Familial Eosinophilia

Familial eosinophilia is a rare autosomal dominant condition of persistent, often lifelong, blood eosinophilia that usually causes no organ damage. It is a benign cause of high eosinophil counts and must be separated from hypereosinophilic syndrome.

Pathophysiology. A locus at chromosome 5q31-q33, which carries the IL-3, IL-4, IL-5 and GM-CSF genes, is linked to the trait in affected families. The mechanism is not known, and the eosinophils appear normal.

It starts in infancy or early life. Many family members have counts of 1.5 x 109/L or more without symptoms.

Eosinophil counts are stable, and eosinophilic organ injury is absent in most families.

• Persistent blood eosinophilia from infancy or childhood
• Often no symptoms, found on routine blood counts
• Several affected members across generations (autosomal dominant)
• Occasional mild itching, rhinitis or wheeze
• Normal growth and development
• No fever, weight loss, rash or organ involvement

• Repeated blood counts showing stable eosinophilia over months and years.
• Family history and testing of parents, siblings and children for eosinophilia.
• Exclusion of secondary causes: parasites (stool microscopy, Strongyloides and Toxocara serology), drugs, allergy, atopic disease, adrenal insufficiency, malignancy, EGPA.
• Baseline screen for organ damage: troponin, ECG, echocardiogram, chest X-ray, liver enzymes, creatinine and urinalysis.
• Tryptase, vitamin B12 and immunoglobulins to exclude myeloid and lymphocytic variants.
• Clonality testing: FIP1L1-PDGFRA and T cell receptor rearrangement if there is any suggestion of progression, with bone marrow only if clonal disease is suspected.

Differential diagnosis.

• Secondary reactive eosinophilia (parasitic, drug, allergic)
• Hypereosinophilic syndrome (myeloid, lymphocytic, idiopathic)
• Eosinophilic granulomatosis with polyangiitis
• Chronic eosinophilic leukaemia
• Primary immunodeficiencies with eosinophilia (hyper IgE syndromes, Omenn syndrome)
• Eosinophilic gastrointestinal disease

• No treatment is needed when there is no organ damage and no symptoms.
• Counselling: explain the benign course, the autosomal dominant inheritance (each child of an affected parent has a 50% chance of the trait), and the need for follow up.
• Treat parasites if found, and avoid unneeded corticosteroid courses, since eosinophilia will not settle.
• Symptoms of allergy (rhinitis, asthma) are treated in the usual way.
• If organ involvement appears, start the hypereosinophilic syndrome regimen: prednisolone 1 mg/kg daily (maximum 60 mg) after ivermectin 200 microgram/kg orally once daily for 2 days in patients from or travelling to endemic regions, with specialist referral.
• Avoid labelling as hypereosinophilic syndrome in people with a stable count and no organ damage.

Special groups.

• Children: confirm family history, and review growth and organ involvement during follow up.

Monitoring. Blood count every 6 to 12 months. Troponin and echocardiogram at baseline and every 1 to 2 years. Review symptoms yearly.

Referral and escalation. Refer to haematology or immunology when the count rises, there are new symptoms, or organ involvement is found. Urgent for cardiac symptoms, neurological signs or thrombosis.