The Relationship of Obesity With the Severity of Psoriasis: A Systematic Review

Abstract Background: Psoriasis is a chronic inflammatory disease associated with obesity. The
increased production of adipocytokines in central adiposity contributes to the systemic inflammation
of obesity and perhaps to psoriasis.

Objective: The objective of this systematic review is to determine the association of obesity with
psoriasis severity.

Methods: We searched PubMed, EMBASE, and Cochrane Database for English-language papers
involving human subjects for all years. We extracted data on age, sex, body mass index (BMI),
proportion obese, and psoriasis severity index score (PASI).

Results: We identified 254 articles in our search and included 9. The sample size was 134 823
psoriasis patients. Seven of the 9 studies found a statistically significant association of increased
psoriasis severity with higher BMI.

Conclusion: Increased severity of psoriasis appears to be associated with increased BMI. Most
studies were cross-sectional or case-control, making it difficult to determine temporality.
Dermatologists should consider recording BMI for psoriasis patients and offering them lifestyle
counseling.

Introduction
Psoriasis is a common immune-mediated, inflammatory disease affecting 2% to 3% of population.1 It
is characterized by chronic, well-defined, erythematous and scaly plaques. This systemic disease has
many comorbidities, including cardiovascular disease, psoriatic arthritis, and depression.

T-cell dysfunction is crucial in the origin of psoriasis. In particular, cytokines play a critical role in both
the immunopathophysiology and the treatment of this chronic disease. Patients with psoriasis have
elevated serum levels of the proinflammatory cytokines interleukin (IL)-1, IL-6, IL-8, and tumor
necrosis factor (TNF)-α.3 Monoclonal antibodies that target TNF-α, IL12/23, and IL-17 have been
shown to be efficacious in treating moderate to severe psoriasis in clinical trials.

Obesity is also a chronic disease and is thought to have a systemic inflammatory effect.4
Adipocytokines are immunemodifying signaling molecules that are released from adipose tissue.
Higher levels of the proinflammatory cytokines are found systemically in patients with obesity,
including IL-6, IL-8, and TNF.5 It is hypothesized that the added inflammatory burden of obesity may
increase the severity of psoriasis in adult patients. The primary objective of this systematic review is
to determine the association of overweight and obesity (defined by body mass index or percent
body fat) with the severity of psoriasis in the adult population as compared with nonobese psoriasis
patients.

Methods

We followed the recommendations of the Preferred Items for the Reporting of Systematic Reviews
and Meta-Analysis (PRISMA) statement as applicable to this review.6 Ethics approval is not required
for this type of research at our institution.
Eligibility

We included observational (cohort, case-control, cross-sectional) and clinical trials that used a
clinical diagnosis of psoriasis in adults aged 18 or older. Studies must have used defined cutoffs for
obesity either by body mass index (BMI) or percent body fat. Body mass index is defined as height (in
meters) divided by weight (kilograms squared). Standard categories typically included normal weight
(18.0-24.9 m/ kg2 ), overweight (25.0-29.9 m/kg2 ), and obese (>30.0 m/ kg2 ). Percent body fat
should be measured using any commonly accepted methods such as bioelectrical impedance, fat-
fold thickness, or duel-energy x-ray absorptiometry (DEXA). We only included studies using
standardized measure of psoriasis severity such as percent body surface area (%BSA), psoriasis
assessment severity index (PASI), or physician global assessment (PGA). We excluded studies with
unclear reporting of data or lack of an appropriate comparator. Review papers and case reports
were also excluded.unclear reporting of data or lack of an appropriate comparator. Review papers
and case reports were also excluded.

Search Strategy

We searched PubMed, EMBASE, and the Cochrane Database for English-language studies performed
involving humans participants (≥18 years old) without date limits in January 2014. Search terms
(using MeSH heading) included psoriasis and obesity and/or weight. We handsearched the reference
lists of included articles for any additional relevant studies.

Study Screening
Two authors (P.F., J.K.) screened the titles and abstracts of articles for inclusion using our
predetermined criteria. The full texts of selected articles were then independently assessed for
inclusion in an unblinded fashion by P.F., J.K., and C.L. Quality was assessed using the US Preventive
Services Task Force quality rating criteria.7 These criteria qualitatively rank studies from good to
poor based on factors such as study attrition, use of appropriate measures, and attention to
confounders.7 Level of evidence was graded using the Centre for Evidence Based Medicine scale.8
Only studies considered “good” or “fair” based on these criteria were included. We adjudicated any
disagreement by consensus.

