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Current Rheumatology Reviews


ISSN (Print): 1573-3971
ISSN (Online): 1875-6360

Research Article

Concomitant Diagnosis of Fibromyalgia and Ankylosing Spondylitis: Relation to Clinical Features and Plasma Pentraxin -3 Level

Author(s): Eman Baraka*, Mona Balata, Shereen Ahmed, Mona El-Blbehisy and Enas Elattar

Volume 17 , Issue 3 , 2021

Published on: 14 January, 2021

Page: [331 - 341] Pages: 11

DOI: 10.2174/1573397117666210114110823

Price: $65


Background: Ankylosing spondylitis (AS) is a chronic systemic inflammatory rheumatic disease that specifically affects the spine and sacroiliac joint. AS diagnosis is often delayed in the clinical practice and this delay may cause the patients to miss the chance of early treatment. Fibromyalgia (FM) is a frequently encountered clinical syndrome, fibromyalgianess is a term used when patients who are diagnosed with inflammatory arthropathies meet the criteria for FM syndrome as shown in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome, and AS.

Objectives: We aimed primarily to assess the frequency of concomitant diagnosis of FM syndrome in AS patients and study its impact on clinical disease aspects. Secondary, our aim extended as a preliminary pilot study to assess the Plasma Pentraxin-3(PTX-3) as a potential marker for the diagnosis of FM syndrome in AS patients.

Methods: Plasma PTX-3 in 61 AS patients was compared to 60 matched controls. FM was diagnosed by FM Rapid Screening Tool.

Bath AS disease activity index (BASDAI) and AS disease assessment score using C- reactive protein (ASDAS-CRP), Bath AS functional impairment index (BASFI), Bath AS metrology index (BASMI), AS quality of life (ASQoL) scale, Beck Depression Inventory, and Bath AS Radiology Index (BASRI) were assessed.

Results: The patients were categorized into two groups according to the concomitant diagnosis of FM syndrome. Group I included 14 (22.9%) AS patients who fulfilled the clinical diagnosis of FM syndrome. Group II included 47 (77.1%) AS patients without FM syndrome. AS patients with FM (Group I) had significantly(p<0.001) increased an average of ages, disease duration, diagnostic delay of AS, switching of bDMARDs, morning stiffness duration, ASDAS-CRP, BASFI, ASQoL score, BASDAI (p=0.008), and BDI score (p=0.005) compared to AS patients without FM (Group II). PTX-3 levels were significantly (p<0.001) higher in Group I (p<0.001) (median, 0.23; IQR, 0.15-0.41 ng/ml) than Group II (median, 0.13; IQR, 0.035-0.21ng/ml) which showed no significant differences (p>0.05) compared to the controls. PTX-3 levels had significant positive correlations (p<0.05) with disease duration, BASFI, and ASQOl. Age, female sex, switch of biologic, ASDAS - CRP, and PTX-3 were significant predictors of FM in AS patients.

Conclusion: These results indicate that concomitant FM is a significant problem in patients with AS and its presence is associated with higher disease activity, impaired function as well as an overall negative impact on QoL. Easy scanning of suspicious cases of FM with FiRST questionnaire can be done in daily practice. PTX-3 is more or less accurate as the clinical features to improve the diagnostic certainty of FM in the presence of AS with a proven sensitivity of 62.3%, a specificity of 90%, a positive predictive value of 82.75%, and a negative predictive value of 73.9%.

Keywords: Fibromyalgia, Ankylosing Spondylitis, plasma Pentraxin- 3, BASDAI, BASFI, BASMI, ASQoL.

