Congenital Neutropenia and Periodontal Diseases: Links, Risks and Management

Yıl 2025, Cilt: 4 Sayı: 3, 181 - 189, 10.11.2025

Seçil Bozoğlan , Gülnur Emingil , Deniz Karapınar , Büşra Yılmaz , Özgün Özçaka Yüksel

https://doi.org/10.58711/turkishjdentres.vi.1737951

Öz

Congenital neutropenia is a rare disorder present at birth that causes a significant reduction in the number of neutrophil granulocytes. If the neutrophil count remains below 500 per microliter (μL) in peripheral blood for three months, the condition is defined as chronic neutropenia. Chronic neutropenia of congenital origin is termed congenital neutropenia . In Congenital neutropenia patients, the immune system’s capacity to defend against infections is considerably reduced. To date, more than
25 genetic mutations have been identified as causes of congenital neutropenia.
Periodontal diseases are chronic, multifactorial infections that begin with gingival inflammation
associated with microbial dental plaque and the host response, progressing with the destruction of supporting tissues. In patients with congenital neutropenia, the pathophysiology of periodontal diseases is associated with impaired infection defense and uncontrolled inflammation due to neutrophil deficiency. Persistently low neutrophil levels can cause severe oral problems such
as ulcerations of the oral mucosa, gingival inflammation, and rapid attachment loss. This clinical picture predisposes to progressive periodontal diseases such as periodontitis. Granulocyte colony-stimulating factor (G-CSF) therapy reduces infection risk by increasing neutrophil count; however, delayed or insufficient treatment may worsen periodontal disease severity. This review discusses the relationship between congenital neutropenia and periodontal diseases, underlying pathophysiological mechanisms, and periodontal treatment approaches in affected individuals. Multidisciplinary collaboration between hematologists and dentists is crucial for early diagnosis and effective treatment in congenital neutropenia patients.

Anahtar Kelimeler

Congenital Neutropenia , GranulocyteColony-Stimulating Factor , Periodontal Disease

Proje Numarası

yoktur

Konjenital Nötropeni ve Periodontal Hastalıklar: Bağlantılar, Riskler ve Yönetim

Öz

Konjenital nötropeni, doğuştan gelen ve nötrofil granülosit sayısında belirgin azalmaya neden olan
nadir bir hastalıktır. Periferik kanda üç ay boyunca mikrolitre (μL) başına 500’ün altında nötrofil sayısı
olması kronik nötropeni olarak tanımlanır. Kronik nötropeninin altta yatan doğumsal nedenlere bağlı olarak gelişmesi ise konjenital nötropeni olarak adlandırılır. Konjenital nötropeni hastalarında, bağışıklık sisteminin enfeksiyonlara karşı korunma kapasitesi ciddi düzeyde azalır. Günümüzde 25’ten fazla gen mutasyonu, konjenital nötropeniye yol açabilmektedir. Periodontal hastalıklar, mikrobiyal dental plak
ve konak yanıtı ile başlayan diş eti iltihabı ve destek dokuların yıkımı ile ilerleyen kronik, multifaktöriyel
enfeksiyonlardır. Konjenital nötropeni hastalarında periodontal hastalıkların patofizyolojisi, nötrofillerin
yetersizliği nedeniyle enfeksiyonlara karşı savunmanın zayıflaması ve enflamasyonun kontrol altına alınamaması ile ilişkilidir. Sürekli düşük seyreden nötrofil sayısı, oral mukozada ülserasyonlar, diş eti iltihabı ve hızlı ataşman kaybı gibi ciddi oral problemler yaratır. Bu durum, periodontitis gibi ilerleyici periodontal hastalıkların gelişmesine zemin hazırlar. Granülosit-koloni uyarıcı faktör (G-CSF) tedavisi, nötrofil sayısını artırarak enfeksiyon riskini azaltır. Ancak, geç kalınan veya yetersiz uygulanan tedavi periodontal hastalıkların şiddetini artırabilir. Bu derlemede, konjenital nötropeni ile periodontal
hastalıklar arasındaki ilişki, ilgili patofizyolojik mekanizmalar ve periodontal tedavi yaklaşımları
ele alınmaktadır. Konjenital nötropeni hastalarının tedavisinde hematolog ve diş hekimlerinin multidisipliner iş birliği, erken tanı ve etkin tedavi açısından kritik öneme sahiptir