Data Extraction

One reviewer (P.F.) extracted data and synthesized it into a tabular format that was triple-checked
for accuracy. We extracted data on study characteristics (publication year, design, sample size,
country, study setting, age, sex, inclusion criteria), comparator, and key variables (PASI, %BSA, PGA,
BMI, percentage obese, waist circumference).

Outcomes

The primary outcome was psoriasis severity measured by PASI or %BSA.

Results

We identified 254 records in our search, of which we included 9 (Figure 1 and Table 1).9-17 All of the
studies were observational, including case-control/case-series (n = 4),9,10,13,15 cross-sectional (n =
4),12,14,16 and prospective cohort (n = 1).11 The total sample size was 134 823 psoriasis patients.
Due to heterogeneity of the data, we were unable to conduct a meta-analysis. Most of the studies
were based on hospital outpatient dermatology departments; however, the largest included study
was a database of general practitioners in the United Kingdom (n = 131 560) that dwarfs the sample
size of the others.14 Most study participants were male (range, 52%- 81%), middle-aged (range,
32.6-55.3 years old), and overweight (range, 24.8-30.6 kg/m2 ).

Seven of the 9 included studies demonstrated an association of the severity of psoriasis with obesity
(Table 2). All of the included studies assessed obesity based on BMI. None used percent body fat.
Most were of fair quality, and most used PASI as the main outcome measure. The largest study, by
Neimann and colleagues,14 used the UK GP Database diagnostic codes to obtain data on a
population-based sample of psoriasis patients (n = 131 560). The investigators defined severe
psoriasis as having received systemic therapy or phototherapy. Using multivariate analysis adjusting
for age, sex, and person-years, they found that the odds ratio (OR) of obesity in patients with severe
psoriasis was 1.47 (95% CI, 1.31- 1.63) and the OR of being overweight in patients with severe
psoriasis was 1.19 (95% CI, 1.09-1.30). In other words, obese/overweight psoriasis patients were
more likely to have severe disease requiring systemic therapy.

A case-control study with 448 subjects found that obesity was associated with increasing PASI (OR =
1.03; 95% CI, 1.01-1.05).10 A cross-sectional study with 399 subjects found an association of severe
psoriasis in obese versus normal BMI (OR = 2.60, 95% CI, 1.40-4.83).12 A case-series with 943
subjects found a higher proportion of patients with obesity among patients with severe psoriasis
(BMI 30 = 56.8%, P = .02).

Three studies found weak to moderate correlations with psoriasis severity. A case-control study (n =
65) found a positive correlation of PASI and BMI (R = 0.35, P = .004). Another case-control study (n =
88) found a positive Spearman’s correlation coefficient of PGA and BMI (r 2 = 0.29, P = .007). Last, a
cross-sectional study (n = 296) found a positive, although weak, correlation of PASI with BMI (r =
0.0154, P = .01).

Discussion

This systematic review describes the effect of overweight/ obesity on psoriasis severity. Seven of the
9 studies found that patients with a higher BMI had more severe psoriasis. Most of the included
literature is from studies of fair to good quality but with a lower level of evidence (3b to 4). A variety
of observational study designs were used, with most having consistent results and moderate effect
sizes. It appears that patients who are overweight or obese have more severe psoriasis than normal
weight patients.

This association has several plausible biological mechanisms. Adipose tissue is quite metabolically
active, producing a variety of systemically released, immune-modifying molecules referred to as
adipocytokines. These include IL-1, IL-6, and TNF-α, which are released by resident macrophages in
close proximity to adipocytes. TNF-α levels rise with increasing weight gain. These cytokines are also
implicated the immunopathogenesis of psoriasis. Likewise, significant associations exist between
higher levels of TNF-α and psoriasis severity.

