- Email: [email protected]
Fibromyalgia and central sensitization in chronic inflammatory joint diseases
Accepted Manuscript Title: Fibromyalgia and Central Sensitization in Chronic Inflammatory Joint Disease Author: Maxime Dougados Serge Perrot PII: DOI: Reference:
S1297-319X(17)30040-4 http://dx.doi.org/doi:10.1016/j.jbspin.2017.03.001 BONSOI 4551
To appear in: Accepted date:
14-12-2016
Please cite this article as: Dougados M, Perrot S, Fibromyalgia and Central Sensitization in Chronic Inflammatory Joint Disease, Joint Bone Spine (2017), http://dx.doi.org/10.1016/j.jbspin.2017.03.001 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Fibromyalgia and Central Sensitization in Chronic Inflammatory Joint Disease
Maxime Dougados (1,2), Serge Perrot (1,3)
ip t
(1) Service de rhumatologie, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, 27 rue du
(2) INSERM U1153, Université Paris Descartes, 75006 Paris, France
us
(3) INSERM U987, Université Paris Descartes, 75006 Paris, France
cr
Faubourg Saint-Jacques 75014 Paris, France
an
Corresponding author: Maxime Dougados, Service de rhumatologie, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, 27 rue du Faubourge Saint-Jacques 75014 Paris,
M
France
ed
[email protected]
Ac
ce pt
Keywords: Fibromyalgia. Rheumatoid arthritis. Spondyloarthritis.
1 Page 1 of 12
Fibromyalgia may complicate the diagnostic and therapeutic approach to chronic inflammatory joint disease (CIJD) in two ways: fibromyalgia may be mistaken for CIJD, and concomitant fibromyalgia may impede assessments of CIJD activity. Adding weight to this point are the probably higher frequency of fibromyalgia in patients with CIJD and the ability
cr
1. Fibromyalgia in chronic inflammatory joint disease (CIJD)
ip t
of any articular inflammatory process to induce chronicity of a pain syndrome.
us
The prevalence of fibromyalgia in unselected populations ranges across studies from 1% to 6% (1,2). In contrast, in patients with known CIJD, considerably higher prevalences of
an
up to 30% have been reported (3). Thus, fibromyalgia was found in 5% to 20% of patients with rheumatoid arthritis (RA) (4,5), spondyloarthritis (6), lupus (7), Sjögren’s syndrome
M
(8), systemic sclerosis (9), or psoriatic arthritis (10). The possible explanations to these findings deserve discussion.One explanation involves the intrinsic validity of the
ed
classification criteria for fibromyalgia. Rigorously applying the 1990 ACR criteria (which include the number of tender point sites with pain upon digital pressure) (11), pain due to the
ce pt
CIJD may be mistaken for a positive response. To eliminate this source of confusion, the 1990 ACR criteria were revised in 2010 (12) and 2011 (13) to remove the physical examination and testing of tender point sites. The revised criteria rely on non-pain symptoms
Ac
such as fatigue, cognitive disorders, and multiple subjective symptoms. However, they remain highly controversial. Another explanation takes the opposite view that the diagnostic criteria for fibromyalgia have strong validity but that the studies included patients who had primary fibromyalgia mistakenly diagnosed as CIJD, i.e., either seronegative RA without erosions or axial spondyloarthritis without radiographic abnormalities. The problem here would lie with the excessive sensitivity and insufficient specificity of tests for CIJD such as assays for
2 Page 2 of 12
rheumatoid factor and antinuclear antibodies, HLA-B27 type determination, and even joint ultrasonography. Another point to be borne in mind is that various treatments, such as fibrates (which are commonly prescribed to patients with CIJD) may induce pain syndromes (14).
ip t
Two other potential mechanisms are less familiar to rheumatologists. One is central sensitization, in which persistence of a painful stimulus from a joint eventually exaggerates
cr
the sensitivity of the central nervous system to pain, inducing manifestations that resemble
us
primary fibromyalgia (15). The other is the recent concept of post-inflammatory joint pain syndrome, for which several mechanisms have been suggested (16-19). Conceivably, in the
an
event of central sensitization, the pain may be accompanied with symptoms generally seen in primary fibromyalgia, such as fatigue and sleep disturbances, whereas post-inflammatory
M
joint pain syndrome may indicate a disorder confined to the joints.
