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Grand debate: Is psoriasis a systemic or skin-only disease?

Presented by
Prof. Brian Kirby & Prof. Stefano Piaserico
EADV 2021
The first of the controversy sessions dealt with the question whether psoriasis is a skin-only disease or a systemic inflammatory disease. The 2 discussants, Prof. Brian Kirby (St. Vincent´s University Hospital, Ireland) and Prof. Stefano Piaserico (University of Padua, Italy) agreed that psoriasis has to be seen as a systemic inflammatory disease.

Prof. Kirby, who supported the view that psoriasis is in most cases a skin-only disease, reminded his audience that psoriasis is characterised by marked epidermal hyperplasia with a rapid transition between basal cell layer and stratum corneum and absence of stratum granulosum [1]. The epidermis turns over 7–8 times more rapid than normal with a loss of differentiation. This causes the development of scales and a significant amount of inflammation in plaques, which makes the skin red, itchy, and sore. “For many centuries, we thought keratinocytes were the main problem; we now know that the immune system is the main problem,” Prof. Kirby said. Antigen presentation is the key event in the development and maintenance of plaques in psoriasis, but activation of dendritic cells is the event that causes all of the subsequent inflammation and epidermal hyperplasia. Crosstalk between epithelial cells and immune cells shapes and maintains the inflammatory milieu  [2]. “The key event happens in the skin; this is a skin disease; this is where the inflammation starts,” Prof. Kirby argued.

Genetic studies have shown that most of the genes related to psoriasis are to do with immune dysregulation, antigen presentation, and skin barrier function. “All of this immunology is skin focused, and the vast majority of the inflammation occurs in the skin. What we see in the systemic circulation leaks from the skin, but the skin is the primary event,” Prof Kirby said.

Another argument in favour of seeing psoriasis as a skin-only disease is the fact that skin-directed therapies are effective, even in severe disease. A recently published study showed that 41% of the participants treated with UVB phototherapy applied 3 times weekly for 6 weeks achieved a Psoriasis Area and Severity Index (PASI) 90 response, and 81% achieved a PASI 75 response [3]. “Local therapies can induce remission and are effective. The reason we do not use these anymore is time expense and inconvenience,” Prof. Kirby said. From epidemiology studies is known that only 20% of patients with psoriasis have moderate-to-severe disease. “80% of our patients have mild-to-moderate disease and the evidence that they have systemic disease is marginal,” Prof. Kirby said.

Studies that looked at the comorbidities of psoriatic patients have shown that they are over-represented in patients with moderate-to-severe disease [4]. Prof. Kirby emphasised that these associations have not been so clear cut in a mild-to-moderate psoriasis population. He reminded the audience that cardiovascular disease may be a consequence of inflammation leaking from the skin, but may also be the consequence of obesity, metabolic syndrome, and smoking, which are not directly related to psoriasis. “Comorbidities are over-represented in the severe psoriasis population, but not part of the main disease. Therefore, psoriasis is mainly a skin disease,” Prof. Kirby concluded.

Psoriatic plaque is only the tip of the iceberg

“A systemic disease is by definition one that affects a number of organs and tissues, or affects the body as a whole,” was the counterargument presented by Prof. Piaserico [5]. But how can psoriasis affect distant organs? “The main link could be systemic inflammation derived from skin to the bloodstream and to other organs,” Prof. Piaserico said. The psoriatic plaque is only the tip of the iceberg, with a systemic inflammatory burden under the waterline that leads to comorbidities, especially cardiovascular comorbidities.

A transcriptome study revealed that genes isolated from lesional skin are linked to functional pathways associated with metabolic diseases/diabetes and to cardiovascular risk pathways, suggesting a potential linkage between altered gene transcription in the skin and cardiovascular comorbidities [6]. “We know since at least 15 years that there is an increased risk of myocardial infarction in patients with severe psoriasis. Cardiologists both in Europe and the United States list psoriasis as an independent risk factor for cardiovascular disease in their guidelines,” Prof. Piaserico said.

Atherosclerosis is also an inflammatory disease, where both big vessels and microvascular tissue are affected. A high prevalence of coronary microvascular dysfunction could be detected in young patients with severe psoriasis [7]. In a study performed by Prof. Piaserico’s group, microvascular dysfunction was present in 15% of psoriasis patients and clearly associated with baseline PASI and higher concentrations of C-reactive protein and TNF-alpha [8]. “Severe disease clearly means a higher burden of systemic inflammation,” Prof. Piaserico said. Another cardiovascular entity that showed an association with systemic inflammation is heart failure with preserved ejection fraction.

“Psoriasis is a disease able to cause these events,” Prof. Piaserico concluded. Thus, psoriasis fulfils the diagnostic criteria of a systemic disease. “Prof. Kirby is right that we should better control conventional risk factors in future studies, but we still have the evidence that if you can control skin inflammation and eventually systemic inflammation, it may have a major effect no matter what other cardiovascular risk factors are present,” Prof. Piaserico concluded. Prof. Kirby concluded that he shares this view, thus demonstrating that there is no real controversy between the 2 discussants when it comes to severe disease.

    1. Kirby B. Psoriasis is a skin-only disease. D1T10.1F, EADV Congress 2021, 29 Sept–2 Oct.
    2. Nestle FO, et al. N Engl J Med 2009;361:496–509.
    3. Watson N, et al. J Eur Acad Dermatol Venereol. 2021;Jul 13. DOI:10.1111/jdv.17519.
    4. Griffiths CE, Barker JN. Lancet. 2007;370:263–271.
    5. Piaserico S. Psoriasis is a systemic disease. D1T10.1G, EADV Congress 2021, 29 Sept–2 Oct.
    6. Suárez-Fariñas M, et al. J Invest Dermatol. 2012;132:2252–2264.
    7. Osto E, et al. Atherosclerosis. 2012;221:113–117.
    8. Piaserico S, et al. Atherosclerosis. 2019;289:57–63.


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