Abstract
Purpose of the Review
Polymyalgia rheumatica (PMR) is one of the most common inflammatory rheumatologic condition occurring in older adults. It is characterized by proximal pain and stiffness in the shoulders, neck, and/or pelvic girdle in individuals over 50 years of age along with evidence of an intense systemic inflammatory response. Although the above clinical symptoms are very characteristic for the condition, it can be mimicked by other autoimmune, infectious, malignant, and endocrine disorders chief among which are giant cell arteritis (GCA) and elderly-onset rheumatoid arthritis (EORA). Recently, PMR was reported in relation to treatment with immune checkpoint inhibitors.
Current treatment of PMR consists of low-to-medium doses of glucocorticosteroids (GC) with variable response rates and disease recurrence estimated to occur in 50% of patients while tapering down GC doses. In addition, GC-based regimens cause much of the morbidity associated with PMR in older adults, requiring close monitoring for GC-induced toxicity during therapy and highlighting the need for novel therapeutic strategies. Here, we review the latest findings in the field regarding specific etiologic factors, genetic associations, diagnostic methods, and advancements in treatment strategies and disease monitoring indices.
Recent Findings
Recent discoveries involving novel therapeutic targets in GCA have accelerated the study of PMR pathophysiology and have advanced treatment strategies in PMR management leading to current trials in IL-6 blocking agents.
Summary
PMR remains an enigmatic inflammatory condition affecting older adults, with current treatment approach causing much morbidity in this patient population. Advancements in our understanding of novel immunopathologic targets can serve as a solid foundation for future treatment strategies in the field.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Barber HS. Myalgic syndrome with constitutional effects; polymyalgia rheumatica. Ann Rheum Dis. 1957;16:230–7.
Michet CJ, Matteson EL. Polymyalgia rheumatica. BMJ. 2008;336:765–9.
Crowson CS, Matteson EL, Myasoedova E, Michet CJ, Ernste FC, Warrington KJ, et al. The lifetime risk of adult-onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases. Arthritis Rheum. 2011;63:633–9.
Matteson EL, Dejaco C. Polymyalgia Rheumatica. Ann Intern Med. 2017;166:ITC65–80.
Dejaco C, Duftner C, Buttgereit F, Matteson EL, Dasgupta B. The spectrum of giant cell arteritis and polymyalgia rheumatica: revisiting the concept of the disease. Rheumatology. 2017;56:506–15.
Dejaco C, Duftner C, Schirmer M. Are regulatory T-cells linked with aging? Exp Gerontol. 2006;41:339–45.
Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54.
Mohan SV, Liao YJ, Kim JW, Goronzy JJ, Weyand CM. Giant cell arteritis: immune and vascular aging as disease risk factors. Arthritis Res Ther. 2011;13:231.
Singh JA, Cleveland JD. The risk of polymyalgia rheumatica in older adults with gout: a Medicare claims study. Rheumatol Adv Pract. 2018;2.
Samson M, Audia S, Fraszczak J, Trad M, Ornetti P, Lakomy D, et al. Th1 and Th17 lymphocytes expressing CD161 are implicated in giant cell arteritis and polymyalgia rheumatica pathogenesis. Arthritis Rheum. 2012;64:3788–98.
Stone JH, Klearman M, Collinson N. Trial of Tocilizumab in Giant-cell arteritis. N Engl J Med. 2017;377:1494–5.
Salvarani C, Gabriel SE, O’Fallon WM, Hunder GG. The incidence of giant cell arteritis in Olmsted County, Minnesota: apparent fluctuations in a cyclic pattern. Ann Intern Med. 1995;123:192–4.
England BR, Mikuls TR, Xie F, Yang S, Chen L, Curtis JR. Herpes zoster as a risk factor for incident giant cell arteritis. Arthritis Rheum. 2017;69:2351–8.
Castañeda S, García-Castañeda N, Prieto-Peña D, Martínez-Quintanilla D, Vicente EF, Blanco R, et al. Treatment of polymyalgia rheumatica. Biochem Pharmacol. 2019;165:221–9.
Salvarani C, Macchioni PL, Tartoni PL, Rossi F, Baricchi R, Castri C, et al. Polymyalgia rheumatica and giant cell arteritis: a 5-year epidemiologic and clinical study in Reggio Emilia, Italy. Clin Exp Rheumatol. 1987;5:205–15.
