PATHOGENESIS OF FIBROMYALGIA IN PATIENTS WITH AUTOIMMUNE DISEASES: SCOPING REVIEW FOR HYPOTHESIS GENERATION

Sakir Ahmed; Able Lawrence

doi:10.47316/cajmhe.2020.1.1.06

Sakir Ahmed Department of Clinical Immunology & Rheumatology, Kalinga Institute of Medical Sciences (KIMS), KIIT University, Bhubaneswar, India http://orcid.org/0000-0003-4631-311X
Able Lawrence Department of Clinical Immunology& Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India https://orcid.org/0000-0003-3439-8048

DOI: https://doi.org/10.47316/cajmhe.2020.1.1.06

Keywords: Fibromyalgia, Pathogenesis, Neuroinflammation, Autoimmunity, Pain

Abstract

Introduction: Fibromyalgia (FM) prevalence is much higher in patients with other rheumatic diseases than in the general population. This leads to increase in the perceived disease activity scores and prevents patients from reaching remission. Elucidating the pathogenesis of such “secondary” FM can help alleviate some unmet needs in these diseases.

Methods: MEDLINE and Scopus databases were searched for a scoping review for hypothesis generation regarding the genesis of secondary FM.

Results: FM has been postulated to be due to cytokine dysfunction, neurogenic neuroinflammation, stress, including social defeat, sleep disturbances, sympathetic overactivity, and small fibre neuropathy. These factors increase in most autoimmune and autoinflammatory diseases. Further the evidence for the role of these factors in the pathogenesis of FM is seems strong. Metabolic syndrome and mitochondrial dysfunction are also associated with FM, but it is difficult to distinguish between cause and effect.

Conclusion: FM is the common phenotype arising from the amalgamation of various aetiologies. Recruitment or amplification of the above 6 factors by various rheumatic diseases may thus lead precipitation of secondary FM in susceptible individuals.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

References

Heidari F, Afshari M, Moosazadeh M. Prevalence of fibromyalgia in general population and patients, a systematic review and meta-analysis. Rheumatol Int 2017;37(9):1527–1539.

Provan SA, Austad C, Halsaa V, Hammer HB, Kvien TK, Uhlig T. Fibromyalgia in patients with rheumatoid arthritis. A 10-year follow-up study, results from the Oslo Rheumatoid Arthritis Register. Clin Exp Rheumatol 2019;37 Suppl 116(1):58–62.

Mease PJ. Fibromyalgia, a missed comorbidity in spondyloarthritis: prevalence and impact on assessment and treatment. Curr Opin Rheumatol 2017;29(4):304–310.

Torrente-Segarra V, Salman-Monte TC, Rúa-Figueroa Í, Pérez-Vicente S, López-Longo FJ, Galindo-Izquierdo M, et al. Fibromyalgia prevalence and related factors in a large registry of patients with systemic lupus erythematosus. Clin Exp Rheumatol 2016;34(2 Suppl 96):S40-S47.

Torrente-Segarra V, Corominas H, Sánchez-Piedra C, Fernández-Castro M, Andreu JL, Martínez-Taboada VM, et al. Fibromyalgia prevalence and associated factors in primary Sjögren’s syndrome patients in a large cohort from the Spanish Society of Rheumatology registry (SJOGRENSER). Clin Exp Rheumatol 2017;35 Suppl 105(3):28–34.

Barton JC, Bertoli LF, Barton JC, Acton RT. Fibromyalgia in 300 adult index patients with primary immunodeficiency. Clin Exp Rheumatol 2017;35 Suppl 105(3):68–73.

Haliloglu S, Ekinci B, Uzkeser H, Sevimli H, Carlioglu A, Macit PM. Fibromyalgia in patients with thyroid autoimmunity: prevalence and relationship with disease activity. Clin Rheumatol 2017;36(7):1617–1621.

Wolfe F, Walitt B, Perrot S, Rasker JJ, Häuser W. Fibromyalgia diagnosis and biased assessment: Sex, prevalence and bias. PloS One 2018;13(9):e0203755.

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):1275–1280.

Salaffi F, Di Carlo M, Carotti M, Sarzi-Puttini P. The subjective components of the Disease Activity Score 28-joints (DAS28) in rheumatoid arthritis patients and coexisting fibromyalgia. Rheumatol Int 2018;38(10):1911–1918.

