Abstract
Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease of childhood and adulthood. Development of systemic amyloidosis and frequent attack influence quality of life and survival. There is sporadic evidence indicating subclinical inflammation in patients with FMF. We aimed to assess subclinical inflammation using neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and C-reactive protein (CRP) in pediatric patients with FMF in the attack-free period. In this retrospective study, we reviewed the files of all FMF patients in our pediatric rheumatology outpatient clinic in a tertiary center and enrolled those with sufficient clinical and laboratory data. We also enrolled 73 controls. We grouped the patients according to being in attack period or attack-free period. We compared CRP, NLR, PLR, and WBC (white blood cell) levels between different mutations and polymorphisms. We also compared patients in the attack period with those in attack-free period. We enrolled 61 patients in attack period, 509 patients in attack-free period, and 73 controls. There was no difference between patients with different mutations with respect to NLR or PLR levels in the attack-free period. However, CRP levels were higher in patients with homozygous exon 10 mutations, especially those with homozygous M694V mutations compared with other mutations. However, CRP levels were mostly normal in these patients. Our data are against the reported fact that patients with FMF have higher NLR or PLR levels in attack-free periods. However, CRP levels were higher in the presence of homozygous exon 10 mutations (in particular homozygous M694V mutations).
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References
Ben-Chetrit E, Levy M (2001) Enigmas in familial Mediterranean fever (FMF). Clin Exp Rheumatol 19(5 Suppl 24):S1–S5
Samuels J, Aksentijevich I, Torosyan Y, Centola M, Deng Z, Sood R, Kastner DL, Familial Mediterranean fever at the millennium (1998) Clinical spectrum, ancient mutations, and a survey of 100 American referrals to the National Institutes of Health. Medicine (Baltimore) 77(4):268–297
Ben-Chetrit E, Peleg H, Aamar S, Heyman SN (2009) The spectrum of MEFV clinical presentations—is it familial Mediterranean fever only? Rheumatology (Oxford) 48(11):1455–1459
(1997) Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. The International FMF Consortium. Cell 90(4):797–807
Chae JJ, Aksentijevich I, Kastner DL (2009) Advances in the understanding of familial Mediterranean fever and possibilities for targeted therapy. Br J Haematol 146(5):467–478
Bakkaloglu A (2003) Familial Mediterranean fever. Pediatr Nephrol 18(9):853–859
Erer B, Demirkaya E, Ozen S, Kallinich T (2015) What is the best acute phase reactant for familial Mediterranean fever follow-up and its role in the prediction of complications? A systematic review. Rheumatol Int
Chua W, Charles KA, Baracos VE, Clarke SJ (2011) Neutrophil/lymphocyte ratio predicts chemotherapy outcomes in patients with advanced colorectal cancer. Br J Cancer 104(8):1288–1295
Papa A, Emdin M, Passino C, Michelassi C, Battaglia D, Cocci F (2008) Predictive value of elevated neutrophil–lymphocyte ratio on cardiac mortality in patients with stable coronary artery disease. Clin Chim Acta 395(1–2):27–31
Shimada H, Takiguchi N, Kainuma O, Soda H, Ikeda A, Cho A, Miyazaki A, Gunji H, Yamamoto H, Nagata M (2010) High preoperative neutrophil-lymphocyte ratio predicts poor survival in patients with gastric cancer. Gastric Cancer 13(3):170–176
Akpek M, Kaya MG, Lam YY, Sahin O, Elcik D, Celik T, Ergin A, Gibson CM (2012) Relation of neutrophil/lymphocyte ratio to coronary flow to in-hospital major adverse cardiac events in patients with ST-elevated myocardial infarction undergoing primary coronary intervention. Am J Cardiol 110(5):621–627
Sakallı H, Kal O (2013) Mean platelet volume as a potential predictor of proteinuria and amyloidosis in familial Mediterranean fever. Clin Rheumatol 32(8):1185–1190
Hu ZD, Chen Y, Zhang L, Sun Y, Huang YL, Wang QQ, Xu YL, Chen SX, Qin Q, Deng AM (2013) Red blood cell distribution width is a potential index to assess the disease activity of systemic lupus erythematosus. Clin Chim Acta 425:202–205
Zahorec R (2001) Ratio of neutrophil to lymphocyte counts—rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 102(1):5–14
Akbas EM, Demirtas L, Ozcicek A, Timuroglu A, Bakirci EM, Hamur H, Ozcicek F, Turkmen K (2014) Association of epicardial adipose tissue, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio with diabetic nephropathy. Int J Clin Exp Med 7(7):1794–1801
Özdel S, Özçakar ZB, Kunt S, Elhan AH, Yalçınkaya F (2016) Late-onset disease is associated with a mild phenotype in children with familial Mediterranean fever. Clin Rheumatol
The registry of hereditary auto-inflammatory disorders mutations (http://fmf.igh.cnrs.fr/ISSAID/infevers/search.php?n=1)
Sharaiha RZ, Halazun KJ, Mirza F, Port JL, Lee PC, Neugut AI, Altorki NK, Abrams JA (2011) Elevated preoperative neutrophil:lymphocyte ratio as a predictor of postoperative disease recurrence in esophageal cancer. Ann Surg Oncol 18(12):3362–3369
Azab B, Jaglall N, Atallah JP, Lamet A, Raja-Surya V, Farah B, Lesser M, Widmann WD (2011) Neutrophil-lymphocyte ratio as a predictor of adverse outcomes of acute pancreatitis. Pancreatology 11(4):445–452
Alkhouri N, Morris-Stiff G, Campbell C, Lopez R, Tamimi TA, Yerian L, Zein NN, Feldstein AE (2012) Neutrophil to lymphocyte ratio: a new marker for predicting steatohepatitis and fibrosis in patients with nonalcoholic fatty liver disease. Liver Int 32(2):297–302
Özer S, Yılmaz R, Sönmezgöz E, Karaaslan E, Taşkın S, Bütün İ, Demir O (2015) Simple markers for subclinical inflammation in patients with familial Mediterranean fever. Med Sci Monit 21:298–303
Uslu AU, Deveci K, Korkmaz S, Aydin B, Senel S, Sancakdar E, Sencan M (2013) Is neutrophil/lymphocyte ratio associated with subclinical inflammation and amyloidosis in patients with familial Mediterranean fever? Biomed Res Int 2013:185317
Demirkaya E, Erer B, Ozen S, Ben-Chetrit E (2016) Efficacy and safety of treatments in familial Mediterranean fever: a systematic review. Rheumatol Int 36(3):325–331
Touitou I (2013) Inheritance of autoinflammatory diseases: shifting paradigms and nomenclature. J Med Genet 50(6):349–359
Habahbeh LA, Hiary MA, Zaben SF, Al-Momani A, Khasawneh R, Mallouh MA, Farahat H (2015) Genetic profile of patients with familial Mediterranean fever (FMF): single center experience at King Hussein Medical Center (KHMC). Mediev Archaeol 69(6):417–420
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We thank David Chapman, who is the formal English editor of Istanbul University, Istanbul Faculty of Medicine, for the editing of the English in the document. All authors meet the criteria for authorship stated in the Uniform Requirements for Manuscripts Submitted to Clinical Rheumatology.
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Kelesoglu, F.M., Aygun, E., Okumus, N.K. et al. Evaluation of subclinical inflammation in familial Mediterranean fever patients: relations with mutation types and attack status: a retrospective study. Clin Rheumatol 35, 2757–2763 (2016). https://doi.org/10.1007/s10067-016-3275-0
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DOI: https://doi.org/10.1007/s10067-016-3275-0