Diagnostic signiffcance of the lymphocyte-monocyte index in Dupuytren's contracture

Introduction World literature data indicate the involvement of inflammatory cells in the pathogenesis of palmar fascial fibromatosis. However, there are no data on possible changes in peripheral blood leukocyte indices in patients with Dupuytren's contracture (DC) in comparison with healthy people.

Aim To assess the diagnostic significance of neutrophil-lymphocyte (N/L) and lymphocyte-monocyte (L/M) indices of peripheral blood in patients with CD.

Materials and methods 162 medical records of patients admitted for surgical treatment were retrospectively studied. To compare the results of their peripheral blood tests with the norm, anonymous leukocytograms of 110 apparently healthy individuals (control) were used.

Results In the group of healthy people and in patients with DC, sexual dimorphism of the absolute content of neutrophils was expressed. In DC males, a statistically significant decrease in the absolute content of lymphocytes (p = 0.05) was found, and in females, a significant increase in the absolute content of monocytes (p = 0.00) compared with the control, while in patients with DC there was no gender-related difference in these indicators, typical for healthy people. N/L ratio was elevated in DC males compared with controls (p = 0.05) and a subgroup of DC females (p = 0.01), but according to the results of ROC analysis, N/L ratio turned out to be diagnostically useless. For the model "L/M – degree of contracture" AUC 0.945, CI 0.918-0.970, p = 0, Se 90.12, Sp 93.21; optimal threshold L/M 3.102. In patients with low L/M (≤ 3.0), the frequency of lesions in both hands and the frequency of grade III-IV contractures are higher by 27.75 % (p = 0.02) and 27.15 % (p = 0.03), respectively than in the high L/M subgroup.

Discussion The multidirectional changes in the content of lymphocytes and monocytes in males and females is consistent with the literature data on dual gender-specific ways of regulating the immune system in healthy people and in patients with various diseases.

Conclusion The findings of the studied sample of patients show that the lymphocyte-monocyte index is a useful additional laboratory indicator for identifying a risk group for severe fascial fibromatosis. It can be used in clinical practice at no additional cost along with the well-known Dupuytren diathesis criteria to identify a risk group for progression of Dupuytren's contracture.

1. Meyerding HW, Black JR, Broders AC. The etiology and pathology of Dupuytren’s contracture. Surg Gynecol Obstet. 1941;72(3):582-590.

2. Vi L, Gan BS, O'Gorman DB. The potential roles of cell migration and extra-cellular matrix interactions in Dupuytren's disease progression and recurrence. Med Hypotheses. 2010;74(3):510-512. doi: 10.1016/j.mehy.2009.10.009

3. Salari N, Heydari M, Hassanabadi M, et al. The worldwide prevalence of the Dupuytren disease: a comprehensive systematic review and metaanalysis. J Orthop Surg Res. 2020;15(1):495. doi: 10.1186/s13018-020-01999-7

4. Murphey MD, Fairbairn KJ, Parman LM, et al. From the archives of the AFIP. Musculoskeletal angiomatous lesions: radiologic-pathologic correlation. Radiographics. 1995;15(4):893-917. doi: 10.1148/radiographics

5. Kraus R, Alzen G, Dreyer T, et al. Morbus dupuytren im kindesalter - fallbericht und literaturrecherche [Dupuytren's disease in children - case report and literature review]. Handchir Mikrochir Plast Chir. 2012;44(3):175-7. (In German) doi: 10.1055/s-0032-1312655

6. Nordenskjöld J, Englund M, Zhou C, Atroshi I. Prevalence and incidence of doctor-diagnosed Dupuytren's disease: a population-based study. J Hand Surg Eur Vol. 2017;42(7):673-677. doi: 10.1177/1753193416687914

7. Diep GK, Agel J, Adams JE. Prevalence of palmar fibromatosis with and without contracture in asymptomatic patients. J Plast Surg Hand Surg. 2015;49(4):247-250. doi: 10.3109/2000656X.2015.1034724

8. Ball C, Izadi D, Verjee LS, et al. Systematic review of non-surgical treatments for early dupuytren's disease. BMC Musculoskelet Disord. 2016;17(1):345. doi: 10.1186/s12891-016-1200-y

9. Denkler KA, Park KM, Alser O. Treatment Options for Dupuytren's Disease: Tips and Tricks. Plast Reconstr Surg Glob Open. 2022;10(1):e4046. doi: 10.1097/GOX.0000000000004046

10. Müller-Seubert W, Cai A, Arkudas A, et al. A Personalized Approach to Treat Advanced Stage Severely Contracted Joints in Dupuytren's Disease with a Unique Skeletal Distraction Device-Utilizing Modern Imaging Tools to Enhance Safety for the Patient. J Pers Med. 2022;12(3):378. doi: 10.3390/jpm12030378

11. Dutta A, Jayasinghe G, Deore S, et al. Dupuytren's Contracture - Current Concepts. J Clin Orthop Trauma. 2020;11(4):590-596. doi: 10.1016/j.jcot.2020.03.026

12. Satish L, Gallo PH, Baratz ME, et al. Reversal of TGF-β1 stimulation of α-smooth muscle actin and extracellular matrix components by cyclic AMP in Dupuytren's-derived fibroblasts. BMC Musculoskelet Disord. 2011;12:113. doi: 10.1186/1471-2474-12-113

13. van Beuge MM, Ten Dam EJ, Werker PM, Bank RA. Matrix and cell phenotype differences in Dupuytren's disease. Fibrogenesis Tissue Repair. 2016;9:9. doi: 10.1186/s13069-016-0046-0

