Acta Dermato-Venereologica 98-4CompleteContent | Page 5

390 CLINICAL REPORT Systemic Inflammation and Evidence of a Cardio-splenic Axis in Patients with Psoriasis Kasper F. HJULER 1 , Lars C. GORMSEN 2 , Mikkel H. VENDELBO 2 , Alexander EGEBERG 3 , Jakob NIELSEN 1 and Lars IVERSEN 1 Departments of 1 Dermatology and 2 Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, and 3 Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark The spleen is thought to play a role in atherosclerosis- associated immunity and cardiovascular research has indicated the existence of a cardio-splenic axis. The aim of this study was to assess splenic 18F-fluorodeoxyglu- cose uptake as a measure of systemic inflammation in patients with untreated psoriasis compared with his- torical controls assessed by positron emission tomo­ graphy-computed tomography. Patients with moderate- to-severe psoriasis (n  = 12, age 61.4  ±  4.1 years, 83% men, mean  Psoriasis Area Severity Index score of 14.5) and controls (n  = 23, age 60.4  ±  4.5 years, 87% men) were included in the study. Splenic inflamma- tion was measured using the background-corrected spleen-liver-ratio (SLR) based on mean standardized uptake values. Mean  ±  SD SLR was increased in patients with psoriasis compared with controls (0.94  ±  0.11 vs. 0.82  ±  0.08; p  = 0.001). SLR was significantly associated with aortic inflammation. These results support the existence of systemic inflammation in patients with psoriasis, and provide the rationale for a mechanistic link between psoriasis-driven inflammation and car- diovascular comorbidity through a spleen-atheroscle- rotic axis. Key words: positron emission tomography computed tomo­ graphy; inflammation; spleen; psoriasis; vascular inflammation; atherosclerosis. Accepted Dec 20, 2017; Epub ahead of print Dec 20, 2017 Acta Derm Venereol 2018; 98: 390–395. Corr: Kasper F. Hjuler, Department of Dermatology, Aarhus University Hospital, P.P. Orums Gade 11, Bldg. 15, DK-8000 Aarhus C, Denmark. E-mail: [email protected] P soriasis is a common immune-mediated inflammatory disease that affects the skin, nails and joints. However, in recent years the disease has also been linked (directly or indirectly) to a host of comorbidities, with a strong focus on cardiovascular comorbidities. For example, psoriasis has been associated with an increased prevalence of all traditional cardiovascular risk factors (1), with premature coronary artery disease (2), and an increased risk of major adverse cardiovascular events and cardiac mortality (3, 4). Exploratory studies indicate shared immunological mechanisms in psoriasis and atherosclerosis (5, 6), Furthermore, patients with psoriasis exhibit increased inflammation of the aortic wall (7–9). In addition, it has been hypothesized that an increased systemic inflamma- tory load in patients with psoriasis, at least in part, causes doi: 10.2340/00015555-2873 Acta Derm Venereol 2018; 98: 390–395 premature atherosclerotic disease (10). Some studies show evidence of systemic inflammation in psoriasis, whereas other studies rebut these findings (11). A recent meta-analysis of soluble biomarkers of systemic inflam- mation shows evidence of mild systemic inflammation in patients with psoriasis compared with healthy control subjects (12). Taken together, it remains unclear to which extent psoriasis causes systemic inflammation, whether this is clinically relevant and if it is causally associated with premature development of cardiovascular disease. Since the approval of the first commercial system in 2001, 18 F-fluorodeoxyglucose-positron emission tomo- graphy computed tomography (FDG-PET/CT) has be- come a valuable imaging method in oncology. In addition, this modality is increasingly being used as an imaging tool for inflammatory conditions in general. Given the focus on inflammation in vascular plaque formation, FDG-PET/ CT imaging has been investigated as an imaging tool in atherosclerosis (13), and it has been shown that FDG accu- mulation correlates with atherosclerotic plaque inflamma- tion (14, 15). Preliminary insights indicate an association between FDG uptake in the vascular wall and increased risk of future cardiovascular events (16, 17). In addition, splenic inflammation can be visualized by FDG-PET/ CT. Splenic FDG uptake is increased in inflammatory, malignant and infectious diseases, and the spleen-to-liver ratio (SLR) correlates with the peripheral neutrophil count (18–22). As shown in a human autopsy study, the spleen may play a role in activating and directing monocytes to the heart following ischaemic events (23). Furthermore, it has been shown that the activation state of the spleen may be closely related to proinflammatory gene activation within circulating leukocytes and that splenic FDG uptake independently predicts the risk of cardiovascular events (24). Based on preclinical and clinical data, a central role of the spleen in the progression of atherosclerotic disease has been suggested and conceptualized as the “cardio-splenic axis” (24–26). This concept entertains the hypothesis of a spleen-atherosclerotic plaque crosstalk. We recently showed that aortic inflammation and subcutaneous adipose tissue inflammation, assessed by FDG-PET/CT, are significantly increased in patients with psoriasis compared with control subjects (9). The primary objective of the present study was to expand on these findings by assessing splenic FDG uptake as a measure of systemic inflammation in the same cohorts of patients with psoriasis and control subjects. A secondary objective was This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2018 Acta Dermato-Venereologica.