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Comorbidities in Psoriasis in the Dermatology Clinic: New Considerations

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - 25th Congress of European Academy of Dermatology and Venerology (EADV)

Vienna, Austria / September 28- October 2, 2016

Vienna - Over the past decade there has been growing recognition that psoriasis is more than just an isolated skin disease as it is has become associated with other disorders. A common trend featured throughout the conference was the overlap of psoriasis with so many different disorders both genetically and pathophysiologically. These comorbidities include already established links, such as psoriatic arthritis (PSA) and depressive disorders. Newer associations that were discussed throughout the conference were cardiovascular disease, metabolic disorder, diabetes, obesity and gastrointestinal manifestations. Despite the wildly different clinical pathologies, a link that is becoming slowly more established with psoriasis are autoimmune disorders of the gut, including Crohn’s disease and ulcerative colitis. These new links can make the management of patients more complicated, and dermatologists at the conference were encouraged to consider other potential comorbidities when presented with a patient with psoriasis in their clinics.

Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec

A recurrent theme during the conference was the idea that psoriasis could be associated with several comorbidities at one time. “Most patients with psoriasis will have two or three comorbidities. These comorbidities significantly impact patients’ quality of life and their morbidity,” said Dr. Brian Kirby. St. Vincent’s University Hospital, Dublin, Ireland, as he discussed the recent updates on metabolic disorders and psoriasis. He talked about the links between psoriasis and obesity, which in turn can be associated with several other disorders: diabetes, infections and non-alcoholic fatty liver disease.

“On a pathophysiological level fat is a pro-inflammatory organ, it produces things like TNF [tumor necrosis factor], interferon, interleukin 2, all of which are also overrepresented in the skin of patients with psoriasis,” explained Dr. Kirby.

Prevalence of Comorbidities and Early Detection

Several groups presented data showing the prevalence of comorbidities among patients with psoriasis. An American group presented data after assessment of the Corrona Psoriasis Registry (launched in April 2015) in the US, which included 1014 patients with psoriasis from 140 sites (Strober B, et al. P2040). At registration 46% (456 patients) were obese (≥30 BMI), 15% (151 patients) had diabetes, 39% (392 patients) had hypertension and 44% (447 patients) also had PSA.

“Dermatologists hold an important role in early detection and determining the course regarding further treatment of their patients’ comorbidities,” said researchers from Germany when presenting their poster on early detection of comorbidity in psoriasis: recommendations of the National Conference on Healthcare in Psoriasis (Radtke MA, et al. P1097). In their study, the authors produced screening algorithms, formulated on an interdisciplinary basis that would enable physicians to recognize comorbidities early. After assessing more than 2000 publications on 15 different comorbidities, the group created algorithms that included target parameters for screening psoriasis patients, referral criteria for further workup to assess for comorbidities, recommended intervals for follow-up and measures in case of treatment-refractory disease.

“Knowledge and early initiation of treatment for comorbidities are also essential with respect to the initiation of adequate systemic psoriasis therapy,” said Dr. Radtke and his team. The comorbidities they considered included various cardiovascular diseases, obesity, diabetes, alcohol abuse, depression, psoriatic arthritis, malignant lymphoma and inflammatory bowel disease.

Gastrointestinal Manifestations

The association between gastrointestinal manifestations and psoriasis is not a new one. These links have been separated from reported cases of patients with inflammatory bowel disease on anti-TNF therapy who suffer with adverse paradoxical psoriasis.1,2 The most recent Canadian guidelines for the management of plaque psoriasis from 2009 has included inflammatory bowel disease among their list of comorbidities for physicians to consider when managing patients with psoriasis.2 The guidelines state there is a well-established epidemiological link between the two disorders; psoriasis is up to seven times more common in individuals with Crohn’s disease than in the general population.2 And conversely patients with psoriasis are up to three times more likely to have Crohn’s disease.2

A preliminary large prospective study (2013) of 4,400 women, who were enrolled in the Nurses’ Health study (between 1991 and 2008) in the UK looked at the association between psoriasis, PSA and IBD.3 The researchers found that 188 participants (4%) developed Crohn’s disease and 240 women (5%) had developed ulcerative colitis. Their results showed that women with psoriasis and concomitant PSA were at a significantly increased risk of developing Crohn’s disease.

