Çocukluk Çağı Nötropenisinin Klinik ve Etiyolojik Özellikleri: Tek Merkezli Retrospektif Bir Çalışma

Öz

Amaç: Nötropeni, çocukluk çağında sık görülen ve enfeksiyon riskini artıran bir  hematolojik anormalliktir. Bu çalışmanın amacı, pediatrik nötropeni olgularının demografik, k linik v e etiyolojik özelliklerini değerlendirmek ve akut ile kronik nötropeni formları arasındaki farklılıkları ortaya koymaktır.
Gereç ve Yöntem: Bu çalışmaya Şanlıurfa Eğitim ve Araştırma Hastanesi Pediatrik  İmmünoloji ve Alerji Hastalıkları ile  Pediatrik Hematoloji Kliniklerinde Mart 2023-Eylül 2024 tarihleri arasında nötropeni tanısı alan toplam 49 hasta dahil edilmiştir. Hastaların verileri hastane kayıtlarından retrospektif olarak incelenmiştir.  Hastaların cinsiyet, nötropeni başlangıç yaşı, nötropeninin saptanma şekli, süresi (akut/kronik), etiyolojik sınıflandırması, şiddeti (hafif, o rta, a ğır) v e c iddi e nfeksiyon/sepsis g elişimi gibi klinik verileri toplanmıştır. Verilerin analizinde tanımlayıcı istatistiksel yöntemler kullanılmış; kategorik değişkenler için Ki-kare testi veya Fisher's Exact testi, sürekli değişkenler için ise bağımsız örneklem t-testi veya Mann-Whitney U testi uygulanmıştır. 
Bulgular: Çalışmaya dahil edilen 49 nötropeni tanılı olgunun %57,1’i erkekti ve ortalama nötropeni başlangıç yaşı  20,2±14,4 ay olarak saptanmıştır. Olguların %67,3’ünde akut nötropeni (n=33) ve %32,7’sinde kronik nötropeni (n=16) tespit edildi. Akut nötropeni grubunda ortalama tanı yaşı 12,6±8,4 ay olup, %75,8’i enfeksiyon, %21,2’si ise ilaç ilişkili etiyolojiye sahipti. Bu grubun %69,7’sini ağır nötropeni olguları oluşturmaktaydı ve akut nötropeni grubunun %15,2’sinde ciddi enfeksiyon veya sepsis izlendi. Kronik nötropeni grubunda ise ortalama tanı yaşı 37,2±26,4 ay olup, %43,8'i idiyopatik,  %31,2'si otoimmün ve %25'i genetik sendromlarla ilişkiliydi.    Kronik nötropenili olguların %50’sinde ciddi enfeksiyon veya sepsis gözlenmiş olup bu oran akut nötropeni grubuna kıyasla anlamlı olarak daha yüksekti (p<0,01).
Sonuç: Bu tek merkezli çalışma, çocukluk çağı nötropenisinin klinik ve etiyolojik açıdan heterojen bir yapı gösterdiğini ortaya koymaktadır. Akut nötropeninin çoğunlukla enfeksiyon veya ilaçlarla ilişkili olduğu ve genellikle benign bir seyir izlediği gözlenirken, kronik nötropeninin daha ileri yaşlarda ortaya çıktığı ve sıklıkla idiyopatik, otoimmün veya genetik nedenlerle ilişkili olduğu saptanmıştır. Kronik nötropenili hastalarda ciddi enfeksiyon riskinin belirgin şekilde artmış olması, bu grubun yakın izlem ve kapsamlı etiyolojik değerlendirme gereksinimini vurgulamaktadır. Sonuç olarak, bu bulgular çocukluk çağı nötropenisinin yönetiminde bireyselleştirilmiş yaklaşımların önemini desteklemekte ve klinisyenlere yol gösterici nitelikte bilgiler sunmaktadır.

Anahtar Kelimeler

• Akut nötropeni
• Kronik nötropeni
• Çocukluk çağı
• Etiyoloji

Etik Beyan

Harran Üniversitesi Klinik Araştırmalar Etik Kurulu tarafından onaylanmıştır (karar no: HRÜ/24.14.21, tarih: 23.09.2024).

