Use of Total-Body PET to Quantify Systemic and Cutaneous Inflammation in Psoriasis Patients Before and After Intervention With a Nutritionally Balanced Diet

Psoriasis is a chronic inflammatory disease that affects the skin and joints in 2-3 % of people in the United States. This inflammation of the skin, joints, and blood vessels in patients with psoriasis has been measured by older PET Scan technology but with limitations. With the new EXPLORER PET scanner technology, the investigators are testing to see if the EXPLORER is better than previous PET scanners and improve our ability to assess inflammation in patients.

Also, it is known that the typical Western Diet - high in saturated fats, added sugars, and low in fiber - contributes to obesity and inflammation worldwide. There is evidence in animals that these signs of inflammation are reversible within 4 weeks when changed to a more balanced diet. Thus, this study aims to assess whether there are detectable decreases in inflammation of the skin and body of psoriasis patients who usually eat a Western Diet on an EXPLORER PET scan following 6 weeks of a more balanced diet.

Psoriasis is a chronic inflammatory disease that affects the skin and joints of up to 2-3% of the US population and well known to be associated with multiple medical co-morbidities, including cardiac disease, type 2 diabetes, and obesity. Skin, joint, vascular and organ inflammation has been measured in patients with psoriasis using older PET imaging methodologies4,5 and correlated with disease6. The Hwang lab has shown that mice triggered with systemic exposure to IL-23, a known pathogenic cytokine in human psoriasis, will develop PET-detectable signs of inflammation in joints, and, that this PET signal is greatly diminished by an antagonist of CCR6, a chemokine receptor believed to play a key role in Th17 cell migration7.

Dietary patterns containing high amounts of saturated fat, added sugars, and low in dietary fiber - also known as Western diet (WD)- are thought to be a major contributor to the epidemic of obesity worldwide. The Hwang lab has recently also shown that mice fed a WD show histologic, clinical, and molecular signs of psoriasis within 4 weeks8 which are accompanied by striking changes in the gut microbiome9. In addition, the WD accentuates IL-23-mediated skin and joint inflammation in mice, which is partially reversible when the animals are then placed on a conventional balanced diet9. Data from studies in humans support that weight loss may be an effective adjunct to medical treatment to ameliorate signs and symptoms of psoriasis, prompting the National Psoriasis Foundation to strongly recommend caloric restriction to achieve weight loss in obese psoriatic patients10. However, the role of diet composition/quality in psoriasis-related outcomes remains currently poorly understood. To this end, the overarching goal of this pilot study is to determine whether or not a 6-week dietary intervention that follows the current nutrition guidelines for chronic disease prevention (healthy diet)11-13 can affect psoriasis-related outcomes in patients with psoriasis who generally consume a WD.

These published studies lead us to hypothesize that dietary intervention, even in as little as 6 weeks, will reduce PET-measurable skin and systemic signs of inflammation in patients with psoriasis who habitually consume a WD that is high in fat and sugar content.

The EXPLORER scanner is unique because it has: (i) an axial field of view of 194 cm that covers the entire adult human body in a single bed position; (ii) increased detection efficiency (by a factor of ~40) for whole-body PET imaging compared to standard scanners, thus enabling dose reduction and/or faster scanning; and (iii) a PET spatial resolution (~3 mm) that significantly exceeds that of most current whole-body PET/CT scanners. The investigators believe that this technology has potential to overcome limitations of current PET/CT technology and significantly positively impact patient assessment.

Given the speed, whole-body coverage, and spatial resolution of the Total-body PET EXPLORER scanner at UC Davis, the investigators propose to test this hypothesis by quantitatively assessing uptake of 18F-FDG in recruited patients before dietary intervention and then 6 weeks later after intervention with a nutritionally recommended diet. Normal, healthy controls who have had previous scans performed under the same protocol will be available for comparative purposes. If several of the planned enrollment of 5 patients show demonstrable decreases in systemic inflammation, the preliminary pilot data will be vital to support an application for NIH R-type grant to explore the use of total-body PET imaging to assess systemic inflammation in psoriatic patients as well as to justify the clinical need for dietary interventions in what are considered autoimmune diseases.