key: cord-102417-xn7m3wqp authors: Blake, T.; Gullick, N. J.; Hutchinson, C. E.; Barber, T. M. title: Psoriatic disease and body composition: a systematic review of the literature date: 2020-05-21 journal: nan DOI: 10.1101/2020.05.18.20104802 sha: doc_id: 102417 cord_uid: xn7m3wqp Background. Obesity is a leading comorbidity in psoriatic disease, including both psoriasis (Pso) and psoriatic arthritis (PsA), and is associated with adverse metabolic and cardiovascular (CV) outcomes. Anthropometric parameters, such as weight, body mass index (BMI) and waist-to-hip ratio, have been extensively reported in psoriatic disease. However, the associations of body composition and fat distribution with psoriasis have not been fully defined. Objectives. To identify whether patients with psoriatic disease, including psoriatic arthritis, have altered body composition compared with the general population, and to review existing modalities for the assessment of body composition. Methods. Electronic searches of the literature were conducted in PubMed, Medline (Ovid), Embase (Ovid), Cochrane Central Register and Google Scholar. Titles and abstracts were reviewed by two authors independently against a set of prespecified inclusion/exclusion criteria. Results. Twenty-five full text articles met the inclusion criteria and were included in the final narrative analysis. The studies were of heterogeneous design and used a range of objective measures to assess body composition, including simple anthropometric measures, bioimpedance analysis (BIA), dual energy X-ray absorptiometry (DXA) and computed tomography (CT). Few studies met all the quality assessment criteria. Conclusions. Patients with psoriatic disease reveal defined body composition changes that are independent of obesity and the customary metabolic syndrome, including higher overall body fat, visceral fat and sarcopenia. These findings emphasize that patients with psoriatic disease should be screened for abnormal adipose effects beyond their weight and body mass index (BMI). Our findings show that the last decade has seen an exciting expansion of research interest in the development and validation of new modalities for the assessment of body composition. There is no consensus on the optimal assessment method of body composition for this diverse group, hence there is a need for validation of existing modalities and standardization of assessment tools. Psoriasis (Pso) is an immune-mediated chronic inflammatory disease affecting the skin, entheses and joints, characterized at the skin level by infiltration of immune cells in the dermis and epidermis, vascular proliferation and atypical keratinocyte differentiation. Pathogenesis is complex and thought to result from the interaction between genetic, environmental and immunologic factors; key players in this process are T cells, antigen presenting cells, keratinocytes, Langerhans' cells, macrophages, natural killer cells, as well as multiple cytokines and growth factors including vascular endothelial growth factor and keratinocyte growth factor [1] . In recent years, the mindset has shifted from one of a Th1-driven immune response with IFN-γ and IL-12 as the signature cytokines to one in which the IL-23/Th17 axis with IL-17, IL-21 and IL-22 plays a more central role [2] . There is increasing recognition that psoriasis is more than skin deep and has important consequences beyond the skin. Proinflammatory molecules released during chronic inflammation are implicated in certain comorbidities, such as obesity, hypertension, diabetes mellitus, cardiovascular disease and depression. Conversely, epidemiological evidence infers that obesity, via pro-inflammatory pathways, predisposes to both development and progression of psoriasis [3] . This association is shared with metabolic syndrome (MetS), not least the increased prevalence of cardiovascular risk factors and the ensuing cardiovascular morbidity [4] [5] [6] [7] [8] . Recent studies have suggested that adipokines, such as leptin, adiponectin and resistin, produced by adipocytes and dysregulated in obesity and MetS, are the linchpins of this metabolic association in psoriatic disease. They have been shown to contribute independently to the adverse cardiovascular 3 outcomes in patients with Pso and can be viewed as biomarkers of obesity-related inflammation and cardiovascular risk (9) . With this is mind, one should consider adipose tissue as an endocrine organ that has the capabilities, through local and systemic factors, to induce a low-level inflammatory state. Moreover, specific IL-17-secreting Th17 cells and IL-22-secreting Th22 cells have been seen to infiltrate the adipose tissue and represent local mediators of inflammation and insulin resistance, something that is being studied in more detail. Sustained inflammation due to psoriatic disease also leads to loss of muscle mass and muscle weakness termed