PRIMARY EBV INFECTION AND HEMATOLOGICAL FINDINGS IN TURKISH CHILDREN: A RETROSPECTIVE, SINGLE-CENTER STUDY

Öz

Abstract Aim: Primary infection with EBV during childhood is usually asymptomatic. Hematologic abnormalities such as hemolytic anemia, thrombocytopenia, and neutropenia are relatively common, but aplastic anemia, severe thrombocytopenia, severe neutropenia, and lymphoid malignancies are rare. In this retrospective study, we have analyzed data from children with primary EBV infection who were examined at our center over 12 years to describe the distribution, clinical features, complications, and outcome of EBV in Turkish children. Materials and Methods: Data from all children (age<18 years) with primary EBV infection who were examined in our center between 2008 and 2020 were retrospectively reviewed. Results: In total, 120 patients were included in the study. Anemia was detected in 13 (11%) children. Mild and severe neutropenia was detected in 12 (10%) and 1 (0.8%) children, respectively. Mild thrombocytopenia without bleeding complications was present in 10 (8%) children with a mean platelet count of 250x109/L ±113x109/L. Seven patients presented with acute idiopathic thrombocytopenia (lowest platelet count, 2x109/L). Large diffuse cell lymphoma developed in 0.8% (n:1) patients. Conclusion: The prognosis for infectious mononucleosis is excellent, although various acute complications may occur. However, severe complications are very rare, and most of the complications resolve spontaneously without certain therapy.

Anahtar Kelimeler

• Primary EBV infection
• Turkish children
• Hematologic findings

TÜRK ÇOCUKLARINDA PRİMER EBV ENFEKSİYONU VE HEMATOLOJİK BULGULARI: RETROSPEKTİF TEK MERKEZLİ BİR ÇALIŞMA

Öz

Özet Amaç: Çocukluk döneminde EBV ile birincil enfeksiyon genellikle asemptomatiktir. Hemolitik anemi, trombositopeni ve nötropeni gibi hematolojik anormallikler nispeten yaygındır, ancak aplastik anemi, şiddetli trombositopeni, şiddetli nötropeni ve lenfoid maligniteler nadirdir. Bu retrospektif çalışmada, EBV'nin Türk çocuklarındaki dağılımını, klinik özelliklerini, komplikasyonlarını ve sonuçlarını tanımlamak için 12 yıl boyunca merkezimizde izlenen primer EBV enfeksiyonu olan çocuklardan elde edilen verileri analiz ettik. Gereç ve Yöntemler: Hastanemizde 2008-2020 yılları arasında izlenen primer EBV enfeksiyonlu tüm çocuklara (18 yaş altı) ait veriler retrospektif olarak incelendi. Bulgular: Çalışmaya toplam 120 hasta dahil edildi. 13 (%11) çocukta anemi saptandı. 12 (%10) çocukta hafif, 1 (%0,8) çocukta şiddetli nötropeni saptandı. Ortalama trombosit sayısı 250x109/L ±113x109/L olan 10 (%8) çocukta kanama komplikasyonu olmaksızın hafif trombositopeni mevcuttu. Yedi hasta akut idiyopatik trombositopeni (en düşük trombosit sayısı, 2x109/L) ile başvurdu. Hastaların %0,8'inde (n:1) büyük diffüz hücreli lenfoma gelişti. Tartışma: Çeşitli akut komplikasyonlar oluşabilmesine rağmen enfeksiyöz mononükleozun prognozu mükemmeldir. Bununla birlikte, ciddi komplikasyonlar çok nadirdir ve komplikasyonların çoğu belirli bir tedavi olmaksızın kendiliğinden düzelir.

Anahtar Kelimeler

• Primer EBV enfeksiyonu
• Türk çocukları
• Hematolojik bulgular

Kaynakça

1. 1.Straus S. E, Cohen J. I, Tosato G, & Meier J. Epstein-Barr virus infections: biology, pathogenesis, and management. Ann Intern Med 1993;118:45-58.
2. 2. Chang R. S, Char D. F, Jones J. H, Halstead S. B. Incidence of infectious mononucleosis at the Universities of California and Hawaii. J Infect Dis 1979;140:479-486.
3. 3. Dan R, Chang R. S. A prospective study of primary Epstein-Barr virus infections among university students in Hong Kong. Am J Trop Med Hyg 1990;42:380-385.
4. 4. Day N. E, Geser A, Lavoué M. F, Ho J. H, Simons M. J, et al. Sero-epidemiology of the Epstein-Barr virus: preliminary analysis of an international study-a review. IARC Sci Publ 1975;11:3-16.
5. 5. Biggar R. J, Henle G, Böcker J, Lennette E. T, Fleisher G, et al. Primary Epstein Barr virus infections in African infants. II. Clinical and serological observations during seroconversion. Int J Cancer 978;22:244-250.
6. 6. Fugl A, Andersen C. L. Epstein-Barr virus and its association with disease-a review of relevance to general practice. BMC Fam Pract 2019;20:62-69.
7. 7. Longnecker R, Kieff E, Cohen JI. Epstein-barr virus. In: Knipe DM, Howley PM, eds. Fields virology. Philadelphia: Lippincott Williams & Wilkins 2013:1898–959.
8. 8. Jenson HB. Acute complications of Epstein– Barr virus infectious mononucleosis. Curr Opin Pediatr 2000;12:263-268.