These adipocytokines either act in a paracrine fashion, influencing local metabolic activity, or are
released in systemic circulation. Visceral adiposity, which is also associated with a higher rate of
cardiovascular disease, is most associated with increased systemic levels of proinflammatory
cytokines. Venous effluent-carrying cytokines and free fatty acids from visceral fat drain into the
hepatic system via the portal vein, providing a potential causative mechanism for the higher
inflammatory burden of central obesity. Why adipose tissue produces so many inflammatory
mediators is less clear, but local tissue hypoxia and oxidative stress have been proposed.
Conversely, it is possible that more severe psoriasis may predispose patients to higher BMI. Psoriasis
has a substantial psychosocial burden in many patients. Since stress is associated with weight gain, it
is possible that severe psoriasis may predispose patients to obesity. As well, obesity is a complex
disease with polygenic origins, and there may be yet unknown gene-environment interactions that
are associated with more severe psoriasis. We did not identify any genetic association studies
examining any commonality between the molecular origins of psoriasis and obesity.

Although there appears to be an association with increasing BMI and increasing severity of psoriasis,
it is unclear what effect interventions may have on this relationship. Several small clinical trials have
evaluated the effect of weight loss on psoriasis severity. A randomized, parallelgroup trial with 60
obese (BMI ≥30) psoriasis patients was conducted in the United States. Patients were randomized to
either a low-energy diet (800-1000 kcal/d for 8 weeks followed by 1200 kcal/d for 8 weeks) or a
usual care group. There was significant weight loss, and there was a trend toward reduction in PASI
(between-group PASI change scores -2.0 to 0.1, P = .06). Given the P value, it is likely that this study
was underpowered to detect a difference. Several case reports and a small case series on bariatric
surgery patients described clinically significant remission of psoriasis in patients postoperatively.
Some authors hypothesize that the reduction obesity-related inflammation may improve clinical
outcomes in psoriasis by the resultant reduction in proinflammatory cytokines.

Given the already increased risk of cardiovascular disease, metabolic syndrome, and dyslipidemia in
patients with psoriasis, our results reinforce the need for dermatologists to encourage healthy
lifestyle choices. At the very least, body weight and BMI should be recorded and tracked on a regular
basis. Dermatologists should be aware of health professionals such as registered dieticians and
family physicians who provide lifestyle counseling in their communities. Although there is mixed
evidence regarding the benefit of dietary or exercise-based treatments, in the long-term
management of chronic disease, such treatment is a low-risk and low-cost intervention with the
potential for substantial benefit.

Limitations

This systematic review has several limitations. Most of the studies had small sample sizes, and
several did not directly measure psoriasis severity with PASI. Therefore, the majority of the data
included came from the UK GP Database, which had BMI data on only 61% of participants. The
second largest study we include relied on self-reported body weight, which is often underestimated
in the general population. None of the studies assessed obesity using percent body fat—a tool that is
far less prone to error than BMI, which can overestimate obesity in certain racial groups and in
athletes. None of the included studies had prospective data, so it is impossible to assign causality to
our results. A large prospective cohort would provide more robust data to support our conclusions.
Similarity, the clinical significance is unclear, as only one well-designed, randomized controlled trial
has assessed the effect of weight loss on psoriasis severity, and its primary outcome was
nonsignificant. A more adequately powered clinical trial with long-term follow-up is needed to
further inform clinical practice.

Conclusion
Psoriasis is a complex, chronic, inflammatory disorder associated with obesity. The majority of
studies in our review report a positive association with BMI and the severity of psoriasis. This may
reflect the systemic inflammatory nature of obesity itself and subsequent stimulation of the
underlying immune mechanisms implicated in psoriasis. However, almost all of our studies were
cross-sectional or retrospective, making it difficult to determine the temporality of the relationship.
A large cohort study is needed to definitely support our conclusion. In the meantime, clinicians
should consider offering lifestyle counseling to all patients with psoriasis and should record body
weight and BMI during clinical follow-up.

Declaration of Conflicting Interests

The author(s) declared the following potential conflicts of interest with respect to the research,
authorship, and/or publication of this article: John Kraft has acted as consultant, advisor and/or
speaker for AbbVie, Amgen, Janssen, Leo Pharma, and Novartis. Wayne P. Gulliver has received
honoraria for participation in advisory boards for AbbVie, Amgen, Bio-K, and Janssen and for
participation in speaker engagements and consultative meetings for AbbVie, Actelion, Amgen,
Janssen, Leo Pharma, Novartis, and Roche. Charles Lynde has acted as a principal investigator,
speaker, and/or consultant for AbbVie, Amgen, Celgene, Eli Lilly, Galderma, Janssen, Leo Pharma,
Merck, Novartis, Pfizer, and Valeant.