Systemic therapies are seldom used for mild to moderate psoriasis, and are generally reserved for patients with moderate to severe psoriasis. 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.we will discuss the oral agents only without the biologics treatment .
Acitretinis a retinoid and is a metabolite of etretinate It is used orally in the treatment of severe psoriasis resistant to other forms of therapy, palmoplantar pustular psoriasis, safer than methotrexate or cyclosporine, especially when considering continuous use over many years.
When acitretin is used concurrently with phototherapy (ReUVB or RePUVA, Rotational therapy), there appears to be a synergistic treatment effect, and the number and duration of phototherapy sessions needed to achieve clearance is reduced. RePUVA is a well established treatment regimen for psoriasis.1 When acitretin is used with calcipotriol, improvement and clearance of lesions may be achieved with significantly lower cumulative acitretin dosages.
The dose is adjusted under expert supervision, initially 25–30 mg daily for 2–4 weeks, then adjusted according to response, usual range 25–50 mg daily; up to 75 mg daily for short periods in psoriasis and ichthyosis; CHILD (important: exceptional circumstances 500 micrograms/kg daily (occasionally up to 1 mg/kg daily to max. 35 mg daily) with careful monitoring of musculoskeletal development according to BNF
You should take these precautions exclude pregnancy before starting (test for pregnancy within 2 weeks before treatment and monthly thereafter; start treatment on day 2 or 3 of menstrual cycle)—women (including those with history of infertility) should avoid pregnancy for at least 1 month before, during, and for at least 3 years after treatment; patients should avoid concomitant tetracycline or methotrexate, high doses of vitamin A (more than 4000–5000 units daily) and use of keratolytics, and should not donate blood during or for at least 1 year after stopping therapy (teratogenic risk); check liver function at start, then every 1–2 weeks for 2 months, then every 3 months; monitor plasmalipids; diabetes (can alter glucose tolerance—initial frequent blood glucose checks); radiographic assessment on long-term treatment; investigate atypical musculoskeletal symptoms; in children use only in exceptional circumstances (premature epiphyseal closure reported); avoid excessive exposure to sunlight and unsupervised use of sunlamps.
Side effects include the following dryness of mucous membranes (sometimes erosion), of skin (sometimes scaling, thinning, erythema especially of face, and pruritus), and of conjunctiva (sometimes conjunctivitis and decreased tolerance of contact lenses); sticky skin, dermatitis; other side-effects reported include palmoplantar exfoliation, epistaxis, epidermal and nail fragility,oedema, paronychia, granulomatous lesions, bullouseruptions, reversible hair thinning and alopecia, myalgia and arthralgia, occasional nausea, headache, malaise, drowsiness, rhinitis, sweating, taste disturbance, and gingivitis; benign intracranial hypertension (discontinue if severe headache, vomiting, diarrhoea, abdominal pain, and visual disturbance occur; avoid concomitant tetracyclines); photosensitivity, corneal ulceration, raised liver enzymes, rarely jaundice and hepatitis (avoid concomitant methotrexate); raised serum triglycerides or cholesterol; decreased night vision reported; skeletal hyperostosis and extra-osseous calcification reported following long-term administration of etretinate (and premature epiphyseal closure in children .
Methotrexate is an immunosuppressive agent which blocks DNA synthesis by inhibiting dihydrofolate reductase, an antimetabolite, methotrexate interferes with DNA synthesis, repair, and cellular replication. Actively proliferating tissues are in general more sensitive to this effect of methotrexate. It's 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 used in low doses is one of the mainstays of systemic therapy in the treatment of psoriasis.An initial test dose of 2.5 to 5 mg is recommended. If lab values are normal after 1 week, the dose can be increased to a range of 7.5 to 30 mg/wk. This can be given as a single dose or split into two or three doses given 12 hours apart to minimize gastrointestinal side effects. Methotrexate can be administered orally, subcutaneously, or intramuscularly.
