Overview of Psoriasis

Key points

Psoriasis was first described by the ancient Greeks, Hippocrates and Galen, and grouped together with leprosy. The term psoriasis was derived from the Greek “psora” which means an, “itch, mange, scab.” In the early nineteenth century, Robert Wilan and Hebra refined the description of psoriasis and distinguished it from leprosy. In 1879, Koebner described the appearance of psoriatic lesions at sites of injury, called the “Koebner phenomenon.” Today, psoriasis a global disease affecting 125 million people across the world and causing significant impairment in quality of life, disfiguring morbidity, and even mortality. In the late twentieth century, basic science research demonstrated that psoriasis is an immune-mediated polygenic disorder that can be triggered by various environmental triggers. Over the last 20 years, many of the immunologic drivers of psoriasis have been uncovered, and this research has been translated to the clinic with the development of increasingly powerful but selective biologic drugs targeting these immune pathways. This increased understanding of the immunology of psoriasis has led to remarkable improvements in the treatment of psoriasis and makes it an exciting time to care for patients with psoriasis.

Epidemiology

Psoriasis affects male and female patients equally. Two-thirds of patients are thought to have mild disease, and one-third of patients are thought to have more severe involvement. Psoriasis is found in practically all racial groups and is thought to affect approximately 2% of the world’s population. Although psoriasis is a global disease, there are some regional variations in prevalence, with rates varying from 0.4% in Asians to 2.6% in the United States and 2.9% in Denmark. In Africa, there is a higher prevalence in East Africans as opposed to West Africans, which may help explain racial differences within the United States. Interestingly, a study of 26,000 South American Native Americans did not document a single case of psoriasis.

Age of onset

Psoriasis may appear at any age, but it most commonly presents between the ages of 15 and 30. An earlier age of onset and family history have been associated with particular HLA class I antigens, most notably HLA-Cw6 . Based on this finding, Henseler and Christophers proposed that 2 different forms of psoriasis exist: type I psoriasis, with onset before the age of 40; and type II psoriasis, with age of onset after the age of 40. Both types of psoriasis respond similarly to treatment.

Development of a lesion

Psoriasis is characterized clinically by red and scaly plaques sharply demarcated from normal skin. Histologically, it is characterized by marked proliferation of keratinocytes, altered epidermal differentiation, and proliferation of endothelial cells accompanied by an influx of a variety of inflammatory cells. The development of a psoriatic lesion is a complex and multicellular process that involves keratinocytes, T cells, dendritic cells, macrophages, mast cells, endothelial cells, and neutrophils. Cytokines and growth factors initiate and sustain inflammation in this process through pathways that involve cells of both the innate and the acquired immune systems. Initial pinhead-sized macular lesions show edema and mononuclear cell infiltrates within the upper dermis. The overlying epidermis becomes spongiotic, and there is a focal loss of the granular layer. As the plaque matures, the epidermis becomes thickened in the center with increasing parakeratosis, capillary elongation, and perivascular infiltration of various types of immune cells. Mature psoriatic lesions contain elongated and uniform rete ridges with thinning of the epidermis overlying the dermal papillae. The tips of the rete ridges may become clubbed with dilated, tortuous capillaries in the dermal papillae. There is typically confluent parakeratosis and hyperkeratosis. More inflammatory cells are present with CD4+ T cells and dendritic cells in the upper dermis and CD8+ T cells in the epidermis. Neutrophils are commonly seen in psoriatic lesions and form characteristic collections in the spinous layer (spongiform pustules of Kogoj) and in the stratum corneum (Munro microabscesses). Eosinophils are not seen in psoriasis, unless the disease is drug induced.

T cells

The role of T cells in psoriasis was first documented in the 1980s, and the last 30 years of scientific and clinical research on psoriasis have further highlighted their role in the pathophysiology of the disease. The latest biologic medications for psoriasis target T-cell immune pathways, and their ability to clear plaques underlines the importance of the T-cell pathways these medications target.

In 1984, Dr Baker and colleagues were the first to show a correlation between the eruption of psoriatic skin lesions and the epidermal influx and activation of T cells. Subsequently, deletion of epidermal T cells was shown to predate resolution of psoriatic plaques in patients on phototherapy. In 1986, cyclosporine was shown to be highly efficacious in treating psoriasis due to its blockade of T-cell function. Ten years later in 1996, activated autologous T cells initiated psoriatic lesions when injected into uninvolved psoriatic skin transplanted onto severe combined immunodeficient mice. This showed that T cells were sufficient to induce a psoriatic process. More recently, using xenograft models where human skin is grafted onto immunodeficient mice, trafficking of T cells to the epidermis, particularly CD8+ T cells, was shown to be critical for development of psoriatic plaques, highlighting the importance of these cells in psoriasis.

