Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency

Capucine Picard, Horst Von Bernuth, Pegah Ghandil, Maya Chrabieh, Ofer Levy, Peter D. Arkwright, Douglas McDonald, Raif S. Geha, Hidetoshi Takada, Jens C. Krause, C. Buddy Creech, Cheng Lung Ku, Stephan Ehl, László Maródi, Saleh Al-Muhsen, Sami Al-Hajjar, Abdulaziz Al-Ghonaium, Noorbibi K. Day-Good, Steven M. Holland, John I. GallinHelen Chapel, David P. Speert, Carlos Rodriguez-Gallego, Elena Colino, Ben Zion Garty, Chaim Roifman, Toshiro Hara, Hideto Yoshikawa, Shigeaki Nonoyama, Joseph Domachowske, Andrew C. Issekutz, Mimi Tang, Joanne Smart, Simona Eva Zitnik, Cyrille Hoarau, Dinakantha S. Kumararatne, Adrian J. Thrasher, E. Graham Davies, Claire Bethune, Nicolas Sirvent, Dominique De Ricaud, Yildiz Camcioglu, Júlia Vasconcelos, Margarida Guedes, Artur Bonito Vitor, Carlos Rodrigo, Francisco Almazán, Maria Méndez, Juan Ignacio Aróstegui, Laia Alsina, Claudia Fortuny, Janine Reichenbach, James W. Verbsky, Xavier Bossuyt, Rainer Doffinger, Laurent Abel, Anne Puel, Jean Laurent Casanova

Research output: Contribution to journalReview article

222 Citations (Scopus)

Abstract

Autosomal recessive interleukin-1 receptor-associated kinase (IRAK)-4 and myeloid differentiation factor (MyD)88 deficiencies impair Toll-like receptor (TLR)- and interleukin-1 receptor-mediated immunity. We documented the clinical features and outcome of 48 patients with IRAK-4 deficiency and 12 patients with MyD88 deficiency, from 37 kindreds in 15 countries.The clinical features of IRAK-4 and MyD88 deficiency were indistinguishable. There were no severe viral, parasitic, and fungal diseases, and the range of bacterial infections was narrow. Noninvasive bacterial infections occurred in 52 patients, with a high incidence of infections of the upper respiratory tract and the skin, mostly caused by Pseudomonas aeruginosa and Staphylococcus aureus, respectively. The leading threat was invasive pneumococcal disease, documented in 41 patients (68%) and causing 72 documented invasive infections (52.2%). P. aeruginosa and Staph. aureus documented invasive infections also occurred (16.7% and 16%, respectively, in 13 and 13 patients, respectively). Systemic signs of inflammation were usually weak or delayed. The first invasive infection occurred before the age of 2 years in 53 (88.3%) and in the neonatal period in 19 (32.7%) patients. Multiple or recurrent invasive infections were observed in most survivors (n = 36/50, 72%).Clinical outcome was poor, with 24 deaths, in 10 cases during the first invasive episode and in 16 cases of invasive pneumococcal disease. However, no death and invasive infectious disease were reported in patients after the age of 8 years and 14 years, respectively. Antibiotic prophylaxis (n = 34), antipneumococcal vaccination (n = 31), and/or IgG infusion (n = 19), when instituted, had a beneficial impact on patients until the teenage years, with no seemingly detectable impact thereafter.IRAK-4 and MyD88 deficiencies predispose patients to recurrent life-threatening bacterial diseases, such as invasive pneumococcal disease in particular, in infancy and early childhood, with weak signs of inflammation. Patients and families should be informed of the risk of developing life-threatening infections; empiric antibacterial treatment and immediate medical consultation are strongly recommended in cases of suspected infection or moderate fever. Prophylactic measures in childhood are beneficial, until spontaneous improvement occurs in adolescence.