ed
2. Diagnostic challenges raised by the co-existence of chronic inflammatory joint disease (CIJD) and fibromyalgia
ce pt
Patients with fibromyalgia often feel disoriented by their severe disability (related for instance to pain, fatigue, and psychological distress) contrasting with the absence of objective signs of their disease. A traumatic psychological experience (e.g., sexual, work-
Ac
related, or due to an armed conflict or natural disaster) is often considered among possible causes or precipitating factors (20). The interaction with the physician may aggravate the feelings of isolation and non-recognition, prompting the patient to seek advice from specialists in various medical fields, each of whom performs investigations to look for an organic cause to the symptoms. One of these investigations may be positive (e.g., positive RF assay, synovitis by ultrasonography, or presence of the HLA-B27 antigen) and taken as
3 Page 3 of 12
diagnostic of a CIJD. Clearly, circumspection is in order when obtaining investigations and, above all, interpreting positive results.
3. Difficulties in assessing the activity of the chronic inflammatory joint disease (CIJD)
ip t
The assessment of disease activity in patients with CIJD often relies on both patientreported experience (e.g., about pain and fatigue) and objective evidence of inflammation
cr
(e.g., C-reactive protein in RA and spondyloarthritis or swollen joint count in RA). These
us
various types of information are often aggregated to obtain composite scores such as the DAS28-ESR for RA (21) and the BASDAI (22) and ASDAS (23) for spondyloarthritis.
an
Concomitant fibromyalgia heavily influences several components of these scores, such as the tender joint count and, to an even greater degree, the global disease activity assessment in
M
the DAS28 and fatigue and pain upon digital pressure in the BASDAI (24, 25,26).A strong preference for using these composite scores to monitor disease activity as a means of
ed
following the treat-to-target (T2T) approach has emerged in recent years (27). A treatment target is defined and the score results indicate whether it has been reached. If not, the
ce pt
treatment is intensified and/or modified. Clearly, overlooking fibromyalgia or postinflammatory joint pain syndrome can result in inappropriate treatment decisions. Thus, concomitant fibromyalgia is associated with increased use of biologics in RA (28) and with
Ac
shorter times to biotherapy switching in spondyloarthritis (29).
4. Practical implications: factors to consider when managing a patient with confirmed or suspected, persistent or refractory inflammatory joint disease
a) At presentation, routinely evaluate for fibromyalgia or a primary pain syndrome (due to central or peripheral pain pathway dysfunction), to avoid diagnostic mistakes
4 Page 4 of 12
Several features may suggest that the pain is not related to an active inflammatory process. Thus, the pain is often unresponsive to numerous medications. In particular, back pain may fail to be alleviated by nonsteroidal antiinflammatory drugs (30). The patient evaluates the pain and fatigue as very severe on visual analogue scales or verbal rating
ip t
scales. For instance, pain scores greater than 7 or 8 on a 0- to 10-point scale should suggest fibromyalgia (31). A history of depression or current antidepressant therapy is a common
cr
finding (32).The key point, however, is identifying the pain pattern and concomitant
us
symptoms reported by the patient. A simple 6-item questionnaire known as the Fibromyalgia Rapid Screening Tool (FiRST) (Table 1) had shown good sensitivity and specificity for
an
fibromyalgia in a population of patients with inflammatory or degenerative joint disease (33). A positive response to at least 5 items suggests fibromyalgia rather than an active joint
M
disease. FiRST has been validated for the diagnosis of fibromyalgia and may prove
diagnostic tool (33,34).
ed
extremely useful in clinical practice, despite its being a screening tool rather than a
ce pt
b) When interpreting inflammatory disease activity scores, the co-existence of fibromyalgia and/or postinflammatory joint pain syndrome should be taken into account. These co-existing conditions may translate into increased disease activity scores,
Ac
prompting inappropriate treatment intensification or modification, such as the introduction of a biologic. Biologics are expensive, associated with side effects, and consistently ineffective in these conditions (29). The co-existence of fibromyalgia with CIJD is not a contraindication to all anti-rheumatic drugs but requires considerable circumspection when defining their indications. For instance, it may be appropriate to make a collegial decision (during a meeting of at least 3 rheumatologists), with clear documentation of the discussion in the patient files, before initiating a biologic. The list of situations that deserve this
5 Page 5 of 12
approach could be established by the national society for rheumatology. One such situation is obviously axial spondyloarthritis with no objective evidence of inflammation or structural damage; others may arise in patients with RA or connective tissue diseases such as Sjögren’s syndrome and lupus.
ip t
In conclusion, fibromyalgia should be sought routinely in patients with inflammatory joint disease, not only to avoid diagnostic errors, but also to ensure an accurate assessment of
cr
the treatment response. Fibromyalgia should no longer be viewed merely as the physical
us
manifestation of psychological distress but instead as a central and peripheral pain hypersensitivity syndrome that is secondary, in some cases, to the chronic inflammation.
an
Fibromyalgia should be diagnosed based on positive criteria instead of by elimination and
M
should be managed in its own right in patients with CIJD.