A complete blood count (CBC), liver function tests, and serum creatinine levels are obtained before start of treatment . CBC, Liver Function, and Creatinine These have to be monitored every 3 months. In patients with normal liver chemistries and no risk factors present, a liver biopsy should be done after a cumulative dose of approximately 1500 mg MTX; if the post-MTX liver biopsy is normal, repeat liver biopsy should be done after further therapy with an additional 1000 to 1500 mg MTX. Be aware of the various drug interactions with MTX . Monitoring PIIINP (the aminoterminal propeptide of type III procollagen) at least three times yearly may reduce the number of repeat liver biopsies required. Pulmonary toxicity testing should also be conducted.
The combination of methotrexate and UVB seems to be synergistic; responses may occur with lower cumulative doses of both methotrexate and UVB.However, stopping methotrexate may cause rebound and there is some concern about photosensitivity. Methotrexate and PUVA have been used together in patients refractory to other treatments; however, there is additive carcinogenesis (especially increasing the risk of squamous cell cancer) and subacute phototoxicity .
Methotrexate has been used successfully with cyclosporine, either concurrently or in rotation. Rotational therapy is particularly effective since it minimizes the serious adverse effects of both agents: hepatotoxicity from methotrexate and hypertension and nephrotoxicity from cyclosporine. Having an overlapping treatment period may not be necessary and patients have been successfully switched after a 1-week washout period. This is a very useful combination of systemic agents in the longterm management of this chronic disease . It is contraindicated in pregnancy because it is teratogenic. Folic acid 5 mg can be given once weekly to reduce the possibility of side-effects associated with methotrexate; alternative regimens of folic acid may be used in some settings. Methotrexate has toxic effects on hematologic, renal, GIT, pulmonary, and neurologic systems; discontinue if significant drop in blood counts occur; fatal reactions reported when administered concurrently with NSAIDs .
Cyclosporine An 11-amino acid cyclic peptide and natural product of fungi. Acts on T-cell replication and activity. Specific modulator of T-cell function and an agent that depresses cell-mediated immune responses by inhibiting helper T-cell function. Preferential and reversible inhibition of T lymphocytes in G0 or G1 phase of cell cycle suggested. Binds to cyclophilin, an intracellular protein, which, in turn, prevents formation of interleukin 2 and the subsequent recruitment of activated T cells . It is used in the treatment of both cutaneous and arthritis manifestations of severe psoriasis.
Cyclosporine is used in low doses whether alone or in combination with other agents. The usual dose range is 2 to 2.5 mg/kg . For patients with severe inflammatory flares of psoriasis, or recalcitrant cases who fail to respond to numerous other therapies, or for a highly distressed patient in a crisis situation, the starting dose is higher at 5 mg/kg per day in two divided doses. This dose should not be exceeded and once there is a clear response should be decreased by 0.5 to 1 mg/kg per day at weekly or longer periods, to the lowest effective maintenance dose. If started at 2.5 mg/kg per day, and the response is inadequate, it is recommended to wait at least 1 month before considering a dosage increase. If necessary, the dosage may be increased by 0.5 to 1 mg/kg per day monthly to a maximum of 5 mg/kg per day. Always titrate to the lowest effective dose for maintenance .
You should not use this medication if you are allergic to cyclosporine. You may not be able to use cyclosporine if you have kidney disease, untreated or uncontrolled high blood pressure; or any type of cancer. Blood pressure and serum creatinine (SCr) should be assessed prior to beginning cyclosporine therapy to obtain accurate baselines, and should be reassessed biweekly once therapy is started for at least the first 12 weeks of therapy (until values stabilize), and then closely monitored during therapy. If SCr increases to 30% above the patient’s baseline, the cyclosporine dosage needs to be decreased and SCr rechecked in a month. If the SCr is still above 30% of the patient’s baseline, cyclosporine should be discontinued and only resumed when the SCr returns to within 10% of the patient’s baseline. Cyclosporine should also be discontinued for inadequate response after 3 months’ use at the maximum dose. Adverse effects include nephrotoxicity, hypertension, hypomagnesemia, hyperkalemia, alterations in liver function tests, elevations of serum lipids, GI intolerance, paresthesias, hypertrichosis, and gingival hyperplasia. Cumulative treatment for more than 2 years may increase the risk of malignancy, including skin cancers and lymphoproliferative disorders.