Graphical Abstract
Liu Q, Liao Z, Zhang Y, et al. Pain- and Fatigue-Related Functional and Structural Changes in Ankylosing Spondylitis: An fRMI Study. Front Med (Lausanne) 2020; 7: 193.
[] [PMID: 32500077]
Fallahi S, Jamshidi AR. Diagnostic Delay in Ankylosing Spondylitis: Related Factors and Prognostic Outcomes. Arch Rheumatol 2015; 31(1): 24-30.
[] [PMID: 29900990]
Yunus MB. The prevalence of fibromyalgia in other chronic pain conditions. Pain Res Treat 2012; 2012: 584573.
[] [PMID: 22191024]
Atzeni F, Sallì S, Benucci M, Di Franco M, Alciati A, Sarzi-Puttini P. Fibromyalgia and arthritides. Reumatismo 2012; 64(4): 286-92.
[] [PMID: 23024973]
Duffield SJ, Miller N, Zhao S, Goodson NJ. Concomitant fibromyalgia complicating chronic inflammatory arthritis: a systematic review and meta-analysis. Rheumatology (Oxford) 2018; 57(8): 1453-60.
[] [PMID: 29788461]
Haliloglu S, Carlioglu A, Akdeniz D, Karaaslan Y, Kosar A. Fibromyalgia in patients with other rheumatic diseases: prevalence and relationship with disease activity. Rheumatol Int 2014; 34(9): 1275-80.
[] [PMID: 24589726]
Salaffi F, De Angelis R, Carotti M, Gutierrez M, Sarzi-Puttini P, Atzeni F. Fibromyalgia in patients with axial spondyloarthritis: epidemiological profile and effect on measures of disease activity. Rheumatol Int 2014; 34(8): 1103-10.
[] [PMID: 24509896]
Azevedo VF, Paiva E dos S, Felippe LRH, Moreira RA. Occurrence of fibromyalgia in patients with ankylosing spondylitis. Rev Bras Reumatol 2010; 50(6): 646-50.
[] [PMID: 21243305]
García JJ, Cidoncha A, Bote ME, Hinchado MD, Ortega E. Altered profile of chemokines in fibromyalgia patients. Ann Clin Biochem 2014; 51(Pt 5): 576-81.
[] [PMID: 24106344]
Pay S, Calgüneri M, Calişkaner Z, et al. Evaluation of vascular injury with proinflammatory cytokines, thrombomodulin and fibronectin in patients with primary fibromyalgia. Nagoya J Med Sci 2000; 63(3-4): 115-22.
[PMID: 11201985]
García JJ, Carvajal-Gil J, Herrero-Olea A, Gómez-Galán R. Altered Inflammatory Mediators in Fibromyalgia. Rheumatology (Sunnyvale) 2017; 7: 215.
Jafari-Nakhjavani M, Ghorbanihaghjo A, Pourghassem E, Abediazar S, Pourlak T, Malekmah A. Serum pentraxin 3 levels in rheumatoid arthritis patients and its association with disease activity. Egypt Rheumatol 2019; 41(4): 251-4.
Luchetti MM, Piccinini G, Mantovani A, et al. Expression and production of the long pentraxin PTX3 in rheumatoid arthritis (RA). Clin Exp Immunol 2000; 119(1): 196-202.
[] [PMID: 10606983]
Balbaloglu O, Ozcan SS. Is pentraxin 3 level an effective biomarker in disease activity in patients with rheumatoid arthritis? Arch Med Sci 2019; 16(1): 81-6.
[] [PMID: 32051709]
Cieślik P, Hrycek A. Pentraxin 3 as a biomarker of local inflammatory response to vascular injury in systemic lupus erythematosus. Autoimmunity 2015; 48(4): 242-50.
[] [PMID: 25401491]
Iwata Y, Yoshizaki A, Ogawa F, et al. Increased serum pentraxin 3 in patients with systemic sclerosis. J Rheumatol 2009; 36(5): 976-83.
[] [PMID: 19273457]
Surdacki A, Sulicka J, Korkosz M, et al. Blood monocyte heterogeneity and markers of endothelial activation in ankylosing spondylitis. J Rheumatol 2014; 41(3): 481-9.
[] [PMID: 24488416]
van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984; 27(4): 361-8.
[] [PMID: 6231933]
Akkoc Y, Karatepe AG, Akar S, Kirazli Y, Akkoc N. A Turkish version of the Bath Ankylosing Spondylitis Disease Activity Index: reliability and validity. Rheumatol Int 2005; 25(4): 280-4.
[] [PMID: 14730386]
van der Heijde D, Lie E, Kvien TK, et al. Assessment of SpondyloArthritis international Society (ASAS). ASDAS, a highly discriminatory ASAS-endorsed disease activity score in patients with ankylosing spondylitis. Ann Rheum Dis 2009; 68(12): 1811-8.
[] [PMID: 19060001]
