Psoriasis is a chronic debilitating skin disorder characterized by well-defined erythematous plaques with silvery scales that can affect any part of the skin. Psoriasis is now recognized as one of the most common immune-mediated disorders with significant physical, psychological and social implications and had a significant negative impact on patient quality of life.
- The prevalence of psoriasis is approximately 0.5% to 11.4% of adults and 0% to 1.4% of children worldwide.
- The pathogenesis of psoriasis can be explained by the abnormal proliferation of epidermal keratinocytes.
Immune dysfunction, genetic abnormalities, and environmental factors have also been linked to the etiologies of psoriasis. Although psoriasis itself is rarely life-threatening, psoriatic patients are at increased risk of comorbidities such as metabolic syndrome, cardiovascular disease, asthma, and inflammatory bowel disease.
Colorectal cancer ( CRC) is prevalent throughout the world and is immensely destructive to people’s health and well-being. The incidence of CRC in the general population has increased especially in many developing nations during recent decades.
CRC is a leading cause of cancer-related death and remains the fourth most frequently diagnosed cancer in men and women worldwide. According to the World Health Organization’s GLOBOCAN database, CRC causes approximately 900,000 deaths and causes 1.8 million new cases annually.
Predisposing factors for CRC include male sex, age, number of first-degree relatives with CRC, African American ethnicity, and inflammatory bowel conditions. Patients with early-stage CRC initially have no symptoms and can be diagnosed through screening or health tests.
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Interleukin (IL)-17 has been shown to be involved in the pathogenesis of psoriasis and the initiation of CCR18. Therefore, people with psoriasis have a theoretically increased risk of comorbid CRC. However, the relationship between psoriasis and CRC remains unclear.
Background
The relationship between psoriasis and colorectal cancer (CRC) was unclear.
Aim
The objective of the present study was to evaluate the evidence on the relationship between psoriasis and CRC.
Methods
A systematic review and meta-analysis was conducted of observational studies examining the association of psoriasis with CRC. MEDLINE and Embase were searched on March 24, 2020 for relevant studies.
The Newcastle-Ottawa scale was used to assess the risk of bias of the included studies. We performed a meta-analysis of the random effects model and a subgroup analysis in different sexes.
Results
Nine cohort studies with 10,544,609 subjects were included. We found a significantly increased risk of CRC in patients with psoriasis (hazard ratio (HR) 1.16; 95% confidence interval (CI): 1.08-1.24).
Subgroup analysis based on sex found a significantly increased risk of CRC in female psoriatic patients (HR 1.41, 95% CI 1.16 to 1.72) but not in men (HR 1.18, 95% CI 95%: 0.92 to 1.50).
Limitation
There are no data on psoriatic arthritis.
Discussion
Our systematic review demonstrates an increased risk of CRC among psoriatic patients. Evidence from the included cohort studies indicates that psoriatic patients had 1.16 times the risk of CRC, 1.14 times the risk of colon cancer, and 1.18 times the risk of rectal cancer compared to controls without psoriasis, respectively.
Our meta-analysis has high generalizability because it includes studies from various ethnicities, for example, the United States, Sweden, Switzerland, Denmark, and Taiwan.
Recent reports have expanded the concept that psoriasis is a systemic inflammatory immune disease caused by a dysfunctional immune system and accelerated proliferation of skin cells.
A normal immune system can regulate tissue homeostasis, eliminate damaged cells, defend against foreign organisms and many types of cancer. Published data indicate that epidermal T cells play an essential role in the development of psoriatic lesions.
Psoriasis is initiated and maintained by interactions between external environmental factors and intrinsic genetic susceptibility factors. When under environmental stress, keratinocytes trigger the activation of dendritic cells that stimulate T cells through the release of abundant cytokines, including IL-12 and IL-23.
Activated T cells produce IL-17, IL-22, tumor necrosis factor, and result in the stimulation of proliferation and differentiation of epidermal keratinocytes, maturation of myeloid dendritic cells, and attraction of neutrophils and macrophages that create the typical characteristic psoriatic lesions. Among these mediators, IL-17 is the main effector cytokine in the pathogenesis of psoriatic squamous plaques because it promotes keratinocyte proliferation directly.
Furthermore, chronic inflammation has long been considered a potential risk for cancer development since Rudolf Virchow hypothesized that cancers arise from sites of infection, chronic irritation, and inflammation in 1863.
Recent evidence supports that chronic inflammation plays an important role in cancer development. T helper 17 cells and their cytokine IL-17 have been shown to be involved in the pathogenesis of both psoriasis and CRC.
Therefore, chronic inflammation may explain the association between psoriasis and CRC.
On the other hand, accumulating evidence supports a strong and bidirectional association between the skin and the intestine. Physiologically, the skin and gut share similar characteristics, such as microbial diversity and abundant blood supply. Because the skin and gut are directly exposed to the external environment , both organs are important for defending harmful pathogens, maintaining homeostasis, and regulating immune responses.
The microbiota , comprising a large population of microorganisms, inhabits and colonizes mainly on the surface of the skin and the gastrointestinal tract. Microbiota can affect immunity and protect against exogenous microbial invasion by competitively binding to epithelial cells. Modulating the immune response of the epithelium through the regulation of biological metabolites, the microbiota plays a crucial role in the systemic inflammatory reaction.
Altered microbiota has been involved in the etiology of CRC. The possible link between CRC and microbiota involves genotoxicity, modulation of host defenses, bacterial metabolism, modulation of antioxidant defenses, dysbiosis, and the possible procarcinogenic properties of bacteria. Therefore, microbiota dysfunction may cause systemic immune impairment with the resulting development of immune-mediated dermatoses such as psoriasis.
Conclusions
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