To our knowledge, this is the first description of in vivo
whole body inflammation in psoriasis detected by FDG-PET/CT simultaneously in three tissues: viscera, vasculature, and musculoskeletal structures. We demonstrate that FDG-PET/CT, a technique validated to assess vascular inflammation, can be employed in patients with psoriasis to visualize and quantify anatomic regions of inflammation.33,42,43,46–48
In our case series, FDG-PET/CT detected numerous areas of inflammation in patients with psoriasis, including increased inflammation in the blood vessels, in the liver, in articular and periarticular structures, and in the skin. Interestingly, all of these findings occurred in psoriasis patients who otherwise felt well (only one patient who had an established diagnosis of psoriatic arthritis had joint symptoms), and had no clinically significant abnormalities in their laboratory data except for one patient (subject 6) who had an elevated hs-CRP of 8.4 mg/L. These foci of inflammatory activity were observed with levels of inflammation far exceeding the range of normal for joint, liver, and vascular inflammation despite a lack of evidence of clinical disease.45
In our nested case-control study, FDG-PET/CT imaging revealed vascular inflammation more severe than age and gender-matched controls. The corresponding magnitude of SUV difference observed between psoriasis patients and controls (0.20) in multiple segments of the aorta is equivalent to the magnitude of vascular inflammation observed over two additional decades of aging.33
Furthermore, FDG-PET/CT imaging of psoriasis patients demonstrated high risk findings49,50
, including diffusely increased vascular inflammation in each segment of the aorta that remained significant after adjusting for traditional CV risk factors and BMI. We also observed that psoriasis was associated with increased hepatic inflammation in multivariate analysis adjusting for confounders and risk factors for liver disease including plasma triglycerides and BMI. This relationship however was no longer significant when adjusted for alcohol intake, suggesting that either patients underreported their alcohol use, because inclusion in the study permitted only light drinking (less than two drinks per day), or that patients with psoriasis may be more susceptible to liver dysfunction in the face of alcohol use. Despite this observation, this degree of hepatic inflammation is similar to that seen in patients with hepatic steatosis or chronic active hepatitis.43
This finding warrants careful follow up and further study, and may present a compelling opportunity to explore the concept of the “psoriatic liver.” Finally, our observations of musculoskeletal inflammation are consistent with previous studies using conventional imaging techniques to demonstrate findings consistent with psoriatic arthritis such as articular inflammation and enthesitis in patients with psoriasis.51–53
In particular, the diffuse distribution of subclinical articular and periarticular involvement observed on imaging suggests that FDG-PET/CT may be a more feasible approach for detecting subclinical
psoriatic arthritis than traditional imaging modalities such as ultrasound or MRI.
The findings of excess vascular, hepatic, musculoskeletal, and cutaneous inflammation on FDG-PET/CT are novel and suggest the potential of FDG-PET/CT technology to investigate systemic inflammation. The underlying inflammation linking chronic inflammatory disease states such as atherosclerosis, metabolic syndrome, diabetes mellitus, and psoriatic arthritis with psoriasis is captured in vivo by FDG-PET/CT, thereby providing a measureable phenotype (i.e. biomarker) in a dynamic disease such as psoriasis. In this study, we demonstrate this novel application of FDG-PET/CT, which has exquisite sensitivity for detecting picomolar to nanomolar concentrations of glucose uptake with inflammatory cells. We further report a systematic approach to image analysis which can be used in future studies to regionally and globally quantify inflammation in the aorta, liver and joints.
We note, however, that the findings we report are based on a pilot study which has important limitations, and thus additional studies are necessary to confirm and extend our findings. First, the small sample size and referral-based source of our patients may affect the generalizability of our results. However, our study is comparable in size and design to other landmark studies using FDG-PET/CT in inflammatory disease states.25,58,59
We also note that use of FDG-PET/CT is limited by the need for sophisticated hardware and software that may not be widely available, the need for subjects to be willing to fast for eight hours, and radiation exposure similar to that of a standard contrast-enhanced CT scan. As a result, patients may need to be highly motivated to enter studies using FDG-PET/CT, which may lead to particular challenges in recruiting healthy controls. Additionally, in this pilot study subjects were not required to undergo washout of topical or ultraviolet light treatments, and systemic treatments were permissible as long as the dose had been stable for 3 months. Thus, additional studies in psoriasis patients who are treatment naïve or have washouts of psoriasis therapies will be necessary to further interpret our findings. Furthermore, the nested-case control study is subject to error introduced by selection bias and confounding. For example, it is possible that one group could have been more health conscious than the other (i.e. selection bias), although the laboratory and anthropometric data do not support this possibility as a potential source of error. We carefully adjusted for confounding variables on which we had detailed data, however, incomplete measurement of confounders such as diet and exercise could affect our measurement of association. Additionally, while our study attempted to adjust for LDL cholesterol and hypertension, it is possible that incomplete adjustment for these confounders still exist and we did not have LDL data for one of the controls. Finally, three patients with psoriasis in the case series, and one patient with psoriasis in the nested case-control study were on active statin therapy. While statins may interfere with vascular inflammation, we would expect that they attenuate vascular inflammation, as demonstrated in a previously published clinical trial using FDG-PET/CT,40
and therefore would bias our results towards the null. In addition, we note that none of the study participants had existing CV disease and most CV risk prediction tools, such as the Framingham Risk Score, use current blood pressure and LDL cholesterol measurements to assess CV risk without regard to medication usage because biometric data is more significantly correlated with CV outcomes.50
In this study, we demonstrate that FDG-PET/CT represents a powerful molecular imaging modality to assess whole body inflammation in association with psoriasis. Further studies are needed to 1) confirm and extend our results of increased vascular and hepatic inflammation in a larger series of patients, carefully selecting cases and controls and measuring confounding variables to determine if increased inflammation measured by FGD-PET is due to psoriasis, its treatments, or other associated factors; 2) understand how to relate these findings to clinical prognosis; and 3) assess the effect of psoriasis treatment on the inflammation observed in various tissues.