The combination of cyclosporine with calcipotriol may be more efficacious than either agent used alone. Cyclosporine and SCAT ( UVB with short-contact anthralin therapy may also be effective). However, cyclosporine should not be used concurrently with PUVA; there is a well documented increased risk of squamous cell cancer and the combination may have a negative effect on lesion clearance. The combination of cyclosporine with methotrexate is extremely effective and minimizes toxicity from either agent as discussed above. Cyclosporine has also been used successfully with mycophenolate mofetil and etanercept.
Topical tacrolimus is an immunosuppressant inhibits T-cell activation has been used in the past for management of refractory atopic dermatitis. However, multiple studies have shown effectiveness with psoriasis affecting intertriginous regions as well as the face. Generally, it seems to be effective in thin-skinned areas. However, it has become somewhat of a second-line agent given other studies showing topical steroid may be more effective and potential serious disease association , Before using tacrolimus topical, tell your doctor if you have skin cancer or a skin infection (including herpes or chicken pox), Netherton's syndrome (a genetic skin disorder), a weak immune system (from cancer treatments, HIV/AIDS or certain medicines such as steroids), kidney disease; or swelling, redness, or irritation of large areas of your skin.
Tacrolimus ointment seems most effective in treating psoriasis where the skin is thin, that is on the face and intertriginous areas. Several case reports indicate that topical tacrolimus is effective in the treatment of facial psoriasis. ADULT and CHILD over 16 years initially apply 0.1% ointment thinly twice daily until lesion clears (consider other treatment if eczema worsens or no improvement after 2 weeks); reduce to once daily or switch to 0.03% ointment if condition allows; CHILD 2– 16 years, initially apply 0.03% ointment twice daily for up to 3 weeks (consider other treatment if eczema worsens or if no improvement after 2 weeks) then reduce to once daily until lesion clears .
Tacrolimus ointment seems most effective in treating psoriasis where the skin is thin, that is on the face and intertriginous areas. Several case reports indicate that topical tacrolimus is effective in the treatment of facial psoriasis. ADULT and CHILD over 16 years initially apply 0.1% ointment thinly twice daily until lesion clears (consider other treatment if eczema worsens or no improvement after 2 weeks); reduce to once daily or switch to 0.03% ointment if condition allows; CHILD 2– 16 years, initially apply 0.03% ointment twice daily for up to 3 weeks (consider other treatment if eczema worsens or if no improvement after 2 weeks) then reduce to once daily until lesion clears .
You should be aware with infection at treatment site, UV light (avoid excessive exposure to sunlight and sunlamps); alcohol consumption (risk of facial flushing and skin irritation); pregnancy, avoid contact with eyes and mucous membranes; application under occlusion. It includes the following side effects application-site reactions including rash, irritation, pain and paraesthesia; herpes simplex infection, Kaposi’s varicelliform eruption; less commonly acne; rosacea and skin malignancy also reported .
Mycophenolate mofetil (CellCept) inhibits DNA and RNA synthesis and has been shown to have a specific lymphocyte antiproliferative effect lowers your body's immune system. oral mycophenolate mofetil appears effective in the treatment of moderate to severe plaque psoriasis. The usual dose is 500 mg orally four times a day, up to a maximum of 4 g/day. You should not use this medication if you are allergic to mycophenolate mofetil, mycophenolic acid (Myfortic) Before using mycophenolate mofetil, tell your doctor if you are allergic to any drugs, or if you have a stomach ulcer or other disorders of your stomach or intestines , kidney disease; a viral, bacterial, or fungal infection; or a rare hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndrome. This medication can cause harm to an unborn baby, especially if used during the first trimester of pregnancy . Common adverse effects include GI toxicity (diarrhea, nausea, vomiting), hematologic effects (anemia, neutropenia, thrombocytopenia), and viral and bacterial infections. Lymphoproliferative disease or lymphoma has been reported
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. Toxicity associated with tacrolimus has limited its use in psoriasis. Azathioprine has a slow onset and significant toxicity.
hydroxyurea
Hydroxyurea Capsules Consumer Information
hydroxyurea
Hydroxyurea Capsules Consumer Information
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
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