Original languageEnglish
Pages (from-to)403-425
Number of pages23
JournalMedicine
Volume89
Issue number6
DOIs
Publication statusPublished - Nov 2010

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Interleukin-1 Receptor-Associated Kinases
Infection
Bacterial Infections
Pseudomonas aeruginosa
Toll-Like Receptor 1
Myeloid Differentiation Factor 88
Inflammation
Parasitic Diseases
Interleukin-1 Receptors
Antibiotic Prophylaxis
Mycoses
Virus Diseases
Respiratory Tract Infections
Communicable Diseases
Survivors
Staphylococcus aureus
Immunity
Vaccination
Fever
Referral and Consultation

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Picard, C., Von Bernuth, H., Ghandil, P., Chrabieh, M., Levy, O., Arkwright, P. D., ... Casanova, J. L. (2010). Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency. Medicine, 89(6), 403-425. https://doi.org/10.1097/MD.0b013e3181fd8ec3

Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency. / Picard, Capucine; Von Bernuth, Horst; Ghandil, Pegah; Chrabieh, Maya; Levy, Ofer; Arkwright, Peter D.; McDonald, Douglas; Geha, Raif S.; Takada, Hidetoshi; Krause, Jens C.; Creech, C. Buddy; Ku, Cheng Lung; Ehl, Stephan; Maródi, László; Al-Muhsen, Saleh; Al-Hajjar, Sami; Al-Ghonaium, Abdulaziz; Day-Good, Noorbibi K.; Holland, Steven M.; Gallin, John I.; Chapel, Helen; Speert, David P.; Rodriguez-Gallego, Carlos; Colino, Elena; Garty, Ben Zion; Roifman, Chaim; Hara, Toshiro; Yoshikawa, Hideto; Nonoyama, Shigeaki; Domachowske, Joseph; Issekutz, Andrew C.; Tang, Mimi; Smart, Joanne; Zitnik, Simona Eva; Hoarau, Cyrille; Kumararatne, Dinakantha S.; Thrasher, Adrian J.; Davies, E. Graham; Bethune, Claire; Sirvent, Nicolas; De Ricaud, Dominique; Camcioglu, Yildiz; Vasconcelos, Júlia; Guedes, Margarida; Vitor, Artur Bonito; Rodrigo, Carlos; Almazán, Francisco; Méndez, Maria; Aróstegui, Juan Ignacio; Alsina, Laia; Fortuny, Claudia; Reichenbach, Janine; Verbsky, James W.; Bossuyt, Xavier; Doffinger, Rainer; Abel, Laurent; Puel, Anne; Casanova, Jean Laurent.

In: Medicine, Vol. 89, No. 6, 11.2010, p. 403-425.