Ac
ce pt
ed
Disclosure of interests: None of the authors has any conflicts of interest to declare.
6 Page 6 of 12
References
1. Jones GT, Atzeni F, Beasley M, Flüß E, Sarzi-Puttini P, Macfarlane GJ. The prevalence of fibromyalgia in the general population: a comparison of the American College of
ip t
Rheumatology 1990, 2010, and modified 2010 classification criteria. Arthritis Rheumatol 2015;67:568-75.
cr
2. Perrot S, Vicaut E, Servant D, Ravaud P. Prevalence of fibromyalgia in France: a multi-
us
step study research combining national screening and clinical confirmation: The DEFI study (Determination of Epidemiology of Fibromyalgia). BMC Musculoskelet Disord
an
2011;12:224.
3. Clauw DJ, Katz P. The overlap between fibromyalgia and inflammatory rheumatic
M
disease: when and why does it occur? J Clin Rheumatol 1995 ;1:335-42. 4. Ranzolin A, Brenol JC, Bredemeier M, et al. Association of concomitant fibromyalgia
ed
with worse disease activity score in 28 joints, health assessment questionnaire, and short form 36 scores in patients with rheumatoid arthritis. Arthritis Rheum 2009;61:794-800.
ce pt
5. Andersson ML, Svensson B, Bergman S. Chronic widespread pain in patients with rheumatoid arthritis and the relation between pain and disease activity measures over the first 5 years. J Rheumatol 2013;40:1977-85.
Ac
6-. 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. 7. Torrente-Segarra V, Salman-Monte TC, Rúa-Figueroa Í, Pérez-Vicente S, López-Longo FJ, Galindo-Izquierdo M,et al. RELESSER Study Group of the Spanish Society of Rheumatology (SER) and the Study Group of Systemic Autoimmune Diseases of the SER
7 Page 7 of 12
(EAS-SER). Fibromyalgia prevalence and related factors in a large registry of patients with systemic lupus erythematosus. Clin Exp Rheumatol 2016 Mars-Apr;34(2 Suppl 96):S40-7. 8. Vitali C, Del Papa N. Pain in primary Sjögren's syndrome. Best Pract Res Clin Rheumatol 2015;29:63-70.
ip t
9.Perrot S, Dieudé P, Pérocheau D, Allanore Y. Comparison of pain, pain burden, coping strategies, and attitudes between patients with systemic sclerosis and patients with
cr
rheumatoid arthritis: a cross-sectional study. Pain Med 2013;14:1776-85.
us
10. Marchesoni A, Atzeni F, Spadaro A, et al. Identification of the clinical features distinguishing psoriatic arthritis and fibromyalgia. J Rheumatol 2012;39(4):849-55.
an
11. Wolfe F, Smythe HA, Yunus MB, , et al.. The American College of Rheumatology 1990
Arthritis Rheum 1990;33:160-72.
M
criteria for the classification of fibromyalgia: report of the Multicenter Criteria Committee.
12. Wolfe F, Clauw DJ, Fitzcharles MA, et al. The American College of Rheumatology
ed
preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken) 2010;62:600-10.
ce pt
13. Wolfe F, Clauw DJ, FitzCharles MA, et al. Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR preliminary diagnostic criteria for fibromyalgia. J Rheumatol 2011; 38(6):1113-22.
Ac
14. Gillet RC Jr, Norrell A. Considerations for safe use of statins: liver enzyme abnormalities and muscle toxicity. Am Fam Physicians 2011;83(6):711-6. 15. - Lee YC, Nassikas NJ, Clauw DJ. The role of the central nervous system in the generation and maintenance of chronic pain in rheumatoid arthritis, osteoarthritis and fibromyalgia. Arthritis Res Ther 2011;13:211-20.
