Staphylokokkeninfektionen bei Patienten mit primären Immundefekten

Horst von Bernuth; Stephan Ehl

doi:10.1055/s-0038-1628954

Kinder- und Jugendmedizin, Table of Contents

Kinder- und Jugendmedizin 2008; 08(02): 93-100
DOI: 10.1055/s-0038-1628954

Infektiologie

Schattauer GmbH

Staphylokokkeninfektionen bei Patienten mit primären Immundefekten

Staphylococcal disease in children with primary immunodeficiencies

Horst von Bernuth

¹Laboratoire de génétique humaine des maladies infectieuses, Université René Descartes – INSERM U550, Faculté de Médecine Necker, Paris (Direktor: Dr. Laurent Abel)

,

Stephan Ehl

³Zentrum für Kinder- und Jugendmedizin, Universtitätsklinikum Freiburg (Direktor: Prof. Dr. med. Andrea Superti-Furga)

› Author Affiliations

Abstract

Zusammenfassung

Schwere, invasive und rezidivierende Staphylokokkeninfektionen können ein Hinweis für einen angeborenen Immundefekt sein. Insbesondere angeborene Störungen der Anzahl der neutrophilen Granulozyten, der Phagozytenaktivierung, der Leukozytenadhäsion, der Neutrophilen- Granula, des intrazellulären Abtötens phagozytierter Erreger und Hyper-IgE-Syndrome gehen mit einer erhöhten Anfälligkeit für Staphylokokkeninfektionen einher. Bei jeder schweren invasiven Staphylokokkeninfektion im Kindesund insbesondere im Säuglingsalter sollte daher auch an einen angeborenen Immundefekt gedacht werden. Ein rationales Vorgehen, das durch Anamnese, klinischen Befund und orientierende Labordiagnostik entscheiden hilft, ob ein Patient mit Staphylokokkeninfektion an einem auf Immundefekte spezialisierten Zentrum vorgestellt und betreut werden muss, wird vorgestellt.

Summary

Severe, invasive and recurrent staphylococcal disease can be a warning sign for inborn immunodeficiencies. In particular defects in neutrophil numbers, in the capacity of phagocytes to become activated, in leucocyte adhesion, in specific neutrophilic granules, in intracellular killing and Hyper-IgE-syndromes are accompanied with an increased susceptibility for staphylococcal disease. Severe invasive staphylococcal disease in children and in particular in newborns and infants should therefore raise the suspicion for an inborn immunodeficiency. A rationale, based on history, clinical status and basic laboratory tests, is presented in order to decide whether a patient with staphylococcal disease has to be referred to and taken care of by a specialised center for immunodeficiencies.

Schlüsselwörter

Staphylokokkeninfektionen - angeborene Immundefekte - Phagozyten - Granulozyten - angeborene Immunität

Keywords

Staphylococcal disease - primary immunodeficiencies - phagocytes - granulocytes - innate immunity

