Retrospective Evaluation of Hemophagocytic Lymphohistiocytosis Cases Treated

Yıl 2020, Cilt: 18 Sayı: 1, 125 - 133, 15.04.2020

Aytül Temuroğlu , Melike Sezgin Evim , Betül Sevinir , Birol Baytan , Salih Güler , Adalet Meral Güneş

Öz

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare inflammatory syndrome resulting from uncontrolled proliferation in the monocyte / macrophage system. It is divided into two classes as familial (primary) and secondary. Since the rate of consanguineous marriage in our country is high with 29.2%, the frequency of HLH is also increasing. Secondary HLH can be seen at any age, but its true incidence is unknown. It can accompany malignancies, infections and inflammatory processes. Major clinical findings are persistent high fever, cytopenia, splenomegaly and / or hepatomegaly. The first finding is usually fever. The goal of treatment is to stop abnormal inflammation and treat the underlying cause.

MATERIALS and METHODS: We retrospectively reviewed 15 patients diagnosed and treated in our clinic between 2010 and 2019. Statistical analysis was performed with kruskal-wallis test.

RESULTS: The median age of diagnosis of 15 patients diagnosed and treated in our clinic was 18 months (1 month-17 years). The female to male ratio was 6/9. Fever was seen in all patients, hepatosplenomegaly was 80%. The mean ferritin value was 33.927 ± 51.461µ / l (964-201.074). In our patient group, consanguineous marriage rate was 53% (n = 8) and it was high and the factor was EBV in all patients who developed secondary to infection. 33% (n = 5) of the cases were primary and 67% (n = 10) were secondary. 40% (n = 4) of secondary cases had malignancy in etiology, 50% (n = 5) infection and 10% (n = 1) metabolic disease.

CONCLUSIONS: HLH is important for early diagnosis in cases with persistent high fever, hepatosplenomegaly and high ferritin conditions in our country. In cases presenting with HLH, malignancy should not be forgotten in etiology besides primary causes.

Anahtar Kelimeler

Hemophagocytic lymphohistiocytosis, cytopenia, hepatosplenomegaly

Hemofagositik Lenfohistiyositozisile Tedavi Edilen Olgularının Retrospektif Olarak Değerlendirilmesi

Öz

GİRİŞ ve AMAÇ: Hemofagositik lenfohistiyositoz (HLH) monosit/makrofaj sistemindeki kontrolsüz proliferasyon sonucu oluşan nadir görülen enflamatuar bir sendromdur. Ailesel (primer) ve sekonder olmak üzere iki sınıfa ayrılmaktadır. Ülkemizde akraba evliliği oranı %29.2 ile yüksek olduğu için HLH sıklığı da artmaktadır. Sekonder HLH her yaşta görülebilmekle beraber gerçek insidansı bilinmemektedir. Maligniteler, enfeksiyonlar ve inflamatuar süreçlere eşlik edebilir. Major klinik bulgular persistan yüksek ateş, sitopeni, splenomegali ve/veya hepatomegalidir. İlk bulgu genellikle ateştir. Tedavide amaç anormal inflamasyonu durdurmaktır ve altta yatan nedeni tedavi etmektir.

YÖNTEM ve GEREÇLER: Kliniğimizde 2010 ile 2019 yılları arasında tanı konulup tedavi edilen 15 hastayı retrospektif olarak değerlendirdik. İstatistiksel analiz kruskal- wallis testi ile yapıldı.

BULGULAR: Kliniğimizde tanı alıp tedavi edilen 15 hastanın ortanca tanı yaşı 18 aydı(1ay- 17 yaş). Olguların kız erkek oranı 6/9 idi. Ateş bütün hastalarda görüldü, hepatosplenomegali %80 oranında vardı. Ortalama ferritin değeri 33.927±51.461µ/l (964-201.074)idi. Hasta grubumuzda akraba evliliği oranı %53 (n=8) olup yüksekti ve enfeksiyona sekonder gelişen hastaların tümünde etken EBV idi. Olguların %33’ü (n=5) primer, %67’si(n=10) sekonderdi. Sekonder olguların %40’ında(n=4) etyolojide malignite, %50’sinde (n=5) enfeksiyon ve %10’unda (n=1) metabolik hastalık vardı.