8 Page 8 of 12
16. Nieto FR, Clark AK, Grist J, Hathway GJ, Chapman V, Malcangio M. Neuron-immune mechanisms contribute to pain in early stages of arthritis. J Neuroinflammation. 2016 29 Apr29;13(1):96. doi :10.1186/1 12974-016-0556-0. 17. Su J, Gao T, Shi T, Xiang Q, et al. Phenotypic changes in dorsal root ganglion and spinal
ip t
cord in the collagen antibody-induced arthritis mouse model. J Comp Neurol. 2015 Jul 1;523(10):1505-28.
cr
18. Christianson CA, Corr M, Yaksh TL, Svensson CI. K/BxN serum transfer arthritis
us
as a model of inflammatory joint pain. Methods Mol Biol 2012;851:249-60
19. Wigerblad G, Bas DB, Fernades-Cerqueira C, et al. Autoantibodies to citrullinated
an
proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism. Ann Rheum Dis 2016 75(4):730-8. doi: 10.1136/annrheumdis-2015-208094.
M
Epub 2015 Nov 27. PubMed PMID: 26613766; PubMed Central PMCID: PMC4819624. 20. Häuser W, Galek A, Erbslöh-Möller Bet al. Posttraumatic stress disorder in fibromyalgia
ed
syndrome: prevalence, temporal relationship between posttraumatic stress and fibromyalgia symptoms, and impact on clinical outcome. Pain 2013;154(8):1216-23.
ce pt
21. van Riel PL. The development of the disease activity score (DAS) and the disease activity score using 28 joint counts (DAS28). Clin Exp Rheumatol 2014;32(5 Suppl 85):S65-74.
Ac
22. Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. À new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J. Rheumatol 1994, 21(12):2286-2291. 23. Lukas C, Landewé R, Sieper J, et al. Assessment of SpondyloArthritis international Society. Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis 2009; 68(1):18-24.
9 Page 9 of 12
24. Leeb BF, Andel I, Sautner J, Nothnagl T, Rintelen B. The DAS28 in rheumatoid arthritis and fibromyalgia patients. Rheumatology (Oxford) 2004;43:1504-7. 25. Sieper J. How to define remission in ankylosing spondylitis? Ann Rheum Dis 2012; 71:93-5.
ip t
26. 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
cr
27. Smolen JS, Aletaha D, Bijlsma JW, et al. T2T Expert Committee. Treating rheumatoid
us
arthritis to target: recommendations of an international task force. Ann Rheum Dis 2010; 69(4):631-7.
an
28 Lage-Hansen PR, Chrysidis S, Lage-Hansen M, Hougaard A, Ejstrup L, Amris K. Concomitant fibromyalgia in rheumatoid arthritis is associated with the more frequent use of
M
biological therapy: a cross-sectional study. Scand J Rheumatol 2015 ;16:1-4. 29. Bello N, Etcheto A, Béal C, Dougados M, Moltó A. Evaluation of the impact of
ed
fibromyalgia in disease activity and treatment effect in spondyloarthritis. Arthritis Res Ther 2016; 9(2);18:42. doi:10.1186/s13075-016-0943-z.
ce pt
30. Perrot S, Russell IJ. More ubiquitous effects from non-pharmacologic than from pharmacologic treatments for fibromyalgia syndrome: a meta-analysis examining six core symptoms. Eur J Pain 2014 ;18(8):1067-80.
Ac
31. Atzeni F, Cazzola M, Benucci M, Di Franco M, Salaffi F, Sarzi-Puttini P. Chronic widespread pain in the spectrum of rheumatological diseases. Best Pract Res Clin Rheumatol 2011;25:165-71.
32. Crofford LJ. Psychological aspects of chronic musculoskeletal pain. Best Pract Res Clin Rheumatol 2015;29(1):147-55.
10 Page 10 of 12
33. 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. 34. Salaffi F, Sarzi-Puttini P. Old and new criteria for the classification and diagnosis of
Ac
ce pt
ed
M
an
us
cr
ip t
fibromyalgia: comparison and evaluation. Clin Exp Rheumatol 2012;30:3-9.
11 Page 11 of 12
Table 1: Fibromyalgia Rapid Screening Tool (FiRST) * [33]. 1. I have pain all over my body. 2. My pain is accompanied by a continuous and very unpleasant general fatigue. 3. My pain feels like burns, electric shocks, or cramps.
cr
5. My pain is accompanied by other health problems such as digestive problems, urinary problems, headaches, or restless legs.
ip t
4. My pain is accompanied by other unusual sensations throughout my body, such as pins and needles, tingling, or numbness.
