Background Psoriatic disease is composed of skin, entheseal and joint disease, which can manifest isolated or combined. Little is known about the systemic inflammation levels in psoriatic disease as a robust IL-6 signal is missing and therefore acute phase reactants such as C-reactive protein are often normal. Measuring systemic inflammation in the different manifestations of psoriatic disease is therefore a continuous unmet need.

Objectives To better define systemic inflammation in patients with psoriatic disease limited to the skin (S), the entheses (E) or the joints (arthritis, A) or with a combination of these disease manifestations (SE, SA, EA, SEA).

Methods Hypothesis-driven approach selecting markers that are (i) either targets of IL-23/IL-17 pathway activation (b-defensin 2, lipocalin 2, IL-22), (ii) associated with neutrophil/monocyte activation (calprotectin, IL-8) and (iii) achieve serum concentrations sufficient for reliable detection by standard ELISA. Parameters were assessed in 210 individuals comprising 105 healthy controls and 105 patients with psoriatic disease (each 15 for isolated (S, E, A) and composed disease manifestations SE, SA, EA, SEA). Results are expressed as percent positive patients with levels above three standard deviations over the mean level in healthy controls. In addition, 6-months sequential data on levels of these markers were collected in 20 patients treated with secukinumab or adalimumab to test treatment effects.

Results CRP levels were normal in the majority of individuals. The respective percentages of patients with normal CRP (<5mg/L) were as follows: S: 100%, E: 100%, A: 80%, SE: 93%, SA: 67%, EA: 73%, SEA: 67% (Figure). Thus, CRP is only elevated in a subset of patients with arthritis. In sharp contrast, beta-defensin 2 levels (>1.88 ng/mL) and lipocalin-2 (>24.7 ng/mL) were elevated in the majority of patients with isolated skin and entheseal, but not joint disease. Conversely, elevations of calprotectin (>3.58 mig/mL) and IL-8 (>10.3 pg/mL) were found in the majority of patients with isolated joint disease. IL-22 was elevated (>17.1 pg/mL) in all three manifestations of psoriatic disease. Reflecting a combination of the findings the vast majority of patients with composed disease manifestation (SE, SA, EA, SEA) showed widespread marker elevation. IL-17 and TNF inhibition differentially lowered and partially normalized elevated markers of inflammation.

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Conclusion Systemic inflammation is detectable in the majority of patients with psoriatic disease, even if CRP is normal. The respective marker pattern depends on the manifestation (skin, entheses, joints) of psoriatic disease, with beta-defensin 2 and lipocalin-2 reflecting skin and entheseal disease, calprotectin and IL-8 joint disease and IL-22 a combination of these disease manifestations.

Disclosure of Interests Maria Sokolova Grant/research support from: M. Sokolova was a PARTNER Fellow, Celgene Sàrl, Kemal Nas: None declared, Yubin Luo: None declared, David Simon Grant/research support from: Novartis, Consultant for: Lilly, Speakers bureau: Janssen, Yi Zhao: None declared, Jürgen Rech Grant/research support from: Bristol-Myers Squibb and Celgene (greater than $10,000), Consultant for: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Speakers bureau: Bristol-Myers Squibb, Celgene, Chugai, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Roche, Sanofi Aventis, and UCB (in total more than $10,000), Mario Zaiss: None declared, Georg Schett: None declared