Özlem Aktaş HANIMELİ, Özge YILMAZ, Hasan YÜKSEL

Primer immün yetmezlikli çocuğa yaklaşım

Primer immün yetmezlikler seyrek görülen bir hastalık grubu olmakla birlikte ciddi morbidite ve mortaliteye yol açması nedeni ile klinik ve epidemiyolojik açıdan önem taşır. En sık karşılaşılan primer immün yetmezlikler hümöral immün sistem kusurları, hücresel immün sistem kusurları, kombine immün yetmezlikler, fagositer sistem kusurları ve kompleman sistemi kusurlarıdır. İmmün yetmezliklerin klasik klinik bulguları arasında yineleyen, ağır ve tedaviye iyi yanıt vermeyen ya da komplikasyonların ortaya çıktığı enfeksiyon öyküsü yanında virulansı düşük mikroorganizmalarla enfeksiyonlara duyarlılık yer alır. Ayrıca, otoimmünite, otoinflamatuvar veya hemofagositoz sendromları ile ortaya çıkabildiği de gösterilmiştir. Doğumsal hastalıklar genellikle erken çocukluk döneminde başlayıp, morbidite ve mortaliteye yol açmaktadır. Bu nedenle erken tanı yaşam kurtarıcı olabileceği gibi, uzun dönemde yaşam kalitesinin artırılmasını, genetik danışma ya da prenatal tanıyı olanaklı kılmaktadır. Primer immün yetmezlik hastalıklarının ayırıcı tanıda daha sıklıkla düşünülmesi ve immünolojik değerlendirmenin öncelikli yapılması, bu hastaların erken dönemde tanı almasını böylece de erken tedavi ya da koruyucu önlemlere ulaşımını sağlamaktadır.

Approach to a child with primary immunodeficiency

Primary immunodeficiencies are clinically and epidemiologically important, despite their low prevalence, due to the associated risk of high morbidity and mortality. Most commonly encountered primary immunodeficiencies include humoral immune system deficiencies, cellular immune system defects, combined immunodeficiencies, phagocyte system defects, complement system defects. Classical clinical findings of immunodeficiencies include recurrent, severe infections which do not respond to treatment or which progress with complications as well as tendency to develop infections with low virulence microorganisms. Moreover, they may present with autoimmunity, autoinflammatory or hemaphagocytic syndromes. Congenital diseases usually start in early childhood and lead to morbidity and mortality. Therefore, early diagnosis may be life saving and allow increasing quality of life, genetic counseling or prenatal diagnosis. Considering primary immunodeficiencies more frequently in differential diagnosis and early immunological evaluation would lead to early diagnosis of these patients and allow them to reach early treatment or preventive measures.

