MISSED DIAGNOSES AND THE SILENT ENEMY THREATENING OUR HEALTH: SOFT TISSUE RHEUMATIC DISEASES

Öz

Soft tissue rheumatic diseases (STRD) encompass a wide variety of conditions characterized by inflammation and degeneration of connective tissues surrounding joints, including muscles, tendons, and ligaments. This review examines the epidemiology, pathophysiology, clinical presentation, diagnostic criteria, and management strategies associated with STRD. Epidemiological studies indicate that these diseases have a significant prevalence in various populations due to the influence of genetic, environmental, and lifestyle factors. Pathophysiological mechanisms involve immune dysregulation and chronic inflammation, which can lead to symptoms such as pain, swelling, and functional impairment. Accurate diagnosis is quite challenging due to overlapping symptoms with other rheumatic diseases. Clinical evaluations require a comprehensive approach integrating imaging and laboratory tests. Management strategies for STRD are multifaceted, combining pharmacological interventions such as NSAIDs and DMARDs with non-pharmacological approaches like physical therapy and lifestyle modifications. Despite advances in treatment, significant research gaps remain, particularly regarding the prevalence and pathophysiology of emerging soft tissue disorders. This review emphasizes the importance of a collaborative, team-based approach to improve patient care and outcomes for individuals affected by STRD.

Anahtar Kelimeler

• Fibromyalgia
• Polymyalgia Rheumatica
• Degenerative Diseases
• Connective Tissues
• Inflammation

Kaynakça

1. 1. Olufemi A, Hakeem O, Olalade W, Sunday O, Oluwole A. Epidemiology of rheumatic and musculoskeletal diseases in a Nigerian peri-urban community: results of a cross-sectional survey using the COPCORD stage 1 model. Reumatologia. 2022;60(6):366-375. doi:10.5114/reum.2022.123667
2. 2. Misra D, Sharma A, Dharmanand B, Chandrashekara S. The epidemiology of rheumatic diseases in India. Indian J Rheumatol. 2024;19(1):54-61. doi:10.1177/09733698241229779
3. 3. Dilekçi E, Can G, Gürler M, Dilekçi E, Kayhan M. Does fibromyalgia affect the quality of life in patients with inflammatory bowel disease? J Health Sci Med. 2021;4(3):377-382. doi:10.32322/jhsm.913298 4. Peck MM, Maram R, Mohamed A, Ochoa Crespo D, Kaur G, Ashraf I, Malik BH. The Influence of Pro-inflammatory Cytokines and Genetic Variants in the Development of Fibromyalgia: A Traditional Review. Cureus. 2020;6;12(9):e10276. doi: 10.7759/cureus.10276. PMID: 33042712; PMCID: PMC7538208
4. 5. Mezhov V, Guymer E, Littlejohn G. Central sensitivity and fibromyalgia. Intern Med J. 2021;51(12): 1990-1998. doi: 10.1111/imj.15430. PMID: 34139045
5. 6. Nasuruddin DN, Hannoodee S. Acute Inflammatory Response. Stat Pearls. 2025. Bookshelf ID: NBK556083. PMID: 32310543
6. 7. Liu T, Zhang L, Joo D. NF-κB signaling in inflammation. Signal Transduct. Target. Ther. 2017;2:e17023. doi: 10.1038/sigtrans.2017.23. PMID: 29158945
7. 8. Iba T, Helms J, Maier CL, Levi M, Scarlatescu E, Levy JH. The role of thromboinflammation in acute kidney injury among patients with septic coagulopathy. J. Thromb. Haemost. 2024;22(6):1530-1540. doi: 10.1016/j.jtha.2024.02.006. PMID: 38382739
8. 9. Basil MC, Levy BD. Specialized pro-resolving mediators: endogenous regulators of infection and inflammation. Immunology. 2015;16(1):51–67. doi: 10.1038/nri.2015.4. PMID: 26688348

9. 10. Shin Y, Shin J, Moon S, et al. Autoimmune inflammatory rheumatic diseases and COVID-19 outcomes in South Korea: a nationwide cohort study. Lancet Rheumatol. 2021;3(10):e698-e706. doi:10.1016/s2665-9913(21)00151-x
10. 11. Ding L, Li X, Zhu H, Luo H. Single-cell sequencing in rheumatic diseases: new insights from the perspective of the cell type. Aging Dis. 2022;13(6):1633. doi:10.14336/ad.2022.0323.