Anahtar Kelimeler

konjenital nötropeni , granülosit -koloni uyarıcı faktör , periodontal hastalık

Etik Beyan

yoktur

Destekleyen Kurum

yoktur

Proje Numarası

yoktur

Kaynakça

• 1. Park MS, Tenenbaum HC, Dror Y, Gloguaer M. Oral Health Comparison Between Children With Neutropenia And Healthy Controls. Spec Care Dentist. 2014;34(1):12–18.
• 2. Donadieu J, Fenneteau O, Beaupain B, Mahlaoui N, Chantelot CB. Congenital Neutropenia: Diagnosis, Molecular Bases And Patient Management. Orphanet J Rare Dis. 2011;6(1):1–28.
• 3. Szczawinska-Poplonyk A, Gerreth K, Breborowicz A, Borysewicz-Lewicka M. Oral Manifestations Of Primary Immune Deficiencies In Children. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;108(3):e9–e20.
• 4. Tirali RE, Yalçınkaya-Erdemci Z, Çehreli SB. Oral Findings And Clinical Implications Of Patients With Congenital Neutropenia: A Literature Review. Turk J Pediatr. 2013;55:143–150.
• 5. Carlsson G, Åhlin A, Dahllöf G, Elinder G, Henter JI, Palmblad J. Efficacy And Safety Of Two Different rG-CSF Preparations In The Treatment Of Patients With Severe Congenital Neutropenia. Br J Haematol. 2004;126(1):127– 132.
• 6. Skokowa J, Dale DC, Touw IP, Zeidler C, Welte K. Severe Congenital Neutropenias. Nat Rev Dis Primers. 2017;3:17032.
• 7. Saǧlam F, Atamer T, Onan U, Soydinç M, Kiraç K. Infantile Genetic Agranulocytosis (Kostmann Type): A Case Report. J Periodontol. 1995;66(9):808–810.
• 8. Scott DA, Krauss J. Neutrophils In Periodontal Inflammation. Front Oral Biol. 2011;15:56–83.
• 9. Rijkschroeff P, Loos BG, Nicu EA. Oral Polymorphonuclear Neutrophil Contributes To Oral Health. Curr Oral Health Rep. 2018;5(4):211–218.
• 10. Papapanou PN, Sanz M, Buduneli N, et al. Periodontitis: Consensus Report Of Workgroup 2 Of The 2017 World Workshop On The Classification Of Periodontal And Peri-Implant Diseases And Conditions. J Periodontol. 2018;89(Suppl 1):S173–S182.
• 11. Righolt AJ, Jevdjevic M, Marcenes W, Listl S. Global-, Regional-, And Country-Level Economic Impacts Of Dental Diseases In 2015. J Dent Res. 2018;97(5):501–507.
• 12. Jepsen S, Caton JG, Albandar JM, et al. Periodontal Manifestations Of Systemic Diseases And Developmental And Acquired Conditions: Consensus Report Of Workgroup 3 Of The 2017 World Workshop On The Classification Of Periodontal And Peri-Implant Diseases And Conditions. J Periodontol. 2018;89(Suppl 1):S237–S248.
• 13. Bui FQ, Almeida-da-Silva CLC, Huynh B, et al. Association Between Periodontal Pathogens And Systemic Disease. Biomed J. 2019;42:27–35.
• 14. Bullon P, Newman HN, Battino M. Obesity, Diabetes Mellitus, Atherosclerosis And Chronic Periodontitis: A Shared Pathology Via Oxidative Stress And Mitochondrial Dysfunction? Periodontol 2000. 2014; 64:139–153.
• 15. Beck JD, Papapanou PN, Philips KH, Offenbacher S. Periodontal Medicine: 100 Years Of Progress. J Dent Res. 2019;98:1053–1062.
• 16. Tozum T, Berker A, Ersoy F, Tezcan I, Sanal O. The Relationship Between Periodontal Status And Peripheral Levels Of Neutrophils In Two Consanguineous Siblings With Severe Congenital Neutropenia: Case Reports. J Periodontol. 2005;76(9):1651–1657.