sarcopenia; however, the reasons for these muscle changes in the context of inflammation are multifactorial and difficult to define. External factors, such as aging, decreased physical activity secondary to stiffness and pain, hormonal changes and disturbances in protein metabolism are likely to exert considerable influence on this process. Despite this knowledge about the associations between psoriatic disease, adipogenesis and metabolic dysfunction, there is less emphasis on body mass alterations and distribution between separate internal compartments: fat-free tissue (lean body mass), extracellular water and adipose tissue. Body composition, a measure of lean and fat mass proportions, provides a useful indicator of metabolic health [10] , and its measurement in psoriatic disease can provide a useful insight into cardiometabolic risk, something that could well influence patient management. Our principal aim was to determine evidence for association between psoriasis and abnormal patterns of fat (including preponderance of visceral fat content) and muscle distribution. We also explored and compared different modalities used for assessment of fat distribution. We hope that this analysis may guide future clinical decision making with respect to risk assessment, screening and management of psoriatic patients in day-to-day practice, encouraging more individualized care and leading to better patient outcomes. This systematic review was performed following methodology recommended by the Cochrane Collaboration and is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines [11, 12] . Studies were included where the primary aim was to elucidate an association between psoriasis or psoriatic arthritis and abnormal body composition. Studies were not required to include a comparator group. The following inclusion and exclusion criteria were applied. Types of studies • Publication date 1999 (inclusive) -present • Studies from any geographical location • English language • Published studies (including conference papers) • Grey literature (not published in a peer-reviewed journal) including dissertations/theses • Any quantitative study (RCT, non-RCT, observational, cohort, case control) • Studies using qualitative methods of analysis (to describe patterns or themes raised by studies) seeking to understand body composition phenotypes of psoriatic disease. This includes original qualitative studies, studies involving secondary analysis of data, and a qualitative study as part of a mixed methods study e.g. the study also has a quantitative component 4 • The reference lists of the final articles included for full data extraction were hand searched for further relevant articles. Types of participants • Anything that is not concerned with demonstrating either a metabolic, structural or functional relationship to psoriatic disease; studies focusing on individual components of metabolic syndrome (diabetes mellitus, hypertension, hyperlipidemia or fatty liver disease) and any association with psoriatic disease The search strategy was developed by two of the authors (TB and NG) and a librarian. Database searches were performed in PubMed, Medline (Ovid ® ), Embase (Ovid ® ), Cochrane Central Register and Google Scholar for reports published between 1999 to November 2019 using a sensitive methodological filter for studies. Search terms and criteria are shown in Table 1 . Search results were combined into a single Endnote file and duplicates removed. 5 Two authors (TB, NG) independently reviewed all titles/abstracts in the web-based software platform Covidence [13] and selected articles for full-text review. Discrepancies were resolved by consensus. The data extraction tool was designed by TB and included a Quality Assessment incorporating a Critical Appraisal Skills Programme (CASP) checklist [14] specific for the study design. The checklists included criteria for information and selection bias addressing the following domains: participants, controls, measurement of variables, statistical power, confounding factors and applicability of results. All included studies were appraised with the Risk Of Bias In Non-randomized Studies of Interventions assessment tool (ROBINS-I) [15] . The initial search yielded 2202 titles. After removing duplicates, 1848 titles and abstracts were screened, then 238 retained for full text review. A further 213 studies were excluded due to: incorrect outcomes (197), incorrect study design (9) , duplicate material (3), incorrect intervention (3) and non-English language (1). A total of 25 studies from 25 publications met the inclusion criteria ( Figure 1 ) with differing methodology: 1 randomized control trial, 1 case-control study, 19 cross-sectional and 4 prospective cohorts. A search of the grey literature (the first 100 articles sorted by relevance on Google Scholar) retrieved no additional studies. A summary of the included