title: Autosomal recessive hyperimmunoglobulin E syndrome: a distinct disease entity.
abstract: OBJECTIVE
  The autosomal-dominant form of the hyperimmunoglobulin E syndrome (AD-HIES) has been described as a multisystem disorder including immune, skeletal, and dental abnormalities. Variants of AD-HIES are known but not well defined.
  
  
  METHODS
  We evaluated 13 human immunodeficiency virus-seronegative patients from six consanguineous families with an autosomal-recessive form of hyperimmunoglobulin E syndrome (AR-HIES) and 68 of their relatives.
  
  
  RESULTS
  Persons affected with AR-HIES presented with the classical immunologic findings of hyperimmunoglobulin E syndrome, including recurrent staphylococcal infections of the skin and respiratory tract, eczema, elevated serum immunoglobulin E, and hypereosinophilia. In addition, severe recurrent fungal and viral infections with molluscum contagiosum, herpes zoster, and herpes simplex were noted. Autoimmunity was seen in two patients. Central nervous system sequelae, including hemiplegia, ischemic infarction, and subarachnoid hemorrhages, were common and contributed to high mortality. Notably, patients with AR-HIES did not have skeletal or dental abnormalities and did not develop pneumatoceles, as seen in AD-HIES. In lymphocyte proliferation assays, patients' cells responded poorly to mitogens and failed to proliferate in response to antigens, despite the presence of normal numbers of lymphocyte subpopulations.
  
  
  CONCLUSIONS
  The autosomal-recessive form of hyperimmunoglobulin E syndrome is a primary immunodeficiency with elevated immunoglobulin E, eosinophilia, vasculitis, autoimmunity, central nervous system symptoms, and high mortality. AR-HIES lacks several of the key findings of AD-HIES and therefore represents a different, previously unrecognized disease entity.
authors.affiliation: Department of Infectious Diseases and Clinical Immunology, University Children's Hospital, Dr v. Haunersches Kinderspital, Munich, Germany.
authors.forename: Eleonore D
authors.initials: ED
authors.lastname: Renner
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Puck
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
authors.forename: Markus
authors.initials: M
authors.lastname: Schmitt
authors.forename: Michael
authors.initials: M
authors.lastname: Weiss
authors.forename: Michael
authors.initials: M
authors.lastname: Frosch
authors.forename: Markus
authors.initials: M
authors.lastname: Bergmann
authors.forename: Joie
authors.initials: J
authors.lastname: Davis
authors.forename: Bernd H
authors.initials: BH
authors.lastname: Belohradsky
authors.forename: Bodo
authors.initials: B
authors.lastname: Grimbacher
mesh_terms: D015551:Autoimmunity; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007589:Job Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D008297:Male; D010375:Pedigree