Anatomical pattern of entheseal and synovial fibroblast activation in patients with psoriasis and its risk of developing psoriatic arthritis
Georg Schett,
Andreas Ramming,
Filippo Fagni,
Christian Schmidkonz,
Armin Atzinger,
Arnd Kleyer,
Torsten Kuwert,
David Simon,
Michael Sticherling,
Verena Schoenau,
Maria Gabriella Raimondo,
Melek Yalcin Mutlu,
Selahattin Alp Temiz,
Rita Noversa de Sousa,
Giulia Corte
Affiliations
Georg Schett
Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany
Andreas Ramming
Department of Internal Medicine 3, Rheumatology and Immunology, Erlangen University Hospital, Erlangen, Germany
Filippo Fagni
3 Deutsches Zentrum fuer Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
Christian Schmidkonz
Department of Nuclear Medicine, Erlangen University Hospital, Erlangen, Germany
Armin Atzinger
Department of Nuclear Medicine, Erlangen University Hospital, Erlangen, Germany
Arnd Kleyer
5 Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany
Torsten Kuwert
Department of Nuclear Medicine, Erlangen University Hospital, Erlangen, Germany
David Simon
Department of Internal Medicine 3—Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany
Michael Sticherling
Deutsches Zentrum fuer Immuntherapie (DZI), Erlangen University Hospital, Erlangen, Germany
Verena Schoenau
Department of Internal Medicine 3, Rheumatology and Immunology, Erlangen University Hospital, Erlangen, Germany
Maria Gabriella Raimondo
Department of Internal Medicine 3, Rheumatology and Immunology, Erlangen University Hospital, Erlangen, Germany
Melek Yalcin Mutlu
Department of Internal Medicine 3—Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany
Selahattin Alp Temiz
Department of Internal Medicine 3, Rheumatology and Immunology, Erlangen University Hospital, Erlangen, Germany
Rita Noversa de Sousa
Department of Internal Medicine 3, Rheumatology and Immunology, Erlangen University Hospital, Erlangen, Germany
Giulia Corte
Department of Internal Medicine 3, Rheumatology and Immunology, Erlangen University Hospital, Erlangen, Germany
Objectives To assess the presence and anatomical distribution of activated fibroblasts in the joints and entheses of patients with psoriasis with arthralgia and to test how fibroblast activation visualised by 68gallium-labelled fibroblast activation protein inhibitor-04 (68Ga-FAPI-04)-positron emission tomography (PET)/CT correlates with clinical tenderness, musculoskeletal ultrasound findings and progression to psoriatic arthritis (PsA).Methods We conducted a prospective cohort study in patients with psoriasis and arthralgia who underwent clinical and ultrasound evaluation and whole-body PET/CT imaging with 68Ga-FAPI-04. 68Ga-FAPI-04 uptake at synovial and entheseal sites was assessed by maximal standardised uptake values (SUVmax) and PET/CT Joint Index (JI); logistic regression models were used to investigate its correlation with clinical and ultrasound findings. Survival analyses were performed on patients with at least 6 months of follow-up.Results 36 patients with psoriasis were enrolled. 68Ga-FAPI-04 uptake was found in 318 (7.9%) joints and 369 (7.3%) entheses in 29 (80.6%) participants, with a mean SUVmax (SD) of 3.2 (1.8) for joints and 2.9 (1.6) for entheses. Large joints and the lower limbs were predominantly affected. A significant positive relationship was found between 68Ga-FAPI-04-PET/CT signal intensity and the 68 tender joint count (SUVmax: p<0.001; PET/CT-JI: p<0.001) and tender entheses count (SUVmax: p<0.001; PET/CT-JI: p=0.002). No correlations were found with ultrasound findings (SUVmax: p=0.969; PET/CT-JI: p=0.720). Patients with relevant synovio-entheseal 68Ga-FAPI-04 uptake showed a statistically significant higher risk of developing PsA (p=0.02), independent of ultrasound findings.Conclusions Patients with psoriasis presenting with arthralgia show localised signs of resident tissue activation in joints and entheses, which are associated with higher risk of developing PsA.