studies is shown in Table 2 . Twenty-five studies represented a population of 2468 psoriatic patients from 10 countries: Belgium, Brazil, Denmark, France, Italy, Poland, Portugal, Spain, Turkey and UK. Demographics are shown in Table 3 . Studies did not differentiate outcomes according to subtypes of psoriatic disease, however five of the studies focused purely on psoriatic arthritis [16] [17] [18] [19] [20] . Only three studies [19] [20] [21] reported racial and ethnic group of participants. A control group was assessed in 10 studies [16, 18, 19, 21, , and this information was missing in another study [17] . None of the studies reported socio-economic status including employment or educational attainment of subjects. All studies included clinical anthropometric data to varying degrees for overall measurement of participant shape and size. In all but one study [17] In general, 24 studies confirmed discrete biological and body composition changes in patients with psoriatic disease, which correlated positively with other indicators of metabolic syndrome, including waist circumference, waist-to-hip ratio, weight, BMI, plasma concentrations of low-density lipoprotein (LDL)cholesterol, leptin and apolipoprotein-B (apo-B). 6 One study failed to reveal statistically significant differences between psoriatic patients and controls with respect to maximal aerobic capacity, resting metabolic rate, pulmonary function tests, body fatness, body fat distributions and quality of life [29] . Moreover, not all studies found that these changes were correlated to either skin or joint disease activity [17, [33] [34] [35] . Three studies focused on muscle mass and reported levels of sarcopenia [16, 19, 20] . Aguiar et al evaluated muscle mass by way of a muscle mass index (muscle/height 2 ) and demonstrated reductions for spondyloarthritis with no significant variation between psoriatic arthritis and ankylosing spondylitis patients; however, their findings were not correlated with disease duration activity, function or radiological indices. A more recent study assessed sarcopenia and presarcopenia on the basis of European Working Group On Sarcopenia in Older People (EWGSOP) criteria and by using defined MMI cut-offs, and identified sarcopenia in 20.0% and presarcopenia in 25.7% of PsA patients [19] . Ten techniques were used to describe body composition: BIA 10, DXA 6, CT 2, ultrasonography 1, transthoracic echocardiography 1 and other techniques 5 (including novel automated systems for measurement). Body composition outcomes by modality are shown in , showed age, CRP and disability were associated with sarcopenia, whereas the type of rheumatic disease (RA, PsA or AS), gender, calorie and protein intake, physical activity level, biologic treatment, duration of disease and ESR were not associated with an increased risk of sarcopenia. Six studies reported on cardiometabolic and body composition improvements on patient profiles after receiving specific interventions: hypocaloric diet with omega-3 supplementation [17] , phosphodiesterase-4 (PDE4) inhibition with apremilast [18] The risk of bias quality assessment of included studies is presented in Table 3 . Six of the studies, whilst identifying as case-control, were reassigned as cross-sectional design on account of their methodology [20, 22, 35, [37] [38] [39] . Nine studies did not include a control group [16, 18, To our knowledge, this is the first systematic review examining the relationship between psoriatic disease and whole-body composition as a distinct entity from metabolic syndrome. Strengths of the review include use of a high degree of rigor in its search strategy and screening procedures, using relevant standards for performing systematic reviews. We tried to reflect the complete picture of both published and unpublished literature on this topic. The last decade has seen an exciting expansion of interest in the development and validation of new modalities for the assessment of body composition. Our study provides evidence for a relationship between certain body composition phenotypes and the occurrence of psoriasis, including higher overall body fat, visceral fat and sarcopenia that is similar, yet distinct, from the metabolic syndrome. Several aspects of body composition, specifically the amount and distribution of body fat and lean mass, are now understood to be important health outcomes in adults and should form an important part of the ongoing clinical assessment of patients with psoriasis. However, the issue of whether body compartment distribution is a result of severe psoriasis or a causative factor in its development remains contentious. It is likely that novel systems will eventually supplement less sophisticated bedside measurements and influence key aspects of risk assessment, prognostication and management. We found an increased prevalence of body composition derangements in psoriatic