Caylor TL, Perkins A. Recognition and management of polymyalgia rheumatica and giant cell arteritis. Am Fam Physician. 2013;88:676–84.
Wise CM, Agudelo CA, Chmelewski WL, McKnight KM. Temporal arteritis with low erythrocyte sedimentation rate: a review of five cases. Arthritis Rheum. 1991;34:1571–4.
Hazleman B. Laboratory investigations useful in the evaluation of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). Clin Exp Rheumatol. 2000;18:S29–31.
Chakravarty K, Pountain G, Merry P, Byron M, Hazleman B, Scott DG. A longitudinal study of anticardiolipin antibody in polymyalgia rheumatica and giant cell arteritis. J Rheumatol. 1995;22:1694–7.
Patil P, Dasgupta B. Polymyalgia rheumatica in older adults. Aging Health. 2013;9:483–95.
Camellino D, Cimmino MA. Are the new ACR/EULAR criteria the ultimate answer for polymyalgia rheumatica classification? J Rheumatol. 2016;43:836–8.
Dejaco C, Singh YP, Perel P, Hutchings A, Camellino D, Mackie S, et al. 2015 recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Arthritis Rheum. 2015;67:2569–80.
Dasgupta B, Cimmino MA, Maradit-Kremers H, Schmidt WA, Schirmer M, Salvarani C, et al. 2012 provisional classification criteria for polymyalgia rheumatica: a European league against rheumatism/American College of Rheumatology collaborative initiative. Ann Rheum Dis. 2012;71:484–92.
Macchioni P, Boiardi L, Catanoso M, Pazzola G, Salvarani C. Performance of the new 2012 EULAR/ACR classification criteria for polymyalgia rheumatica: comparison with the previous criteria in a single-centre study. Ann Rheum Dis. 2014;73:1190–3.
Ozen G, Inanc N, Unal AU, Bas S, Kimyon G, Kisacik B, et al. Assessment of the new 2012 EULAR/ACR clinical classification criteria for polymyalgia rheumatica: a prospective multicenter study. J Rheumatol. 2016;43:893–900.
González-Gay, García-Porrúa, Salvarani, Olivieri, Hunder. Polymyalgia manifestations in different conditions mimicking polymyalgia rheumatica. Clin Exp Rheumatol. 2000;18:755–9.
Ceccato F, Uña C, Regidor M, Rillo O, Babini S, Paira S. Conditions mimicking polymyalgia rheumatica. Reumatol Clin. 2011;7:156–60.
•• Partington R, Helliwell T, Muller S, Abdul Sultan A, Mallen C. Comorbidities in polymyalgia rheumatica: a systematic review. Arthritis Res Ther. 2018;20:258 This study is an excellent systematic review on the literature examining the prevalence of comorbidities associated with PMR.
Hancock AT, Mallen CD, Muller S, Belcher J, Roddy E, Helliwell T, et al. Risk of vascular events in patients with polymyalgia rheumatica. Can Med Assoc J. 2014;186:E495–501.
Ungprasert P, Koster MJ, Warrington KJ, Matteson EL. Polymyalgia rheumatica and risk of coronary artery disease: a systematic review and meta-analysis of observational studies. Rheumatol Int. 2017;37:143–9.
Maradit Kremers H, Reinalda MS, Crowson CS, Davis JM, Hunder GG, Gabriel SE. Glucocorticoids and cardiovascular and cerebrovascular events in polymyalgia rheumatica. Arthritis Rheum. 2007;57:279–86.
Bowness P, Shotliff K, Middlemiss A, Myles AB. Prevalence of hypothyroidism in patients with polymyalgia rheumatica and giant cell arteritis. Br J Rheumatol. 1991;30:349–51.
Juchet H, Labarthe MP, Ollier S, Vilain C, Arlet P. Prevalence of hypothyroidism and hyperthyroidism in temporal arteritis and rhizomelic pseudopolyarthritis. A controlled study of 104 cases. Rev Rhum Ed Fr. 1993;60:493–8.
Li X, Sundquist J, Sundquist K. Subsequent risks of Parkinson disease in patients with autoimmune and related disorders: a nationwide epidemiological study from Sweden. Neurodegener Dis. 2012;10:277–84.