14. Mayerl C, Del Frari B, Parson W, et al. Characterisation of the inflammatory response in Dupuytren's disease. J Plast Surg Hand Surg. 2016;50(3):171- 9. doi: 10.3109/2000656X.2016.1140054

15. Shchudlo NA, Varsegova TN, Stupina TA, Shchudlo MM. Types and stages of vascular remodeling in Dupuytren's contracture (analysis of 506 arteries in the surgical material of 111 patients). Genij Ortopedii. 2020;26(2):179-184. doi: 10.18019/1028-4427-2020-26-2-179-184

16. Shchudlo NA, Kostin VV. Pathogenesis of neuropathy in Dupuytren's contracture. Genij Ortopedii. 2019;25(1):58-64. doi: 10.18019/1028-4427-2019-25-1-58-64

17. Andrew JG, Andrew SM, Ash A, Turner B. An investigation into the role of inflammatory cells in Dupuytren's disease. J Hand Surg Br. 1991;16(3):267-271. doi: 10.1016/0266-7681(91)90051-o

18. Gudmundsson KG, Arngrímsson R, Arinbjarnarson S, et al. T-and B-lymphocyte subsets in patients with Dupuytren's disease. Correlations with disease severity. J Hand Surg Br. 1998;23(6):724-7. doi: 10.1016/s0266-7681(98)80083-1

19. Garcia Rojo E, García Gómez B, Santos-Pérez de la Blanca R, et al. Role of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in Peyronie's disease: a new diagnostic approach to predict the stage of the disease? Asian J Androl. 2021;23(3):325-329. doi: 10.4103/aja.aja_74_20

20. Chen Y, Zhang Y, Zhao G, et al. Difference in Leukocyte Composition between Women before and after Menopausal Age, and Distinct Sexual Dimorphism. PLoS One. 2016;11(9):e0162953. doi: 10.1371/journal.pone.0162953

21. Ruettermann M, Hermann RM, Khatib-Chahidi K, Werker PMN. Dupuytren's Disease-Etiology and Treatment. Dtsch Arztebl Int. 2021;118(46):781- 788. doi: 10.3238/arztebl.m2021.0325

22. Hueston J.T. Dupuytren diathesis. In: McFarlane RM, McGrouther DA, Flint M, eds. Dupuytren’s Disease Biology and Treatment. Edinburgh: Churchill Livingstone; 1990:246-252.

23. Abe Y, Rokkaku T, Ofuchi S, et al. An objective method to evaluate the risk of recurrence and extension of Dupuytren's disease. J Hand Surg Br. 2004;29(5):427-30. doi: 10.1016/j.jhsb.2004.06.004

24. Hindocha S, Stanley JK, Watson S, Bayat A. Dupuytren's diathesis revisited: Evaluation of prognostic indicators for risk of disease recurrence. J Hand Surg Am. 2006;31(10):1626-34. doi: 10.1016/j.jhsa.2006.09.006

25. Werker P, Dias J, Eaton C, eds. Dupuytren disease and related diseases - The cutting edge. Springer. 2017:450. doi: 10.1007/978-3-319-32199-8

26. Li P, Li H, Ding S, Zhou J. NLR, PLR, LMR and MWR as diagnostic and prognostic markers for laryngeal carcinoma. Am J Transl Res. 2022;14(5):3017-3027.

27. Romano A, Laura Parrinello N, Cerchione C, et al. The NLR and LMR ratio in newly diagnosed MM patients treated upfront with novel agents. Blood Cancer J. 2017;7(12):649. doi: 10.1038/s41408-017-0019-6

28. Miyahara Y, Takashi S, Shimizu Y, Ohtsuka M. The prognostic impact of neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) in patients with distal bile duct cancer. World J Surg Oncol. 2020;18(1):78. doi: 10.1186/s12957-020-01847-2

29. Huang Y, Liu Y, Mo G, et al. Inflammation Markers Have Important Value in Predicting Relapse in Patients with papillary thyroid carcinoma: A Long-Term Follow-Up Retrospective Study. Cancer Control. 2022;29:10732748221115236. doi: 10.1177/10732748221115236

30. Berghella AM, Contasta I, Del Beato T, Pellegrini P. The discovery of how gender influences age immunological mechanisms in health and disease, and the identification of ageing gender-specific biomarkers, could lead to specifically tailored treatment and ultimately improve therapeutic success rates. Immun Ageing. 2012;9(1):24. doi: 10.1186/1742-4933-9-24

31. Garcia Rojo E, García Gómez B, Santos-Pérez de la Blanca R, et al. Role of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in Peyronie's disease: a new diagnostic approach to predict the stage of the disease? Asian J Androl. 2021;23(3):325-329. doi: 10.4103/aja.aja_74_20

32. Özbir S, Değirmentepe RB, Atalay HA, et al. The role of inflammatory parameters (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-eosinophil ratio) in patients with Peyronie's disease. Andrology. 2020;8(2):348-352. doi: 10.1111/andr.12702

33. Greenberg JW, Kim J, Pincus J, et al. Are neutrophil-lymphocyte and platelet-lymphocyte ratios useful for determining active phase of Peyronie’s disease? Journal of Clinical Urology. 2022;0(0). doi: 10.1177/20514158221094636

34. Eftimie G, Eftimie R. Quantitative predictive approaches for Dupuytren disease: a brief review and future perspectives. Math Biosci Eng. 2022;19(3):2876-2895. doi: 10.3934/mbe.2022132

35. Plander M, Salamon A, Toldy E, et al. Cellular immune response in Dupuytren’s disease. Biochemia Medica. 2008;18(2):193-200.