Psoriasis etiology

Discuss the etiology of psoriasis including genetic and immune changes. 

Psoriasis is a disease of the immune system that involves T lymphocytes. The etiology and pathogenesis of psoriasis results from complex communications that cause activation of T lymphocytes and trafficking to the skin. Further reactivation causes inflammation and overproduction of skin, resulting in lesions and plaques. In psoriatic skin, there is an upregulation of intracellular adhesion molecule-1 (ICAM-1) on endothelium and keratinocytes. 

Psoriasis is a common, chronic, papulosquamous disorder of unknown etiology with characteristic histopathological features and many biochemical, physiological, and immunological abnormalities. 

The role of both T and B lymphocytes in a variety of disease states beyond transplantation has become increasingly important in the past decade. This is especially true of those diseases frequently referred to as autoimmune in their etiology, such as rheumatoid arthritis, nephrotic syndrome, systemic lupus erythematosus, inflammatory bowel disease, and so on. In addition, several other major diseases are also known to have a component of T- or B-cell-mediated pathogenesis, for example, atopic dermatitis, psoriasis, and asthma. Until very recently, the mainstay of therapy for these diseases was the corticosteroids, which were often less than satisfactory in efficacy and often associated with undesirable side effects, especially in growing children and the elderly. Thus, the search for new agents with different mechanisms of action and which did not have the same adverse event profile as conventional corticosteroids led to the subsequent evaluation of drugs such as tacrolimus and sirolimus to treat several of these diseases. 

As mentioned (vide supra), P450 4F8 expression is associated with psoriasis [1623, 1624], but its role in the etiology of the disease is unclear. P450 4F8 has also been identilled as a potential target in prostate cancer [1628]. 

The role that cyclic nucleotides may play in the etiology and/or maintenance of a number of disease states is becoming clearer. In asthma, the ability of patients with this disease to excrete increased amounts of cyclic AMP in urine in response to epinephrine is greatly diminished, possibly due to a disease-related decrease in the sensitivity of adenylyl cyclase (AC) to the catecholamine. This lack of AC sensitivity however could be reversed by corticoid therapy in accord with the long established permissive effects of these hormones on cyclic AMP synthesis. In nephrogenic diabetes insipidus, diminished urinary production of cyclic AMP in response to ADH was also reported. Other conditions that may involve deficient cyclic AMP production include hypertension , psoriasis and stroke . On the other hand, cyclic AMP production appears... 

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