Ac
ce pt
ed
M
an
us
6. My pain has a significant impact on my life, particularly on my sleep and my ability to concentrate, making me feel slower generally.
12 Page 12 of 12
S1297-319X(17)30040-4 http://dx.doi.org/doi:10.1016/j.jbspin.2017.03.001 BONSOI 4551
To appear in: Accepted date:
14-12-2016
Please cite this article as: Dougados M, Perrot S, Fibromyalgia and Central Sensitization in Chronic Inflammatory Joint Disease, Joint Bone Spine (2017), http://dx.doi.org/10.1016/j.jbspin.2017.03.001 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Fibromyalgia and Central Sensitization in Chronic Inflammatory Joint Disease
Maxime Dougados (1,2), Serge Perrot (1,3)
ip t
(1) Service de rhumatologie, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, 27 rue du
(2) INSERM U1153, Université Paris Descartes, 75006 Paris, France
us
(3) INSERM U987, Université Paris Descartes, 75006 Paris, France
cr
Faubourg Saint-Jacques 75014 Paris, France
an
Corresponding author: Maxime Dougados, Service de rhumatologie, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, 27 rue du Faubourge Saint-Jacques 75014 Paris,
M
France
ed
[email protected]
Ac
ce pt
Keywords: Fibromyalgia. Rheumatoid arthritis. Spondyloarthritis.
1 Page 1 of 12
Fibromyalgia may complicate the diagnostic and therapeutic approach to chronic inflammatory joint disease (CIJD) in two ways: fibromyalgia may be mistaken for CIJD, and concomitant fibromyalgia may impede assessments of CIJD activity. Adding weight to this point are the probably higher frequency of fibromyalgia in patients with CIJD and the ability
cr
1. Fibromyalgia in chronic inflammatory joint disease (CIJD)
ip t
of any articular inflammatory process to induce chronicity of a pain syndrome.
us
The prevalence of fibromyalgia in unselected populations ranges across studies from 1% to 6% (1,2). In contrast, in patients with known CIJD, considerably higher prevalences of
an
up to 30% have been reported (3). Thus, fibromyalgia was found in 5% to 20% of patients with rheumatoid arthritis (RA) (4,5), spondyloarthritis (6), lupus (7), Sjögren’s syndrome
M
(8), systemic sclerosis (9), or psoriatic arthritis (10). The possible explanations to these findings deserve discussion.One explanation involves the intrinsic validity of the
ed
classification criteria for fibromyalgia. Rigorously applying the 1990 ACR criteria (which include the number of tender point sites with pain upon digital pressure) (11), pain due to the
ce pt
CIJD may be mistaken for a positive response. To eliminate this source of confusion, the 1990 ACR criteria were revised in 2010 (12) and 2011 (13) to remove the physical examination and testing of tender point sites. The revised criteria rely on non-pain symptoms
Ac
such as fatigue, cognitive disorders, and multiple subjective symptoms. However, they remain highly controversial. Another explanation takes the opposite view that the diagnostic criteria for fibromyalgia have strong validity but that the studies included patients who had primary fibromyalgia mistakenly diagnosed as CIJD, i.e., either seronegative RA without erosions or axial spondyloarthritis without radiographic abnormalities. The problem here would lie with the excessive sensitivity and insufficient specificity of tests for CIJD such as assays for
2 Page 2 of 12
rheumatoid factor and antinuclear antibodies, HLA-B27 type determination, and even joint ultrasonography. Another point to be borne in mind is that various treatments, such as fibrates (which are commonly prescribed to patients with CIJD) may induce pain syndromes (14).
ip t
Two other potential mechanisms are less familiar to rheumatologists. One is central sensitization, in which persistence of a painful stimulus from a joint eventually exaggerates
cr
the sensitivity of the central nervous system to pain, inducing manifestations that resemble
us
primary fibromyalgia (15). The other is the recent concept of post-inflammatory joint pain syndrome, for which several mechanisms have been suggested (16-19). Conceivably, in the
an
event of central sensitization, the pain may be accompanied with symptoms generally seen in primary fibromyalgia, such as fatigue and sleep disturbances, whereas post-inflammatory
M
joint pain syndrome may indicate a disorder confined to the joints.
ed
2. Diagnostic challenges raised by the co-existence of chronic inflammatory joint disease (CIJD) and fibromyalgia
ce pt
Patients with fibromyalgia often feel disoriented by their severe disability (related for instance to pain, fatigue, and psychological distress) contrasting with the absence of objective signs of their disease. A traumatic psychological experience (e.g., sexual, work-
Ac
related, or due to an armed conflict or natural disaster) is often considered among possible causes or precipitating factors (20). The interaction with the physician may aggravate the feelings of isolation and non-recognition, prompting the patient to seek advice from specialists in various medical fields, each of whom performs investigations to look for an organic cause to the symptoms. One of these investigations may be positive (e.g., positive RF assay, synovitis by ultrasonography, or presence of the HLA-B27 antigen) and taken as
3 Page 3 of 12
diagnostic of a CIJD. Clearly, circumspection is in order when obtaining investigations and, above all, interpreting positive results.