Giacomelli R, Afeltra A, Alunno A, Baldini C, Bartoloni-Bocci E, Berardicurti O, et al. International consensus: What else can we do to improve diagnosis and therapeutic strategies in patients affected by autoimmune rheumatic diseases (rheumatoid arthritis, spondyloarthritides, systemic sclerosis, systemic lupus erythematosus, antiphospholipid syndrome and Sjogren’s syndrome)?: The unmet needs and the clinical grey zone in autoimmune disease management. Autoimmun Rev 2017;16(9):911–924.

Macfarlane GJ, Barnish MS, Jones GT. Persons with chronic widespread pain experience excess mortality: longitudinal results from UK Biobank and meta-analysis. Ann Rheum Dis 2017;76(11):1815–1822.

Gasparyan AY, Ayvazyan L, Blackmore H, Kitas GD. Writing a narrative biomedical review: considerations for authors, peer reviewers, and editors. Rheumatol Int 2011;31(11):1409–1417.

Wallace DJ, Bowman RL, Wormsley SB, Peter JB. Cytokines and immune regulation in patients with fibrositis. Arthritis Rheum 1989;32(10):1334–1335.

Hader N, Rimon D, Kinarty A, Lahat N. Altered interleukin-2 secretion in patients with primary fibromyalgia syndrome. Arthritis Rheum 1991;34(7):866–872.

Maes M, Libbrecht I, Van Hunsel F, et al. The immune-inflammatory pathophysiology of fibromyalgia: increased serum soluble gp130, the common signal transducer protein of various neurotrophic cytokines. Psychoneuroendocrinology 1999;24(4):371–383.

Coskun Benlidayi I. Role of inflammation in the pathogenesis and treatment of fibromyalgia. Rheumatol Int 2019;39(5):781–791.

Metyas S, Rezk T, Arkfeld D, Leptich T. Autoinflammation and Immunomodulation in Inflammatory Fibromyalgia Syndrome- A Review. Curr Rheumatol Rev 2017;13(2):98–102.

Pereira Pernambuco A, de Souza Cota Carvalho L, Pereira Leite Schetino L, Cunha Polese J, de Souza Viana R, d’ Ávila Reis D. Effects of a health education program on cytokines and cortisol levels in fibromyalgia patients: a randomized controlled trial. Adv Rheumatol 2018;58(1):21.

Parkitny L, Younger J. Reduced Pro-Inflammatory Cytokines after Eight Weeks of Low-Dose Naltrexone for Fibromyalgia. Biomedicines 2017;5(2).

Zhang Z, Feng J, Mao A, Le K, La Placa D, Wu X, et al. SNPs in inflammatory genes CCL11, CCL4 and MEFV in a fibromyalgia family study. PloS One 2018;13(6):e0198625.

Nollet M, Guisquet A-ML, Belzung C. Models of Depression: Unpredictable Chronic Mild Stress in Mice. Curr Protoc Pharmacol 2013; Chapter 5:Unit 5.65.

Gill J, Luckenbaugh D, Charney D, Vythilingam M. Sustained Elevation of Serum Interleukin-6 and Relative Insensitivity to Hydrocortisone Differentiates Posttraumatic Stress Disorder with and Without Depression. Biol Psychiatry 2010;68(11):999–1006.

Wallace DJ, Gavin IM, Karpenko O, Barkhordar F, Gillis BS. Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis. Rheumatol Int 2015;35(6):991–996.

Snyder-Mackler N, Sanz J, Kohn JN, Brinkworth JF, Morrow S, Shaver AO, et al. Social status alters immune regulation and response to infection in macaques. Science 2016;354(6315):1041–1045.

Kosek E, Altawil R, Kadetoff D, Finn A, Westman M, Le Maître E, et al. Evidence of different mediators of central inflammation in dysfunctional and inflammatory pain--interleukin-8 in fibromyalgia and interleukin-1 β in rheumatoid arthritis. J Neuroimmunol 2015;280:49–55.

Bäckryd E, Tanum L, Lind A-L, Larsson A, Gordh T. Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma. J Pain Res 2017;10:515–525.

Bäckryd E, Lind A-L, Thulin M, Larsson A, Gerdle B, Gordh T. High levels of cerebrospinal fluid chemokines point to the presence of neuroinflammation in peripheral neuropathic pain: a cross-sectional study of 2 cohorts of patients compared with healthy controls. Pain 2017;158(12):2487–2495.

Littlejohn G. Neurogenic neuroinflammation in fibromyalgia and complex regional pain syndrome. Nat Rev Rheumatol 2015;11(11):639–648.

Brites D, Fernandes A. Neuroinflammation and Depression: Microglia Activation, Extracellular Microvesicles and microRNA Dysregulation. Front Cell Neurosci 2015;9:476.