• 17. Krasuska-Sławińska E, Klaudel-Dreszler M, Minota M, Pożyczka-Fedor M, Olczak-Kowalczyk D, Minko- Chojnowska I. Manifestation Of Severe Congenital Neutropenia In The Oral Cavity: Case Report. Cent Eur J Immunol. 2013;48:70–74.
• 18. Antonio AG, Alcantara PCDC, Ramos MEB, De Souza IPR. The Importance Of Dental Care For A Child With Severe Congenital Neutropenia: A Case Report. Spec Care Dentist. 2010;30:261–265.
• 19. Goultschin J, Attal U, Goldstein M, Boyan BD, Schwartz Z. The Relationship Between Peripheral Levels Of Leukocytes And Neutrophils And Periodontal Disease Status In A Patient With Congenital Neutropenia. J Periodontol. 2000;71(9):1499–1505.
• 20. Hajishengallis E, Hajishengallis G. Neutrophil Homeostasis And Periodontal Health In Children And Adults. J Dent Res. 2014;93(3):231–237.
• 21. Zaromb A, Chamberlain D, Schoor R, Almas K, Blei F. Periodontitis As A Manifestation Of Chronic Benign Neutropenia. J Periodontol. 2006;77(11):1921–1926.
• 22. Tao SY, Yao M, Dong YL, Lin XJ, Sunchuri D, Guo ZL. Oral Health Management In Children With Severe Congenital Neutropenia With Periodontitis: Case Report. Medicine (Baltimore). 2024;103:e39086.
• 23. Goultschin J, Attal U, Goldstein M, Boyan BD, Schwartz Z. The Relationship Between Peripheral Levels Of Leukocytes And Neutrophils And Periodontal Disease Status In A Patient With Congenital Neutropenia. J Periodontol. 2000;71(9):1499–1505.
• 24. Ye Y, Carlsson G, Wondimu B, et al. Mutations In The ELANE Gene Are Associated With Development Of Periodontitis In Patients With Severe Congenital Neutropenia. J Clin Immunol. 2011;31(6):936–944.
• 25. Halai H, Somani C, Donos N, Nibali L. Periodontal Status Of Children With Primary Immunodeficiencies: A Systematic Review. Clin Oral Investig. 2020;24(6):1939– 1951.
• 26. Lebel A, Yacobovich J, Krasnov T, et al. Genetic Analysis And Clinical Picture Of Severe Congenital Neutropenia In Israel. Pediatr Blood Cancer. 2015;62(1):103–108.
• 27. Coşkun S, Yılmaz Ş, Çırakoğlu A, et al. Miyelodisplastik Sendromlu Olguların Kan Ve Kemik İliği Örneklerinin Konvansiyonel Sitogenetik Ve Floresan In Situ Hibridizasyon (FISH) Yöntemiyle İncelenmesi. Istanbul Univ Inst Health Sci J Adv Res Health Sci. 2020;3(3):122– 129.
• 28. Dale DC. How I Diagnose And Treat Neutropenia. Curr Opin Hematol. 2016;23(1):1–4.
• 29. Schilke R, Adam K, Zeidler C, Mellor-Heineke S. Parodontitis Als Manifestation Von Neutropenie. Parodontologie. 2024;35(3):183–205.
• 30. Hauck F, Klein C. Pathogenic Mechanisms And Clinical Implications Of CongenitalNeutropenia Syndromes. Curr Opin Allergy Clin Immunol. 2013;13(6):596–606.
• 31. Hakki SS, Aprikyan AAG, Yildirim S, et al. Periodontal Status In Two Siblings With Severe Congenital Neutropenia: Diagnosis And Mutational Analysis Of The Cases. J Periodontol. 2005;76(5):837–844.
• 32. Aydoğdu S, Çelik A, Karakaş Z. How To Approach Neutropenia. J Child. Published Online 2016.
