Dezember 2023

Association between infection and the onset of giant cell arteritis and polymyalgia rheumatica: a systematic review and meta-analysis

VASAS summary
Why some patients get autoimmune diseases, including vasculitis, is still not well understood. Besides genetic predisposition (in the case of GCA HLA-DR4), infections have been associated with different autoimmune diseases. The theory states that infections activate the immune system causing inflammation. Inflammation can accidentally also target healthy tissue. Such collateral damage can be mediated by unspecific immune cell activation (so-called ‘bystander activation’) or by a specific immune response against the pathogen that also recognizes proteins from the healthy cells due to similarities to pathogen-derived proteins (‘molecular mimicry’). To date, however, there is no conclusive evidence of whether infections in general or specific infections may trigger autoimmunity. In giant cell arteritis (GCA), several studies suggested a correlation between disease onset and herpes zoster, parainfluenza virus, or other infections.

A French group now performed a review and meta-analysis of the literature on infections and the onset of GCA (and polymyalgia rheumatica, PMR). The study found a significant and positive association between overall infections and the onset of GCA. This effect was consistent, but with only about 1.3 times increased risk, it was not very strong. Interestingly, the effect was only detectable when the infection occurred within the year before the GCA/PMR diagnosis was made and not if the infection was >12 months ago. Given that this data supports that infection and disease onset are time-related, this supports the hypothesis that any infection can be a potential trigger for GCA/PMR.

When looking at specific infections, a similar association was observed between GCA/PMR and herpes zoster infections. Interestingly, this association was regardless of the timing of the infection, suggesting that a Zoster might not be a trigger but a pre-existing condition potentially influencing GCA pathogenesis through cross-reactive T cells (‘molecular mimicry’). VASAS members and other research groups previously investigated this question studying GCA patients at diagnosis for the presence of Varicella Zoster Virus (VZV) specific and artery-specific T cells. We found no evidence for enhanced anti-Zoster or artery immunity compared to healthy controls (Bigler MB et al, Arthritis & Rheumatol. 2018). The link between infection may, therefore, be more complex than just molecular mimicry.

In summary, the meta-analysis further supports the role of infections in GCA. The study also highlights the need for further research to understand whether infections act as triggers of autoimmunity or are rather indicators of an age-related immune dysfunction contributing to GCA pathogenesis.

Pacoureau L et al. Association between infection and the onset of giant cell arteritis and polymyalgia rheumatica: a systematic review and meta-analysis. RMD Open. 2023 Nov;9(4):e003493. doi: 10.1136/rmdopen-2023-003493.

Verfasst von
Prof. Dr. med. Christoph T. Berger
Senior Physician, Clinical Immunology
PI Translational Immunology
University Hospital Basel
December 2023

November 2023

Subclinical giant cell arteritis increases the risk of relapse in polymyalgia rheumatica

Die vorliegende Studie hatte zum Ziel, die klinische Bedeutung der subklinischen Riesenzellarteriitis (RZA) bei Polymyalgie (PMR) zu untersuchen und den optimalen Behandlungsansatz zu ermitteln.

October 2023

Sarilumab for Relapse of Polymyalgia Rheumatica during Glucocorticoid Taper

Die Polymyalgia rheumatica (PMR) rezidiviert häufig bei Reduktion der Glucokortikoid-(GC)-dosis. Traditionell wird dann als GC-sparende Massnahme Methotrexat (MTX) eingesetzt.

August 2023

Serum proteomics in giant cell arteritis in response to a three-day pulse of glucocorticoid followed by tocilizumab monotherapy (the GUSTO trial)

Interleukin-6 wird oft als pro-inflammatorisches Zytokin, ähnlich dem TNFa und dem IL-1b verstanden. Dies stimmt nicht, denn IL-6 löst auch entzündungsbegrenzende Mechanismen aus, beispielsweise die Expression des Tissue Inhibitors of Metalloproteinasen (TIMP).

May 2023

Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial

Trotz eines deutlich verbesserten Outcomes durch den Einsatz von Glukokortikoide und Cyclophosphamid sind Rückfälle bei der Granulomatose mit Polyangiitis (GPA) und der mikroskopische Polyangiitis (MPA) nach wie vor ein großes Problem.