3. Difficulties in assessing the activity of the chronic inflammatory joint disease (CIJD)
ip t
The assessment of disease activity in patients with CIJD often relies on both patientreported experience (e.g., about pain and fatigue) and objective evidence of inflammation
cr
(e.g., C-reactive protein in RA and spondyloarthritis or swollen joint count in RA). These
us
various types of information are often aggregated to obtain composite scores such as the DAS28-ESR for RA (21) and the BASDAI (22) and ASDAS (23) for spondyloarthritis.
an
Concomitant fibromyalgia heavily influences several components of these scores, such as the tender joint count and, to an even greater degree, the global disease activity assessment in
M
the DAS28 and fatigue and pain upon digital pressure in the BASDAI (24, 25,26).A strong preference for using these composite scores to monitor disease activity as a means of
ed
following the treat-to-target (T2T) approach has emerged in recent years (27). A treatment target is defined and the score results indicate whether it has been reached. If not, the
ce pt
treatment is intensified and/or modified. Clearly, overlooking fibromyalgia or postinflammatory joint pain syndrome can result in inappropriate treatment decisions. Thus, concomitant fibromyalgia is associated with increased use of biologics in RA (28) and with
Ac
shorter times to biotherapy switching in spondyloarthritis (29).
4. Practical implications: factors to consider when managing a patient with confirmed or suspected, persistent or refractory inflammatory joint disease
a) At presentation, routinely evaluate for fibromyalgia or a primary pain syndrome (due to central or peripheral pain pathway dysfunction), to avoid diagnostic mistakes
4 Page 4 of 12
Several features may suggest that the pain is not related to an active inflammatory process. Thus, the pain is often unresponsive to numerous medications. In particular, back pain may fail to be alleviated by nonsteroidal antiinflammatory drugs (30). The patient evaluates the pain and fatigue as very severe on visual analogue scales or verbal rating
ip t
scales. For instance, pain scores greater than 7 or 8 on a 0- to 10-point scale should suggest fibromyalgia (31). A history of depression or current antidepressant therapy is a common
cr
finding (32).The key point, however, is identifying the pain pattern and concomitant
us
symptoms reported by the patient. A simple 6-item questionnaire known as the Fibromyalgia Rapid Screening Tool (FiRST) (Table 1) had shown good sensitivity and specificity for
an
fibromyalgia in a population of patients with inflammatory or degenerative joint disease (33). A positive response to at least 5 items suggests fibromyalgia rather than an active joint
M
disease. FiRST has been validated for the diagnosis of fibromyalgia and may prove
diagnostic tool (33,34).
ed
extremely useful in clinical practice, despite its being a screening tool rather than a
ce pt
b) When interpreting inflammatory disease activity scores, the co-existence of fibromyalgia and/or postinflammatory joint pain syndrome should be taken into account. These co-existing conditions may translate into increased disease activity scores,
Ac
prompting inappropriate treatment intensification or modification, such as the introduction of a biologic. Biologics are expensive, associated with side effects, and consistently ineffective in these conditions (29). The co-existence of fibromyalgia with CIJD is not a contraindication to all anti-rheumatic drugs but requires considerable circumspection when defining their indications. For instance, it may be appropriate to make a collegial decision (during a meeting of at least 3 rheumatologists), with clear documentation of the discussion in the patient files, before initiating a biologic. The list of situations that deserve this
5 Page 5 of 12
approach could be established by the national society for rheumatology. One such situation is obviously axial spondyloarthritis with no objective evidence of inflammation or structural damage; others may arise in patients with RA or connective tissue diseases such as Sjögren’s syndrome and lupus.
ip t
In conclusion, fibromyalgia should be sought routinely in patients with inflammatory joint disease, not only to avoid diagnostic errors, but also to ensure an accurate assessment of
cr
the treatment response. Fibromyalgia should no longer be viewed merely as the physical
us
manifestation of psychological distress but instead as a central and peripheral pain hypersensitivity syndrome that is secondary, in some cases, to the chronic inflammation.
an
Fibromyalgia should be diagnosed based on positive criteria instead of by elimination and
M
should be managed in its own right in patients with CIJD.