Calin A, Garrett S, Whitelock H, et al. A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol 1994; 21(12): 2281-5.
[PMID: 7699629]
Jenkinson TR, Mallorie PA, Whitelock HC, Kennedy LG, Garrett SL, Calin A. Defining spinal mobility in ankylosing spondylitis (AS). The Bath AS Metrology Index. J Rheumatol 1994; 21(9): 1694-8.
[PMID: 7799351]
Zochling J. Measures of symptoms and disease status in ankylosing spondylitis: Ankylosing Spondylitis Disease Activity Score (ASDAS), Ankylosing Spondylitis Quality of Life Scale (ASQoL), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Global Score (BAS-G), Bath Ankylosing Spondylitis Metrology Index (BASMI), Dougados Functional Index (DFI), and Health Assessment Questionnaire for the Spondylarthropathies (HAQ-S). Arthritis Care Res (Hoboken) 2011; 63(Suppl. 11): S47-58.
[] [PMID: 22588768]
Beck AT, Steer RA, Garbin MG. Psychometric properties of the Beck depression inventory: twenty-five years of evaluation. Clin Psychol Rev 1988; 8: 77-100.
Perrot S, Bouhassira D, Fermanian J. Cercle d’Etude de la Douleur en Rhumatologie. Development and validation of the Fibromyalgia Rapid Screening Tool (FiRST). Pain 2010; 150(2): 250-6.
[] [PMID: 20488620]
MacKay K, Mack C, Brophy S, Calin A. The Bath Ankylosing Spondylitis Radiology Index (BASRI): a new, validated approach to disease assessment. Arthritis Rheum 1998; 41(12): 2263-70.
[<2263::AID-ART23>3.0.CO;2-I] [PMID: 9870884]
Ablin JN, Eshed I, Berman M, et al. Prevalence of axial spondyloarthritis among patients with fibromyalgia: a magnetic resonance imaging study with application of the assessment of spondyloarthritis international society classification criteria. Arthritis Care Res (Hoboken) 2017; 69(5): 724-9.
[] [PMID: 27390225]
Zhao SS, Duffield SJ, Goodson NJ. The prevalence and impact of comorbid fibromyalgia in inflammatory arthritis. Best Pract Res Clin Rheumatol 2019; 33(3): 101423.
[] [PMID: 31703796]
Almodóvar R, Carmona L, Zarco P, et al. Fibromyalgia in patients with ankylosing spondylitis: prevalence and utility of the measures of activity, function and radiological damage. Clin Exp Rheumatol 2010; 28(6)(Suppl. 63): S33-9.
[PMID: 21176420]
Macfarlane GJ, Barnish MS, Pathan E, et al. The co-occurrence and characteristics of patients with axial spondyloarthritis who meet criteria for fibromyalgia: results from a UK national register (BSRBR-AS). Arthritis Rheumatol 2017; 69(11): 2144-50.
[] [PMID: 28622461]
Aloush V, Ablin JN, Reitblat T, Caspi D, Elkayam O. Fibromyalgia in women with ankylosing spondylitis. Rheumatol Int 2007; 27(9): 865-8.
[] [PMID: 17476510]
Fillingim RB, King CD, Ribeiro-Dasilva MC, Rahim-Williams B, Riley JL III. Sex, gender, and pain: a review of recent clinical and experimental findings. J Pain 2009; 10(5): 447-85.
[] [PMID: 19411059]
Demirdal S, Çakir T, Tugrul T, Suba¸si V. Coexisting of fibromyalgia syndrome and ankylosing spondylitis. Acta Med Mediter 2013; 29: 827.
Segura-Jiménez V, Álvarez-Gallardo IC, Carbonell-Baeza A, et al. Fibromyalgia has a larger impact on physical health than on psychological health, yet both are markedly affected: the al-Ándalus project. Semin Arthritis Rheum 2015; 44(5): 563-70.
[] [PMID: 25440155]
Häuser W, Perrot S, Sommer C, Shir Y, Fitzcharles MA. Diagnostic confounders of chronic widespread pain: not always fibromyalgia. Pain Rep 2017; 2(3): e598.
[] [PMID: 29392213]
Borchers AT, Gershwin ME. Fibromyalgia: a critical and comprehensive review. Clin Rev Allergy Immunol 2015; 49(2): 100-51.
[] [PMID: 26445775]
Poole JL, Siegel P. Effectiveness of occupational therapy interventions for adults with fibromyalgia: a systematic review. Am J Occup Ther 2017; 71(1): 1-10.
