ObjectivesTo assess and compare molecular tissue changes at the entheses in patients with psoriasis (PsO), psoriatic arthritis (PsA), and healthy controls (HC) in vivo using multispectral optoacoustic tomography (MSOT) and to describe their relationship with clinical and ultrasound findings of enthesitis.MethodsA cross‐sectional study (MAPSA) in bDMARD‐naïve PsA and PsO patients and HC was performed. Participants underwent clinical, ultrasonographic and MSOT examination of six entheses (lateral humeral epicondyle, distal patellar tendon attachment, Achilles tendon attachment). MSOT‐measured haemoglobin (Hb), oxygen saturation (SO2), collagen, and lipid levels were quantified and mean differences between groups were calculated using linear mixed‐effects models. MSOT‐measured analytes were compared between entheses with and without clinical and ultrasound anomalies.ResultsNinety participants were included (30 PsO, 30 PsA, 30 HC), 540 entheses were clinically assessed, and 540 ultrasound and 830 MSOT scans were obtained. Both PsA and PsO patients showed increased oxygenated Hb (PsA: p=0.003; PsO: p=0.054) and SO2 (PsA: p<0.001; Pso: p=0.001) levels and decreased collagen signals (PsA: p<0.001; PsO: <0.001) compared to HC, with more pronounced changes in PsA. Significantly lower collagen levels (p=0.01) and increased lipids (p=0.03) were recorded in tender entheses compared to non‐tender ones. Erosions and enthesophytes on ultrasound were associated with significant differences in SO2 (p=0.014) and lipid signals (p=0.020), respectively.ConclusionsPsA and PsO patients exhibit an analogous metabolic pattern at the entheses that is exacerbated in the presence of inflammation. These findings support the notion of a psoriatic disease spectrum characterized by common immuno‐metabolic tissue changes.