TARTIŞMA ve SONUÇ: Ülkemiz koşullarında persistan yüksek ateş,hepatosplenomegali ve ferritin yüksekliği ile gelen olgularda HLH düşünülmesi erken tanı açısından önemlidir. HLH tablosu ile gelen olgularda primer nedenler yanı sıra etyolojide malignite de unutulmamalıdır

Anahtar Kelimeler

Hemofagositik lenfohistiyositoz, sitopeni, hepatosplenomegali

Kaynakça

• 1. Farquhar JW, Claireaux AE. Familial haemophagocytic reticulosis. Arch Dis Child. 1952; 27( 136): 519‐ 25.
• 2. Orkin S.H., Fisher D.E., Ginsburg D., Histiocytoses. In:Nathan and Oski’s Pediatric Hematology and Oncology of Infancy and Childhood. 8th edition. New York: Elsevier; 2015:2100-23
• 3. Nagafuji K, Nonami A, Kumano T, et al. Perforin gene mutations in adult-onset hemophagocytic lymphohistiocytosis. Haematologica. 2007;92(7): 978-81.
• 4. Lanzkowsy P , Arceci J.R .Histiocytosis Syndromes. In: Manual of Pediatric Hematology and Oncology. 5th ed. New York: Elsevier; 2011:567-98.
• 5. Duval M, Fenneteau O, Doireau V, et al. Intermittent hemophagocytic lymphohistiocytosis is a regular feature of lysinuric protein intolerance. J Pediatr 1999; 134: 236-9.
• 6. Ikeda H, Kato M, Matsunaga A, Shimizu Y, Katsuura M, Hayasaka K. Multiple sulphatase deficiency and haemophagocytic syndrome. Eur J Pediatr 1998; 157: 553-554.
• 7. HLH-2004: Diagnostic and Therapeutic Guidelines for Hemophagocytic Lymphohistiocytosis Pediatr Blood Cancer 2007;48:124–31.
• 8. Henter JI, Elinder G, Soder O, Ost A. Incidence in Sweden and clinical features of familial hemophagocytic lymphohistiocytosis. Acta Paediatr Scand. 1991;80(4):428–35.
• 9. Gürgey A, Göğüş S, Ozyürek E, Aslan D, Gümrük F, Cetin M et al. Primary hemophagocytic lymphohistiocytosis in Turkish children. Pediatr Hematol Oncol. 2003;20(5):367-71.
• 10. Kaya Z, Bay A, Albayrak M, Kocak U, Yenicesu I, Gursel T. Prognostic Factors and Long-Term Outcome in 52 Turkish Children With Hemophagocytic Lymphohistiocytosis. Pediatr Crit Care Med. 2015;16(6):165-73.
• 11. Zur Stadt U, Beutel K, Kolberg S, Schneppenheim R, Kabisch H, Janka G, Hennies HC. Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A. Hum Mutat. 2006;27:62-8
• 12. Burçin B. Hacettepe Üniversitesi Tıp Fakültesi Çocuk Hematoloji Ünitesi’nde izlenen familyal hemofagositik lenfohistiyositoz hastalarının değerlendirilmesi (Uzmanlık Tezi) Ankara: Hacettepe Üniversitesi;2013
• 13. George, Melissa R. Hemophagocytic lymphohistiocytosis: review of etiologies and management. Journal of blood medicine 5 (2014): 69.
• 14. Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124-31.
• 15. Özdemir, M. A., Torun, Y. A., Yıkılmaz, A., Karakükcü, M., Çoban, D. Hemofagositik lenfohistiositozda kranial MR ve proton MR spektroskopi bulguları. Çocuk Sağlığı ve Hastalıkları Dergisi, 2006; 49(4), 307-11.
• 16. Horne A, Trottestam H, Aricò M, et al. Frequency and spectrum of central nervous system involvement in 193 children with haemophagocytic lymphohistiocytosis. Br J Haematol 2008;140:327-35
• 17. Jordan MB, Allen CE, Greenberg J, Henry M, Hermiston ML, Kumar A et al. Challenges in the diagnosis of hemophagocytic lymphohistiocytosis: Recommendations from the North American Consortium for Histiocytosis (NACHO). Pediatr Blood Cancer. 2019 ;66(11):e27929