Mild Course of Hemorrhagic Fever with Renal Syndrome in A Patient with HLA-B27 Positive-Spondylarthritis

Hemorrhagic fever with renal syndrome (HFRS) is an acute infectious disease of viral etiology, the main complication of which is severe kidney damage. The disease is characterized by a cyclic course, there are 4 periods (febrile, oliguric, polyuric, recollection). In Russia, the disease occurs almost everywhere, but endemic areas are the Far East, the Urals, and the Volga region. In the pathogenesis of the disease, the greatest significance is the development of vascular endothelial damage, where virus reproduction occurs, leading to increased permeability of the vascular wall with the development of hemorrhagic syndrome, edema. In addition, hemorrhages are promoted by a decrease in coagulation factors, as well as platelets. Cases of mild course of this disease in patients carrying the human leukocyte antigen (HLA)-B27 allele have been described in the literature. The aim of our article is to demonstrate a clinical case of mild course of HFRS in a patient with spondyloarthritis associated with HLA-B27. The patient presented with prolonged subfebrileitis as well as inguinal lymphadenopathy. The disease proceeded without kidney damage, development of hemorrhagic syndrome, which are characteristic manifestations of HFRS. Detected IgG and IgM to hantaviruses (causative agents of HFRS) confirmed the diagnosis. The patient had spondyloarthritis associated with HLA-B27, which, according to the literature, can make the clinical picture less vivid, which is observed in our case. Pathogenetic treatment with glucocorticoids resulted in regression of complaints and improvement of the patient’s condition. This article will be useful for specialists of different profiles, as the clinical picture of HFRS has many nonspecific symptoms that can be considered as manifestations of various diseases.

1. Morozov V.G., Ishmukhametov A.A., Dzagurova T.K. et al. Clinical manifestations of hemorrhagic fever with renal syndrome in Russia. Meditsinskiy sovet = Medical Council. 2017;(5):156-161 [In Russian]. https://doi.org/10.21518/2079-701X-2017-5-156-161

2. . Ivanov M.F. Haemorrhagic fever with renal syndrome as a socially significant naturally occurring infection. International Research Journal. 3(129), Mar. 2023. (In Russ.). DOI: 10.23670/IRJ.2023.129.6.

3. Borodina Zh.I., Tsarenko O.Ye., Monakhov K.M. et al. Hemorrhagic fever with renal syndrome: the challenge of our time. The Russian Archives of Internal Medicine. 2019; 9(6): 419-427. [In Russian]. DOI: 10.20514/2226-6704-2019-9-6-419-427.

4. Noh JY, Jung J, Song JW. Hemorrhagic Fever with Renal Syndrome. Infect Chemother. 2019 Dec;51(4):405-413. doi: 10.3947/ic.2019.51.4.405. Epub 2019 Oct 31. Erratum in: Infect Chemother. 2020 Jun;52(2):305-306. doi: 10.3947/ic.2020.52.2.305.

5. Lupuşoru G, Lupuşoru M, Ailincăi I et al. Hanta hemorrhagic fever with renal syndrome: A pathology in whose diagnosis kidney biopsy plays a major role (Review). Exp Ther Med. 2021 Sep;22(3):984. doi: 10.3892/etm.2021.10416.

6. Sehgal A, Mehta S, Sahay K et al. Hemorrhagic Fever with Renal Syndrome in Asia: History, Pathogenesis, Diagnosis, Treatment, and Prevention. Viruses. 2023 Feb 18;15(2):561. doi: 10.3390/v15020561.

7. Cho M.R., Hwang J.Y., Park H.S. Hantaan Virus Reduces the von Willebrand Factor in Human Umbilical Vein Endothelial Cells. J. Bacteriol. Virol. 2007 Dec; 4(37): 225-230. doi: 10.4167/jbv.2007.37.4.225

8. Khaiboullina SF, Morzunov SP, St Jeor SC et al. Hantavirus Infection Suppresses Thrombospondin-1 Expression in Cultured Endothelial Cells in a Strain-Specific Manner. Front Microbiol. 2016 Jul 19;7:1077. doi: 10.3389/fmicb.2016.01077.

9. Outinen TK, Laine OK, Mäkelä S et al. Thrombocytopenia associates with the severity of inflammation and variables reflecting capillary leakage in Puumala Hantavirus infection, an analysis of 546 Finnish patients. Infect Dis (Lond). 2016 Sep;48(9):682-7. doi: 10.1080/23744235.2016.1192719.

10. Koskela S, Mäkelä S, Strandin T et al. Coagulopathy in Acute Puumala Hantavirus Infection. Viruses. 2021 Aug 6;13(8):1553. doi: 10.3390/v13081553.

11. Plyusnin A, Hörling J, Kanerva M et al. Puumala hantavirus genome in patients with nephropathia epidemica: correlation of PCR positivity with HLA haplotype and link to viral sequences in local rodents. J Clin Microbiol. 1997 May;35(5):1090-6. doi: 10.1128/jcm.35.5.1090-1096.1997.

12. Evander M, Eriksson I, Pettersson L et al. Puumala hantavirus viremia diagnosed by real-time reverse transcriptase PCR using samples from patients with hemorrhagic fever and renal syndrome. J Clin Microbiol. 2007 Aug;45(8):2491-7. doi: 10.1128/JCM.01902-06.

13. Saksida A, Duh D, Korva M et al. Dobrava virus RNA load in patients who have hemorrhagic fever with renal syndrome. J Infect Dis. 2008 Mar 1;197(5):681-5. doi: 10.1086/527485.

14. Xiao R, Yang S, Koster F el al. Sin Nombre viral RNA load in patients with hantavirus cardiopulmonary syndrome. J Infect Dis. 2006 Nov 15;194(10):1403-9. doi: 10.1086/508494.

15. International Association of Professionals in Infection Control (IAPCI). Clinical guidelines. Hemorrhagic fever with renal syndrome in adults. 2016. [Electronic resource]. URL: https://libftp.mededtech.ru/GLPS/ (date of the application 31.03.2025) [In Russian]

16. Parameswaran P, Lucke M. HLA-B27 Syndromes. 2025. [Electronic resource] URL: https://www.ncbi.nlm.nih.gov/books/NBK551523/. (date of the application 29.03.2025)

17. Bowness P. HLA-B27. Annu Rev Immunol. 2015;33:29-48. doi: 10.1146/annurev-immunol-032414-112110.

18. Kaya S. Prognostic factors in hantavirus infections. Bulletin of microbiology. 2014 Jan;48(1):179-87. [In Turkish].

19. Korva M, Saksida A, Kunilo S et al. HLA-associated hemorrhagic fever with renal syndrome disease progression in slovenian patients. Clin Vaccine Immunol. 2011 Sep;18(9):1435-40. doi: 10.1128/CVI.05187-11. Epub 2011 Jul 20.

20. Mustonen J, Partanen J, Kanerva M et al. Association of HLA B27 with benign clinical course of nephropathia epidemica caused by Puumala hantavirus. Scand J Immunol. 1998 Mar;47(3):277-9. doi: 10.1046/j.1365-3083.1998.00302.x.