Chakravarty E, Genovese MC. Rheumatic syndromes associated with malignancy. Curr Opin Rheumatol. 2003;15:35–43.
Muller S, Hider SL, Belcher J, Helliwell T, Mallen CD. Is cancer associated with polymyalgia rheumatica? A cohort study in the General Practice Research Database. Ann Rheum Dis. 2014;73:1769–73.
Ji J, Liu X, Sundquist K, Sundquist J, Hemminki K. Cancer risk in patients hospitalized with polymyalgia rheumatica and giant cell arteritis: a follow-up study in Sweden. Rheumatology. 2010;49:1158–63.
Pfeifer EC, Crowson CS, Major BT, Matteson EL. Polymyalgia rheumatica and its association with cancer. Rheumatology (Sunnyvale). 2015;Suppl 6.
Myklebust G, Wilsgaard T, Jacobsen BK, Gran JT. No increased frequency of malignant neoplasms in polymyalgia rheumatica and temporal arteritis. A prospective longitudinal study of 398 cases and matched population controls. J Rheumatol. 2002;29:2143–7.
Naschitz JE, Slobodin G, Yeshurun D, Rozenbaum M, Rosner I. Atypical polymyalgia rheumatica as a presentation of metastatic cancer. Arch Intern Med. 1997;157:2381.
Gonzalez-Gay MA, Garcia-Porrua C, Salvarani C, Olivieri I, Hunder GG. The spectrum of conditions mimicking polymyalgia rheumatica in northwestern Spain. J Rheumatol. 2000;27:2179–84.
Gonzalez-Gay MA. Giant cell arteritis and polymyalgia rheumatica: two different but often overlapping conditions. Semin Arthritis Rheum. 2004;33:289–93.
Blockmans D, De Ceuninck L, Vanderschueren S, Knockaert D, Mortelmans L, Bobbaers H. Repetitive 18-fluorodeoxyglucose positron emission tomography in isolated polymyalgia rheumatica: a prospective study in 35 patients. Rheumatology. 2007;46:672–7.
Schmidt WA, Gromnica-Ihle E. Incidence of temporal arteritis in patients with polymyalgia rheumatica: a prospective study using colour Doppler ultrasonography of the temporal arteries. Rheumatology. 2002;41:46–52.
Salvarani C, Cantini F, Hunder G. Polymyalgia rheumatica and giant-cell arteritis. Lancet. 2008;372:234–45.
Laskou F, Coath F, Mackie SL, Banerjee S, Aung T, Dasgupta B. A probability score to aid the diagnosis of suspected giant cell arteritis. Clin Exp Rheumatol. 2019;37(Suppl 117):104–8.
González-Gay MA, García-Porrúa C, Vázquez-Caruncho M. Polymyalgia rheumatica in biopsy proven giant cell arteritis does not constitute a different subset but differs from isolated polymyalgia rheumatica. J Rheumatol. 1998;25:1750–5.
McCarty DJ, O’Duffy JD, Pearson L, Hunter JB. Remitting seronegative symmetrical synovitis with pitting edema. RS3PE syndrome. JAMA. 1985;254:2763–7.
Varshney AN, Singh NK. Syndrome of remitting seronegative symmetrical synovitis with pitting edema: a case series. J Postgrad Med. 2015;61:38–41.
Belloli L, Massarotti M, Marasini B. Polymyalgia rheumatica and elderly onset rheumatoid arthritis. J Clin Rheumatol. 2008;14:59.
Goldstein BL, Gedmintas L, Todd DJ. Drug-associated polymyalgia rheumatica/giant cell arteritis occurring in two patients after treatment with ipilimumab, an antagonist of ctla-4. Arthritis Rheum. 2014;66:768–9.
Garel B, Kramkimel N, Trouvin A-P, Frantz C, Dupin N. Pembrolizumab-induced polymyalgia rheumatica in two patients with metastatic melanoma. Joint Bone Spine. 2017;84:233–4.
• Calabrese C, Cappelli LC, Kostine M, Kirchner E, Braaten T, Calabrese L. Polymyalgia rheumatica-like syndrome from checkpoint inhibitor therapy: case series and systematic review of the literature. RMD Open. 2019;5:e000906 This systematic review is unique in highlighting atypical clinical features of ICI-related PMR.
