Psoriasis azathioprine

Hydroxyurea is an older agent still used occasionally today for patients with psoriasis however, there have been recent precautions about its use in the elderly and cutaneous vasculitic toxicities in patients with myeloproliferative disorders.29 Toxicity associated with tacrolimus has limited its use in psoriasis. Azathioprine has a slow onset and significant toxicity.29 Oral corticosteroids are reserved for severe or life-threatening conditions such as severe psoriatic arthritis or exfoliative psoriasis prolonged oral steroid use should be avoided.10... 

Systemic therapies are seldom used for mild to moderate psoriasis, and are generally reserved for patients with moderate to severe psoriasis.17 29 Oral agents include sulfasalazine, acitretin, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus, and hydroxyurea. Parenteral agents include the biologic response modifiers alefacept, efalizumab, etanercept, infliximab, and many others, currently at various stages of research or approval for psoriasis. 

Thioguanine is a purine analogue structurally related to 6-mercaptopurine and azathioprine. Thioguanine interferes with several enzymes required for de novo purine synthesis, and its metabolites are incorporated into DNA and RNA, further impeding nucleic acid synthesis. The mechanism of action of thioguanine in psoriasis is not clearly understood it has been hypothesized to affect the proliferation and trafficking of lymphocytes as well as the proliferation of keratinocytes. 

Cyclosporine is an important drug in preventing rejection after kidney, hver, heart and other organ transplantation (Haberal et al., 2004). Cyclosporine usually is combined with other immunosuppressives especially glucocorticoids and either azathioprine or mycophenolate mofedl and sirolimus (Krensky et al., 2005). In renal alio transplants it has improved graft acceptance in most clinics to 95 percent. In addition to its use in transplantation cyclosporine is used for the treatment of a number of autoimmune diseases. In autoimmune diseases, as might be anticipated, cyclosporine is most effective in those which are T cell mediated. These include several forms of psoriasis, rheumatoid arthritis refractive to all other therapy, uveitis, nephrotic syndrome and type I diabetes mellitus. 

Mycophenolate has also been studied in various chronic inflammatory disorders, such as rheumatoid arthritis, pemphigus vulgaris, and psoriasis. In 70 patients with chronic active Crohn s disease, mycophenolate plus glucocorticoids produced benefit on disease activity comparable to azathioprine plus glucocorticoids (7). Two of the 35 patients randomized to mycophenolate had significant adverse effects that required drug withdrawal, namely rashes and vomiting. 

Azathioprine, a l-methyl-4-nitroimidazolyl derivative of 6MP, deserves mention. Since 6-mercaptopurine exhibits considerable, but short-lived, suppression of the immune reaction, it seemed desirable to slow the rate of excretion in order to achieve a more sustained reaction. This was accomplished with this pro-drug, when the nitro-activated C-S bond is slowly cleaved, releasing the parent drug. Azathioprine has been used in preventing transplant rejections, the graft-versus-host reaction, and as a supplementary treatment for autoimmune diseases such as systemic lupus erythematosus and psoriasis. Table 4-6 lists metabolites and their corresponding antimetabolites. 

---