Hyper-IgE syndrome is a hereditary combined B- and T-cell immunodeficiency characterized by recurrent staphylococcal abscesses of the skin, sinopulmonary infections, and severe pruritic eosinophilic dermatitis. Diagnosis is confirmed by measurement of serum IgE levels. Treatment consists of supportive measures, including lifelong prophylactic antistaphylococcal antibiotics.
(See also Overview of Immunodeficiency Disorders and Approach to the Patient With an Immunodeficiency Disorder.)
Hyper-IgE syndrome is a primary immunodeficiency disorder that involves combined humoral and cellular immunity deficiencies. Inheritance can be
Autosomal dominant: Caused by mutations in the STAT3 (signal transducer and activator of transcription 3) gene
Autosomal recessive: Appears to be caused by homozygous null mutations in TYK2 (tyrosine kinase 2) or DOCK8 (dedicator of cytokinesis 8) genes
Hyper-IgE syndrome starts during infancy.
Patients with hyper-IgE syndrome have tissue and blood eosinophilia and very high IgE levels (> 2000 IU/mL [> 4800 mcg/L]). The elevated IgE is thought to be a secondary phenomenon rather than pathogenic.
Various mutations may result in hyper-IgE syndrome, but most result in an alteration of class switching and dysfunctional helper type 17 (Th17) differentiation and alteration of immunoglobulin class switching in activated B cells.
Symptoms and Signs of Hyper-IgE Syndrome
Hyper-IgE syndrome typically causes recurrent staphylococcal abscesses of the skin, lungs, joints, and viscera. Patients may also have sinopulmonary infections, pulmonary pneumatoceles, and a severe pruritic eosinophilic dermatitis.
Patients have coarse facial features, delayed shedding of baby teeth, osteopenia, and recurrent fractures.
Diagnosis of Hyper-IgE Syndrome
Serum IgE levels
Diagnosis of hyper-IgE syndrome is suspected based on symptoms and confirmed by serum IgE levels > 2000 IU/mL (> 4800 mcg/L).
Genetic testing can identify the gene mutations and is done mainly to confirm the diagnosis or to help predict inheritance patterns. Close family members of patients with clinical symptoms consistent with hyper-IgE syndrome should be screened with an IgE level and possibly evaluated further if IgE levels are positive.
Treatment of Hyper-IgE Syndrome
Prophylactic antistaphylococcal antibiotics
Sometimes interferon gamma for severe infection
Treatment of hyper-IgE syndrome consists of lifelong prophylactic antistaphylococcal antibiotics (usually trimethoprim/sulfamethoxazole).
Dermatitis is treated with skin hydration, emollient creams, antihistamines. and, if infections are suspected, antibiotics. Pulmonary infections are treated early and aggressively with antibiotics.
Significant osteopenia should be screened for and managed under current guidelines for patients without a primary immunodeficiency disorder.
Interferon gamma has been used successfully for life-threatening infections.
