Hematological Complications in Familial Mediterranean Fever: A Case Report and Literature Review
Abstract
Background: Familial Mediterranean Fever (FMF) is an inherited autoinflammatory disease caused by mutations in the MEFV gene. These patients typically present with lymphocytosis and thrombocytosis during periods of inflammation; however, some patients may manifest leukopenia along with other symptoms.
Methods: Demographic data, medical history, laboratory data, and genetic findings of the cases were collected by reviewing clinical records of the patient. Whole-genome sequencing test revealed a mutation in MEFV gene. A systematic searched was conducted in four databases: PubMed, Web of Science, Scopus, and PerQuest, using keywords related to blood abnormalities in FMF disease.
Results: A mutation in the MEFV gene was confirmed in a 29-year-old patient with FMF. He experienced periodic and regular decreases in the number of neutrophils, lymphocytes, and platelets during periods of inflammation. Our literature review revealed neutropenia (17.6%), lymphopenia (8.8%), thrombocytopenia (11.8%), leukopenia (61.8%), and anemia (20.6%) are the frequent most common hematologic complications. Genetic analysis in 28 patients revealed M694V as the most prevalent mutation (57.1%), followed by E148Q (21.4%), M680I (10.7%), and others.
Conclusions: Reporting this case and others highlights that hematological manifestations in FMF can be observed periodic and simultaneous decreases in neutrophils, lymphocytes, and platelet counts can in patients with FMF.
2. Goldfinger S. The inherited autoinflammatory syndrome: a decade of discovery. Trans Am Clin Climatol Assoc. 2009;120:413-8.
3. Tufan A, Lachmann HJ. Familial Mediterranean fever, from pathogenesis to treatment: a contemporary review. Turk J Med Sci. 2020;50(Si-2):1591-610.
4. Mitroulis I, Kourtzelis I, Kambas K, Chrysanthopoulou A, Ritis K. Evidence for the involvement of mTOR inhibition and basal autophagy in familial Mediterranean fever phenotype. Human Immunology. 2011;72(2):135-8.
5. Koca E, Buyukasik Y, Cetiner D, Yilmaz R, Sayinalp N, Yasavul U, et al. Copper deficiency with increased hematogones mimicking refractory anemia with excess blasts. Leuk Res. 2008;32(3):495-9.
6. Harris R, Marx G, Gillett M, Kark A, Arunanthy S. Colchicine-induced bone marrow suppression: Treatment with granulocyte colony-stimulating factor. Journal of Emergency Medicine. 2000;18(4):435-40.
7. Ben-Chetrit E, Navon P. Colchicine-induced leukopenia in a patient with familial Mediterranean fever: the cause and a possible approach. Clin Exp Rheumatol. 2003;21(4 Suppl 30):S38-40.
8. Sakallioglu O. Leucopenia resoluted with colchicine in familial mediterranean Fever. J Pediatr Hematol Oncol. 2012;34(2):162.
9. Guler AA, Inel TY, Kasifoglu T, Coskun C, Karadeniz H, Yildirim D, et al. COVID-19 in familial Mediterranean fever: Clinical course and complications related to primary disease. MODERN RHEUMATOLOGY. 2023;33(4):786-91.
10. Sag E, Bayindir Y, Adiguzel A, Demir S, Bilginer Y, Aytac S, et al. Colchicine and Leukopenia: Clinical Implications. J Pediatr. 2020;224:166-70.e1.
11. Finkelstein Y, Aks SE, Hutson JR, Juurlink DN, Nguyen P, Dubnov-Raz G, et al. Colchicine poisoning: the dark side of an ancient drug. Clin Toxicol (Phila). 2010;48(5):407-14.
12. Uruthirakumar R, Fagbola E, Tse TT, Moodie RG, Etoom Y, Laxer RM, et al. A 5-year-old girl with recurrent fever. Paediatrics and Child Health (Canada). 2019;24(6):368-70.
13. Kishida D, Yazaki M, Nakamura A, Nomura F, Kondo T, Uehara T, et al. One novel and two uncommon MEFV mutations in Japanese patients with familial Mediterranean fever: a clinicogenetic study. Rheumatology International. 2018;38(1):105-10.
14. Çakan M, Aktay-Ayaz N, Keskindemirci G, Karadağ ŞG. Two cases of periodic fever syndrome with coexistent mevalonate kinase and Mediterranean fever gene mutations. Turkish Journal of Pediatrics. 2017;59(4):467-70.
15. Aslan D. Leukopenia in familial Mediterranean fever: case series and literature review with special emphasis on pathogenesis. Pediatr Hematol Oncol. 2014;31(2):120-8.
16. Aslan D. Alpha thalassemia in a symptomatic carrier of familial mediterranean fever. Gazi Medical Journal. 2013;24(1):20-2.
17. Adragna F, Taormina G, Seidita A, D'Alcamo A, Randazzo G, Rini GB, et al. Periodic fever: A case report. Acta Medica Mediterranea. 2013;29(1):11-8.
18. Koo KY, Park SJ, Wang JY, Shin JI, Jeong HJ, Jin Lim B, et al. The first case of familial mediterranean fever associated with renal amyloidosis in Korea. Yonsei Medical Journal. 2012;53(2):454-8.
19. Tone Y, Toma T, Toga A, Sakakibara Y, Wada T, Yabe M, et al. Enhanced exon 2 skipping caused by c.910G>A variant and alternative splicing of MEFV genes in two independent cases of familial Mediterranean fever. Modern Rheumatology. 2011;22(1):45-51.
20. Lidar M, Zandman-Goddard G, Shinar Y, Zaks N, Livneh A, Langevitz P. Systemic lupus erythematosus and familial Mediterranean fever: A possible negative association between the two disease entities - Report of four cases and review of the literature. Lupus. 2008;17(7):663-9.
21. Schreiber BE, Lachmann HJ, Mackworth-Young CG. Possible familial Mediterranean fever in a Caucasian patient with systemic lupus erythematosus. Lupus. 2008;17(8):752-3.
22. Woodard J, Sleasman JW, Dorsey M. Selective B Cell Lymphopenia Associated with Systemic Amyloidosis in a Patient with Familial Mediterranean Fever. Clinical Immunology, suppl Suppl 1. 2008;127:1.
23. Tidjani KG, Ailal F, Najib J, Bellanné-Chantelot C, Donadieu J, Bousfiha AA. Intermittent chronic neutropenia in a patient with familial mediterranean fever. Pediatric Blood & Cancer. 2008;51(5):701-3.
24. Koca E, Buyukasik Y, Cetiner D, Yimaz R, Sayinalp N, Yasavul U, et al. Copper deficiency with increased hematogones mimicking refractory anemia with excess blasts. Leukemia Research. 2008;32(3):495-9.
25. Balbir-Gurman A, Nahir AM, Braun-Moscovici Y. Vasculitis in siblings with familial Mediterranean fever: A report of three cases and review of the literature. Clinical Rheumatology. 2007;26(7):1183-5.
26. Metin A, Ersoy F, Tinaztepe K, Beşbaş N, Tezcan I, Sanal O. Cyclic neutropenia complicated by renal AA amyloidosis. Turk J Pediatr. 2000;42(1):61-4.
| Files | ||
| Issue | Vol 8, No 4 (2025); in press | |
| Section | Original Article | |
| DOI | https://doi.org/10.18502/igj.v8i4.20104 | |
| Keywords | ||
| Familial Mediterranean Fever autoinflammatory disease hematological manifestations MEFV. | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