PDF

___

1. Geha RS, Notarangelo LD, Casanova JL et al. � � Primary immunodeficiency diseases: an update from the International Union of Imunological Societies Primary Immunodeficiency Diseases Classification Committee. J Allergy Clin Immunol. 2007;120:776–94.
2. Bonilla FA, Bernstein IL, Khan DA et al. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol 2005;94:1–63.
3. Fischer A. Immunodeficiency diseases. an experimental model for molecular medicine. Lancet 2001;357:1863–69.
4. Puck JM. Primary immunodeficiency diseases. JAMA 1997;278:1835-41.
5. Notarangelo LD. Primary immunodeficiencies. J Allergy Clin Immunol. 2010; 125: S182–94.
6. Tangsinmankong N, Bahna SL and Good RA. Immunologic workup of the child suspected of immunodeficiency. Ann Allergy Asthma Immunol 2001;87:362–70.
7. A.Farhoudi, A. Aghamohammadi, M. Moin and at all. Distribution of primary immunodeficiency disorders diagnosed in the Children’s Medical Center in Iran. J Invest Allergol Clin Immunol 2005;15:177–82.
8. Behrman R, Kliegman R, Jenson H. The Immunologic System and Disorders. Nelson Textbook of Pediatrics. 17th ed. Phila-delphia. Elsevier. 2004.p 681–742.
9. Oliveira JB, Fleisher TA. Laboratory evaluation of primary immunodeficiencies. J Allergy Clin Immunol 2010;125:S297–305.
10. Javier FC 3rd, Moore CM, Sorensen RU. Distribution of primary immunodeficiency diseases diagnosed in a pediatric tertiary hospital. Ann Allergy Asthma Immunol 2000;84:25–30.
11. Stray-Pedersen A, Abrahamsen TG, Froland SS. Primary immunodeficiency diseases in Norway. J Clin Immunol 2000; 20:477–85.
12. Yorulmaz A, Artaç H, Kara R, Keles S, Reisli İ. Primer İmmün Yetmezlikli 1054 olgunun retrospektif olarak değerlendirilmesi. Asthma Allergy Immunology 2008;6:127–34.
13. Filipe-Santos O, Bustamante J, Chapgier A et al .Inborn errors of IL-12/23- and IFN-gamma-mediated immunity: molecular, cellular, and clinical features.Semin Immunol 2006;18: 347–61.
14. Sancho-Shimizu V, Zhang SY, Abel L et al. Genetic susceptibility to herpes simplex virus 1 encephalitis in mice and humans. Curr Opin Allergy Clin Immunol 2007;7: 495-505.
15. Ku CL, Picard C, Erdös M et al. IRAK4 and NEMO mutations in otherwise healthy children with recurrent invasive pneu-mococcal disease. J Med Genet 2007;44:16–23.
16. Kovar MG, Serdula MK, Marks JS, et al: Review of the epidemiologic evidence for an association between infant feeding and infant health. Pediatrics 1984;74:615–38.
17. Rich RR, Fleisher TA, Schwartz BD, et al (eds). Development of the Fetal and Neonatal Immune System. Clinical Immunology: Principles and Practice. 3th ed. Philadelphia. Elsevier. 2008. p493–503
18. Stiehm RE, Fudenberg HH. Serum levels of immune globulins on health and disease: A survey. Pediatrics 1966;37:715–27.
19. Campi Catherine. Primary Immunodeficiency Disorders in Children: Prompt Diagnosis Can Lead to Lifesaving Treatment. J Pediatr Health Care 2002:16;16–21.
20. Cunningam-Rundles C, Bodian C. Common variable immunodeficiency: Clinical and immunological features of 248 patients. Clin Immunol 1999; 92:34–48.
21. Segal BH, Holland SM. Primary phagocytic disorders of childhood. Pediatr Clin N Am 2000; 47:1311–38
22. Misbah SA, Spickett GA, Ryba PC, et al. Chronic enteroviral meningoenephalitis in agammaglobulinemia. J Clin Immunol 1992;12:266–70.
23. Bruton O. A Gammaglobulinemia. Pediatrics 1952; 9:722–28.
24. Hashimoto S, Tsukada S, Matsushita M, et al. Identification of the derived proteins in 35 X-linked agammaglobulinemia fam-ilies: A nationwide study of Btk deficiency in Japan. Blood 1996; 88:561–73.
25. Howie PW, Forsyth Js, Ogston SA, et al. Protective effect of breastfeeding against infection. BMJ 1990; 300:11-16.
26. Bonilla FA, Geha RS. Primary immunodeficiency diseases.J Allergy Clin Immunol 2003;111: 571–81
27. Levy J, Espanol-Boren T, Thomas C, et al. Clinical spectrum of X-linked hyper-Ig M syndrome. J Pediatr 1997;131: 47–54.
28. Sandoval C, Swift M. Hodgkin disease in ataxia telangiectasia patients with poor outcomes. Med Pediatr Oncol 2003; 40: 162–66.
29. Maródi L, Notarangelo LD. Immunological and genetic bases of new primary immunodeficiencies. Nat Rev Immunol 2007;7:851–61.
30. Casanova JL, Abel L. Human genetics of infectious diseases: a unified theory. EMBO J 2007;26: 915–22.
31. Casanova JL, Abel L. Primary immunodeficiencies: a field in its infancy. Science 2007;317:617–19.