Patients with Rheumatoid Arthritis in Comparison to Other Connective Tissue Diseases Are Mostly Influenced by Concomitant Fibromyalgia Tomš J, Daňková M, Hrnčíř Z 2nd Department of Medicine Faculty of Medicine and University Hospital Hradec Králové, Czech republic Abstract Background: A number of clinical studies documented that fibromyalgia (FM) can frequently accompany connective tissue diseases (CTD) as a concomitant syndrome. There is a lack of data about differencies in FM impact on individual CTD. Objectives: To compare the impact of concomitant FM on CTD in terms of pain intensity, disease activity, function disability and quality of life (QOL) in a regional, monocentric, cross-sectional study. Methods: 120 consecutive patients (pts) with rheumatoid arthritis (RA), 91 pts with systemic lupus (SLE), 30 pts with polymyositis/dermatomyositis (PM/DM) and 30 pts with systemic sclerosis (SSc) were examined in our outpatient rheumatology department on the presence of FM (ACR criteria,1990). Standard Manual Tender Point Survey was used for the examination of FM tender points. The following data were recorded: demographic data, tender point count (TPC), pain, fatigue and stiffness intensity on a 100 mm visual analog scale (VAS), Fibromyalgia Impact Questionnarie (FIQ) score and disease activity indices according to individual CTD representatives (DAS-28, SLEDAI, serum muscle enzymes). Health Assessment Questionnarie (HAQ) and Short Form 36 items (SF-36) were used for evaluation of functional disability and QOL, respectively. Statistical analysis was based on KruskalWallis nonparametric tests comparing mutually all the CTD cohorts with and without FM. Patient file with SSc and FM was not included into the analysis due to small quantity. Results: FM diagnosis was established in 25 (20.8%) pts with RA, 10 (11.0%) pts with SLE, 4 (13.3%) pts with PM/DM and 1 patient with SSc (3.6%). CTD groups with concomitant FM were shown to have significantly higher levels of pain, fatigue, stiffness, TPC and FIQ (p <0.05). RA/FM pts reached the highest average intensity of pain (VAS pain 63.7 mm), the worst disability level (HAQ 1.832) and the most reduced QOL in some of SF-36 domains. Disease activity assessment was significantly influenced only in RA pts (DAS-28 in RA with and without FM 5.35 1.1 vs. 3.67 1.4; p < 0.0001). Conclusion: Concomitant FM appears most frequently in pts with RA in comparison to other CTD. RA patients are also mostly influenced by FM at the level of pain perception, disability and QOL. This FM impact contributes to significant difficulties in RA disease activity assessment unlike other CTD. Background and Objectives Background A number of clinical studies documented that fibromyalgia (FM) can frequently accompany connective tissue diseases (CTD) as a concomitant syndrome (Table). There is a lack of data about differencies in FM impact on individual CTD. Frequency of concomitant fibromyalgia in CTD (%) Rheumatoid arthritis Systemic lupus erythematodes Poly-/ dermatomyositis Systemic sclerosis Sjögren syndrome 6.6 – 57.0 1.0 – 25.0 8,0 – 13.3 1.0 - 4.0 6.9 – 22.0 Objectives To compare the impact of concomitant FM on connective tissue diseases in terms of pain intensity, disease activity, fucntion disability and quality of life in regional, monocentric, cross-sectional study. Methods • clinical examination of the patients with CTD attending outpatient rheumatology department (terciary centre) • diagnosis of RA according to the criteria ACR 1987, SLE according to the criteria ACR 1982/1997, PM/DM according to Bohan´s and Peter´s criteria (1975), SSc according to the criteria ACR 1980 • examination focused on the presence of FM according to the criteria ACR 1990 • FM tender point examination - the protocol MTPS (Standardised Manual Tender Point Survey) Okifuji et al. J Rheumatol 1997;24:377-83 • disease activity - DAS-28, SLEDAI, creatinkinase (myoglobin) • functional disability - HAQ (Health assessment questionnaire) • quality of life - SF-36 (Short Form 