Hassett AL, Epel E, Clauw DJ, Harris RE, Harte SE, Kairys A, et al. Pain is associated with short leukocyte telomere length in women with fibromyalgia. J Pain Off J Am Pain Soc 2012;13(10):959–969.

Tzeng N-S, Chung C-H, Liu F-C, Chiu Y-H, Chang H-A, Yeh C-B, et al. Fibromyalgia and Risk of Dementia-A Nationwide, Population-Based, Cohort Study. Am J Med Sci 2018;355(2):153–161.

Bialas AR, Presumey J, Das A, et al. Microglia-dependent synapse loss in type I interferon-mediated lupus. Nature 2017;546(7659):539–543.

Clos-Garcia M, Andrés-Marin N, Fernández-Eulate G, et al. Gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia. EBioMedicine 2019; 46:499–511.

Mackay M. Lupus brain fog: a biologic perspective on cognitive impairment, depression, and fatigue in systemic lupus erythematosus. Immunol Res 2015;63(1–3):26–37.

Bang S, Xie Y-K, Zhang Z-J, Wang Z, Xu Z-Z, Ji R-R. GPR37 regulates macrophage phagocytosis and resolution of inflammatory pain. J Clin Invest 2018;128(8):3568–3582.

Calcia MA, Bonsall DR, Bloomfield PS, Selvaraj S, Barichello T, Howes OD. Stress and neuroinflammation: a systematic review of the effects of stress on microglia and the implications for mental illness. Psychopharmacology (Berl) 2016;233(9):1637–1650.

Pagliusi MOF, Bonet IJM, Dias EV, et al. Social defeat stress induces hyperalgesia and increases truncated BDNF isoforms in the nucleus accumbens regardless of the depressive-like behavior induction in mice. Eur J Neurosci. 2018 Jun 9; [Epub ahead of print].

Kakuta Y, Kawai Y, Okamoto D, et al. NUDT15 codon 139 is the best pharmacogenetic marker for predicting thiopurine-induced severe adverse events in Japanese patients with inflammatory bowel disease: a multicenter study. J Gastroenterol 2018;53(9):1065–1078.

Hollis F, Kabbaj M. Social Defeat as an Animal Model for Depression. ILAR J 2014;55(2):221–232.

Rose J, Rillich J, Stevenson PA. Chronic social defeat induces long-term behavioral depression of aggressive motivation in an invertebrate model system. PloS One 2017;12(9):e0184121.

Ramirez K, Fornaguera-Trías J, Sheridan JF. Stress-Induced Microglia Activation and Monocyte Trafficking to the Brain Underlie the Development of Anxiety and Depression. Curr Top Behav Neurosci 2017;31:155–172.

Yavne Y, Amital D, Watad A, Tiosano S, Amital H. A systematic review of precipitating physical and psychological traumatic events in the development of fibromyalgia. Semin Arthritis Rheum 2018;48(1):121–133.

Branco J, Atalaia A, Paiva T. Sleep cycles and alpha-delta sleep in fibromyalgia syndrome. J Rheumatol 1994;21(6):1113–1117.

Choy EHS. The role of sleep in pain and fibromyalgia. Nat Rev Rheumatol 2015;11(9):513–520.

Meresh ES, Artin H, Joyce C, et al. Obstructive sleep apnea co-morbidity in patients with fibromyalgia: a single-center retrospective analysis and literature review. Open Access Rheumatol 2019;11:103–109.

Sangle SR, Tench CM, D’Cruz DP. Autoimmune rheumatic disease and sleep: a review. Curr Opin Pulm Med 2015;21(6):553–556.

Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES. The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev 2000;52(4):595–638.

Kaplan R, Robinson CA, Scavulli JF, Vaughan JH. Propranolol and the treatment of rheumatoid arthritis. Arthritis Rheum 1980;23(2):253–255.

Koopman FA, Chavan SS, Miljko S, Grazio S, Sokolovic S, Schuurman PR, et al. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc Natl Acad Sci 2016;113(29):8284–8289.

Koopman FA, van Maanen MA, Vervoordeldonk MJ, Tak PP. Balancing the autonomic nervous system to reduce inflammation in rheumatoid arthritis. J Intern Med 2017;282(1):64–75.