Belkhir R, Burel SL, Dunogeant L, Marabelle A, Hollebecque A, Besse B, et al. Rheumatoid arthritis and polymyalgia rheumatica occurring after immune checkpoint inhibitor treatment. Ann Rheum Dis. 2017;76:1747–50.
Zhang H, Watanabe R, Berry GJ, Vaglio A, Liao YJ, Warrington KJ, et al. Immunoinhibitory checkpoint deficiency in medium and large vessel vasculitis. Proc Natl Acad Sci U S A. 2017;114:E970–9.
van Assen S, Agmon-Levin N, Elkayam O, Cervera R, Doran MF, Dougados M, et al. EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2011;70:414–22.
Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res. 2012;64:625–39.
Dasgupta B, Borg FA, Hassan N, Barraclough K, Bourke B, Fulcher J, et al. BSR and BHPR guidelines for the management of polymyalgia rheumatica. Rheumatology. 2010;49:186–90.
Matteson EL, Maradit-Kremers H, Cimmino MA, Schmidt WA, Schirmer M, Salvarani C, et al. Patient-reported outcomes in polymyalgia rheumatica. J Rheumatol. 2012;39:795–803.
Hernández-Rodríguez J, Cid MC, López-Soto A, Espigol-Frigolé G, Bosch X. Treatment of polymyalgia rheumatica: a systematic review. Arch Intern Med. 2009;169:1839–50.
Dasgupta B, Dolan AL, Panayi GS, Fernandes L. An initially double-blind controlled 96 week trial of depot methylprednisolone against oral prednisolone in the treatment of polymyalgia rheumatica. Br J Rheumatol. 1998;37:189–95.
Sundahl N, Bridelance J, Libert C, De Bosscher K, Beck IM. Selective glucocorticoid receptor modulation: new directions with non-steroidal scaffolds. Pharmacol Ther. 2015;152:28–41.
van den Hoven JM, Van Tomme SR, Metselaar JM, Nuijen B, Beijnen JH, Storm G. Liposomal drug formulations in the treatment of rheumatoid arthritis. Mol Pharm. 2011;8:1002–15.
Raine C, Stapleton PP, Merinopoulos D, Maw WW, Achilleos K, Gayford D, et al. A 26-week feasibility study comparing the efficacy and safety of modified-release prednisone with immediate-release prednisolone in newly diagnosed cases of giant cell arteritis. Int J Rheum Dis. 2018;21:285–91.
Ferraccioli G, Salaffi F, De Vita S, Casatta L, Bartoli E. Methotrexate in polymyalgia rheumatica: preliminary results of an open, randomized study. J Rheumatol. 1996;23:624–8.
Caporali R, Cimmino MA, Ferraccioli G, Gerli R, Klersy C, Salvarani C, et al. Prednisone plus methotrexate for polymyalgia rheumatica: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2004;141:493–500.
De Silva M, Hazleman BL. Azathioprine in giant cell arteritis/polymyalgia rheumatica: a double-blind study. Ann Rheum Dis. 1986;45:136–8.
Adizie T, Christidis D, Dharmapaliah C, Borg F, Dasgupta B. Efficacy and tolerability of leflunomide in difficult-to-treat polymyalgia rheumatica and giant cell arteritis: a case series. Int J Clin Pract. 2012;66:906–9.
Diamantopoulos AP, Hetland H, Myklebust G. Leflunomide as a corticosteroid-sparing agent in giant cell arteritis and polymyalgia rheumatica: a case series. Biomed Res Int. 2013;2013:120638.
Salvarani C, Macchioni P, Manzini C, Paolazzi G, Trotta A, Manganelli P, et al. Infliximab plus prednisone or placebo plus prednisone for the initial treatment of polymyalgia rheumatica: a randomized trial. Ann Intern Med. 2007;146:631–9.
Kreiner F, Galbo H. Effect of etanercept in polymyalgia rheumatica: a randomized controlled trial. Arthritis Res Ther. 2010;12:R176.
Lally L, Forbess L, Hatzis C, Spiera R. Brief report: a prospective open-label phase IIa trial of tocilizumab in the treatment of polymyalgia rheumatica. Arthritis Rheum. 2016;68:2550–4.
