Eosinophilia

Eosinophilia is an absolute eosinophil count over 0.5 x 10^9/L in peripheral blood: mild 0.5 to 1.5, moderate 1.5 to 5.0, and severe over 5.0 x 10^9/L. Persistent counts over 1.5 x 10^9/L (hypereosinophilia) for more than 6 months, or with organ damage, define hypereosinophilic syndrome and can injure the heart, lungs, skin, and nervous system.

• Reactive (secondary) causes are by far the commonest worldwide:
  • Parasites: helminth infections with tissue migration (strongyloidiasis, hookworm, ascariasis, schistosomiasis, filariasis, toxocariasis, trichinellosis, fascioliasis, echinococcosis, cysticercosis); important in the tropics and in returning travellers.
  • Allergic: asthma, allergic rhinitis, atopic dermatitis, urticaria, food allergy, eosinophilic oesophagitis.
  • Drugs: penicillins, cephalosporins, sulfonamides, NSAIDs, allopurinol, carbamazepine, phenytoin, nitrofurantoin, minocycline, and others (DRESS syndrome).
  • Others: Addison disease, eosinophilic granulomatosis with polyangiitis, chronic eosinophilic pneumonia, tuberculosis, HIV, skin diseases (eczema, pemphigoid), atheroembolic disease, and cancers (Hodgkin lymphoma, T-cell lymphoma, solid tumours).
• Primary (clonal) causes: chronic eosinophilic leukaemia, myeloproliferative neoplasm with PDGFRA, PDGFRB or FGFR1 rearrangements, systemic mastocytosis, and acute leukaemias.
• Idiopathic hypereosinophilic syndrome after exclusion.

• Often asymptomatic; symptoms of the underlying cause predominate: itching, rash, wheeze, diarrhoea, abdominal pain, cough, migratory swellings (Loeffler syndrome during larval lung migration), fever, and weight loss.
• Organ involvement in hypereosinophilia: heart (endomyocardial fibrosis, restrictive cardiomyopathy, thrombus, arrhythmia, heart failure), lungs (cough, infiltrates), skin (urticaria, angio oedema, eczema), nervous system (neuropathy, stroke, encephalopathy), gut (colitis, hepatitis), and thromboembolism.
• Travel and residence in tropical regions, contact with soil or fresh water (schistosomiasis, strongyloidiasis), diet (undercooked pork, fish, freshwater crabs), medicines, atopy, and symptoms of asthma and sinus disease.
• Examination: rash, wheeze, lymph nodes, hepatosplenomegaly, heart sounds, neuropathy.
• Red flags: eosinophils over 1.5 x 10^9/L, cardiac symptoms, neurological deficit, thrombosis, dyspnoea, weight loss, splenomegaly.

• Repeat FBC with differential and a blood film (dysplastic eosinophils, blasts, other cytopenias).
• First tests: stool microscopy for ova, cysts and parasites on three samples (and Strongyloides serology or culture), urine microscopy for schistosome eggs, serology for schistosomiasis, filariasis, toxocariasis and strongyloidiasis, HIV test, ESR, CRP, renal and liver function, IgE, vitamin B12, and morning cortisol.
• Organ assessment if count over 1.5 x 10^9/L: troponin, ECG, echocardiogram, chest X-ray, spirometry, and CT chest.
• Specific tests: ANCA (eosinophilic granulomatosis with polyangiitis), serum tryptase (mastocytosis), T-cell receptor gene rearrangement and immunophenotyping, FIP1L1-PDGFRA FISH or PCR, bone marrow biopsy with cytogenetics, endoscopy with biopsy for eosinophilic oesophagitis.
• Differentials: other causes of leukocytosis, spurious counts, drug reaction, hypereosinophilic syndrome, and haematological malignancy.

Treat the cause (most patients)

• Strongyloidiasis: ivermectin 200 micrograms/kg orally once daily for 2 days (repeat after 2 weeks in hyperinfection or immunosuppression; give before starting steroids in endemic patients).
• Hookworm and ascariasis: albendazole 400 mg orally as a single dose; schistosomiasis: praziquantel 40 mg/kg orally as a single dose (60 mg/kg in 2 to 3 divided doses for Asian species), repeated at 4 to 6 weeks; filariasis: diethylcarbamazine 6 mg/kg/day for 12 days or doxycycline 200 mg daily for 4 to 6 weeks (specialist); toxocariasis: albendazole 400 mg twice daily for 5 days; trichinellosis: albendazole 400 mg twice daily for 8 to 14 days with prednisolone; cysticercosis and neurological disease: specialist care.
• Drug related: stop the drug; DRESS syndrome needs prednisolone 0.5 to 1 mg/kg daily, tapered over 6 to 8 weeks.
• Allergic: allergen avoidance, antihistamine (cetirizine 10 mg daily), inhaled corticosteroid and asthma treatment, topical steroids, oral prednisolone for severe flares.
• Adrenal insufficiency: hydrocortisone replacement 15 to 25 mg daily in divided doses.
• Eosinophilic granulomatosis with polyangiitis: prednisolone 1 mg/kg daily and immunosuppression; mepolizumab 300 mg subcutaneously every 4 weeks (specialist).

Hypereosinophilic syndrome

• Urgent haematology referral. Prednisolone 1 mg/kg orally daily (maximum 60 mg) with gradual taper over months; imatinib 100 to 400 mg orally daily for FIP1L1-PDGFRA positive disease (rapid response); mepolizumab 300 mg subcutaneously every 4 weeks for FIP1L1-PDGFRA negative disease; hydroxycarbamide 500 mg to 2 g daily or interferon alfa as steroid sparing agents.
• Organ protection: anticoagulation for thrombus, heart failure treatment, and anti-platelet agents according to specialist advice.
• Before steroids in anyone from an endemic area, empirical ivermectin 200 micrograms/kg to avoid Strongyloides hyperinfection.

Mild asymptomatic eosinophilia

• Take a travel history, repeat the count in 4 to 6 weeks, test stool and serology, and give empirical albendazole 400 mg once plus ivermectin 200 micrograms/kg for travellers or migrants from endemic areas when tests are negative or unavailable.

Follow up

• Recheck the count 4 to 6 weeks after treatment (expected to fall within weeks; schistosomiasis may take months); refer to haematology if the count stays over 1.5 x 10^9/L for more than 3 months, or if there is organ damage or a clonal marker.