Full Text

References

Literatur
1 Almuneef M, Al Khenaizan S, Al Ajaji S, Al Anazi A. Pyogenic liver abscess and Papillon-Lefevre syndrome: not a rare association. Pediatrics 2003; 111: e85-e88.
2 Boxer LA, Newburger PE. A molecular classification of congenital neutropenia syndromes. Pediatr Blood Cancer 2007; 49: 606-614.
3 Breton-Gorius J, Mason DY, Buriot D. et al. Lactoferrin deficiency as a consequence of a lack of specific granules in neutrophils from a patient with recurrent infections. Detection by immunoperoxidase staining for lactoferrin and cytochemical electron microscopy. Am J Pathol 1980; 99: 413-428.
4 Bunting M, Harris ES, McIntyre TM. et al. Leukocyte adhesion deficiency syndromes: adhesion and tethering defects involving beta 2 integrins and selectin ligands. Curr Opin Hematol 2002; 9: 30-35.
5 Carneiro-Sampaio M, Coutinho A. Immunity to microbes: lessons from primary immunodeficiencies. Infect Immun 2007; 75: 1545-1555.
6 Clark R, Griffiths GM. Lytic granules, secretory lysosomes and disease. Curr Opin Immunol 2003; 15: 516-521.
7 Enders A, Pannicke U, Berner R. et al. Two siblings with lethal pneumococcal meningitis in a family with a mutation in Interleukin-1 receptor-associated kinase 4. J Pediatr 2004; 145: 698-700.
8 Etzioni A, Alon R. Leukocyte adhesion deficiency III: a group of integrin activation defects in hematopoietic lineage cells. Curr Opin Allergy Clin Immunol 2004; 4: 485-490.
9 Figueroa JE, Densen P. Infectious diseases associated with complement deficiencies. Clin Microbiol Rev 1991; 4: 359-395.
10 Fischer A, Lisowska-Grospierre B, Anderson DC, Springer TA. Leukocyte adhesion deficiency: molecular basis and functional consequences. Immunodefic Rev 1988; 1: 39-54.
11 Ganz T, Metcalf JA, Gallin JI. et al. Microbicidal/ cytotoxic proteins of neutrophils are deficient in two disorders: Chediak-Higashi syndrome and „specific“ granule deficiency. J Clin Invest 1988; 82: 552-556.
12 Grimbacher B, Holland SM, Gallin JI. et al. Hyper-IgE syndrome with recurrent infections – an autosomal dominant multisystem disorder. N Engl J Med 1999; 340: 692-702.
13 Horwitz MS, Duan Z, Korkmaz B. et al. Neutrophil elastase in cyclic and severe congenital neutropenia. Blood 2007; 109: 1817-1824.
14 Howard MW, Strauss RG, Johnston Jr RB. Infections in patients with neutropenia. Am J Dis Child 1977; 131: 788-790.
15 Klein C, Grudzien M, Appaswamy G. et al. HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease). Nat Genet 2007; 39: 86-92.
16 Minegishi Y, Saito M, Tsuchiya S. et al. Dominantnegative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature 2007; 448: 1058-1062.
17 Pasvolsky R, Feigelson SW, Kilic SS. et al. A LAD-III syndrome is associated with defective expression of the Rap-1 activator CalDAG-GEFI in lymphocytes, neutrophils, and platelets. J Exp Med 2007; 204: 1571-1582.
18 Peterson CL, Mascola L, Chao SM. et al. Children hospitalized for varicella: a prevaccine review. J Pediatr 1996; 129: 529-536.
19 Pham CT, Ivanovich JL, Raptis SZ. et al. Papillon-Lefevre syndrome: correlating the molecular, cellular, and clinical consequences of cathepsin C/dipeptidyl peptidase I deficiency in humans. J Immunol 2004; 173: 7277-7281.
20 Puel A, Picard C, Ku CL. et al. Inherited disorders of NF-kappaB-mediated immunity in man. Curr Opin Immunol 2004; 16: 34-41.
21 von Bernuth H, Ku CL, Rodriguez-Gallego C. et al. A fast procedure for the detection of defects in Toll-like receptor signaling. Pediatrics 2006; 118: 2498-2503.
22 Winkelstein JA, Marino MC, Johnston Jr RB. et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore) 2000; 79: 155-169.
23 Winkelstein JA, Marino MC, Lederman HM. et al. X-linked agammaglobulinemia: report on a United States registry of 201 patients. Medicine (Baltimore) 2006; 85: 193-202.
24 Wolk K, Kunz S, Witte E. et al. IL-22 increases the innate immunity of tissues. Immunity 2004; 21: 241-254.
25 Yang XO, Panopoulos AD, Nurieva R. et al. STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem 2007; 282: 9358-9363.
26 Ku C-L, von Bernuth H, Picard C. et al. Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity. J Exp Med 2007; 204: 2407-2422.