Publikationen im Thema Vaskulitis von Mitgliedern der VASAS - 2023

  1. Frank Moosig, Paolo Bottero, Alberto Pesci, et al: Cluster Analysis to Explore Clinical Subphenotypes of Eosinophilic Granulomatosis With Polyangiitis. The Journal of Rheumatology 2023;50:1446–53. doi:10.3899/jrheum.2023-0325

  2. Geetha D, Dua A, Yue H, et al. ADVOCATE Study Group. Efficacy and safety of avacopan in patients with ANCA-associated vasculitis receiving rituximab in a randomised trial. Ann Rheum Dis. 2023 Nov 18:ard-2023-224816. doi: 10.1136/ard-2023-224816. PMID: 37979959

  3. Hemmig AK, Aschwanden M, Berger CT, et al. Prior polymyalgia rheumatica is associated with sonographic vasculitic changes in newly diagnosed patients with giant cell arteritis. Rheumatology (Oxford). 2023 Aug 30: doi: 10.1093/rheumatology/kead450. Online ahead of print. PMID: 37647653

  4. Mensch N, Hemmig AK, Aschwanden M, et al. Rapid glucocorticoid tapering regimen in patients with giant cell arteritis: a single centre cohort study. RMD Open. 2023 Jul;9(3):e003301. doi: 10.1136/rmdopen-2023-003301. PMID: 37460275

  5. Hemmig AK, Aschwanden M, Seiler S, et al. Long delay from symptom onset to first consultation contributes to permanent vision loss in patients with giant cell arteritis: a cohort study. RMD Open. 2023 Jan;9(1):e002866. doi: 10.1136/rmdopen-2022-002866. PMID: 36635003

  6. Hemmig AK, Aschwanden M, Imfeld S, et al. A diagnostic performance study of the 2022 American College of Rheumatology/EULAR classification criteria for giant cell arteritis in a cohort of patients presenting with suspected giant cell arteritis. Arthritis Rheumatol. 2023 Jun;75(6):1075-1077. doi: 10.1002/art.42440. PMID: 36622332

  7. Rose K, Turner JE, Iking-Konert C. [Immunoglobulin A vasculitis (IgAV)]. Z Rheumatol. 2023 Sep;82(7):587-598. doi: 10.1007/s00393-023-01355-0.

  8. Cortazar FB, Niles JL, Jayne DRW, et al. ADVOCATE Study Group. Renal Recovery for Patients with ANCA-Associated Vasculitis and Low eGFR in the ADVOCATE Trial of Avacopan. Kidney Int Rep. 2023 Feb 3;8(4):860-870. doi: 10.1016/j.ekir.2023.01.039. PMID: 37069984

  9. Giacomo Emmi, Alessandra Bettiol, et al. Evidence-Based Guideline for the diagnosis and management of eosinophilic granulomatosis with polyangiitis. Nat Rev Rheumatol. 2023 Jun;19(6):378-393. doi: 10.1038/s41584-023-00958-w.

  10. Wolfgang A Schmidt, Bhaskar Dasgupta, Jennifer Sloane, et al. A phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of sarilumab in patients with giant cell arteritis. Arthritis Res Ther. 2023 Oct 16;25(1):199. doi: 10.1186/s13075-023-03177-6.

  11. Robert F Spiera, Sebastian Unizony, Kenneth J Warrington, et al (SAPHYR Investigators) Sarilumab for Relapse of Polymyalgia Rheumatica during Glucocorticoid Taper. N Engl J Med. 2023 Oct 5;389(14):1263-1272. doi: 10.1056/NEJMoa2303452.

  12. Lisa Christ, Andrea D Gloor, Florian Kollert, et al. Serum proteomics in giant cell arteritis in response to a three-day pulse of glucocorticoid followed by tocilizumab monotherapy (the GUSTO trial) Front Immunol. 2023 May 23:14:1165758. doi: 10.3389/fimmu.2023.1165758. eCollection 2023.

  13. Michele Iudici, Andrea Katharina Hemmig, Mihaela Stegert, et al. Giant Cell Arteritis SCQM Study Group. Management of giant-cell arteritis in Switzerland: an online national survey Swiss Med Wkly. 2023 Apr 3:153:40051. doi: 10.57187/smw.2023.40051.

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