Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations

Thalhammer J.; Kindle G.; Nieters A.; Rusch S.; Seppanen M. R. J.; Fischer A.; Grimbacher B.; Edgar D.; Buckland M.; Mahlaoui N.; Ehl S.; Boztug K.; Brunner J.; Demel U. F.; Forster-Waldl E.; Gasteiger L. M.; Goschl L.; Kojic M.; Schroll A.; Seidel M. G.; Wintergerst U.; Wisgrill L.; Sharapova S. O.; Goffard J. -C.; Kerre T.; Meyts I.; Roosens F.; Smet J.; Haerynck F.; Eric Z. P.; Milenova V.; Gagro A.; Richter D.; Chovancova Z.; Hlavackova E.; Litzman J.; Milota T.; Sediva A.; Elaziz D. A.; Alkady R. S.; El Sayed El Hawary R.; Eldash A. S.; Galal N.; Lotfy S.; Meshaal S. S.; Reda S. M.; Sobh A.; Elmarsafy A.; Brosselin P.; Courteille V.; De Vergnes N.; Kracker S.; Pergent M.; Randrianomenjanahary P.; Ahrenstorf G.; Albert M. H.; Ankermann T.; Atschekzei F.; Baumann U.; Becker B. C.; Behrends U.; Belohradsky B. H.; Biegner A. -K.; Binder N.; Bode S. F. N.; Boesecke C.; Boetticher B.; Borte M.; Borte S.; Classen C. F.; Dirks J.; Duckers G.; El-Helou S.; Ernst D.; Fasshauer M.; Fecker G.; Felgentreff K.; Foell D.; Ghosh S.; Girschick H. J.; Goldacker S.; Graf N.; Graf D.; Greil J.; Hanitsch L. G.; Hauck F.; Heeg M.; Heine S. I.; Henes J. C.; Hoenig M.; Holzer U.; Holzinger D.; Horneff G.; Hundsdoerfer P.; Jablonka A.; Jakoby D.; Joean O.; Kaiser-Labusch P.; Klemann C.; Kobbe R.; Korholz J.; Kramm C. M.; Kruger R.; Landwehr-Kenzel S.; Lehmberg K.; Liese J. G.; Lippert C. F.; Maccari M. E.; Masjosthusmann K.; Meinhardt A.; Metzler M.; Morbach H.; Muller I.; Naumann-Bartsch N.; Neubert J.; Niehues T.; Peter H. -H.; Rieber N.; Ritterbusch H.; Rockstroh J. K.; Roesler J.; Schauer U.; Scheible R.; Schmalzing M.; Schmidt R. E.; Schneider D. T.; Schreiber S.; Schuetz C.; Schulz A.; Schulze-Koops H.; Schulze-Sturm U.; Schuster V.; Schwaneck E. C.; Schwarz K.; Schwarze-Zander C.; Sirin M.; Skapenko A.; Sogkas G.; Sparber-Sauer M.; Speckmann C.; Steinmann S.; Stiehler S.; Tenbrock K.; von Bernuth H.; Warnatz K.; Wasmuth J. -C.; Weiss M.; Witte T.; Wittke K.; Wittkowski H.; Zeuner R. A.; Farmaki E.; Hatzistilianou M. N.; Kakkas I.; Kanariou M. G.; Kapousouzi A.; Liatsis E.; Maggina P.; Papadopoulou-Alataki E.; Raptaki M.; Speletas M.; Tantou S.; Goda V.; Krivan G.; Marodi L.; Abolhassani H.; Aghamohammadi A.; Rezaei N.; Feighery C.; Leahy T. R.; Ryan P.; Batzir N. A.; Garty B. Z.; Tamary H.; Aiuti A.; Amodio D.; Azzari C.; Barzaghi F.; Baselli L. A.; Cancrini C.; Carrabba M.; Cazzaniga M.; Cesaro S.; Chinello M.; Danieli M. G.; Dellepiane R. M.; Fabio G.; Gambineri E.; Lodi L.; Lougaris V.; Marasco C.; Martire B.; Marzollo A.; Milito C.; Moschese V.; Pignata C.; Plebani A.; Porta F.; Quinti I.; Ricci S.; Soresina A.; Tommasini A.; Vacca A.; Vanessa C.; Blaziene A.; Sitkauskiene B.; Gowin E.; Heropolitanska-Pliszka E.; Pietrucha B.; Szaflarska A.; Wiesik-Szewczyk E.; Wolska-Kusnierz B.; Esteves I.; Faria E.; Marques L. H.; Neves J. F.; Silva S. L.; Teixeira C.; Pereira da Silva S.; Capilna B. R.; Guseva M. N.; Shcherbina A.; Bobcakova A.; Ciznar P.; Gabzdilova J.; Jesenak M.; Kapustova L.; Orosova J.; Petrovicova O.; Raffac S.; Kopac P.; Allende L. M.; Antoli A.; Blanch G. R.; Carbone J.; Dieli-Crimi R.; Garcia-Prat M.; Gil-Herrera J.; Gonzalez-Granado L. I.; Agullo P. L.; Olbrich P.; Parra-Martinez A.; Paz-Artal E.; Pleguezuelo D. E.; Rodriguez N. S.; Sanchez-Ramon S.; Santos-Perez J. L.; Solanich X.; Soler-Palacin P.; Gonzalez-Amores M.; Ekwall O.; Fasth A.; Bitzenhofer-Gruber M.; Candotti F.; Dimitriou F.; Heininger U.; Holbro A.; Jandus P.; Kolios A. G. A.; Marschall K.; Schmid J. P.; Posfay-Barbe K. M.; Prader S.; Reichenbach J.; Steiner U. C.; Truck J.; Bredius R. G.; de Kruijf- Bazen S.; de Vries E.; Henriet S. S. V.; Kuijpers T. W.; Potjewijd J.; Rutgers A.; Stol K.; van Aerde K. J.; Van den Berg J. M.; van de Ven A. A. J. M.; Montfrans J.; Aydemir S.; Baris S.; Dogu F.; Ikinciogullari A.; Karakoc-Aydiner E.; Kilic S. S.; Kiykim A.; Kokcu Karadag S. I.; Kutukculer N.; Ocak S.; UNAL E.; Boyarchuk O.; Hilfanova A.; Kostyuchenko L. V.; Alachkar H.; Arkwright P. D.; Baxendale H. E.; Bernatoniene J.; Coulter T. I.; Garcez T.; Goddard S.; Gompels M. M.; Grigoriadou S.; Herriot R.; Herwadkar A.; Huissoon A.; Ibberson L.; Nademi Z.; Noorani S.; Parvin S.; Steele C. L.; Thomas M.; Waruiru C.; Yong P. F. K.; Bourne H.

Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations

Thalhammer J.

•

Kindle G.

•

Nieters A.

altro

Bourne H.

2021

journal article

Periodico

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Abstract

Background: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations. Objective: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts. Methods: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered. Results: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years. Conclusions: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.