11. 12. Alonso-Pérez A, Guillán-Fresco M, López-Fagúndez M, et al. Effect and regulation of obesity-associated low-grade chronic inflammation in major rheumatic diseases. Rheumato. 2022;2(4):114-125. doi:10.3390/rheumato2040016.
12. 13. Martin F, Blanco-Suárez M, Zambrano P, Cáceres O, Almirall M, Alegre-Martín J, Lobo B, González-Castro AM, Santos J, Domingo JC, Jurek J, Castro-Marrero J. Increased gut permeability and bacterial translocation are associated with fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome: implications for disease-related biomarker discovery. Front Immunol. 2023;7;14:1253121. doi: 10.3389/fimmu.2023.1253121. PMID: 37744357; PMCID: PMC10512706.
13. 14. Akiyama M, Alshehri W, Yoshimoto K, Kaneko Y. T follicular helper cells and T peripheral helper cells in rheumatic and musculoskeletal diseases. Ann Rheum Dis. 2023;82(11):1371-1381. doi:10.1136/ard-2023-224225. 15. Yang J, Liu F, Wang J, et al. Mesenchymal stem cells and mesenchymal stem cell-derived extracellular vesicles: potential roles in rheumatic diseases. World J Stem Cells. 2020;12(7):688-705. doi:10.4252/wjsc.v12.i7.688.
14. 16. Dhungana S, Pandey A, Aryal N, Kayastha K, Pandey S, Thakur M. A rare case report of coexisting rheumatic heart disease and systemic lupus erythematosus. Clin Case Rep. 2024;12(1). doi:10.1002/ccr3.8430.
15. 17. Gao Y, Dunlap G, Elahee M, Rao D. Patterns of T-cell phenotypes in rheumatic diseases from single-cell studies of tissue. Acr Open Rheumatol. 2021;3(9):601-613. doi:10.1002/acr2.11296.
16. 18. Perveen S, Samreen S, Gul H, Salim B, Nasim A. Effect of disease activity on the clinical outcome of SARS-CoV-2 in patients with underlying rheumatic diseases; data from global rheumatology alliance. J Pak Med Assoc. 2024;74(6):1055-1060. doi:10.47391/jpma.9371.
17. 19. Ruff W, Greiling T, Kriegel M. Host–microbiota interactions in immune-mediated diseases. Nat Rev Microbiol. 2020;18(9):521-538. doi:10.1038/s41579-020-0367-2.
18. 20. Dang Q, Watanabe R, Shiomi M, et al. Rheumatic immune-related adverse events due to immune checkpoint inhibitors a 2023 update. Int J Mol Sci. 2023;24(6):5643. doi:10.3390/ijms24065643.
19. 21. Cholerzyńska H, Zasada W, Tselios K, Grygiel-Górniak B. Sleep disorders in connective tissue diseases—coexisting diseases or disease components? J Clin Med. 2024;13(13):3656. doi:10.3390/jcm13133656.
20. 22. Fuentes M, Ruíz-Romero C, Misiego S, et al. Exploring high-throughput immunoassays for biomarker validation in rheumatic diseases in the context of the human proteome project. J Proteome Res. 2022;22(4):1105-1115. doi:10.1021/acs.jproteome.2c00387.
