Das Down-Syndrom als Risikofaktor für einen komplizierten Verlauf bei RSV-Infektion

P. Hoffmann; A. Wagner; A.-M. Jung; T. Rohrer; L. Gortner; A. Simon

doi:10.1055/s-0037-1616308

Kinder- und Jugendmedizin, Table of Contents

Kinder- und Jugendmedizin 2016; 16(02): 125-131
DOI: 10.1055/s-0037-1616308

Infektiologie

Schattauer GmbH

Das Down-Syndrom als Risikofaktor für einen komplizierten Verlauf bei RSV-Infektion

Indikation für eine Palivizumab-Prophylaxe?Down syndrome as risk factor for a complicated course in RSV infectionindication for palivizumab prophylaxis?

Authors

P. Hoffmann

¹Allgemeine Pädiatrie, Neonatologie am Universitätsklinikum des Saarlandes, Kinderklinik Homburg/Saar
A. Wagner

²Pädiatrische Onkologie und Hämatologie am Universitätsklinikum des Saarlandes, Kinderklinik Homburg/Saar
A.-M. Jung

¹Allgemeine Pädiatrie, Neonatologie am Universitätsklinikum des Saarlandes, Kinderklinik Homburg/Saar
T. Rohrer

¹Allgemeine Pädiatrie, Neonatologie am Universitätsklinikum des Saarlandes, Kinderklinik Homburg/Saar
L. Gortner

¹Allgemeine Pädiatrie, Neonatologie am Universitätsklinikum des Saarlandes, Kinderklinik Homburg/Saar
A. Simon

²Pädiatrische Onkologie und Hämatologie am Universitätsklinikum des Saarlandes, Kinderklinik Homburg/Saar

Abstract

Zusammenfassung

Kinder mit Down-Syndrom haben einen nicht abschließend charakterisierten humoralen und zellulären Immundefekt mit unterschiedlicher klinischer Ausprägung, der in den ersten Lebensjahren das Risiko von Atemwegsinfektionen deutlich erhöht. Einige Publikationen beschreiben das Down-Syndrom (auch ohne Frühgeburtlichkeit oder einen hämodynamisch relevanten angeborenen Herzfehler) als unabhängigen Risikofaktor für einen komplizierten Verlauf der RSV-Infektion. Dieser Beitrag stellt die aktuell verfügbaren Informationen aus der Literatur zusammen, die nahelegen, dass Kinder mit Down-Syndrom wahrscheinlich im ersten Lebensjahr von einer Prophylaxe mit Palivizumab profitieren. Die Zahl der für eine randomisierte Prüfung dieser Fragestellung erforderlichen Probanden überstiege die Zahl der in Deutschland pro Jahr geborenen Kinder mit Down-Syndrom (ein Dilemma für Mediziner, die Kinder mit seltenen Erkrankungen oder angeborenen Syndromen behandeln).

Summary

Children with Down syndrome are affected by both humoral and cellular immunodeficiency, which has not been characterized in detail to date. Infants with Down syndrome face an increased risk of respiratory tract infections. Recent studies describe Down syndrome (even without hemodynamically significant congenital heart disease or prematurity) as an independent risk factor for a complicated clinical course in RSV infected children. This article comprises the available information on this topic and comes to the conclusion that palivizumab prophylaxis would probably be beneficial in infants with Down syndrome. A randomized controlled study investigating this issue would have to include a number of infants greater than the yearly birth cohort with Down syndrome in Germany; this is a common ethical dilemma for physicians involved in the treatment of children with rare diseases or genetic syndromes.