Martínez-Martínez L-A, Mora T, Vargas A, Fuentes-Iniestra M, Martínez-Lavín M. Sympathetic nervous system dysfunction in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis: a review of case-control studies. J Clin Rheumatol 2014;20(3):146–150.

de Tommaso M, Ricci K, Libro G, Vecchio E, Delussi M, Montemurno A, et al. Pain Processing and Vegetative Dysfunction in Fibromyalgia: A Study by Sympathetic Skin Response and Laser Evoked Potentials. Pain Res Treat 2017;2017:9747148.

Albrecht PJ, Hou Q, Argoff CE, Storey JR, Wymer JP, Rice FL. Excessive peptidergic sensory innervation of cutaneous arteriole-venule shunts (AVS) in the palmar glabrous skin of fibromyalgia patients: implications for widespread deep tissue pain and fatigue. Pain Med Malden Mass 2013;14(6):895–915.

Lee YH, Kim J-H, Song GG. Association between the COMT Val158Met polymorphism and fibromyalgia susceptibility and fibromyalgia impact questionnaire score: a meta-analysis. Rheumatol Int 2015;35(1):159–166.

Baron R, Hans G, Dickenson AH. Peripheral input and its importance for central sensitization. Ann Neurol 2013;74(5):630–636.

Üçeyler N, Zeller D, Kahn A-K, Kewenig S, Kittel-Schneider S, Schmid A, et al. Small fibre pathology in patients with fibromyalgia syndrome. Brain J Neurol 2013;136(Pt 6):1857–1867.

Levine TD, Saperstein DS. Routine use of punch biopsy to diagnose small fiber neuropathy in fibromyalgia patients. Clin Rheumatol 2015;34(3):413–417.

Ramírez M, Martínez-Martínez L-A, Hernández-Quintela E, Velazco-Casapía J, Vargas A, Martínez-Lavín M. Small fiber neuropathy in women with fibromyalgia. An in vivo assessment using corneal confocal bio-microscopy. Semin Arthritis Rheum 2015;45(2):214–219.

Park D-J, Kim S-H, Nah S-S, et al. Polymorphisms of the TRPV2 and TRPV3 genes associated with fibromyalgia in a Korean population. Rheumatology (Oxford) 2016;55(8):1518–1527.

Vargas-Alarcon G, Alvarez-Leon E, Fragoso J-M, et al. A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia. BMC Musculoskelet Disord 2012;13:23.

Birnbaum J, Lalji A, Saed A, Baer AN. Biopsy-Proven Small-Fiber Neuropathy in Primary Sjögren’s Syndrome: Neuropathic Pain Characteristics, Autoantibody Findings, and Histopathologic Features. Arthritis Care Res 2019;71(7):936–948.

Lee J-Y, Choi S-H, Park K-S, et al. Comparison of complex regional pain syndrome and fibromyalgia: Differences in beta and gamma bands on quantitative electroencephalography. Medicine (Baltimore) 2019;98(7):e14452.

Loevinger BL, Muller D, Alonso C, Coe CL. Metabolic syndrome in women with chronic pain. Metabolism 2007;56(1):87–93.

Malatji BG, Meyer H, Mason S, et al. A diagnostic biomarker profile for fibromyalgia syndrome based on an NMR metabolomics study of selected patients and controls. BMC Neurol 2017;17(1):88.

Alcocer-Gómez E, Garrido-Maraver J, Bullón P, et al. Metformin and caloric restriction induce an AMPK-dependent restoration of mitochondrial dysfunction in fibroblasts from Fibromyalgia patients. Biochim Biophys Acta 2015;1852(7):1257–1267.

Sánchez-Domínguez B, Bullón P, Román-Malo L, et al. Oxidative stress, mitochondrial dysfunction and, inflammation common events in skin of patients with Fibromyalgia. Mitochondrion 2015;21:69–75.

Culmsee C, Michels S, Scheu S, Arolt V, Dannlowski U, Alferink J. Mitochondria, Microglia, and the Immune System-How Are They Linked in Affective Disorders? Front Psychiatry 2018;9:739.

Rivat C, Ballantyne J. The dark side of opioids in pain management: basic science explains clinical observation. PAIN Rep 2016;1(2):e570.

Ferrini F, Trang T, Mattioli T-AM, et al. Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl− homeostasis. Nat Neurosci 2013;16(2):183–192.

Marques AP, Santo A de S do E, Berssaneti AA, Matsutani LA, Yuan SLK. Prevalence of fibromyalgia: literature review update. Rev Bras Reumatol Engl Ed 2017;57(4):356–363.

Queiroz LP. Worldwide epidemiology of fibromyalgia. Curr Pain Headache Rep 2013;17(8):356.