21. 23. Alghamdi M. Red blood cell distribution width: a potential inexpensive marker for disease activity in patients with rheumatic diseases; scoping review. Open Access Rheumatol Res Rev. 2023;15:173-180. doi:10.2147/oarrr.s424168.
22. 24. Haque H, Ahmed A, Uddin K, et al. Spectrum of rheumatologic disorders among patients attending with musculoskeletal symptoms: experience from medicine outpatient department of a tertiary care hospital of Bangladesh. Birdem Med J. 2021;11(2):116-120. doi:10.3329/birdem.v11i2.53131.
23. 25. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB, Yunus MB. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken). 2010 ;62(5):600-10. doi: 10.1002/acr.20140. PMID: 20461783. 26. Bhargava J, Goldin J. Fibromyalgia. [Updated 2025 Jan 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK540974 Access date: October 7, 2025.
24. 27. Royal College of Physicians, The Diagnosis of Fibromyalgia Syndrome UK Clinical Guidelines. the-diagnosis-of-fibromyalgia-syndrome-guidelines_1_2_0.pdf Access date: October 7, 2025.
25. 28. Kang JH, Choi SE, Park DJ, Lee SS. Disentangling Diagnosis and Management of Fibromyalgia. J Rheum Dis. 2022 Jan 1;29(1):4-13. doi: 10.4078/jrd.2022.29.1.4. PMID: 37476701; PMCID: PMC10324920.
26. 29. Winslow BT, Vandal C, Dang L. Fibromyalgia: Diagnosis and Management. Am Fam Physician. 2023 Feb;107(2):137-144. PMID: 36791450.
27. 30. Kang JH, Choi SE, Park DJ, Lee SS. Disentangling Diagnosis and Management of Fibromyalgia. J Rheum Dis. 2022 Jan 1;29(1):4-13. doi: 10.4078/jrd.2022.29.1.4. PMID: 37476701; PMCID: PMC10324920.
28. 31. American College of Rheumatology (ACR) 2016 Fibromyalgia Diagnostic Criteria. Fibromyalgia Diagnostic Criteria - PN2206048 Rev A Access date: October 7, 2025.
29. 32. Wolfe F, Clauw DJ, Fitzcharles M-A, Goldenberg DL, Häuser W, Katz RL, Mease PJ, Russell AS, Russell IJ, Walitt B. 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Seminars in Arthritis and Rheumatism. 2016; 46(3); 319–329. doi: 10.1016/j.semarthrit.2016.08.012.
30. 33. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Häuser W, Katz RL, Mease PJ, Russell AS, Russell IJ, Walitt B. 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum. 2016 Dec;46(3):319-329. doi: 10.1016/j.semarthrit.2016.08.012. Epub 2016 Aug 30. PMID: 27916278.
31. 34. Dasgupta B, Cimmino MA, Maradit-Kremers H, Schmidt WA, Schirmer M, Salvarani C, Bachta A, Dejaco C, Duftner C, Jensen HS, Duhaut P, Poór G, Kaposi NP, Mandl P, Balint PV, Schmidt Z, Iagnocco A, Nannini C, Cantini F, Macchioni P, Pipitone N, Amo MD, Espígol-Frigolé G, Cid MC, Martínez-Taboada VM, Nordborg E, Direskeneli H, Aydin SZ, Ahmed K, Hazleman B, Silverman B, Pease C, Wakefield RJ, Luqmani R, Abril A, Michet CJ, Marcus R, Gonter NJ, Maz M, Carter RE, Crowson CS, Matteson EL. 2012 provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Ann Rheum Dis. 2012;71(4):484-92. doi: 10.1136/annrheumdis-2011-200329. PMID: 22388996; PMCID: PMC3298664.
32. 35. Malik A, Kelam M, Sharma S. Prevalence and spectrum of rheumatological diseases in a newly formed peripheral medical college in northern India. Int J Res Med Sci. 2023;11(6):2077-2081. doi:10.18203/2320-6012.ijrms20231621. 36. Alkilany R, Einstadter D, Antonelli M. Urate-lowering therapy for patients with gout on hemodialysis. Int J Rheum Dis. 2022;25(7):769-774. doi:10.1111/1756-185x.14334.