Bello N, Etcheto A, Béal C, Dougados M, Moltó A. Evaluation of the impact of fibromyalgia in disease activity and treatment effect in spondyloarthritis. Arthritis Res Ther 2016; 18: 42.
Palomo-López P, Becerro-de-Bengoa-Vallejo R, Elena-Losa-Iglesias M, et al. Relationship of depression scores and ranges in women who suffer from fbromyalgia by age distribution: a case-control study. Worldviews Evid Based Nurs 2019; 16(3): 211-20.
[] [PMID: 31021513]
Braun J, Sieper J. Ankylosing spondylitis. Lancet 2007; 369(9570): 1379-90.
[] [PMID: 17448825]
Shen CC, Hu LY, Yang AC, Kuo BI, Chiang YY, Tsai SJ. Risk of psychiatric disorders following ankylosing spondylitis: a nationwide population-based retrospective cohort study. J Rheumatol 2016; 43(3): 625-31.
[] [PMID: 26834219]
Miller AH, Raison CL. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat Rev Immunol 2016; 16(1): 22-34.
[] [PMID: 26711676]
Dowlati Y, Herrmann N, Swardfager W, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry 2010; 67(5): 446-57.
[] [PMID: 20015486]
Webers C, Vanhoof L, Leue C, Boonen A, Köhler S. Depression in ankylosing spondylitis and the role of disease-related and contextual factors: a cross-sectional study. Arthritis Res Ther 2019; 21(1): 215.
[] [PMID: 31639012]
Kotsis K, Voulgari PV, Drosos AA, Carvalho AF, Hyphantis T. Health-related quality of life in patients with ankylosing spondylitis: a comprehensive review. Expert Rev Pharmacoecon Outcomes Res 2014; 14(6): 857-72.
[] [PMID: 25193010]
Baysal O, Durmuş B, Ersoy Y, et al. Relationship between psychological status and disease activity and quality of life in ankylosing spondylitis. Rheumatol Int 2011; 31(6): 795-800.
[] [PMID: 20221605]
Bodur H, Ataman S, Rezvani A, et al. Quality of life and related variables in patients with ankylosing spondylitis. Qual Life Res 2011; 20(4): 543-9.
[] [PMID: 20978859]
Ward MM. Health-related quality of life in ankylosing spondylitis: a survey of 175 patients. Arthritis Care Res 1999; 12(4): 247-55.
[<247::AID-ART3>3.0.CO;2-H] [PMID: 10689989]
Davis JCJ Jr, Mease PJ. Insights into the pathology and treatment of spondyloarthritis: from the bench to the clinic. Semin Arthritis Rheum 2008; 38(2): 83-100.
[] [PMID: 18166219]
Graceffa D, Maiani E, Sperduti I, Ceralli F, Bonifati C. Clinical remission of psoriatic arthritis in patients receiving continuous biological therapies for 1 year: the experience of an outpatient dermatological clinic for psoriasis. Clin Exp Dermatol 2015; 40(2): 136-41.
[] [PMID: 25438647]
Wach J, Letroublon MC, Coury F, Tebib JG. Fibromyalgia in spondyloarthritis: effect on disease activity assessment in clinical practice. J Rheumatol 2016; 43(11): 2056-63.
[] [PMID: 27633820]
Brikman S, Furer V, Wollman J, et al. The effect of the presence of fibromyalgia on common clinical disease activity indices in patients with psoriatic arthritis: a cross-sectional study. J Rheumatol 2016; 43(9): 1749-54.
[] [PMID: 27252430]
Fan A, Tournadre A, Pereira B, et al. Performance of Fibromyalgia Rapid Screening Tool (FiRST) to detect fibromyalgia syndrome in rheumatic diseases. Rheumatology (Oxford) 2016; 55(10): 1746-50.
[] [PMID: 27313278]
da Silva Chakr RM, Brenol JCT, Behar M, et al. Is ultrasound a better target than clinical disease activity scores in rheumatoid arthritis with fibromyalgia? A case-control study. PLoS One 2015; 10(3): e0118620.
[] [PMID: 25738587]
Ghib LJ, Tămaş MM, Damian LO, et al. The role of ultrasonography in assessing disease activity in patients with rheumatoid arthritis and associated fibromyalgia. Med Ultrason 2015; 17(3): 339-44.
[] [PMID: 26343083]
Nawito Z, Rady HM, Maged LA. The impact of fibromyalgia on disease assessment in rheumatoid arthritis patients. Egypt Rheumatol 2013; 35(3): 115-1199.
