rash, and WBC casts. Eosinophiluria may be present. - Treatment of hypereosinophilic syndrome: corticosteroids, and imatinib if FIP1L1-PDGFRA is positive. - Drug reactions to remember: DRESS (drug reaction with eosinophilia and systemic symptoms) presents with fever, rash, lymphadenopathy, and organ involvement 2–8 weeks after starting the drug (allopurinol, anticonvulsants, sulfonamides, vancomycin).

**Compared with Other Granulocytes** - Neutrophils: bacterial and fungal defense, acute inflammation. - Basophils: heparin and histamine, with deeply basophilic granules (seen in CML). - Mast cells: tissue-resident, IgE-mediated degranulation.