Koniushevska A. A., Parkhomenko T. A., Balychevtseva I. V., Tуmoshуna O. V., Akуmova L. G.

LITERATURE REVIEWS

Scentific article

The article is devoted to the problem of diagnosis and treatment of neutropenic conditions in children. A literary review of the modern understanding of the etiology, pathogenetic variants, classification, course, clinical picture, observation and treatment of neutropenic conditions is made. The severity of neutropenia, including agranulocytosis, has been clarified. The types of neutropenia are discussed: congenital (genetically determined), acquired and chronic benign neutropenia of childhood. The differentiation of the competence of pediatric and hematological services has been made. The concept of pseudoneutropenic syndrome is analyzed. The causes of acquired neutropenia are stated. It is emphasized that acquired neutropenia must be differentiated primarily by isoimmune neutropenia of newborns, neutropenia against the background of myelodysplastic syndrome; infectious-associated (including AIDS); nutritional (folate deficiency, vitamin B12 deficiency, copper deficiency, etc.); caused by radiation; drug-induced; associated with a malignant disease. The article presents its own clinical 4-year observation of a patient with Chronic benign neutropenia of childhood. The characteristics of congenital neutropenia and neutropenic syndromes are given, their laboratory and genetic diagnostics are highlighted. The article presents its own clinical, as well as 4-year-old, observation of a child with primary immunodeficiency – severe congenital neutropenia (D72.0), caused by a pathogenic heterozygous mutation in the ELANE gene and unspecified lymphopenia. Differential diagnosis, treatment, and patient follow-up are discussed. The general principles of treating patients with neutropenia are highlighted.

neutropenia, children, acquired, congenital, treatment.