Clinical and Etiological Characteristics of Childhood Neutropenia: A Single-Center Retrospective Study

Öz

Background: Neutropenia is a common hematological abnormality in childhood and is associated with an increased risk of infection. This study aimed to evaluate the demographic, clinical, and etiological characteristics of pediatric patients with neutropenia and to identify differences b etween a cute a nd c hronic f orms of neutropenia.
Materials and Methods: A total of 49 patients diagnosed with neutropenia between March 2023 and September 2024 in the Pediatric Immunology and Allergy Clinic and the Pediatric Hematology Clinic  of Şanlıurfa Training and Research Hospital were included in this retrospective study. Patient data were reviewed from hospital records. Clinical data, including sex, age at onset of neutropenia, mode of detection, duration of neutropenia (acute/chronic), etiological classification, severity (mild, moderate, severe), and development of severe infection or sepsis, were collected. Descriptive statistical methods were used for data analysis. The chi-square test or Fisher’s exact test was used for categorical variables, while the independent samples t-test or Mann-Whitney U test was used for continuous variables.
Results: Among the 49 patients diagnosed with neutropenia, 57.1%were male, and the mean age at onset of neutropenia was 20.2±14.4 months. Acute neutropenia was detected in 67.3%of the cases (n = 33), while chronic neutropenia was identified in 32.7%(n = 16). In the acute neutropenia group, the mean age at diagnosis was 12.6±8.4 months; 75.8%of cases were infection-related, and 21.2%were drug-related. Severe neutropenia accounted for 69.7%of cases in this group, and severe infection or sepsis was observed in 15.2%of patients with acute neutropenia. In the chronic neutropenia group, the mean age at diagnosis was 37.2±26.4 months; 43.8%of cases were idiopathic, 31.2%were autoimmune, and 25.0%were associated with genetic syndromes. Severe infection or sepsis was observed in 50.0%of patients with chronic neutropenia, a rate significantly higher than that in the acute neutropenia group (p<0.01).
Conclusion: This single-center study demonstrates that childhood neutropenia has a clinically and etiologically heterogeneous nature. Acute neutropenia was most commonly associated with infections or medications and generally followed a benign clinical course. In contrast, chronic neutropenia tended to occur at older ages and was frequently associated with idiopathic, autoimmune, or genetic causes. The markedly increased risk of severe infection among patients with chronic neutropenia highlights the need for close follow-up and comprehensive etiological evaluation in this group. Overall, these findings s upport t he i mportance o f individualized approaches in the management of childhood neutropenia and 
provide clinically useful guidance for clinicians.

Anahtar Kelimeler

• Acute neutropenia
• Chronic neutropenia
• Childhood
• Etiology

Etik Beyan

Harran Üniversitesi Klinik Araştırmalar Etik Kurulu tarafından onaylanmıştır (karar no: HRÜ/24.14.21, tarih: 23.09.2024).

Kaynakça

1. 1. Kobayashi SD, DeLeo FR. Role of neutrophils in innate immunity: a systems biology-level approach. Wiley Interdiscip Rev Syst Biol Med. 2009;1(3):309-33.
2. 2. Rungelrath V, Kobayashi SD, DeLeo FR. Neutrophils in innate immunity and systems biology-level approaches. Wiley Interdiscip Rev Syst Biol Med. 2020;12(1):e1458.
3. 3. Mortaz E, Alipoor SD, Adcock IM, Mumby S, Koenderman L. Update on Neutrophil Function in Severe Inflammation. Front Immunol. 2018;9:2171.
4. 4. Liew PX, Kubes P. The Neutrophil's Role During Health and Disease. Physiol Rev. 2019;99(2):1223-48.
5. 5. Gupta AK, Meena JP. Neutropenia in Pediatric Infections. Indian J Pediatr. 2019;86(11):983-4.
6. 6. Welte K, Zeidler C, Dale DC. Severe congenital neutropenia. Semin Hematol. 2006;43(3):189-95.
7. 7. Newburger PE, Dale DC. Evaluation and management of patients with isolated neutropenia. Semin Hematol. 2013;50(3):198-206.
8. 8. Lirette MP, Wright N, Trottier ED, Beck CE. Management of febrile neutropenia in immunocompetent children and youth. Paediatr Child Health. 2023;28(5):324-30.