33. 37. Çapkın E. Musculoskeletal ultrasonography in rheumatic diseases. Turk J Med Sci. 2023;53(6):1537-1551. doi:10.55730/1300-0144.5723.
34. 38. Weaver J, Omar I, Epstein K, et al. High-resolution ultrasound in the evaluation of musculoskeletal infections. J Ultrasonography. 2023;23(95):270-282. doi:10.15557/jou.2023.0034.
35. 39. Riaz M. Anti-rheumatic potential of biological DMARDs and protagonistic role of biomarkers in early detection and management of rheumatoid arthritis. Innate Immun. 2025;31. doi:10.1177/17534259251324820.
36. 40. Korol I, Baumeister R. Treating rheumatoid arthritis. JAAPA. 2023;36(9):1-5. doi:10.1097/01.jaa.0000937316.70181.ff.
37. 41. Andreica I, Blázquez-Navarro A, Sokolar J, et al. Different humoral but similar cellular responses of patients with autoimmune inflammatory rheumatic diseases under disease-modifying antirheumatic drugs after COVID-19 vaccination. RMD Open. 2022;8(2):e002293. doi:10.1136/rmdopen-2022-002293.
38. 42. Ren Y, Yang Q, Luo T, et al. Better clinical outcome of total knee arthroplasty for rheumatoid arthritis with glucocorticoids and disease-modifying anti-rheumatic drugs after an average of 11.4-year follow-up. doi:10.22541/au.158948937.78361509.
39. 43. Shu H, Chen X, Zhao J, Pin L, Sun Z. Efficacy and safety of tripterygium wilfordii glycosides tablets combined with western medicine for patients with rheumatic immune diseases. World J Clin Cases. 2025;13(6). doi:10.12998/wjcc.v13.i6.95513.
40. 44. D’Silva K, Wallace Z. COVID-19 and rheumatoid arthritis. Curr Opin Rheumatol. 2021;33(3):255-261. doi:10.1097/bor.0000000000000786.
41. 45. Sengler C, Eulert S, Niewerth M, et al. SARS-CoV-2 infections in children and adolescents with rheumatic musculoskeletal diseases – data from the national pediatric rheumatology database in Germany. doi:10.1101/2021.03.28.21254496.
42. 46. Sudoł-Szopińska I. Radiography in inflammatory arthritis: current roles and updates in automated assessment. Semin Musculoskelet Radiol. 2025;29(02):183-195. doi:10.1055/s-0045-1802349.
43. 47. Valladales-Restrepo L, Delgado-Araujo A, Aristizábal-Carmona B, Rivera L, Machado-Alba J. Autoimmune idiopathic inflammatory myopathies: pharmacological differences and similarities by type of myositis and by sociodemographic variables. Int J Rheumatol. 2022;2022:1-11. doi:10.1155/2022/1807571.
44. 48. Gao Y, Zhang Y, Liu X. Rheumatoid arthritis: pathogenesis and therapeutic advances. MedComm. 2024;5(3). doi:10.1002/mco2.509.
45. 49. Alhayali M. Successful treatment of refractory synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome with tofacitinib: a case report. Cureus. 2024. doi:10.7759/cureus.66169.
46. 50. Hill S, Frey N. Conventional disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis. Can J Health Technol. 2021;1(5). doi:10.51731/cjht.2021.72.
47. 51. Kerschbaumer A, Sepriano A, Smolen J, et al. Efficacy of pharmacological treatment in rheumatoid arthritis: a systematic literature research informing the 2019 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis. 2020;79(6):744-759. doi:10.1136/annrheumdis-2019-216656.