patients compared with controls. As expected, parameters associated with obesity, such as weight, body fat percentage, fat mass, and degree of obesity, were higher in the psoriasis groups than in the control groups, irrespective of therapy. Such an association between obesity and psoriasis has been well documented, first described in 1986 [42] . Traditional epidemiological studies have focused on weight or BMI to define obesity rather than altered body composition. We found conflicting data on the association between psoriasis severity, such as PASI, and body composition parameters, indicating that a causal link is not definitive. Previous studies have alluded to a dose-response relationship between psoriasis severity and metabolic syndrome [43], supported by translational studies showing T-helper cell cytokine upregulation in the blood and skin of psoriasis patients, leading to effects on lipid metabolism and insulin resistance [44] . In this review, treatment with anti-IL-12/23 or PDE4 inhibitors was associated with more favorable body composition profiles than anti-TNFα treatments, findings which mirror previous observations of increases in BMI seen with this drug class [45, 46] . IL-17, one of the key proinflammatory cytokines in psoriasis, mechanistically links inflammation with insulin resistance and adipocyte dysfunction [47] . IL-17A producing cells are thought to be pathogenic in driving inflammation in obesity and progression of obesityrelated inflammatory diseases, suggesting that causality between psoriasis and adipogenesis is likely to be bidirectional [48] . From this perspective, there are likely to be therapeutic implications of targeting proinflammatory factors like IL-17 or IL-12/23 in metabolic dysfunction associated with psoriatic disease. Due to its non-invasiveness, low cost and portability, it is easy to appreciate how BIA was adopted by most researchers. The technique relies on the assumption that the volume of fat-free tissue will be proportional to the electrical conductivity of the body. It employs a small electric current to measure the resistance and reactance at difference frequencies against various tissues in the body e.g. lipid has a high resistance to the All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 21, 2020. . https://doi.org/10.1101/2020.05.18.20104802 doi: medRxiv preprint 8 flow of current, therefore shows a high impedance reading, whereas muscle, which stores most of our body water, has lower impedance. BIA assessment tools have been considered a promising approach for the quantitative measurement of tissue characteristics over time, as well as demonstrating the direct relativity between fluctuations in body composition and prognosis, clinical condition and quality of life [49] . The technique offers reliable data on body composition provided that suitable (i.e. age-, sex-and populationspecific) equations for the calculation of body compartments are applied [50]. However, a major limitation of this technique pertains to measurement discrepancies between devices from different manufacturers and the lack of internationally recognized standard reference values. PhA is thought to be one of the most clinically relevant parameters of BIA. It is defined as the ratio of resistance (intracellular and extracellular resistance) to reactance (cell membrane-specific resistance), expressed as an angle. It is considered an indicator of cellular health, where higher values reflect cell membrane integrity and better cell function. In healthy populations, increasing age bestows a lower PhA due to a reduction in reactance and a parallel loss of muscle mass and an increase in resistance due to the declining proportion of body water at the expense of fat mass. In disease, PhA is often reduced because of infection, inflammation or disease-specific determinants [51] . Recent studies have reported that PhA in humans follows a linear relationship with cellular health and can be considered a prognostic tool in certain medical disorders, including cancer, cirrhosis and diabetes mellitus [22, [52] [53] [54] [55] [56] . It is important to note that not all BIA devices can detect phase-sensitive impedance variation that can be used for assessment of phase angle. It is important to recognize that there is no single measurement method of body composition that allows for the delineation of all tissues and organs and there are pros and cons of all techniques. The seemingly unsophisticated measurements of skin thickness, BMI and waist circumference can provide simple longitudinal assessments of fatness and metabolic risk despite their poor accuracy and inability to differentiate fat and lean masses. The value of any approach in supporting clinical practice is enhanced by the availability of reference data. Recent developments include MRI for fat distribution. This systematic review should be interpreted in the