Psoriasis methotrexate therapy

The main folate antagonist is methotrexate, an analogue of folic acid. Methotrexate competitively inhibits dihydrofolate reductase, the enzyme responsible for the synthesis of purine and pyramidine from folic acid. Trimetrexate, a methotrexate analogue, is useful in treating methotrexate-resistant tumours. It is also used to treat Pneumocystis carinii infections. Methotrexate is usually given orally, but may also be given intravenously or intrathecally. In addition to its use in cancer therapy, it is used in the treatment of psoriasis. Methotrexate can cause an obstructive nephropathy due to its precipitation in the renal calyx. 

Almeyda, J., et al. Structural and functional abnormalities of the liver in psoriasis before and during methotrexate therapy. 

BaiUn PL, Tindall JP, Roenigk HH Jr, Hogan MD. Is methotrexate therapy for psoriasis carcinogenic A modified retrospective-prospective analysis. JAMA 1975 232(4) 359-62. 

Mayall B, Poggi G, Parkin JD. Neutropenia due to low-dose methotrexate therapy for psoriasis and rheumatoid arthritis may be fatal. Med J Aust 1991 155(7) 480-4. 

Muller-Sutter, T., Schwarz, M., and Schwarz, K., Untersuchung der Serumpro-teine bei Psoriasis unter Methotrexate-Therapie. Dermatologica 137, 202-207 (1968). 

O Connor GT, Olmstead EM, Sug K, et al. Detection of hepatotoxicity associated with methotrexate therapy for psoriasis. Arch Dermatol 1989 125 1209-1217. 

Patrizi A, Spadola G, Bassi P, Albertini F, Ballardini G, Briganti E, Casolari S, De Dona D, Menni B, Zanotti M, De Angelis P. A case of aseptic pleuropericarditis in a patient with chronic plaque psoriasis under methotrexate therapy. Dermatol OnUne J 2010 16(2) 13. 

Thomas JA, Aithal GP. Monitoring liver function during methotrexate therapy for psoriasis are routine biopsies really necessary Am J Clin Dermatol 2005 6 357-363. 

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. 

Methotrexate, an antimetabolite, is indicated for moderate to severe psoriasis. It is particularly beneficial for psoriatic arthritis. It is also indicated for patients refractory to topical or UV therapy. Methotrexate can be administered orally, subcutaneously, or intramuscularly. The starting dose is 7.5 to 15 mg per week, increased incrementally by 2.5 mg every 2 to 4 weeks until response maximal doses are approximately 25 mg/wk. Adverse effects include nausea, vomiting, mucosal ulceration, stomatitis, malaise, headache, macrocytic anemia, and hepatic and pulmonary toxicity. Nausea and macrocytic anemia can be ameliorated by giving oral folic acid 1 to 5 mg/day. Methotrexate should be avoided in patients with active infections and in those with liver disease. It is contraindicated in pregnancy because it is teratogenic. 

Thioguanine is a purine analog that has been used as an alternative treatment for psoriasis when conventional therapies have failed. The typical dose is 80 mg twice weekly, increased by 20 mg every 2 to 4 weeks the maximum dose is 160 mg three times a week. Adverse effects include bone marrow suppression, GI complications (e.g., nausea, diarrhea), and elevation of liver fimction tests. 6-Thioguanine may be less hepatotoxic and therefore more useful than methotrexate in hepatically compromised patients with severe psoriasis. 

UVB light (290 to 320 nm) therapy is an important phototherapeutic intervention for psoriasis. The most effective wavelength is 310 to 315 nm, which led to development of a UVB narrowband light source, in which 83% of the UVB emission is at 310 to 313 nm. Topical and systemic psoriatic therapies are used adj unctively to hasten and improve the response to UVB phototherapy. Emollients enhance efficacy of UVB and can be applied just before treatments. Combining short-contact anthralin, calcipotriene, or topical retinoids to UVB may also improve results. However, topical application should be done after or at least 2 hours before UVB therapy because phototherapy can inactivate the topical product. UVB phototherapy may also be more effective when added to systemic treatments such as methotrexate and oral retinoids. 

Psoriasis Neoral and Gengraf are indicated for the treatment of adult, nonimmunocompromised patients with severe (ie, extensive and/or disabling), recalcitrant, plaque psoriasis who have failed to respond to at least 1 systemic therapy (eg, PUVA, retinoids, methotrexate) or in patients for whom other systemic therapies are contraindicated or cannot be tolerated. While rebound rarely occurs, most patients will experience relapse with Neoral or Gengraf as with other therapies upon cessation of treatment. 

Hypersensitivity to polyoxyethylated castor oil (injection only see Warnings and Administration and Dosage), cyclosporine, or any component of the products Gengraf and Neoral in psoriasis or RA patients with abnormal renal function, uncontrolled hypertension, or malignancies Gengraf and A/eora/concomitantly with PUVA or DVB, methotrexate or other immunosuppressive agents, coal tar or radiation therapy in psoriasis patients. 

Severe reactions Because of the possibility of severe toxic reactions (which can be fatal), fully inform patients of the risks involved and assure constant supervision. Deaths Use methotrexate only in life-threatening neoplastic diseases, or in patients with psoriasis or rheumatoid arthritis (RA) with severe, recalcitrant, disabling disease that is not adequately responsive to other forms of therapy. Deaths have occurred with the use of methotrexate in malignancy, psoriasis, and RA. Closely monitor patients for bone marrow, liver, lung, and kidney toxicities. 

Metabolism - Methotrexate undergoes hepatic and intracellular metabolism. The terminal half-life reported is approximately 3 to 10 for patients receiving treatment for psoriasis, RA, or low-dose antineoplastic therapy (less than 30 mg/m ). 

Methotrexate is approved for use in severe disabling psoriasis recalcitrant to other less toxic treatments. The standard regimen is similar to low-dose therapy used for the treatment of rheumatoid arthritis (see Chapter 36). Although toxicities are similar to those described in the treatment of other diseases, hepatic cirrhosis and unexpected pancytopenia are of special concern given the chronicity of treatment. 

Beck HI, Foged EK. Toxic hepatitis due to combination therapy with methotrexate and etretinate in psoriasis. Dermatologica 1983 I67(2) 94-6. 

Methotrexate is a folic acid antagonist that inhibits the enzyme dihydrofolate reductase. This agent is mainly used in the treatment of both cancer [trophoblastic neoplasms, leukemias, breast carcinoma, carcinoma of gastric, esophagus, testes, lymphomas] and non-cancer diseases [psoriasis rheumatoid arthritis]. Recent successful results using high-dose [>lg/ m ] methotrexate followed by leucoverin in the treatment of head and neck carcinomas and osteosarcoma has led to a more widespread use of this therapy in patients with these and other tumors. 

Sulfasalazine, commonly used in the treatment of inflammatory bowel disease and rheumatoid arthritis, is selectively used as an alternative treatment, particularly in patients with concurrent psoriatic arthritis. Sulfasalazine is an anti-inflammatory agent that inhibits 5-lipoxygenase. When used as a single agent in the treatment of psoriasis, it is not as effective as is therapy with methotrexate, PUVA, or acitretin. One possible advantage of sulfasalazine therapy compared with other systemic treatments is its relatively high margin of safety. The usual dose of oral sulfasalazine is 3 to 4 g/day for 8 weeks. ... 

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