Research output: Contribution to journalReview article

Picard, C, Von Bernuth, H, Ghandil, P, Chrabieh, M, Levy, O, Arkwright, PD, McDonald, D, Geha, RS, Takada, H, Krause, JC, Creech, CB, Ku, CL, Ehl, S, Maródi, L, Al-Muhsen, S, Al-Hajjar, S, Al-Ghonaium, A, Day-Good, NK, Holland, SM, Gallin, JI, Chapel, H, Speert, DP, Rodriguez-Gallego, C, Colino, E, Garty, BZ, Roifman, C, Hara, T, Yoshikawa, H, Nonoyama, S, Domachowske, J, Issekutz, AC, Tang, M, Smart, J, Zitnik, SE, Hoarau, C, Kumararatne, DS, Thrasher, AJ, Davies, EG, Bethune, C, Sirvent, N, De Ricaud, D, Camcioglu, Y, Vasconcelos, J, Guedes, M, Vitor, AB, Rodrigo, C, Almazán, F, Méndez, M, Aróstegui, JI, Alsina, L, Fortuny, C, Reichenbach, J, Verbsky, JW, Bossuyt, X, Doffinger, R, Abel, L, Puel, A & Casanova, JL 2010, 'Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency', Medicine, vol. 89, no. 6, pp. 403-425. https://doi.org/10.1097/MD.0b013e3181fd8ec3
Picard C, Von Bernuth H, Ghandil P, Chrabieh M, Levy O, Arkwright PD et al. Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency. Medicine. 2010 Nov;89(6):403-425. https://doi.org/10.1097/MD.0b013e3181fd8ec3
Picard, Capucine ; Von Bernuth, Horst ; Ghandil, Pegah ; Chrabieh, Maya ; Levy, Ofer ; Arkwright, Peter D. ; McDonald, Douglas ; Geha, Raif S. ; Takada, Hidetoshi ; Krause, Jens C. ; Creech, C. Buddy ; Ku, Cheng Lung ; Ehl, Stephan ; Maródi, László ; Al-Muhsen, Saleh ; Al-Hajjar, Sami ; Al-Ghonaium, Abdulaziz ; Day-Good, Noorbibi K. ; Holland, Steven M. ; Gallin, John I. ; Chapel, Helen ; Speert, David P. ; Rodriguez-Gallego, Carlos ; Colino, Elena ; Garty, Ben Zion ; Roifman, Chaim ; Hara, Toshiro ; Yoshikawa, Hideto ; Nonoyama, Shigeaki ; Domachowske, Joseph ; Issekutz, Andrew C. ; Tang, Mimi ; Smart, Joanne ; Zitnik, Simona Eva ; Hoarau, Cyrille ; Kumararatne, Dinakantha S. ; Thrasher, Adrian J. ; Davies, E. Graham ; Bethune, Claire ; Sirvent, Nicolas ; De Ricaud, Dominique ; Camcioglu, Yildiz ; Vasconcelos, Júlia ; Guedes, Margarida ; Vitor, Artur Bonito ; Rodrigo, Carlos ; Almazán, Francisco ; Méndez, Maria ; Aróstegui, Juan Ignacio ; Alsina, Laia ; Fortuny, Claudia ; Reichenbach, Janine ; Verbsky, James W. ; Bossuyt, Xavier ; Doffinger, Rainer ; Abel, Laurent ; Puel, Anne ; Casanova, Jean Laurent. / Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency. In: Medicine. 2010 ; Vol. 89, No. 6. pp. 403-425.
@article{77d0173d12814914bbea4f231ff34421,
title = "Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency",
abstract = "Autosomal recessive interleukin-1 receptor-associated kinase (IRAK)-4 and myeloid differentiation factor (MyD)88 deficiencies impair Toll-like receptor (TLR)- and interleukin-1 receptor-mediated immunity. We documented the clinical features and outcome of 48 patients with IRAK-4 deficiency and 12 patients with MyD88 deficiency, from 37 kindreds in 15 countries.The clinical features of IRAK-4 and MyD88 deficiency were indistinguishable. There were no severe viral, parasitic, and fungal diseases, and the range of bacterial infections was narrow. Noninvasive bacterial infections occurred in 52 patients, with a high incidence of infections of the upper respiratory tract and the skin, mostly caused by Pseudomonas aeruginosa and Staphylococcus aureus, respectively. The leading threat was invasive pneumococcal disease, documented in 41 patients (68{\%}) and causing 72 documented invasive infections (52.2{\%}). P. aeruginosa and Staph. aureus documented invasive infections also occurred (16.7{\%} and 16{\%}, respectively, in 13 and 13 patients, respectively). Systemic signs of inflammation were usually weak or delayed. The first invasive infection occurred before the age of 2 years in 53 (88.3{\%}) and in the neonatal period in 19 (32.7{\%}) patients. Multiple or recurrent invasive infections were observed in most survivors (n = 36/50, 72{\%}).Clinical outcome was poor, with 24 deaths, in 10 cases during the first invasive episode and in 16 cases of invasive pneumococcal disease. However, no death and invasive infectious disease were reported in patients after the age of 8 years and 14 years, respectively. Antibiotic prophylaxis (n = 34), antipneumococcal vaccination (n = 31), and/or IgG infusion (n = 19), when instituted, had a beneficial impact on patients until the teenage years, with no seemingly detectable impact thereafter.IRAK-4 and MyD88 deficiencies predispose patients to recurrent life-threatening bacterial diseases, such as invasive pneumococcal disease in particular, in infancy and early childhood, with weak signs of inflammation. Patients and families should be informed of the risk of developing life-threatening infections; empiric antibacterial treatment and immediate medical consultation are strongly recommended in cases of suspected infection or moderate fever. Prophylactic measures in childhood are beneficial, until spontaneous improvement occurs in adolescence.",
author = "Capucine Picard and {Von Bernuth}, Horst and Pegah Ghandil and Maya Chrabieh and Ofer Levy and Arkwright, {Peter D.} and Douglas McDonald and Geha, {Raif S.} and Hidetoshi Takada and Krause, {Jens C.} and Creech, {C. Buddy} and Ku, {Cheng Lung} and Stephan Ehl and L{\'a}szl{\'o} Mar{\'o}di and Saleh Al-Muhsen and Sami Al-Hajjar and Abdulaziz Al-Ghonaium and Day-Good, {Noorbibi K.} and Holland, {Steven M.} and Gallin, {John I.} and Helen Chapel and Speert, {David P.} and Carlos Rodriguez-Gallego and Elena Colino and Garty, {Ben Zion} and Chaim Roifman and Toshiro Hara and Hideto Yoshikawa and Shigeaki Nonoyama and Joseph Domachowske and Issekutz, {Andrew C.} and Mimi Tang and Joanne Smart and Zitnik, {Simona Eva} and Cyrille Hoarau and Kumararatne, {Dinakantha S.} and Thrasher, {Adrian J.} and Davies, {E. Graham} and Claire Bethune and Nicolas Sirvent and {De Ricaud}, Dominique and Yildiz Camcioglu and J{\'u}lia Vasconcelos and Margarida Guedes and Vitor, {Artur Bonito} and Carlos Rodrigo and Francisco Almaz{\'a}n and Maria M{\'e}ndez and Ar{\'o}stegui, {Juan Ignacio} and Laia Alsina and Claudia Fortuny and Janine Reichenbach and Verbsky, {James W.} and Xavier Bossuyt and Rainer Doffinger and Laurent Abel and Anne Puel and Casanova, {Jean Laurent}",
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pages = "403--425",
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TY - JOUR