1. Rumjanceva AG, Maschana AA, Zhukovskoj EV, redaktor. Detskaja gematologija. Moskva: GJeOTAR-Media; 2015. 656 s. [in Russian].
2. Deordieva EA. Strategija terapii detej s vrozhdennoj nejtropeniej v zavisimosti ot klinicheskih i molekuljarno-geneticheskih osobennostej [avtoreferat]. Moskva: NMIC DGOI im. Dmitrija Rogacheva; 2018. 23 s. [in Russian].
3. Deordieva EA, Shherbina AJu. Nejtropenii v praktike detskogo gematologa/onkologa. Onkogematologija. 2015;1:46-52. DOI: 1 10.17650/1818-8346-2015-1-46-52 [in Russian].
4. Il’chenko SI, Korenjuk ES, Fialkovskaja AA. Nejtropenija u detej: klinicheskie maski i vrachebnaja taktika. Zdorov’e rebenka. 2018;4(13):387- 93. DOI: 10.22141/2224-0551.13.4.2018.137025 [in Russian].
5. Judina NB, Brezhneva NV. Izolirovannaja nejtropenija u detej: ot pediatra k gematologu (obzor literatury). Ros. zhurn detskoj gematologii i onkologii. 2015;1:75-80. [in Russian].
6. Ozhegov AM. Nejtropenii u detej. Prakt medicina. 2009;7(39):92-4. [in Russian].
7. Kazakova LM. Nejtropenii u detej. Mat’ i Ditja v Kuzbasse. 2010;1(40):3-6. [in Russian].
8. Newburger PE, Dale DC. Evaluation and management of patients with isolated neutropenia. Semin Hematol. 2013 Jul;50(3):198-206.
9. Husain EH, Mullah-Ali A, Al-Sharidah S, Azab AF, Adekile A. Infectiousetiologies of transient neutropenia in previously healthy children. Pediatr Infect Dis J. 2012 Jun;31(6):575-7. DOI: 10.1097/INF.0b013e318250084a
10. Lavrent’eva IN, Finogenova NA, Mamedova EA, Polovceva TV, Karazhas NV, Kalugina MJu, i dr. Vlijanie ificirovannosti gerpesvirusami na dlitel’nost’ cirkuljacii antigranulocitarnyh antitel i sroki nastuplenija remissii nejtropenii u detej rannego vozrasta. Pediatrija. 2015;1(94):57- 61. [in Russian].
11. Ostroumova OD, Kochetkov AI, Pavleeva EE, Kravchenko EV. Lekarstvenno-inducirovannye nejtropenija i agranulocitoz. Bezopasnost’ i risk farmakoterapii. 2020;8(3):109-22. Dostupno: https://doi.org/10.30895/2312-7821-2020-8-3-109-122 [in Russian].
12. Andrès E, Maloisel F. Idiosyncratic drug-induced agranulocytosis or acute neutropenia. Curr Opin Hematol. 2008;15(1):15-21. Available from: https://doi.org/10.1097/MOH.0b013e3282f15fb9
13. Andersohn F, Konzen C, Garbe E. Systematic review: agranulocytosis induced by nonchemotherapy drugs. Ann Intern Med. 2007;146(9):657-65. Available from: https://doi.org/10.7326/0003-4819-146-9-200705010-00009
14. Huber M, Andersohn F, Bronder E, Klimpel A, Thomae M, Konzen C, et al. Drug-induced agranulocytosis in the Berlin case-control surveillance study. Eur J Clin Pharmacol. 2014;70(3):339-45. Available from: https://doi.org/10.1007/s00228-013-1618-1
15. Volodin NN, Rumjancev AG, Shherbina AJu. Diagnostika i lechenie nejtropenii u novorozhdennyh. Vopr. prakt. pediatrii. 2012;7(1):33-9. [in Russian].
16. Autrel-Moignet A, Lamy T. Autoimmune neutropenia. Presse Med. 2014;43(4.2):105-18.
17. Rumjancev AG, Maschan AA, Shherbina AJu. Federal’nye klinicheskie rekomendacii po diagnostike i lecheniju detej s vrozhdennoj nejtropeniej. Moskva: Standartinform; 2015. 23 s. [in Russian].
18. Tirali RE, Yalçınkaya Erdemci Z, Çehreli SB. Oral findings and clinical implications of patients with congenital neutropenia: a literature review. Turk J Pediatr. 2013 May;55(3):241-5.
19. Rosenberg PS, Zeidler C, Bolyard AA, Alter BP, Bonilla MA, Boxer LA, et al. Stable long-term risk of leukaemia in patients with severe congenital neutropenia maintained on G-CSF therapy. Br J Haematol. 2010;150(2):196-9.
20. Borregaard N. Severe congenital neutropenia: new lane for ELANE. Blood. 2014;123(4):462-3.
21. Boztug K, Klein C. Genetic etiologies of severe congenital neutropenia. Curr Opin Pediatr. 2011;23(1):21-6.
22. Boztug K, Klein C. Genetics and pathophysiology of severe congenital neutropenia syndromes unrelated to neutrophil elastase. Hematol Oncol Clin North Am. 2013 Feb;27(1):43-60.
23. Deordieva EA, Varlamova TV, Rajkina EV, Shherbina AJu. Geneticheskie prediktory neblagoprijatnogo techenija tjazheloj vrozhdennoj nejtropenii u pacientov s mutaciej v gene ELANE. Vopr. gematologii/onkologii i immunopatologii v pediatrii. 2016;1:41-5. [in Russian].
24. Celkan T, Koç BŞ. Approach to the patient with neutropenia in childhood. Turk Pediatri Ars. 2015 Sep 1;50(3):136-44.
25. Dale DC. ELANE-related neutropenia [Internet]. University of Washington, Seattle (WA): Gene Reviews TM; 2002. Available from: http:// www.ncbi.nlm.nih.gov/books/ NBK1533/ [updated 14 July 2011].
26. Klein C, Grudzien M, Appaswamy G, Germeshausen M, Sandrock I, Schäffer A, et al. HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease). Nat Genet. 2007;39(1):86-92.
27. Dale DC, Welte K. Cyclic and chronic neutropenia. Cancer Treat Res. 2011;157:97-108.
28. Touw IP, Palande K, Beekman R. Granulocyte colony-stimulating factor receptor signaling: implications for G-CSF responses and leukemic progression in severe congenital neutropenia. Hematol Oncol Clin North Am. 2013 Feb;27(1):61-73.
29. Skrypnik KA, Kosorukov VS. Chelovecheskij granulocitarnyj koloniestimulirujushhij faktor v klinicheskoj praktike. Ros. bioterapevt. zhurn. 2011;2(10):19-24. [in Russian].

«Bulletin of problems biology and medicine» Issue 4 (158), 2020 year, 24-30 pages, index UDK 616.155.3-053.2-02-092-07-08

10.29254/2077-4214-2020-4-158-24-30