9. 9. Hammond WP, Harlan JM, Steinberg SE. Severe neutropenia in infectious mononucleosis. West J Med 1979;131:92–97.
10. 10. Hess R. D, Routine Epstein-Barr virus diagnostics from the laboratory perspective: still challenging after 35 years, J Clin Microbiol 2004;42:3381–3387.
11. 11. Khan G, Hashim MJ. Global burden of deaths from Epstein-Barr virus attributable malignancies 1990-2010. Infect Agent Cancer 2014;9:38-48.
12. 12. Hsu JL, Glaser SL. Epstein-barr virus-associated malignancies: epidemiologic patterns and etiologic implications. Crit Rev Oncol Hematol 2000;34:27-53.
13. 13. Bozlak S, Varkal M.A, Yildiz I, Toprak S, Karaman S, et al. Cervical lymphadenopathies in children: A prospective clinical cohort study. Int. J. Pediatr Otorhinolaryngol 2016;82:81–87.
14. 14. Celenk F, Gulsen S, Baysal E, Aytac I, Kul S, Kanlikama M. Predictive factors for malignancy in patients with persistent cervical lymphadenopathy. Eur Arch Oto-Rhino-Laryngol 2015;273:251–256.
15. 15. Karaman A, Karaman I, Cavusoglu Y.H, Erdogan D. The ongoing problem with peripheral lymphadenopathies: Which ones are malignant? Pediatr Surg. Int 2010;26:247–250.
16. 16. Glaser S. L, Lin R. J, Stewart S. L, Ambinder R. F, Jarrett R. F, et al. Epstein-Barr virus-associated Hodgkin’s disease: epidemiologic characteristics in international data. Int J Cancer 1997;70:375–82.
17. 17. Dinand V, Arya LS. Epidemiology of childhood Hodgkins disease: is it different in developing countries? Indian Pediatr 2006;43:141-7.
18. 18. Gandhi MK, Tellam JT, Khanna R. Epstein-Barr virus-associated Hodgkin’s lymphoma. Br J Haematol 2004;125:267- 81.
19. 19. Kennedy-Nasser AA, Hanley P, Bollard CM. Hodgkin disease and the role of the immune system. Pediatr Hematol Oncol 2011;28:176-86.
20. 20. Hjalgrim H, Askling J, Rostgaard K, Hamilton-Dutoit S, Frisch M, et al. Characteristics of Hodgkin's lymphoma after infectious mononucleosis. N Engl J Med 2003;349:1324–32.
21. 21. Okano M, Gross TG. Epstein-Barr virus-associated hemophagocytic syndrome and fatal infectious mononucleosis. Am J Hematol 1996;53:111–115.
22. 22. Ohshima K, Shimazaki K, Sugihara M, Haraoka S, Suzumiya J et al. Clinicopathological findings of virus-associated hemophagocytic syndrome in bone marrow: association with Epstein-Barr virus and apoptosis. Pathol Int 1999;49:533–540.
23. 23. Connelly KP, DeWitt LD. Neurologic complications of infectious mononucleosis. Pediatr Neurol 1994;10:181-4.
24. 24. Chan CW, Chiang AK, Chan KH, Lau AS. Epstein-Barr virus-associated infectious mononucleosis in Chinese children. Pediatr Infect Dis J 2003;22:974-8.
25. 25. Henle G, Henle W. Observations on childhood infections with the Epstein-Barr virus. J Infect Dis 1970;121:303–310.
26. 26. Marsh RA. Epstein–Barr virus and hemophagocytic lymphohistiocytosis. Front Immunol 2018;8:1902-1911.
27. 27. Dumancas C. Y, Reyes H. A. G, Cosico J, Savadkar A, Lah S. Streptococcus pneumonia related hemophagocytic lymphohistiocytosis treated with intravenous immunoglobulin (IVIG) and steroids. Am J Case Rep 2018;19:25–28.
28. 28. Hernández-Jiménez P, Díaz-Pedroche C, Laureiro J, Madrid O, Martín E, Lumbreras C. Hemophagocytic lymphohistiocytosis: analysis of 18 cases. Med Clın (English Edition) 2016;147:495–498.
29. 29. Lossius A, Johansen J. N, Torkildsen Ø, Vartdal F, Holmøy T. Epstein---Barr virus in systemic lupus erythematosus, rheuma-toid arthritis and multiple sclerosis association and causation. Viruses 2012;4:3701-3730.
30. 30. Thomas D, Karachaliou F, Kallergi K, Vlachopapadopoulou E, Antonaki G, et al. Herpes virus antibodies sero prevalence in children with autoimmune thyroid disease. Endocrine 2008;33:171–5.
31. 31. Akahori H, Takeshita Y, Saito R, Kaneko S, Takamura T. Graves' disease associated with infectious mononucleosis due to primary Epstein-Barr virus infection: report of 3 cases. Intern Med 2010;49:2599–603.
32. 32. Keles S, Artac H, Kara R, Gokturk B, Ozen A, Reisli I. Transient hypogammaglobulinemia and unclassified hypogammaglobulinemia: 'similarities and differences'. Pediatr Allergy Immunol 2010;21:843-51.
33. 33. Saulsbury FT. Selective IgA deficiency temporally associated with Epstein-Barr virus infection. J Pediatr 1989;115:268-70.
34. 31. Swain S, Selmi C, Gershwin M. E, Teuber S. S. The clinical implications of selective IgA deficiency. J Transl Autoimmun 2019;2:100025.
35. 34. Goldacre MJ, Wotton CJ, Yeates DG. Associations between infectious mononucleosis and cancer: record-linkage studies. Epidemiol Infect 2009; 137:672–80.