Devauchelle-Pensec V, Berthelot JM, Cornec D, Renaudineau Y, Marhadour T, Jousse-Joulin S, et al. Efficacy of first-line tocilizumab therapy in early polymyalgia rheumatica: a prospective longitudinal study. Ann Rheum Dis. 2016;75:1506–10.
Langford CA, Cuthbertson D, Ytterberg SR, Khalidi N, Monach PA, Carette S, et al. A randomized, double-blind trial of abatacept (CTLA-4Ig) for the treatment of giant cell arteritis. Arthritis Rheum. 2017;69:837–45.
O’Shea JJ, Kontzias A, Yamaoka K, Tanaka Y, Laurence A. Janus kinase inhibitors in autoimmune diseases. Ann Rheum Dis. 2013;72(Suppl 2):ii111–5.
Zhang H, Watanabe R, Berry GJ, Tian L, Goronzy JJ, Weyand CM. Inhibition of JAK-STAT signaling suppresses pathogenic immune responses in medium and large vessel vasculitis. Circulation. 2018;137:1934–48.
Dejaco C, Duftner C, Cimmino MA, Dasgupta B, Salvarani C, Crowson CS, et al. Definition of remission and relapse in polymyalgia rheumatica: data from a literature search compared with a Delphi-based expert consensus. Ann Rheum Dis. 2011;70:447–53.
Leeb BF, Bird HA. A disease activity score for polymyalgia rheumatica. Ann Rheum Dis. 2004;63:1279–83.
Chuang TY, Hunder GG, Ilstrup DM, Kurland LT. Polymyalgia rheumatica: a 10-year epidemiologic and clinical study. Ann Intern Med. 1982;97:672–80.
Gran JT, Myklebust G, Wilsgaard T, Jacobsen BK. Survival in polymyalgia rheumatica and temporal arteritis: a study of 398 cases and matched population controls. Rheumatology. 2001;40:1238–42.
Doran MF, Crowson CS, O’Fallon WM, Hunder GG, Gabriel SE. Trends in the incidence of polymyalgia rheumatica over a 30 year period in Olmsted County, Minnesota, USA. J Rheumatol. 2002;29:1694–7.
Myklebust G, Wilsgaard T, Jacobsen BK, Gran JT. Causes of death in polymyalgia rheumatica. A prospective longitudinal study of 315 cases and matched population controls. Scand J Rheumatol. 2003;32:38–41.
Gabriel SE, Sunku J, Salvarani C, O’Fallon WM, Hunder GG. Adverse outcomes of antiinflammatory therapy among patients with polymyalgia rheumatica. Arthritis Rheum. 1997;40:1873–8.
Buckley L, Guyatt G, Fink HA, Cannon M, Grossman J, Hansen KE, et al. 2017 American College of Rheumatology Guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheum. 2017;69:1521–37.
• Miloslavsky EM, Naden RP, Bijlsma JWJ, Brogan PA, Brown ES, Brunetta P, et al. Development of a glucocorticoid toxicity index (GTI) using multicriteria decision analysis. Ann Rheum Dis. 2017;76:543–6 This study is the official report delineating the development and outcome measures incorporated into the GTI.
Slobodin G, Rimar D, Boulman N, Kaly L, Rozenbaum M, Rosner I, et al. Acute sacroiliitis. Clin Rheumatol. 2016;35:851–6.
Gazitt T, Kibari A, Nasrallah N, Abu Elhija M, Zisman D. Polymyalgia rheumatica: the great imitator. Isr Med Assoc J. 2019;21:627–8.
Mallia C, Coleiro B, Crockford M, Ellul B. Raynaud’s phenomenon caused by giant cell arteritis. A case report. Adv Exp Med Biol. 1999;455:517–20.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare that they have no conflicts of interest.
Human and Animal Rights and Informed Consent
The patient’s written consent was obtained for the figures found in this manuscript.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Rheumatoid Arthritis
Electronic supplementary material
ESM 1
(DOC 115 kb)
Rights and permissions
About this article
Cite this article
Gazitt, T., Zisman, D. & Gardner, G. Polymyalgia Rheumatica: a Common Disease in Seniors. Curr Rheumatol Rep 22, 40 (2020). https://doi.org/10.1007/s11926-020-00919-2
Published:
DOI: https://doi.org/10.1007/s11926-020-00919-2