Ac
ce pt
ed
Disclosure of interests: None of the authors has any conflicts of interest to declare.
6 Page 6 of 12
References
1. Jones GT, Atzeni F, Beasley M, Flüß E, Sarzi-Puttini P, Macfarlane GJ. The prevalence of fibromyalgia in the general population: a comparison of the American College of
ip t
Rheumatology 1990, 2010, and modified 2010 classification criteria. Arthritis Rheumatol 2015;67:568-75.
cr
2. Perrot S, Vicaut E, Servant D, Ravaud P. Prevalence of fibromyalgia in France: a multi-
us
step study research combining national screening and clinical confirmation: The DEFI study (Determination of Epidemiology of Fibromyalgia). BMC Musculoskelet Disord
an
2011;12:224.
3. Clauw DJ, Katz P. The overlap between fibromyalgia and inflammatory rheumatic
M
disease: when and why does it occur? J Clin Rheumatol 1995 ;1:335-42. 4. Ranzolin A, Brenol JC, Bredemeier M, et al. Association of concomitant fibromyalgia
ed
with worse disease activity score in 28 joints, health assessment questionnaire, and short form 36 scores in patients with rheumatoid arthritis. Arthritis Rheum 2009;61:794-800.
ce pt
5. Andersson ML, Svensson B, Bergman S. Chronic widespread pain in patients with rheumatoid arthritis and the relation between pain and disease activity measures over the first 5 years. J Rheumatol 2013;40:1977-85.
Ac
6-. 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. 7. Torrente-Segarra V, Salman-Monte TC, Rúa-Figueroa Í, Pérez-Vicente S, López-Longo FJ, Galindo-Izquierdo M,et al. RELESSER Study Group of the Spanish Society of Rheumatology (SER) and the Study Group of Systemic Autoimmune Diseases of the SER
7 Page 7 of 12
(EAS-SER). Fibromyalgia prevalence and related factors in a large registry of patients with systemic lupus erythematosus. Clin Exp Rheumatol 2016 Mars-Apr;34(2 Suppl 96):S40-7. 8. Vitali C, Del Papa N. Pain in primary Sjögren's syndrome. Best Pract Res Clin Rheumatol 2015;29:63-70.
ip t
9.Perrot S, Dieudé P, Pérocheau D, Allanore Y. Comparison of pain, pain burden, coping strategies, and attitudes between patients with systemic sclerosis and patients with
cr
rheumatoid arthritis: a cross-sectional study. Pain Med 2013;14:1776-85.
us
10. Marchesoni A, Atzeni F, Spadaro A, et al. Identification of the clinical features distinguishing psoriatic arthritis and fibromyalgia. J Rheumatol 2012;39(4):849-55.
an
11. Wolfe F, Smythe HA, Yunus MB, , et al.. The American College of Rheumatology 1990
Arthritis Rheum 1990;33:160-72.
M
criteria for the classification of fibromyalgia: report of the Multicenter Criteria Committee.
12. Wolfe F, Clauw DJ, Fitzcharles MA, et al. The American College of Rheumatology
ed
preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken) 2010;62:600-10.
ce pt
13. Wolfe F, Clauw DJ, FitzCharles MA, et al. Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR preliminary diagnostic criteria for fibromyalgia. J Rheumatol 2011; 38(6):1113-22.
Ac
14. Gillet RC Jr, Norrell A. Considerations for safe use of statins: liver enzyme abnormalities and muscle toxicity. Am Fam Physicians 2011;83(6):711-6. 15. - Lee YC, Nassikas NJ, Clauw DJ. The role of the central nervous system in the generation and maintenance of chronic pain in rheumatoid arthritis, osteoarthritis and fibromyalgia. Arthritis Res Ther 2011;13:211-20.
