Markers of Systemic Inflammation in Psoriasis
Studies investigating systemic inflammation in psoriasis use different serum markers and report discrepant results. We set out to determine whether systemic inflammation is elevated in patients with psoriasis compared with healthy controls, and to measure the extent of this elevation, by summarizing available data on serum inflammatory markers. PubMed, Embase and Web of Science were searched from inception to March 2011. We included studies comparing the serum inflammatory markers interleukin (IL)-1β, IL-6, IL-10, C-reactive protein (CRP), intracellular adhesion molecule (ICAM)-1, E-selectin and tumour necrosis factor (TNF)-α in patients with psoriasis and healthy controls. Differences in serum marker levels between patients and controls were pooled as standardized mean differences (SMDs; Cohen's d) using a random-effects model. Seventy-eight studies were eligible. Of the 7852 individuals included, 3085 had (severe plaque) psoriasis. The pooled SMDs were higher in patients with psoriasis than in healthy controls for IL-6 [d = 1·32, 95% confidence interval (CI) 0·83–1·81], CRP (d = 1·83, 95% CI 0·76–2·90), TNF-α (d = 1·32, 95% CI 0·86–1·79), E-selectin (d = 1·78, 95% CI 1·32–2·25) and ICAM-1 (d = 1·77, 95% CI 1·15–2·39). The SMD between cases and controls for IL-1β and IL-10 was not significant. Age had a significant effect on the SMD for IL-6 and TNF-α. For IL-6 the effect size was higher for plaque psoriasis studies (d = 1·98). The effect size was not influenced by the Psoriasis Area and Severity Index, measurement method or quality assessment. The pooled analyses suggest modest but significantly elevated levels of the proinflammatory cytokines in the serum of patients with psoriasis with predominantly severe disease. To what extent this modest increment is clinically relevant could be investigated in a synthesis of all studies measuring inflammation before and after antipsoriatic therapy.
Psoriasis is a chronic, relapsing, inflammatory skin disease that affects 2% of the white population. This skin condition is histologically characterized by abnormal proliferation of keratinocytes and infiltration of immune cells, predominantly T cells and dendritic cells in psoriatic lesions. The majority of inflammatory cells and cytokines remain in the tissue, and a relatively small proportion can be measured in the peripheral blood, including interleukins (ILs), which have shown to be elevated in patients with cardiovascular disease, metabolic syndrome and diabetes.
The search for markers in psoriasis was revived, as not only were these found in the skin, but researchers also identified a spillover of inflammatory markers into the systemic circulation, using them to measure disease severity, to monitor treatment response objectively, to find new targets for therapy and to explain comorbidities in patients with psoriasis.
Much attention has been drawn towards 'upgrading' psoriasis from a skin condition to a systemic disease, as serum biomarkers for inflammation are raised in psoriasis, and patients could therefore have a higher risk of developing systemic comorbidities. Data on serum levels of pro- and anti-inflammatory cytokines in patients with psoriasis compared with controls are controversial, with some authors not observing any difference, while others report elevated or decreased levels in psoriasis. The studies to date have small sample sizes, or have investigated different markers and techniques to assess inflammation; moreover, measurement of serum inflammation is often not their primary objective.
We conducted the first systematic review and meta-analysis to determine whether six well-known proinflammatory serum markers IL-1β, IL-6, C-reactive protein (CRP), tumour necrosis factor (TNF)-α, intracellular adhesion molecule (ICAM)-1 and E-selectin are elevated and anti-inflammatory IL-10 decreased in treatment-naive patients with psoriasis compared with controls.
Abstract and Introduction
Abstract
Studies investigating systemic inflammation in psoriasis use different serum markers and report discrepant results. We set out to determine whether systemic inflammation is elevated in patients with psoriasis compared with healthy controls, and to measure the extent of this elevation, by summarizing available data on serum inflammatory markers. PubMed, Embase and Web of Science were searched from inception to March 2011. We included studies comparing the serum inflammatory markers interleukin (IL)-1β, IL-6, IL-10, C-reactive protein (CRP), intracellular adhesion molecule (ICAM)-1, E-selectin and tumour necrosis factor (TNF)-α in patients with psoriasis and healthy controls. Differences in serum marker levels between patients and controls were pooled as standardized mean differences (SMDs; Cohen's d) using a random-effects model. Seventy-eight studies were eligible. Of the 7852 individuals included, 3085 had (severe plaque) psoriasis. The pooled SMDs were higher in patients with psoriasis than in healthy controls for IL-6 [d = 1·32, 95% confidence interval (CI) 0·83–1·81], CRP (d = 1·83, 95% CI 0·76–2·90), TNF-α (d = 1·32, 95% CI 0·86–1·79), E-selectin (d = 1·78, 95% CI 1·32–2·25) and ICAM-1 (d = 1·77, 95% CI 1·15–2·39). The SMD between cases and controls for IL-1β and IL-10 was not significant. Age had a significant effect on the SMD for IL-6 and TNF-α. For IL-6 the effect size was higher for plaque psoriasis studies (d = 1·98). The effect size was not influenced by the Psoriasis Area and Severity Index, measurement method or quality assessment. The pooled analyses suggest modest but significantly elevated levels of the proinflammatory cytokines in the serum of patients with psoriasis with predominantly severe disease. To what extent this modest increment is clinically relevant could be investigated in a synthesis of all studies measuring inflammation before and after antipsoriatic therapy.
Introduction
Psoriasis is a chronic, relapsing, inflammatory skin disease that affects 2% of the white population. This skin condition is histologically characterized by abnormal proliferation of keratinocytes and infiltration of immune cells, predominantly T cells and dendritic cells in psoriatic lesions. The majority of inflammatory cells and cytokines remain in the tissue, and a relatively small proportion can be measured in the peripheral blood, including interleukins (ILs), which have shown to be elevated in patients with cardiovascular disease, metabolic syndrome and diabetes.
The search for markers in psoriasis was revived, as not only were these found in the skin, but researchers also identified a spillover of inflammatory markers into the systemic circulation, using them to measure disease severity, to monitor treatment response objectively, to find new targets for therapy and to explain comorbidities in patients with psoriasis.
Much attention has been drawn towards 'upgrading' psoriasis from a skin condition to a systemic disease, as serum biomarkers for inflammation are raised in psoriasis, and patients could therefore have a higher risk of developing systemic comorbidities. Data on serum levels of pro- and anti-inflammatory cytokines in patients with psoriasis compared with controls are controversial, with some authors not observing any difference, while others report elevated or decreased levels in psoriasis. The studies to date have small sample sizes, or have investigated different markers and techniques to assess inflammation; moreover, measurement of serum inflammation is often not their primary objective.
We conducted the first systematic review and meta-analysis to determine whether six well-known proinflammatory serum markers IL-1β, IL-6, C-reactive protein (CRP), tumour necrosis factor (TNF)-α, intracellular adhesion molecule (ICAM)-1 and E-selectin are elevated and anti-inflammatory IL-10 decreased in treatment-naive patients with psoriasis compared with controls.
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