36 items) • FIQ (Fibromyalgia Impact Questionnaire) • SDS (Zung´s self-rating depression scale) • pain, fatigue and stiffness intenstity evaluated on a 100 mm horizontal visual analogue scale (VAS) • statistical analysis was based on Kruskal-Wallis nonparametric tests comparing mutually all the CTD cohorts with and without FM • patient file with SSc and FM was not included into the analysis due to small quantity Patient groups n RA SLE 120 91 PM/DM 30 SSc 30 (PM = 18, DM = 12) Age (years – median, range) Sex ratio (M : F) Disease duration (years – median, range) Disease activity 57.0 (22 - 74) 43.0 (18 -75) 50.0 (19 - 74) 61.5 (41 - 76) 29 : 91 (24.2 : 75.8 %) 6 : 85 (6.6 : 93.4 %) 13 : 17 (43.3 : 56.7 %) 10 : 20 (33.3 : 66.6 %) 11.2 (0.1 - 57.1) 8.8 (0.3 - 36.0) 3.6 (0.3 - 21.0) 6.0 (1.0 - 25.0) CK = 2.15 µkat/l (0.55 – 30.9) Not DAS-28 4.02 ± 1.52 SLEDAI 3 (0 – 13) Myogl = 50.1 µkat/l (22.3 – 650.5) Explanation: data of disease activity are median and 5th – 95th percentile evaluated Results I. RA/FM- RA/FM+ SLE/FM- SLE/FM+ PDM/FM- PDM/FM+ SSc/FM- N 95 25 81 10 26 4 29 Age (years) 55.9 ± 13.6 61.4 ± 10.7 43.0 ± 14.3 44.8 ± 9.7 48.5 ± 16.8 54.3 ± 11.5 61.9 ± 9.9 Sex ratio (M : F) 25 : 70 4 : 21 6 : 75 0 : 10 13 : 13 0:4 10 : 19 Disease duration (years) 10.9 ± 9.1 12.8 ± 12.5 10.1 ± 7.8 11.1 ± 7.0 2,5 11.2 7.1 ± 5.2 CK = 2.00 µkat/l (1.3 – 5.1) CK = 2.20 µkat/l (1.9 – 9.6) Not Myogl = 52.6 µkat/l (30.0 – 135.0) Myogl = 37,2 µkat/l (27.0 – 96.0) Disease activity *DAS-28 *DAS-28 3.67 ± 1.4 5.35 ± 1.1 SLEDAI 3 (0 – 13) SLEDAI 3.5 (0 – 9.0) Evaluated Explanation: parameters characterized by more numbers: average ± standard deviation or median and5th-95th percentile * Difference in DAS-28 is statistically significant: p < 0.0001 Results II. CTD groups with concomitant FM were shown to have significantly higher levels of pain, fatigue, stiffness, TPC and FIQ (p <0.05). RA/FM+ patients reached the highest average intensity of pain (VAS pain 63.7 mm). 70 60 RA/FM+ 50 RA/FMSLE/FM+ 40 SLE/FM- 30 PDM/FM+ 20 PMD/FMSSc/FM- 10 0 VAS pain VAS fatigue VAS stiffness FIQ TPC Explanation: CTD – connective tissue diseases, VAS - visual analogue scale, FIQ – Fibromyalgia Impact Questionnaire, TPC – tender point count Results III. RA/FM+ patients reached the worst disability level (HAQ 1.832), p < 0.05, and the highest depression score (SDS 0.508), p < 0.05. 2 1,8 1,6 1,4 1,2 1 0,8 0,6 0,4 0,2 0 RA/FM+ RA/FMSLE/FM+ SLE/FMPDM/FM+ PMD/FMSSc/FM- HAQ SDS Explanation: HAQ - Health Assessment Questionnaire, SDS – Zung´s depression self-rating scale Results IV. PF 80 Short Form 36 items (SF-36) 70 MH 60 RP 50 40 RA/FM+ 30 RA/FM- 20 10 RE SLE/FM+ BP 0 SLE/FMPDM/FM+ PMD/FM- SF GH p < 0,001 VT Values on individual axes are mean scores of quality of life domains. PF – physical functioning, RP – role physical, BP – bodily pain, GH – General health, VT – vitality, SF – social functioning, RE - role emotoinal, MH – mental health. Disease Activity in Rheumatoid arthritis Components of DAS-28 index p < 0.0001 Count (or mm) 60 p = 0.438 50 40 30 RA p < 0.0001 RA/FM 20 p = 0.022 10 0 TJC SJC FW Pain - VAS Explanation: DAS-28 – disease activity score evaluating 28 joints, TJC – tender joint count, SJC – swollen joint count, FW – erythrosite sedimentation rate, VAS - visual analogue scale 1 7 80% 17 60% 36 45 40% 14 20% 0% < 3,2 3,2 - 5,1 > 5,1 RAF+ 1 7 17 RAF- 36 45 14 Relativnicount cetnost Relative 40,0 20,0 0,0 0,0 DAS-28 60,0 60,0 R elativni cetnost count Relative % count Relative Relativní četnost (%) 100% 1,0 2,0 3,0 4,0 5,0 DAS_28_RA 6,0 7,0 8,0 40,0 20,0 0,0 0,0 1,0 2,0 3,0 4,0 5,0 DAS_28_FM 6,0 7,0 8,0 Conclusion • concomitant fibromyalgia appears most frequently in patients with rheumatoid arthritis in comparison to other connective tissue disease • RA patients are mostly influenced by FM at the level of pain perception, disability and in some domains of life quality • FM impact contributes to significant difficulties in RA disease activity assessment unlike other connective tissue diseases