PURPOSE: Autosomal Dominant Hyper IgE Recurrent Infection Syndrome (AD-HIES) is caused by mutations in STAT3 and characterized by eczema, recurrent bacterial infections, and skeletal and connective tissue abnormalities. To further understand the minimal trauma fractures of AD-HIES, we examined bone mineral density (BMD) and laboratory markers of bone turnover. METHODS: Patients with AD-HIES enrolled in a prospective natural history study were examined with dual x-ray absorptiometry (DEXA) scans and laboratory studies of bone metabolism. The number of fractures was recorded as well as clinical features of AD-HIES including scoliosis and retained primary teeth. Patients on medications with skeletal effects, including bisphosphonates, were examined separately. RESULTS: Twenty-three AD-HIES children (6-18 years) and 33 AD-HIES adults (21-50 years) not receiving bone-active drugs were studied. Fourteen of the 23 children (61%) had histories of minimal trauma fractures, as did 26 of the 33 adults (79%). Osteopenia or osteoporosis was found in 79% of children and adults. Only radial BMD correlated with the qualitative occurrence of fractures but it did not correlate with the numbers of fractures. Markers of bone metabolism did not correlate with minimal trauma fractures or BMD. Patients on bone-active medications had improved BMD, but still sustained fractures. CONCLUSIONS: Minimal trauma fractures and decreased BMD are common in AD-HIES. Low radial BMD is associated with fractures, but hip and spine BMD are not. Treatment with bisphosphonates increased BMD but its role in fracture prevention remains undefined.
PURPOSE:Autosomal Dominant Hyper IgE Recurrent Infection Syndrome (AD-HIES) is caused by mutations in STAT3 and characterized by eczema, recurrent bacterial infections, and skeletal and connective tissue abnormalities. To further understand the minimal trauma fractures of AD-HIES, we examined bone mineral density (BMD) and laboratory markers of bone turnover. METHODS:Patients with AD-HIES enrolled in a prospective natural history study were examined with dual x-ray absorptiometry (DEXA) scans and laboratory studies of bone metabolism. The number of fractures was recorded as well as clinical features of AD-HIES including scoliosis and retained primary teeth. Patients on medications with skeletal effects, including bisphosphonates, were examined separately. RESULTS: Twenty-three AD-HIESchildren (6-18 years) and 33 AD-HIES adults (21-50 years) not receiving bone-active drugs were studied. Fourteen of the 23 children (61%) had histories of minimal trauma fractures, as did 26 of the 33 adults (79%). Osteopenia or osteoporosis was found in 79% of children and adults. Only radial BMD correlated with the qualitative occurrence of fractures but it did not correlate with the numbers of fractures. Markers of bone metabolism did not correlate with minimal trauma fractures or BMD. Patients on bone-active medications had improved BMD, but still sustained fractures. CONCLUSIONS: Minimal trauma fractures and decreased BMD are common in AD-HIES. Low radial BMD is associated with fractures, but hip and spine BMD are not. Treatment with bisphosphonates increased BMD but its role in fracture prevention remains undefined.
Authors: Steven M Holland; Frank R DeLeo; Houda Z Elloumi; Amy P Hsu; Gulbu Uzel; Nina Brodsky; Alexandra F Freeman; Andrew Demidowich; Joie Davis; Maria L Turner; Victoria L Anderson; Dirk N Darnell; Pamela A Welch; Douglas B Kuhns; David M Frucht; Harry L Malech; John I Gallin; Scott D Kobayashi; Adeline R Whitney; Jovanka M Voyich; James M Musser; Cristina Woellner; Alejandro A Schäffer; Jennifer M Puck; Bodo Grimbacher Journal: N Engl J Med Date: 2007-09-19 Impact factor: 91.245
Authors: B Grimbacher; S M Holland; J I Gallin; F Greenberg; S C Hill; H L Malech; J A Miller; A C O'Connell; J M Puck Journal: N Engl J Med Date: 1999-03-04 Impact factor: 91.245
Authors: Zhiyuan Zhang; Thomas Welte; Nancy Troiano; Stephen E Maher; Xin-Yuan Fu; Alfred L M Bothwell Journal: Biochem Biophys Res Commun Date: 2005-03-18 Impact factor: 3.575
Authors: M Cohen-Solal; A M Prieur; L Prin; M A Denne; J M Launay; A M Graulet; M Brazier; C Griscelli; M C de Vernejoul Journal: Clin Immunol Immunopathol Date: 1995-07
Authors: Yael Gernez; Alexandra F Freeman; Steven M Holland; Elizabeth Garabedian; Niraj C Patel; Jennifer M Puck; Kathleen E Sullivan; Javeed Akhter; Elizabeth Secord; Karin Chen; Rebecca Buckley; Elie Haddad; Hans D Ochs; Ramsay Fuleihan; John Routes; Mica Muskat; Patricia Lugar; Julien Mancini; Charlotte Cunningham-Rundles Journal: J Allergy Clin Immunol Pract Date: 2017-09-19
Authors: Kylie A Corry; Hongkang Zhou; Tatiana Brustovetsky; Evan R Himes; Nicoletta Bivi; M Ryne Horn; Yukiko Kitase; Joseph M Wallace; Teresita Bellido; Nickolay Brustovetsky; Jiliang Li Journal: Bone Rep Date: 2019-07-29