9. 9. Palmblad J, Papadaki HA, Eliopoulos G. Acute and chronic neutropenias. What is new?. J Intern Med. 2001;250(6):476-91.
10. 10. James RM, Kinsey SE. The investigation and management of chronic neutropenia in children. Arch Dis Child. 2006;91(10):852-8.
11. 11. Donadieu J, Fenneteau O, Beaupain B, Mahlaoui N, Chantelot CB. Congenital neutropenia: diagnosis, molecular bases and patient management. Orphanet J Rare Dis. 2011;6:26.
12. 12. Celkan T, Koç BŞ. Approach to the patient with neutropenia in childhood. Turk Pediatri Ars. 2015;50(3):136-44.
13. 13. Zhou J, Zhou N, Liu Q, Xie ZP, Xu Y, Dai SC, et al. Prevalence of neutropenia in US residents: a population based analysis of NHANES 2011-2018. BMC Public Health. 2023;23(1):1254. 14. Akyol Ş, Tüfekçi Ö, Yılmaz Ş, Ören H. Clinical spectrum of pediatric neutropenia: mostly benign, but not to be overlooked. Turk J Pediatr. 2025;67(4):465-72.
14. 15. Matushita L, Valera ET, Aragon DC, Scridelli CA, Roxo-Junior P, de Carvalho LM. Chronic neutropenia in childhood: experience of a tertiary center. J Pediatr (Rio J). 2024;100(3):311-7.
15. 16. Long B, Koyfman A. Incidental neutropenia: An emergency medicine focused approach. Am J Emerg Med. 2025;89:190-4.
16. 17. Hsieh MM, Everhart JE, Byrd-Holt DD, Tisdale JF, Rodgers GP. Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences. Ann Intern Med. 2007;146(7):486-92.
17. 18. Farruggia P, Fioredda F, Puccio G, Onofrillo D, Russo G, Barone A, et al. Idiopathic neutropenia of infancy: Data from the Italian Neutropenia Registry. Am J Hematol. 2019;94(2):216-22.
18. 19. Lalezari P, Khorshidi M, Petrosova M. Autoimmune neutropenia of infancy. J Pediatr. 1986;109(5):764-9.
19. 20. Neglia JP, Watterson J, Clay M, Kline W, Luban NL, Smith CM, et al. Autoimmune neutropenia of infancy and early childhood. Pediatr Hematol Oncol. 1993;10(4):369-76.
20. 21. Farruggia P, Dufour C. Diagnosis and management of primary autoimmune neutropenia in children: insights for clinicians. Ther Adv Hematol. 2015;6(1):15-24.
21. 22. Katsaras G, Koutsi S, Psaroulaki E, Gouni D, Tsitsani P. Neutropenia in Childhood-A Narrative Review and Practical Diagnostic Approach. Hematol Rep. 2024;16(2):375-89.
22. 23. Dale DC. How I manage children with neutropenia. Br J Haematol. 2017;178(3):351-63.
23. 24. Alexandropoulou O, Kossiva L, Haliotis F, Giannaki M, Tsolia M, Panagiotou IP, et al. Transient neutropenia in children with febrile illness and associated infectious agents: 2 years' follow-up. Eur J Pediatr. 2013;172(6):811-9.
24. 25. Min KI, Byeon S. Diagnosis and management of neutropenia. Blood Res. 2025;60(1):30.
25. 26. Njue L, Porret N, Andres M, Rovó A. Isolated Chronic Neutropenia in Adults: Causes, Diagnostic Work-Up, and Management-A Narrative Review. J Clin Med. 2025;14(21):7495.
26. 27. Dobrewa W, Bielska M, Bąbol-Pokora K, Janczar S, Młynarski W. Congenital neutropenia: From lab bench to clinic bedside and back. Mutat Res Rev Mutat Res. 2024;793:108476.
27. 28. Xiao Y, Wang N, Jin X, Liu A, Zhang Z. Clinical relevance of SCN and CyN induced by ELANE mutations: a systematic review. Front Immunol. 2024;15:1349919.