Schlüsselwörter

Down-Syndrom - Respiratory Syncytial Virus - Palivizumab-Prophylaxe

Keywords

Down syndrome - Respiratory Syncytial Virus - palivizumab prophylaxis

Full Text

References

Literatur
1 Watts R, Vyas H. An overview of respiratory problems in children with Down’s syndrome. Arch Dis Child 2013; 98: 812-817.
2 Bloemers BL, Broers CJ, Bont L. et al. Increased risk of respiratory tract infections in children with Down syndrome: the consequence of an altered immune system. Microbes Infect 2010; 12: 799-808.
3 Nisihara RM, Utiyama SR, Oliveira NP, Messias-Reason IJ. Mannan-binding lectin deficiency increases the risk of recurrent infections in children with Down’s syndrome. Hum Immunol 2010; 71: 63-66.
4 Bloemers BL, Bont L, de Weger RA, Otto SA. et al. Decreased thymic output accounts for decreased naive T cell numbers in children with Down syndrome. J Immunol 2011; 186: 4500-4507.
5 Kusters MA, Gemen EF, Verstegen RH. et al. Both normal memory counts and decreased naive cells favor intrinsic defect over early senescence of Down syndrome T lymphocytes. Pediatr Res 2010; 67: 557-562.
6 Verstegen RH, Kusters MA, Gemen EF. E DEV. Down syndrome B-lymphocyte subpopulations, intrinsic defect or decreased T-lymphocyte help. Pediatr Res 2010; 67: 563-569.
7 Loh RK, Harth SC, Thong YH, Ferrante A. Immunoglobulin G subclass deficiency and predisposition to infection in Down’s syndrome. Pediatr Infect Dis J 1990; 9: 547-551.
8 Simon A, Volz S, Fleischhack G. et al. Human coronavirus OC43 pneumonia in a pediatric cancer patient with down syndrome and acute lymphoblastic leukemia. J Pediatr Hematol Oncol 2007; 29: 432-434.
9 Bloemers BL, van Furth AM, Weijerman ME. et al. Down syndrome: a novel risk factor for respiratory syncytial virus bronchiolitis – a prospective birthcohort study. Pediatrics 2007; 120: e1076-1081.
10 Paes B, Mitchell I, Li A, Lanctot KL. Respiratory hospitalizations and respiratory syncytial virus prophylaxis in special populations. Eur J Pediatr 2012; 171: 833-841.
11 Megged O, Schlesinger Y. Down syndrome and respiratory syncytial virus infection. Pediatr Infect Dis J 2010; 29: 672-673.
12 Perez-Padilla R, Fernandez R, Garcia-Sancho C. et al. Pandemic (H1N1) 2009 virus and Down syndrome patients. Emerg Infect Dis 2010; 16: 1312-1314.
13 Kusters MA, Verstegen RH, Gemen EF, de Vries E. Intrinsic defect of the immune system in children with Down syndrome: a review. Clin Exp Immunol 2009; 156: 189-193.
14 Boghossian NS, Hansen NI, Bell EF. et al. Survival and morbidity outcomes for very low birth weight infants with Down syndrome. Pediatrics 2010; 126: 1132-1140.
15 Hilton JM, Fitzgerald DA, Cooper DM. Respiratory morbidity of hospitalized children with Trisomy 21. J Paediatr Child Health 1999; 35: 383-386.
16 Garrison MM, Jeffries H, Christakis DA. Risk of death for children with down syndrome and sepsis. J Pediatr 2005; 147: 748-752.
17 Bruijn M, van der Aa LB, van Rijn RR. et al. High incidence of acute lung injury in children with Down syndrome. Intensive Care Med 2007; 33: 2179-2182.
18 Kabbani MS, Giridhar S, Elbarbary M. et al. Post-operative cardiac intensive care outcome for Down syndrome children. Saudi Med J 2005; 26: 943-946.
19 Seki M, Kato T, Masutani S. et al. Pulmonary arterial hypertension associated with gastroesophageal reflux in a 2-month-old boy with Down syndrome. Circ J 2009; 73: 2352-2354.
20 Deutsche Gesellschaft für Pädiatrische Infektiologie (DGPI), Deutsche Gesellschaft für Pädiatrische Kardiologie (DGPK), Gesellschaft für Pädiatrische Pneumologie (GPP), Gesellschaft für Neonatologie und Pädiatrische Intensivmedizin (GNPI), Berufsverband der Kinder- und Jugendärzte (BVKJ), Bundesverband „Das frühgeborene Kind“ e.V.. AWMF-LL 048–012 – Leitlinie zur Prophylaxe von schweren Erkrankungen durch Respiratory Syncytial Virus (RSV) bei Risikokindern 28. Oktober 2012
21 The IMpact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. The IMpact-RSV Study Group. Pediatrics 1998; 102 (03) (Suppl. 01) 531-537.