• 33. Carlsson G, Fasth A. Infantile Genetic Agranulocytosis, Morbus Kostmann: Presentation Of Six Cases From The Original “Kostmann Family” And A Review. Acta Paediatr. 2001;90(7):757–764.
• 34. Goultschin J, Attal U, Goldstein M, Boyan BD, Schwartz Z. The Relationship Between Peripheral Levels Of Leukocytes And Neutrophils And Periodontal Disease Status In A Patient With Congenital Neutropenia. J Periodontol. 2000;71(9):1499–1505.
• 35. Skokowa J, Zeidler C, Welte K. Chronic Neutropenia In Childhood. Monatsschr Kinderheilkd. 2018;166(11):977– 986.
• 36. Allen RC, Stevens PR, Price TH, Chatta GS, Dale DC. In Vivo Effects Of Recombinant Human Granulocyte Colony- Stimulating Factor On Neutrophil Oxidative Functions In Normal Human Volunteers. J Infect Dis. 1997;175:1184– 1192.
• 37. Pogozhykh D, Yilmaz Karapinar D, Klimiankou M, et al. HAX1-Related Congenital Neutropenia: Long-Term Observation In Paediatric And Adult Patients Enrolled In The European Branch Of The Severe Chronic Neutropenia International Registry (SCNIR). Br J Haematol. 2023;202(2):393–411.
• 38. Carlsson G, Wahlin YB, Johansson A, et al. Periodontal Disease In Patients From The Original Kostmann Family With Severe Congenital Neutropenia. J Periodontol. 2006;77(4):744–751.
• 39. Nussbaum G, Shapira L. How Has Neutrophil Research Improved Our Understanding Of Periodontal Pathogenesis? J Clin Periodontol. 2011;38(Suppl 11):49–59.
• 40. Bao K, Li X, Poveda L, et al. Proteome And Microbiome Mapping Of Human Gingival Tissue In Health And Disease. Front Cell Infect Microbiol. 2020;10:588155.
• 41. Cheng WC, Saleh F, Abuaisha Karim B, Hughes FJ, Taams LS. Comparative Analysis Of Immune Cell Subsets In Peripheral Blood From Patients With Periodontal Disease And Healthy Controls. Clin Exp Immunol. 2018;194(3):380–390.
• 42. Slots J. Periodontitis: Facts, Fallacies And The Future. Periodontol 2000. 2017;75(1):7–23.
• 43. Consonni F, Gambineri E, Veltroni M, Callea M. Extensive Dental Caries And Periodontal Disease In A Child With GATA2 Deficiency. J Clin Exp Dent. 2023;15(9):e787– e790.
• 44. Baehni PC, Payot P, Tsai CC, Cimasoni G. Periodontal Status Associated With Chronic Neutropenia. J Clin Periodontol. 1983;10(2):222–230.
• 45. Consonni F, Gambineri E, Veltroni M, Callea M. Extensive Dental Caries And Periodontal Disease In A Child With GATA2 Deficiency. J Clin Exp Dent. 2023;15(9):e787– e790.
• 46. Pütsep K, Carlsson G, Boman HG, Andersson M. Deficiency Of Antibacterial Peptides In Patients With Morbus Kostmann: An Observation Study. Lancet. 2002;360:1144–1149.
• 47. Nilsson BO. What Can We Learn About Functional Importance Of Human Antimicrobial Peptide LL-37 In The Oral Environment From Severe Congenital Neutropenia (Kostmann Disease)? Peptides. 2020;128:170311.
• 48. Ye Y, Carlsson G, Karlsson-Sjöberg JMT, et al. The Antimicrobial Propeptide hCAP-18 Plasma Levels In Neutropenia Of Various Aetiologies: A Prospective Study. Sci Rep. 2015;5:11685.