48. 52. Smolen J, Landewé R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020;79(6):685-699. doi:10.1136/annrheumdis-2019-216655.
49. 53. Barth K, Gill H, Singh N. Long-term safety of biologic and targeted synthetic disease-modifying drugs in rheumatology. Curr Opin Rheumatol. 2023;36(2):113-119. doi:10.1097/bor.0000000000000995.
50. 54. Anyfanti P, Angeloudi E, Pagkopoulou E, Bekiari E. JAK inhibition in patients with rheumatoid arthritis: haemodynamic effects and impact on micro- and macrovascular function. Study design and rationale. Mediterr J Rheumatol. 2022;33(4):471. doi:10.31138/mjr.33.4.471.
51. 55. Yos E, Hines E, Thomas M, Angeles C, Chetrit D. Fexofenadine as successful adjunctive treatment of rheumatoid arthritis and trochanteric bursitis: a case report. Cureus. 2024. doi:10.7759/cureus.69401.
52. 56. Sadri M, Esalatmanesh K, Khabbazi A. Efficacy of leflunomide in the treatment of palindromic rheumatism. Int J Rheum Dis. 2022;25(8):893-896. doi:10.1111/1756-185x.14364.
53. 57. Sidiropoulos P, Bounas A, Galanopoulos N, et al. Treatment satisfaction, patient preferences, and the impact of suboptimal disease control in rheumatoid arthritis patients in Greece: analysis of the Greek cohort of SENSE study. Mediterr J Rheumatol. 2022;33(1):14. doi:10.31138/mjr.33.1.14.
54. 58. Mutoh T, Nagai T, Shirai T, et al. Predictive factors for retention of golimumab over a median 4-year duration in Japanese patients with rheumatoid arthritis in a real-world setting: a retrospective study and literature review. Int J Rheum Dis. 2022;25(3):335-343. doi:10.1111/1756-185x.14281.
55. 59. Gul H, Matteo A, Anioke I, et al. Predicting flare in patients with rheumatoid arthritis in biologic-induced remission, on tapering, and on stable therapy. Acr Open Rheumatol. 2024;6(5):294-303. doi:10.1002/acr2.11656.
56. 60. Sahebari M, Mirfeizi Z, Shariati-Sarabi Z, et al. Influence of biologic and conventional disease-modifying antirheumatic drugs on COVID-19 incidence among rheumatic patients during the first and second wave of the pandemic in Iran. Reumatologia. 2022; 60(4): 231-241. doi:10.5114/reum.2022.119039.
57. 61. Imane EB, Salma B, Samira R, Hajar EA, Salma Z, Bouchra A, Rachid B. Insights into diagnosis and treatment of fibromyalgia among Moroccan rheumatologists: a cross sectional online survey. Reumatologia. 2025;20;63(3):166-173. doi: 10.5114/reum/201416. PMID: 40678027; PMCID: PMC12264735.
58. 62. Maidoub F, Ben Nessib D, Ferjani HL, Kaffel D, Triki W, Maatallah K, Hamdi W. Non-pharmacological therapies in Fibromyalgia: New horizons for physicians, new hopes for patients. Musculoskeletal Care. 2023;9. doi: 10.1002/msc.1741. Epub ahead of print. PMID: 36757930.
59. 63. Chadwick AL, Shi C, McMillan M, Miller J, Hu J, Geiger PC. The impact of a heat therapy intervention on pain and fibromyalgia symptoms in patients with fibromyalgia: a pilot study. Front Pain Res (Lausanne). 2025;13;6:1526491. doi: 10.3389/fpain.2025.1526491. PMID: 40182803; PMCID: PMC11966051.
60. 64. Rozenbajgier M, Wójcik-Grudzień J, Pawłowska P, Ozga-Stachurska A. Non-pharmacological therapy in fibromyalgia. Journal of Education Health and Sport. 2022;12(9):433-438. doi: 10.12775/JEHS.2022.12.09.049.