Psoriasis is a common, chronic, relapsing, inflammatory skin disease affecting up to 3% of the world’s population [9, 10].

Up to 90% of patients with psoriasis have plaque psoriasis or psoriasis vulgaris, characterized by the presence of raised, well-demarcated, erythematous oval plaques with adherent silvery scales involving mainly the elbows, knees, scalp, and rima ani.

The scales are a result of a hyperproliferative epidermis (increased mitotic rate of basal keratinocytes) with premature maturation of keratinocytes and incomplete cornification, together with retention of nuclei in the stratum corneum (parakeratosis). As a result, the epidermis is thickened (acanthosis), with elongated rete ridges.

In the dermis, a dermal inflammatory infiltrate of dendritic cells, macrophages, and T cells in the dermis and neutrophils can be observed.

Last, an increased number of tortuous capillaries that reach the skin surface through a markedly thinned epithelium are often present [11].

Substantial advances have recently been made in elucidating the molecular mechanisms of psoriasis, and new efficacious drugs have been introduced for the treatment of this disease. However, major issues remain unresolved, including the primary nature of the disease, the immune cause of the inflammatory process, the relevance of cutaneous and systemic factors, and the role of genetic and environmental influences on disease initiation, progression, and response to therapy [11].

Psoriasis is well known to be associated with a high degree of morbidity. Patients’ quality of life is severely compromised; they are embarrassed about the appearance of their skin, and they have reduced levels of employment and income [10, 12, 13].

The costs of the disease and long-term therapy have a major impact on healthcare systems and on society in general [10, 12, 13].

Regarding the immunopathogenesis of psoriasis, the presence of an immune imbalance (characterized by an altered ratio between specific cytokines released by T helper (Th) 1/Th17 and Treg/Th2 lymphocyte subsets) is considered a key etiological factor [1, 2, 9, 14]. Various immune cell types play an important role, particularly CD4+ Th17 and Th1 cells. Together with CD4+ T cells, other T-cell subsets (Th22 and Th21) and CD8+ T cells infiltrating the epidermis represent the major source of interferon-γ, interleukin (IL)-17, IL-22, and tumor necrosis factor (TNF)-α [14].

In psoriatic lesional skin, a large number of these cytokines is observed. In addition, dendritic cell–derived cytokines (IL-23, IL-20, TNF-α) and keratinocyte-derived cytokines and chemokines (i.e., CXCL8, CXCL1, CCL20, IL-36) offer a relevant contribution to psoriatic lesional skin formation [1, 9, 14].

Whether because of the high incidence of metabolic syndrome or because of systemic inflammation, an important association between psoriasis and heart comorbidities has been reported [14–23]. Increased rates of concurrent CV disease, including hypertension, diastolic dysfunction, and heart failure have been noted in patients with psoriasis.

Epidemiological studies reported the association with shorter life expectancy, frequently attributable to CV events. Although an increased prevalence of CV events, such as myocardial infarction, stroke, ventricular dysfunction, and atherosclerosis, has been reported among psoriatic patients, psoriasis likely plays an independent role in the increased CV risk. This could be at least partly explained by the chronic systemic inflammatory state [32].

In fact, evidence is accumulating with regard to the improvement of early subclinical vascular alterations and CV morbidity and mortality by treatment with anti-inflammatory drugs, such as anti-TNF-α and methotrexate [29–32].

The inflammatory state that characterizes psoriasis and cardiometabolic diseases, e.g., obesity and atherosclerosis, recognizes a potentially shared pathophysiology involving immune activation of T helper cell (Th)-1, Th-17, regulatory T cell, and inflammatory cytokine signaling, such as TNF-a, IL-6, IL-8, IL-17, L-22, IL-36, and chemokines CCL-2 and CXC-1, -3, -10 [14, 32, 33].

The common pathophysiology potentially explains common treatment strategies and response to treatments [29–32].

With increased evidence and definition of cardiometabolic comorbidities in patients with psoriasis, there has been a growing interest from the dermatology community in elucidating the link and the common pathogenesis of psoriasis and cardiometabolic diseases [14]. Furthermore, there is a need for the stratification of the diseases according to valuable biomarkers.

Biomarkers are crucial within the context of stratified medicine in the diagnosis of diseases, the evaluation of systemic involvement, and therapy for “systemic” psoriasis.

Furthermore, novel, cheap, and non- or low-invasive techniques will be fundamental in the identification and quantification of systemic involvement.

Low-dose cytokine treatment is aimed at correcting the psoriatic immune imbalance, characterized by the hyperproduction of Th1/Th17 cytokines. A multicenter, double-blind, placebo-controlled clinical study [34] described the efficacy of specific low-dose cytokines (IL-4, IL-10, and IL-11, at a concentration of 10 fg/mL, GUNA., Milan, Italy) for the 8-month treatment of psoriasis vulgaris. The study evaluated the effectiveness on the extension of psoriatic lesions (measured using the Psoriasis Area Severity Index [PASI]) and the improvement in the quality of life (with the use of the Dermatology Life Quality Index [DLQI]). The study reported a significant reduction of psoriasis extension (PASI) together with an improvement in the quality of life (DLQI). No adverse event was reported during the whole trial. Similarly, an observational study [9] evaluated the pharmacological activity of the treatment based on the use of UVA-1 laser therapy with or without the co-administration of low-dose cytokines (interleukin [IL]-4, IL-10) and anti-IL-1 antibodies in patients affected by psoriasis vulgaris (LOTTI). The co-administration of low-dose cytokines in combination with a UVA-1 laser was shown to be more effective in ameliorating psoriasis skin involvement (PASI) in comparison with UVA-1 laser alone.

It is well known among insiders that it is always more important to consider and treat a patient with skin psoriasis as a patient with a systemic immune inflammatory disease, with well-characterized skin involvement. The sequence of events is not known. Many cytokines are involved: in Table 20.1, some of these and their effects on the skin and dermal vessels are reported [7, 40]. This may suggest that inflammation does precede the diseases and, later, specific organ inflammation, psoriasis, and atherosclerosis develop.