T1 - Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency

AU - Picard, Capucine

AU - Von Bernuth, Horst

AU - Ghandil, Pegah

AU - Chrabieh, Maya

AU - Levy, Ofer

AU - Arkwright, Peter D.

AU - McDonald, Douglas

AU - Geha, Raif S.

AU - Takada, Hidetoshi

AU - Krause, Jens C.

AU - Creech, C. Buddy

AU - Ku, Cheng Lung

AU - Ehl, Stephan

AU - Maródi, László

AU - Al-Muhsen, Saleh

AU - Al-Hajjar, Sami

AU - Al-Ghonaium, Abdulaziz

AU - Day-Good, Noorbibi K.

AU - Holland, Steven M.

AU - Gallin, John I.

AU - Chapel, Helen

AU - Speert, David P.

AU - Rodriguez-Gallego, Carlos

AU - Colino, Elena

AU - Garty, Ben Zion

AU - Roifman, Chaim

AU - Hara, Toshiro

AU - Yoshikawa, Hideto

AU - Nonoyama, Shigeaki

AU - Domachowske, Joseph

AU - Issekutz, Andrew C.

AU - Tang, Mimi

AU - Smart, Joanne

AU - Zitnik, Simona Eva

AU - Hoarau, Cyrille

AU - Kumararatne, Dinakantha S.

AU - Thrasher, Adrian J.

AU - Davies, E. Graham

AU - Bethune, Claire

AU - Sirvent, Nicolas

AU - De Ricaud, Dominique

AU - Camcioglu, Yildiz

AU - Vasconcelos, Júlia

AU - Guedes, Margarida

AU - Vitor, Artur Bonito

AU - Rodrigo, Carlos

AU - Almazán, Francisco

AU - Méndez, Maria

AU - Aróstegui, Juan Ignacio

AU - Alsina, Laia

AU - Fortuny, Claudia

AU - Reichenbach, Janine

AU - Verbsky, James W.