context of the reported studies which were heterogeneous in several aspects. Firstly, the observational studies recruited different extents and subtypes of psoriatic disease, some with associated arthritis, and measured different aspects of body composition, making definitive conclusions problematic. Secondly, there was poor matching of patients and controls across all studies and little consideration for the potential confounding effects of key determinants of metabolism, e.g. physical activity, age and smoking. Finally, BIA-estimated percentage of body fat varies greatly with population and age and is directly and closely related to various health outcomes such as cardiovascular diseases. Despite its prognostic potential, BIA has not been validated in population studies or clinical practice due to lack of normal population reference limits for comparison and is also influenced by other factors such as age, sex and race [57]. We suggest that body composition indices should be analyzed in more detail with a broader range of techniques and imaging systems across the clinical spectrum of psoriatic patients in order to generate validated methods of assessment, particularly with regards to the prognostic ability of BIA and PhA. Further studies are needed to address the discrepancies in bioimpedance parameters within body compartments and between different devices and the deviation from health to disease. We hope that future studies will reveal insights into drug-specific alterations in body composition profiles in psoriatic disease, enabling clinicians to practice more stratified medicine and treat more effectively the metabolic components of patients' disease that are so often neglected in clinical practice and associated with worse outcomes. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 21, 2020. . (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 21, 2020. . Diniz Mdos S, Bavoso NC, Kakehasi AM, Lauria MW, Soares MM, Machado-Pinto J. Assessment of adiposity in psoriatic patients by dual energy X-ray absorptiometry compared to conventional methods. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 21, 2020. . Humans Last 15 years of publication All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 21, 2020. . All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. , 2012 ? ? et al., 2017 ? ? N: no; N/A: not applicable; Y: yes; ?: unclear. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 21, 2020. . Compared to men, women had several significantly higher bioelectrical impedance parameters including reactance, fat mass% and adipose tissue%. The values of adipose tissue were positively correlated only with patients' age (p ¼ .021) and age at disease onset (p ¼ .0006) but not with disease severity. In addition, the use of BMI cut-offs allowed to categorize 36.7% of women and 19.2% of men as obese, while fat mass% showed that 53.3% of women and 48.1% of men were obese. At baseline, psoriatic patients showed a lower BCM and a lower mean PhA score. During ustekinumab treatment, the mean PhA and BCM scores increased with an improvement in psoriatic disease. Thus, ustekinumab can be an effective drug for improving not only psoriasis but also the general clinical status of patients. Sarcopenia, using ALM index and SMI, was diagnosed in 13.7% and 43.1% of PsA women, and in healthy women in 9% and + All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 20.4%, respectively. In the group of PsA, sarcopenia was associated with a significant increase in the occurrence of disorders of bone mineralization (72.7% vs. 41.3% in patients without a decrease in muscle mass). There was no correlation between the loss of muscle mass, bone density, and activity of PsA. With an identical body mass index, psoriatic patients showed a higher body fat content as calculated by electric bioimpedance, which correlated positively with waist circumference, and higher plasma concentrations of LDL-cholesterol, leptin and apo-B. Vitamin D was low both in patients and controls, and increased in the patients and the end of the phototherapy course. No correlation of its increase with PASI improvement was noted. At the end of the treatment a decrease in ferritin levels was noted, and it was correlated with total cumulative UVB dose. Ferritin, B12 and CRP decreased significantly after NB-UVB therapy. Vitamin D levels reached adequate levels after phototherapy; however, no relationship with PASI improvement was observed. Dual energy X-ray absorptiometry was more capable of identifying obesity compared with BMI and WC both in psoriatic and control patients. Truncal fat percentage was negatively correlated with insulin sensitivity (r=−0.78; P=.01) and positively correlated plasma leptin (r=0.88, P=.002). After 12 weeks of therapy (infliximab=5, adalimumab=4), there were no significant changes in insulin sensitivity or levels of fasting glucose, hemoglobin