22 Feltes TF, Cabalka AK, Meissner HC. et al. Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease. J Pediatr 2003; 143: 532-540.
23 Kristensen K, Stensballe LG, Bjerre J. et al. Risk factors for respiratory syncytial virus hospitalisation in children with heart disease. Arch Dis Child 2009; 94: 785-789.
24 Sigurs N, Aljassim F, Kjellman B. et al. Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life. Thorax 2010; 65: 1045-1052.
25 Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman B. Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. Am J Respir Crit Care Med 2000; 161: 1501-1507.
26 Simoes EA, Groothuis JR, Carbonell-Estrany X. et al. Palivizumab prophylaxis, respiratory syncytial virus, and subsequent recurrent wheezing. J Pediatr 2007; 151: 34-42 e1.
27 Bloemers BL, van Furth AM, Weijerman ME. et al. High incidence of recurrent wheeze in children with down syndrome with and without previous respiratory syncytial virus lower respiratory tract infection. Pediatr Infect Dis 2010; 29: 39-42.
28 Kristensen K, Hjuler T, Ravn H. et al. Chronic diseases, chromosomal abnormalities, and congenital malformations as risk factors for respiratory syncytial virus hospitalization: a population-based cohort study. Clin Infect Dis 2012; 54: 810-817.
29 Zachariah P, Ruttenber M, Simoes EA. Down Syndrome and Hospitalizations due to Respiratory Syncytial Virus: A Population-Based Study. J Pediatr 2012; 160: 827-831.
30 Ralston SL, Lieberthal AS, Meissner HC. et al. Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics 2014; 134: e1474-502.
31 Plint AC, Grenon R, Klassen TP, Johnson DW. Bronchodilator and steroid use for the management of bronchiolitis in Canadian pediatric emergency departments. CJEM 2014; 16: 1-8.
32 Simon A, Nowak H, Sterz R. Use of Palivizumab in Germany: Data from 2002–2007. Klin Padiatr 2011; 223: 292-298.
33 Paes B, Manzoni P. Special populations: do we need evidence from randomized controlled trials to support the need for respiratory syncytial virus prophylaxis?. Early Hum Dev 2011; 87 (Suppl. 01) S55-58.
34 Paes B, Mitchell I, Li A, Lanctot KL. A comparative study of respiratory syncytial virus (RSV) prophylaxis in premature infants within the Canadian Registry of Palivizumab (CARESS). Eur J Clin Microbiol Infect Dis 2012; 31: 2703-2711.
35 Paes B, Mitchell I, Li A, Lanctot KL. Respiratory hospitalizations and respiratory syncytial virus prophylaxis in special populations. Eur J Pediatr 2012; 171: 833-841.
36 Paes B, Mitchell I, Yi H. et al. Hospitalization for respiratory syncytial virus illness in Down syndrome following prophylaxis with palivizumab. Pediatr Infect Dis J 2014; 33: e29-33.
37 Yi H, Lanctot KL, Bont L. et al. Respiratory syncytial virus prophylaxis in down syndrome: a prospective cohort study. Pediatrics 2014; 133: 1031-1037.
38 Hall CB, Weinberg GA, Iwane MK. et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med 2009; 360: 588-598.
39 Simoes EA, Carbonell-Estrany X, Fullarton JR. et al. A predictive model for respiratory syncytial virus (RSV) hospitalisation of premature infants born at 33–35 weeks of gestational age, based on data from the Spanish FLIP Study. Respir Res 2008; 9: 78.
40 Manzoni P, Paes B, Resch B. et al. High risk for RSV bronchiolitis in late preterms and selected infants affected by rare disorders: a dilemma of specific prevention. Early Hum Dev 2012; 88 (Suppl. 02) S34-41.
41 Afghani B, Ngo T. Severe respiratory syncytial virus infection in term infants with genetic or other underlying disorders. Pediatrics 2008; 121: 868 author reply –9.
42 Medrano Lopez C, Garcia-Guereta Silva L, Lirio Casero J. et al. Respiratory infections, Down’s syndrome and congenital heart disease: the CIVIC 21 study. An Pediatr (Barc) 2009; 71: 38-46.
43 Zachariah P, Ruttenber M, Simoes EA. Hospitalization due to Respiratory Syncytial Virus in children with congenital malformations. Pediatr Infect Dis 2011; 30: 442-445.