[18F]Fluoride PET-CT in psoriasis patients at risk for developing psoriatic arthritis

Psoriasis (PsO) is an inflammatory disease that can affect multiple organs,
including the skin and joints. These patients experience a substantial clinical
burden. In order to prevent long-term structural damage and disability, it is
crucial to identify psoriatic arthritis (PsA) as early as possible. Gladman et
al showed that patients have an increased prevalence of clinical joint damage
progression if they present to a specialist with a symptom duration of more
than 2 years, compared to patients with a disease duration shorter than 2
years. Furthermore, patients have a poorer physical function more than 10 years
later, despite active treatment, if patients had a symptom duration of more
than 1 year before diagnosis. Several other studies confirmed that a shorter
disease duration before diagnosis, was associated with better outcomes on the
long term.
In most patients (83-87%), the PsO of the skin (hereafter mentioned as PsO)
precedes the PsA diagnosis [6], so that could be a window of opportunity for
early diagnosis of PsA. However, the prevalence of PsA among patients with
psoriasis ranges from 4 to 42% in various studies. This indicates that
additional risk factors are needed in order to identify patients that are at
risk for the development of PsA. Among patients with PsO or PsA, approximately
40% of them have a family history of these diseases in their first degree
relatives.The presence of arthralgia in women, heel pain, fatigue and stiffness
are the earlier symptoms associated with subsequent development of PsA in
psoriasis patients. Also the gradual worsening of complaints in those four
domains is associated with subsequent development of PsA. This was confirmed by
Zaboitti et al, who described that PsO patients with arthralgia were more prone
to develop PsA compared to PsO patients without musculoskeletal complaints.
It was suggested that PsA is more frequent among patients with severe
psoriasis. In a population-based study, 6% of patients with minimal psoriasis
had PsA compared with 18% of those with 3-10% body surface area (BSA) and 56%
of those with BSA >10%. Psoriatic nail changes have been found to occur more
frequently in patients with cutaneous psoriasis who are at higher risk of
developing arthritis. It has been shown that the nail is anchored to the
skeleton and that subclinical imaging of entheseopathy is common in psoriasis
subjects with nail disease but without psoriasis. Nail psoriasis in PsA
patients is intimately associated with entheseopathy of the distal
interphalangeal joint and that the nail is functionally integrated with the
enthesis. In animal models of PsA, the earliest lesion is at the enthesis.
Sonographically determined tenosynovitis and enthesitis are the key imaging
features present in non-specific PsO arthralgia that are at risk of future PsA
development. Studies have shown that psoriasis patients who develop PsA at
follow-up have higher enthesitis scores on the ultrasound at baseline, years
before developing PsA, which supports the entheses being the key structure in
PsA, and the disease may be initiated at the level of the entheses [20, 23].
Zabiotti et al found that sonographically determined tenosynovitis was the only
US feature linked to the future evolution of PsA [11]. Faustini et al.
confirmed this relationship between subclinical inflammation detected and PsA,
highlighting that patients with hands synovitis detected by MRI and arthralgia
had 55.5% likelihood to develop PsA within one year [24]. It has been suggested
that enthesitis is the primary lesion that underscores the diverse skeletal
manifestations of PsA. Simon et al. described that patients with PsO without
PsA exhibit enthesiophytes as the result of pathological bone formation in the
joints. Bone formation is a pathological hallmark of PsA. The presence of
similar changes in patients with psoriasis strongly supports the hypothesis of
subclinical joint pathology that antedates the clinical onset of PsA.
[18F]Fluoride PET-CT scans might be useful to visualize early axial and
peripheral bone formation in the whole body psoriatic patients, as reflection
of disease activity, which may be related to a higher risk for development of
PsA. [18F]Fluoride uptake represents active bone formation, as fluoride is
incorporated into the skeleton at sites of osteoblastic activity.

This study has been transitioned to CTIS with ID 2024-514759-13-01 check the CTIS register for the current data.

The primary objective of this proof-of-concept study is to investigate the
feasibility of whole body [18F]Fluoride PET-CT scans to detect axial and
peripheral neew bone formation in PsA patients taht are at risk to develop
clinically manifest PsA.
The secondary objective is to investigate the correlation between PET outcome
and the development of PsA in 2 years of follow up.

A prospective cohort study in 15 patients with PsO at risk for PsA.

The total radiation burden will be about 6.0 mSv.