Autosomal recessive hyperimmunoglobulin E syndrome: a distinct disease entity.
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.
Renner
Eleonore D
ED
Department of Infectious Diseases and Clinical Immunology, University Children's Hospital, Dr v. Haunersches Kinderspital, Munich, Germany.
Puck
Jennifer M
JM
Holland
Steven M
SM
Schmitt
Markus
M
Weiss
Michael
M
Frosch
Michael
M
Bergmann
Markus
M
Davis
Joie
J
Belohradsky
Bernd H
BH
Grimbacher
Bodo
B
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