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Highlights in clinical medicine—Giant cell arteritis, polymyalgia rheumatica and Takayasu’s arteritis: pathogenic links and therapeutic implications

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Abstract

Giant cell arteritis (GCA), frequently associated with polymyalgia rheumatica (PMR), and Takayasu’s arteritis (TAK) are characterized by extensive vascular remodeling that results in occlusion and stenosis. The pathophysiological mechanisms underlying the onset of GCA/PMR and TAK are still hypothetical. However, similarities and differences in the immunopathology and clinical phenotypes of these diseases point toward a possible link between them. The loss of tolerance in the periphery, a breakdown of tissue barriers, and the development of granulomatous vasculitis define a disease continuum. However, statistically powered studies are needed to confirm these correlations. In addition to glucocorticoids, inhibition of the interleukin-6 axis has been proposed as a cornerstone in the treatment of GCA/PMR and TAK. Novel biologic agents targeting the pathogenic pathway at various levels hold promise to achieve glucocorticoid-free sustained remission.

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Abbreviations

CCL:

C-C motif chemokine ligand

CCR:

C-C motif chemokine receptor

CD:

Cluster of differentiation

CPK:

Creatine phosphokinase

CRP:

C-reactive protein

CTLA-4:

Cytotoxic T-lymphocyte antigen 4

CXCL:

C-X-C motif ligand

CXCR:

C-X-C motif chemokine receptor

GCA:

Giant cell arteritis

ESR:

Erythrocyte sedimentation rate

ET-1:

Endothelin-1

FGF:

Fibroblast growth factor

GCs:

Glucocorticoids

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

HLA:

Human leukocyte antigen

IFN-γ:

Interferon gamma

IL:

Interleukin

IL-1RA:

Interleukin-1 receptor A

JAK:

Janus kinase

MCP:

Metacarpophalangeal

MICA:

Human major histocompatibility complex (MHC) class I chain-related gene A

MMP-9:

Matrix metalloproteinase-9

mTOR:

Mechanistic target of rapamycin

MTX:

Methotrexate

NK:

Natural killer cells

PD-L1:

Programmed death ligand 1

PD-1:

Programmed death 1

PDGF:

Platelet-derived growth factor

PIP:

Proximal interphalangeal

PMR:

Polymyalgia rheumatica

STAT:

Signal transducer and activator of transcription

T4:

Thyroxine

TAK:

Takayasu's arteritis

Th:

T helper cells

TLR:

Toll-like-receptors

Treg:

T-regulatory cells

Tγδ:

Gamma-delta T cells

VEGF:

Vascular endothelial growth factor

VSMCs:

Vascular smooth muscle cells

VZV:

Varicella zoster virus

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  1. Department of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, Medical School, Polyclinic, Piazza Giulio Cesare, 11, 70124, Bari, Italy

    Antonio Giovanni Solimando, Angelo Vacca & Franco Dammacco

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  1. Antonio Giovanni Solimando
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  2. Angelo Vacca
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All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

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Correspondence to Franco Dammacco.

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Solimando, A.G., Vacca, A. & Dammacco, F. Highlights in clinical medicine—Giant cell arteritis, polymyalgia rheumatica and Takayasu’s arteritis: pathogenic links and therapeutic implications. Clin Exp Med 22, 509–518 (2022). https://doi.org/10.1007/s10238-021-00770-4

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