❷ Keratinocyte proliferation is cen

❷ Keratinocyte proliferation is central to the clinical presentation
of psoriasis. Keratinocytes are skin cells producing keratin
which act as a skin barrier. Increased keratinocyte cell
turnover (hyperkeratosis) results in the characteristic thick
scaly skin lesions seen in patients with psoriasis.10,11
Hyperkeratosis results from immune derangements.
The abnormal immune response seen in psoriasis is mediated
primarily by T lymphocytes (T cells).1 In patients with
psoriasis, certain types of T cells are overactive and migrate to
the skin in large numbers. T cells access the skin by binding to
activated endothelial cells via intracellular cell adhesion molecules
(ICAM-1).1,12 These naïve T cells then encounter antigens
in the skin, which are presented to the T cells by antigenpresenting
cells (APCs), and become activated. There is an
LFA-3–CD2 signal which plays an important part in T-cell
activation: LFA-3 is the leukocyte-function-associated antigen
type 3 found on APCs; CD2 is a cell-surface glycoprotein
expressed on T-cell subtypes.1 When LFA-3 interacts with
CD2, there is an increased proliferation of T cells.13
Activated T cells begin releasing cytokines including
interleukin-2 (IL-2), interferon-, (IFN-), tumor necrosis
factor (TNF-), and others.4,13 Cytokine activity leads to a
rapid proliferation and turnover of skin cells, triggering the
inflammatory process and the development of psoriatic skin
lesions.4,13,14 TNF-may have a role in disease severity; it
upregulates endothelial and keratinocyte expression of ICAM-1,
activates T cells, enhances T-cell infiltration, and augments
keratinocyte proliferation.12
Treatment of psoriasis is based on an understanding of the
underlying pathophysiology.Agents that modulate the abnormal
immune response, such as corticosteroids and biologic response
modifiers, are important treatment strategies for psoriasis. In
addition, topical therapies that affect cell turnover are effective
for psoriasis. Clinically, a treatment regimen should always be
individualized, taking into consideration severity of disease,
patient responses, and tolerability to various interventions.