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Predominant ligament-centric soft-tissue involvement differentiates axial psoriatic arthritis from ankylosing spondylitis

Nature Reviews Rheumatology volume 19, pages 818–827 (2023)Cite this article

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Abstract

Since the original description of spondyloarthritis 50 years ago, results have demonstrated similarities and differences between ankylosing spondylitis (AS) and axial psoriatic arthritis (PsA). HLA-B27 gene carriage in axial inflammation is linked to peri-fibrocartilaginous sacroiliac joint osteitis, as well as to spinal peri-entheseal osteitis, which is often extensive and which provides a crucial anatomical and immunological differentiation between the AS and PsA phenotypes. Specifically, HLA-B27-related diffuse bone marrow oedema (histologically an osteitis) and bone marrow fatty corners detected via magnetic resonance imaging, as well as radiographic changes such as sacroiliitis, vertebral squaring, corner erosions and Romanus lesions, all indicate initial bone phenotypes in HLA-B27+ axial disease. However, in much of PsA with axial involvement, enthesitis primarily manifests in ligamentous soft tissue as ‘ligamentitis’, with characteristic lesions that include para-syndesmophytes and sacroiliac joint bony sparing. Like axial PsA, diffuse idiopathic skeletal hyperostosis phenotypes, which can be indistinguishable from PsA, exhibit a thoracic and cervical spinal ligamentous soft-tissue tropism, clinically manifesting as syndesmophytosis that is soft-tissue-centric, including paravertebral soft-tissue ossification and sacroiliac soft-ligamentous ossification instead of joint-cavity fusion. The enthesis bone and soft tissues have radically different immune cell and stromal compositions, which probably underpins differential responses to immunomodulatory therapy, especially IL-23 inhibition.

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Fig. 1: Commonalities and differences between AS, axial PsA and DISH.
Fig. 2: Bone phenotype in HLA-B27+-related arthritis and soft-tissue phenotype in axial PsA.
Fig. 3: How normal ageing sculpts AS, PsA and DISH axial phenotypes.
Fig. 4: Imaging features of axial psoriatic arthritis.
Fig. 5: Osteitis versus ligamentitis.

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Acknowledgements

D.M.’s work is partially funded by the Leeds Biomedical Research Centre and Versus Arthritis.

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  1. Section of Musculoskeletal Disease, NIHR Leeds Musculoskeletal Biomedical Research Centre, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK

    Dennis McGonagle, Paula David, Tom Macleod & Abdulla Watad

  2. Department of Internal Medicine B & Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Abdulla Watad

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D.M. has received grant support from Abbvie, BMS, Janssen, Lilly, Novartis and UCB. A.W. has received grant support from Janssen. The remaining authors declare no competing interests.

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McGonagle, D., David, P., Macleod, T. et al. Predominant ligament-centric soft-tissue involvement differentiates axial psoriatic arthritis from ankylosing spondylitis. Nat Rev Rheumatol 19, 818–827 (2023). https://doi.org/10.1038/s41584-023-01038-9

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