Joharatnam N, McWilliams DF, Wilson D, Wheeler M, Pande I, Walsh DA. A cross-sectional study of pain sensitivity, disease-activity assessment, mental health, and fibromyalgia status in rheumatoid arthritis. Arthritis Res Ther 2015; 17(1): 11.
[] [PMID: 25600850]
Wolfe F. Stop using the American College of Rheumatology criteria in the clinic. J Rheumatol 2003; 30(8): 1671-2.
[PMID: 12913920]
Deodhar A, Mittal M, Reilly P, et al. Ankylosing spondylitis diagnosis in US patients with back pain: identifying providers involved and factors associated with rheumatology referral delay. Clin Rheumatol 2016; 35(7): 1769-76.
[] [PMID: 26987341]
Rosenbaum JT, Pisenti L, Park Y, Howard RA. Insight into the Quality of Life of Patients with Ankylosing Spondylitis: Real-World Data from a US-Based Life Impact Survey. Rheumatol Ther 2019; 6(3): 353-67.
[] [PMID: 31111433]
Wallace DJ, Linker-Israeli M, Hallegua D, Silverman S, Silver D, Weisman MH. Cytokines play an aetiopathogenetic role in fibromyalgia: a hypothesis and pilot study. Rheumatology (Oxford) 2001; 40(7): 743-9.
[] [PMID: 11477278]
Bazzichi L, Rossi A, Giacomelli C, Bombardieri S. Exploring the abyss of fibromyalgia biomarkers. Clin Exp Rheumatol 2010; 28(6)(Suppl. 63): S125-30.
[PMID: 21176432]
Bazzichi L, Rossi A, Massimetti G, et al. Cytokine patterns in fibromyalgia and their correlation with clinical manifestations. Clin Exp Rheumatol 2007; 25(2): 225-30.
[PMID: 17543146]
Garlanda C, Bottazzi B, Bastone A, Mantovani A. Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility. Annu Rev Immunol 2005; 23: 337-66.
[] [PMID: 15771574]
García JJ, Herrero-Oléa A, Carvajal-Gil J. Gómez- Galán R. PTX-3 release is increased by monocytes from patients with primary fibromyalgia without major depression. Clin Exp Rheumatol 2016; 34: 150.
Higgs GA, Moncada S, Salmon JA, Seager K. The source of thromboxane and prostaglandins in experimental inflammation. Br J Pharmacol 1983; 79(4): 863-8.
[] [PMID: 6652359]
Skare TL, Plawiak AC, Veronese G, Paiva ES, Messias-Reason I, Nisihara R. Pentraxin 3 levels in women with fibromyalgia. Clin Exp Rheumatol 2015; 33(1)(Suppl. 88): S142.
[PMID: 25664655]
Nisihara R, Skare TL, Zeni JO, Rasera H, Lidani K, Messias-Reason I. Plasma levels of pentraxin 3 in patients with spondyloarthritis. Biomarkers 2018; 23(1): 14-7.
[] [PMID: 28043168]
Deniz T, Kizilgul M, Uzunlulu M, Oguz A, Isbilen B. Levels of pentraxin 3 and relationship with disease activity in patients with ankylosing spondylitis. Acta Reumatol Port 2014; 39(2): 137-42.
[PMID: 24861165]
Zhang X, Ding W. Association of genetic variants in Pentraxin 3 gene with ankylosing spondylitis. Med Sci Monit 2016; 22: 2911-6.
[] [PMID: 27538101]
Deyab G, Hokstad I, Whist JE, et al. Anti-rheumatic treatment is not associated with reduction of pentraxin 3 in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. PLoS One 2017; 12(2): e0169830.
[] [PMID: 28225768]
Uysal S, Yılmaz FM, Karatoprak K, Artüz F, Cumbul NU. The levels of serum pentraxin3, CRP, fetuin-A, and insulin in patients with psoriasis. Eur Rev Med Pharmacol Sci 2014; 18(22): 3453-8.
[PMID: 25491620]
Fazzini F, Peri G, Doni A, et al. PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation. Arthritis Rheum 2001; 44(12): 2841-50.
[<2841::AID-ART472>3.0.CO;2-6] [PMID: 11762945]
Dagna L, Salvo F, Tiraboschi M, et al. Pentraxin-3 as a marker of disease activity in Takayasu arteritis. Ann Intern Med 2011; 155(7): 425-33.
[] [PMID: 21969341]
Helseth R, Solheim S, Opstad T, Hoffmann P, Arnesen H, Seljeflot I. The time profile of Pentraxin 3 in patients with acute ST-elevation myocardial infarction and stable angina pectoris undergoing percutaneous coronary intervention. Mediators Inflamm 2014; 2014: 608414.
[] [PMID: 24737925]

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