8 Page 8 of 12
16. Nieto FR, Clark AK, Grist J, Hathway GJ, Chapman V, Malcangio M. Neuron-immune mechanisms contribute to pain in early stages of arthritis. J Neuroinflammation. 2016 29 Apr29;13(1):96. doi :10.1186/1 12974-016-0556-0. 17. Su J, Gao T, Shi T, Xiang Q, et al. Phenotypic changes in dorsal root ganglion and spinal
ip t
cord in the collagen antibody-induced arthritis mouse model. J Comp Neurol. 2015 Jul 1;523(10):1505-28.
cr
18. Christianson CA, Corr M, Yaksh TL, Svensson CI. K/BxN serum transfer arthritis
us
as a model of inflammatory joint pain. Methods Mol Biol 2012;851:249-60
19. Wigerblad G, Bas DB, Fernades-Cerqueira C, et al. Autoantibodies to citrullinated
an
proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism. Ann Rheum Dis 2016 75(4):730-8. doi: 10.1136/annrheumdis-2015-208094.
M
Epub 2015 Nov 27. PubMed PMID: 26613766; PubMed Central PMCID: PMC4819624. 20. Häuser W, Galek A, Erbslöh-Möller Bet al. Posttraumatic stress disorder in fibromyalgia
ed
syndrome: prevalence, temporal relationship between posttraumatic stress and fibromyalgia symptoms, and impact on clinical outcome. Pain 2013;154(8):1216-23.
ce pt
21. van Riel PL. The development of the disease activity score (DAS) and the disease activity score using 28 joint counts (DAS28). Clin Exp Rheumatol 2014;32(5 Suppl 85):S65-74.
Ac
22. Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. À new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J. Rheumatol 1994, 21(12):2286-2291. 23. Lukas C, Landewé R, Sieper J, et al. Assessment of SpondyloArthritis international Society. Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis 2009; 68(1):18-24.
9 Page 9 of 12
24. Leeb BF, Andel I, Sautner J, Nothnagl T, Rintelen B. The DAS28 in rheumatoid arthritis and fibromyalgia patients. Rheumatology (Oxford) 2004;43:1504-7. 25. Sieper J. How to define remission in ankylosing spondylitis? Ann Rheum Dis 2012; 71:93-5.
ip t
26. 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
cr
27. Smolen JS, Aletaha D, Bijlsma JW, et al. T2T Expert Committee. Treating rheumatoid
us
arthritis to target: recommendations of an international task force. Ann Rheum Dis 2010; 69(4):631-7.
an
28 Lage-Hansen PR, Chrysidis S, Lage-Hansen M, Hougaard A, Ejstrup L, Amris K. Concomitant fibromyalgia in rheumatoid arthritis is associated with the more frequent use of
M
biological therapy: a cross-sectional study. Scand J Rheumatol 2015 ;16:1-4. 29. Bello N, Etcheto A, Béal C, Dougados M, Moltó A. Evaluation of the impact of
ed
fibromyalgia in disease activity and treatment effect in spondyloarthritis. Arthritis Res Ther 2016; 9(2);18:42. doi:10.1186/s13075-016-0943-z.
ce pt
30. Perrot S, Russell IJ. More ubiquitous effects from non-pharmacologic than from pharmacologic treatments for fibromyalgia syndrome: a meta-analysis examining six core symptoms. Eur J Pain 2014 ;18(8):1067-80.
Ac
31. Atzeni F, Cazzola M, Benucci M, Di Franco M, Salaffi F, Sarzi-Puttini P. Chronic widespread pain in the spectrum of rheumatological diseases. Best Pract Res Clin Rheumatol 2011;25:165-71.
32. Crofford LJ. Psychological aspects of chronic musculoskeletal pain. Best Pract Res Clin Rheumatol 2015;29(1):147-55.
10 Page 10 of 12
33. 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. 34. Salaffi F, Sarzi-Puttini P. Old and new criteria for the classification and diagnosis of
Ac
ce pt
ed
M
an
us
cr
ip t
fibromyalgia: comparison and evaluation. Clin Exp Rheumatol 2012;30:3-9.
11 Page 11 of 12
Table 1: Fibromyalgia Rapid Screening Tool (FiRST) * [33]. 1. I have pain all over my body. 2. My pain is accompanied by a continuous and very unpleasant general fatigue. 3. My pain feels like burns, electric shocks, or cramps.
cr
5. My pain is accompanied by other health problems such as digestive problems, urinary problems, headaches, or restless legs.
ip t
4. My pain is accompanied by other unusual sensations throughout my body, such as pins and needles, tingling, or numbness.
Ac
ce pt
ed
M
an
us
6. My pain has a significant impact on my life, particularly on my sleep and my ability to concentrate, making me feel slower generally.
12 Page 12 of 12