MODEL FOR PREDICTING THE DEVELOPMENT OF LYME ARTHRITIS IN PATIENTS WITH ERYTHEMA MIGRANS
DOI:
https://doi.org/10.11603/1811-2471.2025.v.i4.15809Keywords:
Lyme arthritis, erythema migrans, predictors of development, prognosis, multifactorial modelAbstract
SUMMARY. The aim – to propose a model for predicting the development of Lyme arthritis (MPDLA) in patients with erythema migrans, based on the presence of certain predictors.
Material and Methods. 51 patients with EM were examined. There were less men than women – 31.4 % versus 68.6 %, respectively, p<0.05. Patients were aged 18 to 66 years. Lyme borreliosis (LB) was diagnosed based on characteristic clinical and epidemiological data, in accordance with the recommendations of the current Standard of Medical Care “Lyme Disease.” A two-step method (ELISA and immunoblot) was used to detect specific IgM and/or IgG to B. burgdorferi s. l. in blood serum. The results were analyzed in accordance with the test system manufacturer's recommendations. The results obtained were calculated using parametric and nonparametric statistical methods with the calculation of Student's and Pearson's criteria using the computer programs “Microsoft Office Excel” and “STATISTICA”. Regression MPRLA was constructed using established predictors of Lyme arthritis development.
Results. To build a model for predicting the possibility of Lyme arthritis in ME patients, we used: patient age – X2; the location of tick bites – X5; the presence of serum antibodies of class M to: native flagellin p41 – X8, highly purified recombinant highly specific dimeric OspC (p25) Bb and Bsp – X11 and X13, respectively. A multivariate regression model was constructed taking into account the five reliable factors mentioned above, which have the most significant impact on MPDLA in patients with ME.
The reliability of the results obtained was assessed using Kruskal-Wallis one-way analysis of variance. An ANOVA analysis was performed to verify the acceptability of the model. A p-value of less than 0.05 was considered statistically significant. Based on the results obtained, a mathematical model was constructed to predict the development of Lyme arthritis in patients with ME.
Conclusions. For the first time, a model for predicting the future development of Lyme arthritis in patients with erythema migrans has been proposed. In patients with erythema migrans, the following predictors of the risk of developing Lyme arthritis have been reliably established: patient age, location of tick bites, presence of serum antibodies of class M to three Borrelia antigens: flagellin p41, highly purified recombinant highly specific dimeric OspC (p25) B. burgdorferi and B. spelmanii. Patients with erythema migrans are recommended to undergo two-stage serological diagnosis of LB to determine the factors of possible LB progression with the development of joint damage in the future.
References
Standart medychnoyi dopomohy. Khvoroba Layma [Standard of medical care. Lyme disease]. Infektsiyni khvoroby. 2024;(4):73–86. Ukrainian. DOI: 10.11603/1681-2727.2024.4.15009. DOI: https://doi.org/10.11603/1681-2727.2024.4.15009
Rochlin I, Toledo A. Emerging tick-borne pathogens of public health importance: a mini-review. J Med Microbiol. 2020;69(6):781–791. DOI: 10.1099/jmm.0.001206. DOI: https://doi.org/10.1099/jmm.0.001206
Bron GM, Fenelon H, Paskewitz SM. Assessing recognition of the vector of Lyme disease using resin-embedded specimens in a Lyme endemic area. J Med Entomol. 2021;58(2):866–872. DOI: 10.1093/jme/tjaa234. DOI: https://doi.org/10.1093/jme/tjaa234
Radolf JD, Strle K, Lemieux JE, Strle F. Lyme disease in humans. Curr Issues Mol Biol. 2021;42:333–384. DOI: 10.21775/cimb.042.333. DOI: https://doi.org/10.21775/cimb.042.333
Karvonen K, Nykky J, Marjomäki V, Gilbert L. Distinctive evasion mechanisms to allow persistence of Borrelia burgdorferi in different human cell lines. Front Microbiol. 2021;12:711291. DOI: 10.3389/fmicb.2021.711291. DOI: https://doi.org/10.3389/fmicb.2021.711291
Wachter J, Martens C, Barbian K, et al. Epigenomic landscape of Lyme disease spirochetes reveals novel motifs. mBio. 2021;12(3):e0128821. DOI: 10.1128/mBio.01288-21. DOI: https://doi.org/10.1128/mBio.01288-21
Trevisan G, Cinco M, Ruscio M, et al. Borrelia Lyme group. J Dermatol Res Rev Rep. 2022;3(3):1–12. DOI: https://doi.org/10.47363/JDMRS/2022(3)142
Trevisan G, Cinco M, Trevisini S, et al. Borreliae part 1: Borrelia Lyme group and Echidna-reptile group. Biology (Basel). 2021;10(10):1036. DOI: 10.3390/biology10101036. DOI: https://doi.org/10.3390/biology10101036
Trevisan G, Cinco M, Trevisini S, et al. Borreliae part 2: Borrelia Relapsing Fever Group and Unclassified Borrelia. Biology (Basel). 2021;10(10):1117. DOI: 10.3390/biology10111117. DOI: https://doi.org/10.3390/biology10111117
Coipan EC, Jahfari S, Fonville M, et al. Imbalanced presence of Borrelia burgdorferi s.l. multilocus sequence types in clinical manifestations of Lyme borreliosis. Infect Genet Evol. 2016;42:66–76. DOI: https://doi.org/10.1016/j.meegid.2016.04.019
Sprong H, Azagi T, Hoornstra D, et al. Control of Lyme borreliosis and other Ixodes ricinus–borne diseases. Parasites Vectors. 2018;11(1):145. DOI: 10.1186/s13071-018-2744-5. DOI: https://doi.org/10.1186/s13071-018-2744-5
Nebohatkin IV, Shul'han AM. Epidemiolohichni y epizootychni osoblyvosti khvoroby Layma u 2019 rotsi v Ukrayini [Epidemiological and epizootic features of Lyme disease in Ukraine in 2019]. Aktual'na infektolohiya. 2020;8(5–6):57–61. Ukrainian.