Psoriatic lesions are typified by T helper 1 (Th1) polarized CD4+ cells and T cytotoxic 1 (Tc1) polarized CD8+ T cells producing interferon (IFN)-γ, which is the dominant cytokine profile of psoriatic lesions. IFN-γ drives the production of interleukin-12 (IL-12) and IL-23 by dendritic cells. IL-23 supports and expands CD4+ T cells, and likely CD8+ T cells, that produce IL-17 and/or IL-22, whereas IL-12 promotes development of Th1 and Tc1 cells. The secretion of IL-17 and IL-22 by these cell types likely maintains the chronic inflammation in psoriasis, but the exact role of IFN-γ in this process is still unclear. T cells also contribute to the production of tumor necrosis factor-α (TNF-α), but TNF-α is a potent proinflammatory cytokine, the main role of which may be to amplify the effect of other cytokines, including IFN-γ and TNF-α. Biologic medications targeted at inhibiting these inflammatory mediators, including TNF-α, IL-12/IL-23, and IL-17, have shown great efficacy in treating psoriasis, underlining the important role this molecule plays in driving the disease.

Macrophages and dendritic cells

Macrophages are important phagocytic cells that reside under the basement membrane, adjacent to proliferating keratinocytes, and are important in the early development of psoriatic lesions. They express Factor XIIIa and secrete the chemokine MCP-1 (CCL2). They are an important source of TNF-α, inducible nitric oxide synthase, and IL-23. It has been shown in mouse models that the selective elimination of macrophages leads to prompt improvement of psoriatic lesions.

Dendritic cells have an important role in both priming the adaptive immune response and inducing self-tolerance. Subtypes of dendritic cells, such as Langerhans cells, dermal dendritic cells, and myeloid dendritic cells, help drive the Th1, Th17/Th22 polarization of psoriatic plaques. In particular, myeloid dendritic cells help make IL-12 and IL-23 cytokines that promote Th1 and Th17 differentiation and responses, respectively. In a psoriatic plaque, myeloid dendritic cells can be increased up to 30-fold as compared with uninvolved skin and make up about 80% to 90% of the dendritic cells.

Neutrophils

Although neutrophils are a common histopathologic finding in the upper epidermis of psoriatic lesions, they do not seem to a have a significant role in lesional development in chronic plaque psoriasis, although they have a key role in pustular variants of psoriasis.

Uninvolved psoriatic skin

Normal-appearing skin of patients with psoriasis has been shown to have subclinical biochemical changes that lead to subtle histologic findings. Lipid biosynthesis is predominantly affected with measurable changes in the levels, constitution of phospholipids, free α-amino acids, and hydrolytic enzymes. These changes lead to histopathologic findings that can be identified on microscopic examination and have been termed “histochemical parakeratosis.”

Clinical findings

Cutaneous lesions

Psoriasis Vulgaris

Psoriasis vulgaris, or chronic plaque psoriasis, is the most common clinical manifestation of psoriasis, affecting approximately 90% of psoriasis patients. Psoriasis vulgaris is characterized by well-demarcated, erythematous, raised plaques with white micaceous scale. Lesions vary in size from pinpoint papules to large plaques and tend to be symmetrically distributed on the scalp, postauricular skin, elbows, gluteal cleft, and knees. These lesions produce significant amounts of scale and removing the scale produces pinpoint bleeding (the Auspitz sign), which is a sign of the dilated capillaries below the epidermis and thinned suprapapillary plate. Disease presentation is impressively variable among patients, and the clinical findings can change quickly even within the same patient.

Psoriatic lesions can be induced by trauma, and this is known as Koebnerization or the isomorphic response. This phenomenon is more likely to occur when the disease is flaring and is an all-or-nothing response (meaning if psoriasis appears at one site of injury then it will appear at all sites of injury). The isomorphic response typically appears 7 to 14 days after injury, and the lifetime prevalence of the phenomenon is estimated to be 25% to 75%. The isomorphic response is not specific to psoriasis.

Historically, psoriasis vulgaris has been subclassified by the shape and scale of the plaques. Today, the terms have little significance clinically, but they connect the modern disease to its long history. Psoriasis geographica describes plaques that resemble a land map. Psoriasis gyrata consists of confluent, connected plaques with a circinate appearance. Rupioid lesions present in the shape of a cone or limpet. Ostraceous plaques have a circular, hyperkeratotic concave lesion resembling an oyster shell. Elephantine psoriasis refers to large, thick, scaly plaques on the lower extremities. Annular lesions have partial central clearing, giving a ring-shaped appearance, and are associated with a good prognosis because the annular shape suggests clearing ( Fig. 1.1 ). Finally, a hypopigmented ring on the periphery of an individual plaque, or Woronoff ring, may be seen after treatment with UV radiation or topical steroids. Woronoff rings are thought to be caused by inhibition of prostaglandin synthesis and are associated with lesional clearing and a good prognosis.