Does Weight Loss Reduce the Severity and Incidence of Psoriasis or Psoriatic Arthritis?

A Critically Appraised Topic

S.K. Mahil; S.M. McSweeney; E. Kloczko; B. McGowan; J.N. Barker; C.H. Smith

Disclosures

The British Journal of Dermatology. 2019;181(5):946-953. 

In This Article

Discussion

Key Findings

The above evidence suggests that weight loss leads to an improvement in pre-existing psoriasis and prevents de novo psoriasis in individuals with obesity. This has potential implications for routine clinical practice, as proactive management of obesity may help to reduce the disease burden of psoriasis on an individual and societal level.

Lifestyle Interventions

Our meta-analysis demonstrated a statistically significant reduction in psoriasis severity following lifestyle-induced weight loss (diet or physical activity). Although the improvement in psoriasis is small in magnitude (mean change in PASI −2·59) it appears to be durable, as Jensen et al. demonstrated sustained disease improvement for up to 64 weeks.[31] The limited change in psoriasis severity may be attributable to the small total weight loss achieved by lifestyle interventions (range −3·0% to −14·8%). Importantly, there is evidence of a linear dose–response relationship, with more weight loss leading to greater improvements in psoriasis severity in two RCTs.[27,30] Although there is a paucity of data for PsA,[42] DiMinno et al. also reported higher odds of achieving MDA in PsA in those achieving greater weight loss.[35] The long-term impact of weight loss in obese individuals with psoriasis or PsA on other comorbid conditions such as cardiovascular disease, nonalcoholic fatty liver disease and depression has not yet been formally assessed, but it is an additional potential benefit.

Although three of the examined RCTs did not show a significant reduction in psoriasis severity following lifestyle weight loss interventions, these studies were limited by low baseline PASI (Naldi et al., Jensen et al.),[30,34] insufficient weight loss achieved with the intervention (Naldi et al.),[30] short follow-up and small sample size (Kimball et al.).[32] Our meta-analysis findings are supported by a systematic review of lifestyle weight loss interventions in individuals with psoriasis and obesity by Upala and Sanguankeo, which examined the same six RCTs.[43]

As sensitivity analyses of our meta-analysis demonstrated that the pooled mean ΔPASI following lifestyle weight loss interventions was robust to the exclusion of biased studies, this finding may be translated into practical advice for patients. For example, obese individuals with moderate-to-severe psoriasis and PASI 10 could thus be advised that their psoriasis can improve by around one-quarter (i.e. 26%) following lifestyle weight loss interventions (resulting in > 5% weight reduction).

Other Interventions

Lifestyle-induced weight loss is often limited to 5–10% and the quality of evidence supporting its overall long-term efficacy in obesity is low.[44] Unfortunately, studies in psoriasis exploring the more effective strategies for obesity, specifically drug- or surgery-induced weight loss, are very few.

There was no evidence available regarding the only NICE-approved antiobesity drug, orlistat, a pancreatic lipase inhibitor, which is reported to induce an additional 3% weight loss when combined with lifestyle interventions.[45] GLP-1 agonists such as liraglutide and exenatide, indicated for the treatment of type 2 diabetes, also induce weight loss, and liraglutide was recently approved by the U.S. Food and Drug Administration as a treatment for obesity.[46] The only RCT we identified[38] showed no benefit of liraglutide in obese nondiabetic patients compared with control, but the study was small and short term, and the weight loss achieved was minimal (4·1%). Two case series did appear to show a small positive effect of GLP-1 agonists on psoriasis severity in obese diabetic patients with psoriasis, although whether this is a direct effect of weight loss per se, or through improved glycaemic control, is unclear.[36,47,48]

Bariatric surgery, which can lead to an additional 16–30% weight loss compared with lifestyle interventions or pharmacological treatments, is widely recognized as the most effective long-term treatment available to individuals with obesity.[49] The impact of bariatric surgery on psoriasis and PsA severity has only been reported in small case series to date, which did not meet the eligibility criteria for inclusion in our analysis.[50–55] However, although follow-up was limited to < 2 years, these reports do highlight the potential for complete psoriasis remission (without systemic medications) and concurrent resolution of comorbidities such as hypertension and type 2 diabetes following surgery.

Cohort studies by Egeberg et al.[39] and Maglio et al.[40] demonstrate a protective effect of surgery-induced weight loss in the development of psoriatic disease in obese individuals. Egeberg et al. demonstrated that gastric bypass surgery in particular reduces the risk of developing both psoriasis and PsA.[39] The observed superiority of gastric bypass compared with gastric banding may be attributed to greater postoperative weight loss with the former surgical modality (approximately 26% more) or direct anti-inflammatory effects on gut microbiota and gastric hormones. For example, GLP-1 levels increase up to 20 times after bypass surgery.[56–59] Similar observations on the incidence of psoriasis postsurgery were made by Maglio et al., although they did not observe a reduction in risk of PsA and the most effective type of surgery could not be identified.[40] This may be attributed to a lack of statistical power due to the study's low incidence of psoriasis (4·3%) and PsA (1·1%).

How weight loss interventions exert their effects on psoriasis is not clear, but they are likely to be multifaceted. A reduction in visceral fat mass may improve psoriasis through decreased proinflammatory cytokine (e.g. tumour necrosis factor-α) release from adipose tissue.[60] Physical activity itself induces an anti-inflammatory environment, independently of any changes in BMI, with upregulation of circulating anti-inflammatory molecules including interleukin-10 and downregulation of Toll-like receptor expression on monocytes leading to inhibition of antigen presentation and proinflammatory cytokine production.[61] Physical activity and diet may also modulate immune responses through changes at both a transcriptional and epigenetic level.[62,63] Together with the reported benefits on anxiety and depression,[64,65] which are both highly prevalent in psoriasis,[66] these data suggest that lifestyle weight loss interventions, alongside potential surgical options, are important adjuncts to conventional skin-focused treatments in obese individuals with psoriasis.

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