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 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.

Inclusion criteria

• Adults (>18 year)
• Both sexes
• Must have a history of psoriasis of at least 3% body surface area affected by skin psoriasis (in a body area that the subject will allow the PI to perform several skin biopsies as noted below (optional)) and may carry a diagnosis of psoriatic arthritis as well
• Patients will have a BMI of >/=25 which is consistent with being overweight - Willing and able to fast for at least 6 hours before and for the duration of the scan visit
• No strenuous exercise for 24 hours prior to being scanned
• Recruited patients must habitually consume a WD-type diet that will be evaluated by using DHQ III food frequency questionnaire along with three-day food record14. Subsequently, the Healthy Eating Index will be calculated and participants with a poor dietary pattern (score below 58) will be eligible for the study15.

Exclusion criteria

• Those taking anti-diabetic oral or injected medications
• Those already ingesting a caloric- or component-restricted diet
• Vegan, vegetarian or food allergy or intolerance to the ingredients of the diet
• >5% change in body weight in the last 2 months
• Those taking systemic medications for the purpose of treating psoriasis or psoriatic arthritis for at least 3 months prior to first PET scan or during the duration of the trial
• Self-reported history of dysphoria or anxiety in closed spaces (claustrophobia)
• Uncontrolled diabetes or blood glucose level greater than 180 mg/dl at the time of radiotracer injection
• Body weight >240 kg due to limitations of the scanner bed
• Known inflammatory or other infectious disease that can confound assessment
• Pregnant or breast-feeding (urine pregnancy test will be administered prior to start of each PET/CT session for all participants who are able to get pregnant between 18 to 60 years old, unless documented hysterectomy or bilateral ovarian removal is available, because of risks from ionizing radiation)
• Inability to lie motionless on the scanner bed with the arms by the side for up to 60 minutes
• Currently participating in another conflicting research study. Concurrent or prior enrollment in a separate research study involving a PET scan performed within the last 12 months for research purposes only.
• Unwilling to sign informed consent
• Inability to understand the risks and benefits of the study
• Prisoners