Association Between Skin and Aortic Vascular Inflammation in Patients With Psoriasis: A Case-Cohort Study Using Positron Emission Tomography/Computed Tomography

Abstract

Importance: Inflammation is critical in the development of atherosclerosis. Psoriasis is a chronic inflammatory skin disease that is associated with increased vascular inflammation by 18fluorodeoxyglucose positron emission tomography/computed tomography in vivo and future cardiovascular events. It provides a human model to understand the effect of treating inflammation in a target organ (eg, the skin) on vascular diseases.

Objective: To investigate the association between change in skin disease severity and change in vascular inflammation at 1 year and to characterize the impact of 1 year of anti-tumor necrosis factor therapy on vascular inflammation.

Design, setting, and participants: In this prospective cohort study, 220 participants from outpatient practices were recruited at the US National Institutes of Health. A total of 115 consecutively recruited patients with psoriasis were followed up at 1 year. The study was conducted from January 1, 2013, through October 31, 2016, with data analyzed in November 2016.

Exposure: Skin inflammation measured as Psoriasis Area and Severity Index (PASI) score.

Main outcomes and measures: Vascular inflammation assessed as target-to-background ratio by 18fluorodeoxyglucose positron emission tomography/computed tomography.

Results: Among the 115 patients, the mean (SD) age at 1-year follow-up was 50.8 (12.8) years and 68 were men (59%). The cohort had a low cardiovascular risk by Framingham risk score and mild-to-moderate psoriasis, with a median PASI score of 5.2 (interquartile range, 3.0-8.9). At follow-up, the total cohort had a median improvement in PASI score of 33%, with use of topical therapy (60%), biological therapy (66%, mostly anti-tumor necrosis factor) and phototherapy (15%) (P < .001). Moreover, improvement in PASI score was associated with improvement in target-to-background ratio of 6%, mainly driven by those with higher responses in PASI score (P < .001). This association persisted beyond traditional risk factors (β = 0.19; 95% CI, 0.012-0.375; P = .03) and was the strongest in those initiated with anti-tumor necrosis factor therapy (β = 0.79; 95% CI, 0.269-1.311; P = .03).

Conclusions and relevance: Improvement in psoriasis skin disease severity was associated with improvement in aortic vascular inflammation by 18fluorodeoxyglucose positron emission tomography/computed tomography, with greater improvement in aortic vascular inflammation observed in those who had higher than 75% reduction in skin disease severity. These findings suggest that controlling remote target organ inflammation (eg, in the skin) may improve vascular diseases; however, randomized clinical trials are needed to confirm these findings.

Figure 1.. Recruitment Scheme for the Patients at the National Institutes of Health

¹⁸FDG PET/CT indicates ¹⁸fluorodeoxyglucose positron emission tomography/computed tomography; TNF, tumor necrosis factor.

Figure 2.. Patient With Improvement in Psoriasis Severity and Aortic Vascular Inflammation

Representative images from a patient who experienced reduction in both Psoriasis Area and Severity Index score and aortic vascular inflammation. The images show a sagittal section at the level of the midaorta at baseline (A) and 1 year (B). Green represents ¹⁸fluorodeoxyglucose tracer uptake in the aorta, which is higher at baseline compared with 1 year of psoriasis treatment (yellow arrowheads).

Figure 3.. Association Between Change in Psoriasis Severity and Change in Aortic Vascular Inflammation

Improvement in psoriasis skin disease severity is associated with improvement in vascular inflammation beyond traditional cardiovascular risk factors at 1 year: in all patients with psoriasis in the cohort (n = 115), skin disease improvement was associated with reduction in vascular inflammation in unadjusted (A) and adjusted (B) analyses. Improvement in psoriasis skin disease severity is associated with improvement in vascular inflammation beyond traditional cardiovascular risk factors at 1 year: in a subcohort of biologically naive patients with psoriasis, who were initiated with anti–tumor necrosis factor (TNF) therapy (n = 17), skin disease improvement was associated with reduction in vascular inflammation in unadjusted (C) and adjusted (D) analyses. Change in psoriasis severity = psoriasis severity at baseline − psoriasis severity at 1 year. Change in target-to-background ratio = target-to-background ratio at 1 year − target-to-background ratio at baseline.