Chronic inflammation in psoriasis and obesity: Implications for therapy

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Summary

A recent study has shown an indisputable relationship between psoriasis and obesity. Obesity leads to a higher risk in developing psoriasis and a poorer long-term clinical outcome of psoriasis. Furthermore, loosing weight may improve the psoriasis.

A network of pro-inflammatory cytokines (especially tumour necrosis factor alpha (TNF-α)) is believed to play an important role in the pathophysiology of both obesity and psoriasis. The chronic low-level inflammation- as seen in obesity – may contribute to the extent of psoriatic lesions in obese patients. TNF-α in obesity is presumed to be derived from inflammatory cells (macrophages) in the adipose tissue and in psoriasis from activated T cells. Several drugs, such as peroxisome proliferator activated receptor (PPAR)-gamma agonists and TNF-α blocking agents, that target the pro-inflammatory pathways involved in both psoriasis and obesity have proven their benefit in the treatment of these entities.

Furthermore, changes in levels of metabolic hormones as ghrelin and leptin in obesity may also play a role in the pathogenesis of deterioration of psoriasis by their potency to release pro-inflammatory mediators (e.g. interleukin (IL) 6 and TNF-α).

We hypothesize that the treatment of obese psoriasis patient could be focused on reducing the obesity-induced inflammation. Reducing this obesity-induced inflammation may finally lead to a better clinical outcome. Weight loss could lead to a less inflammatory state by reducing concentrations of TNF-α, IL-6, leptin and improving insulin sensitivity.

Introduction

In a recent case-control study, risk factors for psoriasis in 560 psoriasis patients were analysed [1]. It appeared that the frequency of psoriasis varied significantly in relation to family history of psoriasis in first-degree relatives, stressful life events, smoking and body mass index (BMI). The combined effect of these risk factors increases the risk for psoriasis even more. The risk of psoriasis was directly related to BMI; the odds ratio (OR) was 1.6 for BMI 26–29 corresponding to overweight subjects, and 1.9 for BMI greater than 29, corresponding to obese people. The OR was around 3 for smokers with a BMI > 30. In terms of population attributable risk BMI accounted for 16% of all the psoriasis cases. The combined effect of tobacco and BMI accounted for 48% of all the cases in this study population [1]. Smoking and obesity could also lead to cardiovascular comorbidity in psoriasis. Severe psoriasis, requiring hospitalisation, has been associated with increased risk for cardiovascular disease [2]. Several other studies have shown a link between psoriasis and obesity. Marino et al. showed that there is a significant association between extent of lesions in psoriasis and BMI [3]. Concerning the long-term prognostic factors which affect clinical outcomes after diagnosis of psoriasis, BMI > 25 turned out to be one of the poor prognostic factors [4]. Furthermore, there seems to be a relation between weight loss and clinical appearances of psoriasis. Higa-Sansone et al. report a patient, who showed complete resolution of psoriasis after a gastric bypass surgery [5].

As shown in above studies, there seems to be indisputably a relation between psoriasis and obesity. Here, we try to explain the relationship between these two entities.

Section snippets

Psoriasis and obesity: both characterized by a chronic low-level inflammation, a central role for TNF-α

Psoriasis is a chronic inflammatory disease of the skin affecting 2–3% of the world’s population. Histopathologically, psoriasis is characterized by hyperproliferation of epidermal keratinocytes and hyperkeratosis, as well as infiltration of immunocytes along with angiogenesis [6]. T cells are almost certainly involved in the initiation of psoriatic lesions. Activated T cells in the region of the dermal epidermal junction are thought to drive the hyperplastic proliferative response through

Hormones and their influence on inflammation

Several hormones are reported to be involved in the regulation of food intake and energy balance, including leptin, ghrelin and alpha-melanocyte stimulating hormone (α-MSH). Levels of these hormones are changed in obesity and influenced by weight loss. Beyond their effects on the central nervous system (CNS) and especially the hypothalamic region, these hormones appear to have effects on a number of other physiologic processes, including immune function and inflammation.

Leptin, which is

Implications for therapy

It appears that a network of pro-inflammatory cytokines (especially TNF-α) plays an important role in the pathophysiology of both obesity and psoriasis. The chronic low-level inflammation – as seen in obesity – may contribute to the extent of psoriatic lesions in obese patients in a negative way. In obese patients, changes in levels of the metabolic hormone leptin, may also play a role in the pathogenesis of deterioration of psoriasis by its potency to release pro-inflammatory mediators.

Because

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