OBSOLETE: Autosomal recessive hyper-IgE syndrome

Autosomal recessive hyper-IgE syndrome (AR-HIES) is an obsolete disease classification that was previously used to describe a group of primary immunodeficiency disorders characterized by markedly elevated serum immunoglobulin E (IgE) levels, recurrent skin and lung infections, and eczema, inherited in an autosomal recessive pattern. This entity has been reclassified as specific genetic conditions have been identified, most notably DOCK8 deficiency (the most common cause of what was formerly called AR-HIES) and TYK2 deficiency. These conditions are now recognized as distinct clinical entities with their own Orphanet and OMIM entries. Patients previously classified under AR-HIES typically presented in early childhood with severe eczema, recurrent staphylococcal skin abscesses, sinopulmonary infections, and susceptibility to viral skin infections (such as molluscum contagiosum, herpes simplex, and human papillomavirus). Unlike the autosomal dominant form of hyper-IgE syndrome (STAT3 deficiency or Job syndrome), patients with AR-HIES generally lacked the connective tissue and skeletal abnormalities (such as retained primary teeth, characteristic facies, and pathologic fractures) but were more prone to severe viral infections, food allergies, autoimmunity, and malignancies, particularly squamous cell carcinoma and lymphoma. The immune system is primarily affected, with dysfunction in T cells, B cells, and natural killer cells. Since this classification is now obsolete, patients previously diagnosed with AR-HIES should be re-evaluated with modern genetic testing to identify the specific underlying molecular defect. Treatment depends on the specific genetic diagnosis but generally includes aggressive management of infections with antimicrobials, immunoglobulin replacement therapy, and careful dermatologic care. For DOCK8 deficiency, hematopoietic stem cell transplantation (HSCT) has emerged as a curative treatment option and is recommended, particularly in severe cases, as it can correct the immunological defects and reduce the risk of malignancy.

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