Petruk AM. Kliniko-patohenetychni osoblyvosti hostroyi kropyv'yanky, poyednanoyi z Laym-boreliozom i lyambliozom, optymizatsiya diahnostyky ta terapiyi. Dysertatsiya doktora filosofiyi z medytsyny [Clinical and pathogenetic features of acute urticaria combined with Lyme borreliosis and giardiasis, optimization of diagnostics and therapy. PhD thesis in medicine]. Ternopil: Ternopil National Medical University; 2020. Ukrainian.
Wojciechowska-Koszko I, Mnichowska-Polanowska M, Kwiatkowski P, et al. Immunoreactivity of Polish Lyme disease patient sera to specific Borrelia antigens – part 1. Diagnostics. 2021;11(11):2157. DOI: 10.3390/diagnostics11112157. DOI: https://doi.org/10.3390/diagnostics11112157
Steinbrink A, Brugger K, Margos G, et al. The evolving story of Borrelia burgdorferi sensu lato transmission in Europe. Parasitol Res. 2022;121:781–803. DOI: 10.1007/s00436-022-07445-3. DOI: https://doi.org/10.1007/s00436-022-07445-3
Dong Y, Zhou G, Cao W, et al. Global seroprevalence and sociodemographic characteristics of Borrelia burgdorferi sensu lato in human populations: a systematic review and meta-analysis. BMJ Glob Health. 2022;7(6):e007744. DOI: 10.1136/bmjgh-2021-007744. DOI: https://doi.org/10.1136/bmjgh-2021-007744
Zadorozhna VI, Rudenko AO, Klius VYu. Laym-borelioz – osoblyvo nebezpechna infektsiya. Zahrozy ta ryzyky [Lyme borreliosis – a particularly dangerous infection. Threats and risks]. Veterynarna medytsyna. 2017;(103):30–32. Ukrainian.
Kozlovska A. Laym-borelioz: suchasni pryntsypy likuvannya vid A do Ya. [Lyme borreliosis: modern principles of treatment from A to Z. Clinical immunology]. Klinichna imunolohiya. Alerholohiya. Infektolohiya. 2020;(5):34–39. Ukrainian.
Leeflang MM, Ang CW, Berkhout J, et al. The diagnostic accuracy of serological tests for Lyme borreliosis in Europe: a systematic review and meta-analysis. BMC Infect Dis. 2016;16:140. DOI: https://doi.org/10.1186/s12879-016-1468-4
Lohr B, Fingerle V, Norris DE, Hunfeld KP. Laboratory diagnosis of Lyme borreliosis: current state of the art and future perspectives. Crit Rev Clin Lab Sci. 2018;55(4):219–245. DOI: https://doi.org/10.1080/10408363.2018.1450353
Wojciechowska-Koszko I, Kwiatkowski P, Sienkiewicz M, et al. Cross-reactive results in serological tests for borreliosis in patients with active viral infections. Pathogens. 2022;11(2):203. DOI: 10.3390/pathogens 11020203. DOI: https://doi.org/10.3390/pathogens11020203
Petruk AM. Kliniko-epidemiolohichni osoblyvosti ta imunni zrushennya u khvorykh na kropyvyanku [Clinico-epidemiological features and immune changes in patients with urticaria]. Medychna ta klinichna khimiya. 2022;24(2):43–48. Ukrainian.
Nabir reahentiv dlya vyznachennya antytil lyudyny klasu M do antyheniv Borrelia burgdorferi s.l. metodom imunoblotynhu EUROLINE Borrelia RN-AT adv. [Reagent set for the determination of human class M antibodies to Borrelia burgdorferi s.l. antigens by immunoblotting EUROLINE Borrelia RN-AT adv.]. Ukrainian. URL: https://www.euroimmun.co.jp/fileadmin/Subsidiaries/Japan/Documents/IFU/IFU_DN_2131-3201-2_M.pdf.
Chukur O, Pasyechko N, Bob A, Sverstiuk A. Prediction of climacteric syndrome development in perimenopausal women with hypothyroidism. Menopause Rev/Przegląd Menopauzalny. 2022;21(4):236–241. DOI: 10.5114/ pm.2022.123522. DOI: https://doi.org/10.5114/pm.2022.123522
Mead P, Petersen J, Hinckley A. Updated CDC recommendation for serologic diagnosis of Lyme disease. MMWR Morb Mortal Wkly Rep. 2019;68:703. DOI: 10.15585/ mmwr.mm6832a4. DOI: https://doi.org/10.15585/mmwr.mm6832a4