• 49. Nakai Y, Ishihara C, Ogata S, Shimono T. Oral Manifestations Of Cyclic Neutropenia In A Japanese Child: Case Report With A 5-Year Follow-Up. Pediatr Dent. 2003;25(4):383–388.
• 50. Zaura E, Brandt BW, Buijs MJ, et al. Dysbiosis Of The Oral Ecosystem In Severe Congenital Neutropenia Patients. Proteomics Clin Appl. 2020;14(3):201900058.
• 51. Pogozhykh D, Yilmaz Karapinar D, Klimiankou M, et al. HAX1-Related Congenital Neutropenia: Long-Term Observation In Paediatric And Adult Patients Enrolled In The European Branch Of The Severe Chronic Neutropenia International Registry (SCNIR). Br J Haematol. 2023;202(2):393–411.
• 52. Cheretakis C, Locker D, Dror Y, Glogauer M. Oral Health- Related Quality Of Life Of Children With Neutropenia. Spec Care Dentist. 2007;27:6–11.
• 53. Topcuoglu N, Erdem AP, Karacan I, Kulekci G. Oral Microbial Dysbiosis In Patients With Kostmann Syndrome. J Med Microbiol. 2019;68:609–615.
• 54. Zaura E, Brandt BW, Buijs MJ, et al. Dysbiosis Of The Oral Ecosystem In Severe Congenital Neutropenia Patients. Proteomics Clin Appl. 2020;14(3):201900058.
• 55. Herrera D, Sanz M, Kebschull M, et al. Treatment Of Stage IV Periodontitis: The EFP S3 Level Clinical Practice Guideline. J Clin Periodontol. 2022;49(Suppl 24):4–71.
• 56. S3-Guideline (Full Version). Treatment Of Stage I–III Periodontitis: The German Implementation Of The S3- Guideline “Treatment Of Stage I–III Periodontitis” Of The European Federation Of Periodontology (EFP). AWMF Registry No. 083-043. Published December 2020. Valid Until November 2025.
• 57. Okada M, Kobayashi M, Hino T, Kurihara H, Miura K. Clinical Periodontal Findings And Microflora Profiles In Children With Chronic Neutropenia Under Supervised Oral Hygiene. J Periodontol. 2001;72(7):945–952.
• 58. S3 Guideline (Long Version). Implant Treatment For Oral Rehabilitation In Connection With Head And Neck Radiation. Association Of The Scientific Medical Societies (AWMF); Registration No. 007-089. Published December 2022. Valid Until December 2027.
• 59. Fernandes KS, da Silva Santos PS, de Rezende NPM, Gallottini M. Kostmann Syndrome: Oral Aspects And 10-Year Follow-Up Case Report. Spec Care Dentist. 2016;36:339–344.
• 60. Delgado V, Ajmone Marsan N, De Waha S, et al. 2023 ESC Guidelines For The Management Of Endocarditis. Eur Heart J. 2023;44:3948–4042.
• 61. Deutsche Society For Dental, Oral And Maxillofacial Medicine. Dental Implants In Patients With Immunodeficiency. Düsseldorf, Germany: DGZMK; 2025. Accessed July 2, 2025.
• 62. Jung S, Gies V, Korganow AS, et al. Primary Immunodeficiencies With Defects In Innate Immunity: Focus On Orofacial Manifestations. Front Immunol. 2020;11:1065.
• 63. Marín-Berná M, Velázquez-Cayón RT, Torres-Lagares D, et al. Failure In Implant Rehabilitation In A Patient With Severe Congenital Neutropenia (Kostmann Syndrome). J Oral Maxillofac Surg. 2012;70:268–272.
• 64. Teughels W, Feres M, Oud V, Martín C, Matesanz P, Herrera D. Adjunctive Effect Of Systemic Antimicrobials In Periodontitis Therapy: A Systematic Review And Meta- Analysis. J Clin Periodontol. 2020;47:257–281.