AU - Bossuyt, Xavier

AU - Doffinger, Rainer

AU - Abel, Laurent

AU - Puel, Anne

AU - Casanova, Jean Laurent

PY - 2010/11

Y1 - 2010/11

N2 - Autosomal recessive interleukin-1 receptor-associated kinase (IRAK)-4 and myeloid differentiation factor (MyD)88 deficiencies impair Toll-like receptor (TLR)- and interleukin-1 receptor-mediated immunity. We documented the clinical features and outcome of 48 patients with IRAK-4 deficiency and 12 patients with MyD88 deficiency, from 37 kindreds in 15 countries.The clinical features of IRAK-4 and MyD88 deficiency were indistinguishable. There were no severe viral, parasitic, and fungal diseases, and the range of bacterial infections was narrow. Noninvasive bacterial infections occurred in 52 patients, with a high incidence of infections of the upper respiratory tract and the skin, mostly caused by Pseudomonas aeruginosa and Staphylococcus aureus, respectively. The leading threat was invasive pneumococcal disease, documented in 41 patients (68%) and causing 72 documented invasive infections (52.2%). P. aeruginosa and Staph. aureus documented invasive infections also occurred (16.7% and 16%, respectively, in 13 and 13 patients, respectively). Systemic signs of inflammation were usually weak or delayed. The first invasive infection occurred before the age of 2 years in 53 (88.3%) and in the neonatal period in 19 (32.7%) patients. Multiple or recurrent invasive infections were observed in most survivors (n = 36/50, 72%).Clinical outcome was poor, with 24 deaths, in 10 cases during the first invasive episode and in 16 cases of invasive pneumococcal disease. However, no death and invasive infectious disease were reported in patients after the age of 8 years and 14 years, respectively. Antibiotic prophylaxis (n = 34), antipneumococcal vaccination (n = 31), and/or IgG infusion (n = 19), when instituted, had a beneficial impact on patients until the teenage years, with no seemingly detectable impact thereafter.IRAK-4 and MyD88 deficiencies predispose patients to recurrent life-threatening bacterial diseases, such as invasive pneumococcal disease in particular, in infancy and early childhood, with weak signs of inflammation. Patients and families should be informed of the risk of developing life-threatening infections; empiric antibacterial treatment and immediate medical consultation are strongly recommended in cases of suspected infection or moderate fever. Prophylactic measures in childhood are beneficial, until spontaneous improvement occurs in adolescence.

AB - Autosomal recessive interleukin-1 receptor-associated kinase (IRAK)-4 and myeloid differentiation factor (MyD)88 deficiencies impair Toll-like receptor (TLR)- and interleukin-1 receptor-mediated immunity. We documented the clinical features and outcome of 48 patients with IRAK-4 deficiency and 12 patients with MyD88 deficiency, from 37 kindreds in 15 countries.The clinical features of IRAK-4 and MyD88 deficiency were indistinguishable. There were no severe viral, parasitic, and fungal diseases, and the range of bacterial infections was narrow. Noninvasive bacterial infections occurred in 52 patients, with a high incidence of infections of the upper respiratory tract and the skin, mostly caused by Pseudomonas aeruginosa and Staphylococcus aureus, respectively. The leading threat was invasive pneumococcal disease, documented in 41 patients (68%) and causing 72 documented invasive infections (52.2%). P. aeruginosa and Staph. aureus documented invasive infections also occurred (16.7% and 16%, respectively, in 13 and 13 patients, respectively). Systemic signs of inflammation were usually weak or delayed. The first invasive infection occurred before the age of 2 years in 53 (88.3%) and in the neonatal period in 19 (32.7%) patients. Multiple or recurrent invasive infections were observed in most survivors (n = 36/50, 72%).Clinical outcome was poor, with 24 deaths, in 10 cases during the first invasive episode and in 16 cases of invasive pneumococcal disease. However, no death and invasive infectious disease were reported in patients after the age of 8 years and 14 years, respectively. Antibiotic prophylaxis (n = 34), antipneumococcal vaccination (n = 31), and/or IgG infusion (n = 19), when instituted, had a beneficial impact on patients until the teenage years, with no seemingly detectable impact thereafter.IRAK-4 and MyD88 deficiencies predispose patients to recurrent life-threatening bacterial diseases, such as invasive pneumococcal disease in particular, in infancy and early childhood, with weak signs of inflammation. Patients and families should be informed of the risk of developing life-threatening infections; empiric antibacterial treatment and immediate medical consultation are strongly recommended in cases of suspected infection or moderate fever. Prophylactic measures in childhood are beneficial, until spontaneous improvement occurs in adolescence.

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