Genetic Links

The association between the autoimmune disorders, inflammatory bowel disease and psoriasis, have led researchers to suspect the involvement of a similar cytokine-dependent inflammatory pathway in both the gut and skin.2 Genetic studies have found several overlapping genetic loci in skin conditions like eczema and psoriasis and other autoimmune disorders like inflammatory bowel disease and ankylosing spondylitis.4,5

“Psoriasis overlaps genetically with many different autoimmune disorders,” said Dr. James Elder, University of Michigan, USA, as he started his talk on psoriasis susceptibility loci. The cells that have the most open chromatin overlapping with psoriasis susceptibility loci tend to be T cells, such as Th17, Th0 and TH1, all of which are implicated in the pathogenesis of autoimmunity explained Dr. Elder. “When you look at the genes for diseases of the gut and of the skin, you will see that many of them are involved in regulating the barrier function in the skin and the ability to deal with prodigiosus bacteria. We think one of the ways that psoriasis overlaps with several different autoimmune or inflammatory diseases is because they are acting at key interfaces with the microbiome.”

When reporting on the study based on patients from the earlier mentioned Nurses Health Study, Dr. Li and colleagues thought their association between psoriasis, PSA and Crohn’s described the potential biological connection. “Both psoriasis and CD are well-recognised autoimmune disorders, for which Th17 cells have been implicated as playing a crucial role in sustaining chronic inflammation. IL-23 stimulates survival and proliferation of Th17 cells and induces the secretion of a characterisation set of cytokines, thus serving a key cytokine regulator in autoimmune inflammatory diseases. Genes implicated in the IL-23 pathway have been commonly associated with both psoriasis and CD. Other overlapping genetics regions have also been uncovered, including the 6P21 locus which encompasses IBD3, associated with CD, and PSORS1 associated with psoriasis.”3

Management and Further Study

The Canadian guidelines recommends that physicians caring for patients with psoriasis should conduct a thorough medical history to uncover any evidence of inflammatory bowel disease.2 In terms of managing patients with both inflammatory bowel disease and psoriasis, the guidelines suggests that patients should be considered for treatments that target both conditions.2

In his session on genetics of psoriasis: linking genetics and clinical manifestations, Professor Jonathan Barker, King’s College, London, talked about how “the biologics revolution” has been fundamental in helping patients but how we should also try and bring genetic science to the clinic.

“An audit that we did looked at our practice in London before the introduction of biologics and after the introduction of biologics. After biologics we had an 85% reduction in inpatient episodes of psoriasis. So they have a crucial and important impact on our clinical practice. But they are not the answer to everything,” said Prof. Barker. He went on to highlight the importance of further research into the genetic architecture of the disorder so that dermatologists can offer their patients personalized medicine and consider how psoriasis is classified in each of their patients.

“We may have predictive ability to talk about age of onset, severity, the clinical phenotype, whether or not it progresses to PSA or not and whether or not patients get comorbidities,” said Prof. Barker.

Going back to the clinic, when talking about the link between psoriasis and metabolic syndrome, Professor Jo Lambert, Ghent University, Belgium, urged dermatologists to not think of psoriasis as just a skin disease. And she referred everyone to the earlier mentioned screening algorithms for assessing overlapping diseases (Radtke MA, et al. P1097) as an excellent tool. “As a clinician I think you should be aware of the risk factors for the patient sitting in front of you. Please don’t just see yourself as just a skin doctor in this case. Don’t also stand in the paradigm of fragmented care. Go for dermatology care that should be personalized and complete, preventing disease and promoting health.”

Summary

Recent research shows that the list of comorbidities associated with psoriasis is increasing and patients with psoriasis are becoming more complex. Dermatologists were urged to think beyond the skin. And as genetic links become established between psoriasis and other disorders, there is hope in the future for further management options for patients.

References:

1. Pugliese D, Guidi L, Ferraro PM, et al. Paradoxical psoriasis in a large cohort of patients with inflammatory bowel disease receiving treatment with anti-TNF alpha: 5-year follow-up study. Aliment Pharmacol Ther 2015; 42: 880-888.

2. Canadian guidelines for the management of plaque psoriasis. 2009 Available at: http://www.dermatology.ca/wp-content/uploads/2012/01/cdnpsoriasisguidelines.pdf

3. Li WQ, Han JL, Chan AT, et al. Psoriasis, psoriatic arthritis and increased risk of incident Crohn’s disease in US women. Ann Rheum Dis 2013; 72: 1200-1205.

4. Jostins L, Ripke S, Weersma RK, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012; 491: 119-124.

5. Paternoster L, Standl M, Waage J, et al. Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis. Nat Genet 2015; 47: 1449-1456.

 

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