A1c, or Cpeptide. Body fat increased by 6.5% and truncal fat increased by 11.4%. Leptin concentrations significantly decreased after anti-TNF treatment. The group on a hypocaloric diet + omega-3 supplementation (3 g/day) had significant weight loss (-1.79 ± 2.4; P = 0.004), as well as waist circumference (-3.28 ± 3.5, P = 0.001 and body fat (-1.2 ± 2.2, P = 0.006) reduction. There was no significant correlation between weight loss and disease activity improvement. In both groups, a significant percent change of body weight, fat, and lean mass, compared to the baseline (PsO: body weight +3.8 ± 2.5%, fat mass 8.6 ± 10.5%, lean mass 1.9 ± 2.4%; PsA: body weight +3.7 ± 3.4%, fat mass 8.9 ± 17.3%, lean mass 2.9 ± 3.4%) was observed. Sarcopenia with decrease in muscle mass and function was observed in 5 RA (7.8%), one SpA (1.7%) and one PsA (9.1%). Sarcopenia in terms of reduced SMI only (1) was not more frequent occurring in 5 RA (7.8%), 3 SpA (5.1%) and one PsA (9.1%). + All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Total fat mass was increased in PsO but not in PsA. Android fat and visceral fat were found higher in PsO (p< 0.05) while the fat mass measurements did not differ between the patients with PsA and their controls. WC was higher in patients with PsO compared to their controls. Leptin, leptin/fat mass ratio, and total adiponectin were elevated in PsA. Insulin levels and HOMA were increased in both PsO and PsA groups. In patients with PsO, android and visceral fat were correlated with SCORE (r=0.3, p=0.02 and r= 0.6, p < 0.0001 respectively). EFT was significantly associated with MS (P < 0.01), age (P < 0.05) and female gender (P < 0.05) in psoriasis patients only. Balci et al., 2010 The mean VFA value and VFA/SFA ratio of the psoriasis patients were significantly higher compared with the control patients (123.4 ± 80.3 vs. 81.2 ± 59.8 cm 2 and 0.734 ± 0.593 vs. 0.491 ± 0.336; P = 0.005 and P = 0.017, respectively). Fasting blood sugar levels were also found to be significantly higher in psoriasis patients, compared with the control patients (101.8 ± 43.5 vs. 83.4 ± 9.1 mg/dl; P = 0.005). Multiple linear regression analysis indicated that waist-to-hip ratio, age, body weight, the presence of psoriasis and metabolic syndrome were significantly associated with VFA. Mean EFA in patients with psoriasis was significantly higher than in controls (13.8± 8.4 vs. 97 ±6.4 cm 2 , respectively, P = 0.02), but mean CACS did not differ significantly between the two groups (55. These results confirm the increased frequency of obesity in patients with psoriasis and are obtained by a fully automated conversational system usable by the patient. A statistically significant difference (P < 0.001) was observed between the LAP index of controls (23.79 ± 13.02) and that of psoriasis patients (46.42 ± 27.2). LAP index was significantly higher (P = 0.028) in the moderate-to-severe psoriasis group + All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 21, 2020. . https://doi.org/10.1101/2020.05.18.20104802 doi: medRxiv preprint Current concepts in the pathogenesis of psoriasis The Th17 axis in psoriatic disease: pathogenetic and therapeutic implications Psoriasis, metabolic syndrome and cardiovascular risk factors. A population-based study Psoriasis and the metabolic syndrome Systematic review and meta-analysis of the association between psoriasis and metabolic syndrome Factors influencing cardiometabolic risk profile in patients with psoriasis Psoriasis and cardiovascular disease: the elusive link Body composition in clinical practice The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration Cochrane Handbook for Diagnostic Test Accuracy Reviews Critical Appraisal Skills Programme Accessed 12 ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions Prevalence of sarcopenia in patients with chronic inflammatory rheumatic diseases Dietetic intervention in psoriatic arthritis: The dieta trial Effect of Phosphodiesterase 4 Inhibition with AFI: abdominal fat index; ALM: appendicular lean mass; AS: ankylosing spondylitis; BCM: body cellular mass; BIA: bioelectric impedance analysis; BMI: body mass index; CACS: coronary artery calcium score DXA: dual energy X-ray absorptiometry; EFA: epicardial fat area; EFT: epicardial fat thickness; FM: fat mass; FMI: fat muscle index; HC: healthy controls; HOMA: Homeostatic Model Assessment; LAP: lipid accumulation product; MetS: metabolic syndrome; MMI: mean muscle index; MRI: magnetic resonance imaging SCORE: Systematic Coronary Risk Evaluation; SMI: skeletal muscle index; SFA: subcutaneous fat area; SpA: spondyloarthritis; TBW: total body water; VFA: visceral fat area; WC: waist circumference. of visceral fat MRI of abdominal fat distribution (56.02 ± 30.09) as compared to the mild psoriasis group Mean weight loss after 3 and 6 months apremilast treatment was -1.4kg (95% CI -2.1, -0.6, P = 0.001) and -2