Hydroxyurea Treatment For Psoriasis

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Hydroxyurea Treatment For Psoriasis

Hydroxyurea is a second line modality for the treatment of psoriasis and has been used since 1965. It is usually reserved for cases where other second line agents have failed or are contraindicated. The dose used has generally been 0.5 to 1.5g daily, give orally either as a single dose, or divided into two doses (morning and evening). Although only a single controlled trial has been performed, it is generally considered to be effective. Hydroxyurea avoids the hepatotoxicity associated with methotrexate, and the nephrotoxicity associated with cyclosporin, and can therefore often be useful when other drugs are contraindicated, although it should be avoided, if possible, when renal function is markedly impaired. The main hazard is myelosuppression and careful monitoring of the full blood count is therefore required. It is recommended that the initial dose in adults should usually be 1g daily and this can be titrated, according to efficacy and toxicity, up to a maximum of 2g daily. Full blood count, including platelet and differential white cell counts, should be performed at least weekly for the first two months.

Efficacy of Hydroxyurea Treatment For Psoriasis

The use of hydroxyurea in the treatment of psoriasis was first reported in 1969, when Yarbro reported a response in 2 patients treated with a dose of 40mg/kg/day, which was halved after 6 - 10 days 1. Yarbro and Leavell reported another patient showing a particularly rapid response to hydroxyurea, at the dose of 1g three times daily for the first 8 days of treatment 2 . These observations were followed by a double-blind, placebo controlled crossover trial. Each treatment period was 4 weeks, and the dose of hydroxyurea was 0.5g twice daily 3 . Twelve subjects were included and 10 completed the protocol. Subjects and investigators considered that improvement had occurred during active therapy in 9 and 7 out of 10 cases repectively. Only one patient improved by either assessment during placebo treatment. The level of response was not quantified and no statistical analysis was presented.

Rosten reported treatment of 12 patients with initial doses of 500 mg twice daily increased to 1g twice daily if required 4. Six of the patients showed a considerable improvement after 4 - 8 weeks. Four discontinued the drug due to side effects and, in two, no response was seen after 8 weeks of treatment. Subsequently, a number of uncontrolled studies have been performed. Hunter et al. reported treatment of 24 patients mostly with severe refactory psoriasis, using 1g of hydroxyurea daily 5. Sixteen showed substantial improvement, although the response was considered somewhat slow relative to methotrexate, often taking 6 to 8 weeks to become established.

Moschella and Greenwald reported a study in which 60 patients were treated intermittently with hydroxyurea, starting at the dose of 500mg twice daily6. Patients who failed to respond to the initial dose were treated with 1.5g daily. During the first 6 weeks of treatment, 63% of the patients showed a good or excellent response, including some with erythrodermic and pustular psoriasis; a fair response was seen in another 10%. Patients in whom the drug was effective generally began to show some improvement within 2 to 3 weeks. In the majority of these patients the response was able to be successfully maintained by subsequent courses of treatment.

A survey of 54 dermatologists, published in 1973, revealed that 33 had used hydroxyurea for a total of 614 patients. Of these patients, 65 had cleared, 350 improved, 188 did not improve and 11 worsened7 . Layton et al. reported their experience of treating 85 patients, at doses of 0.5 -1.5g daily, over a period of eight years 8 . Sixty percent of these patients cleared completely or nearly completely, and a further 20% showed partial clearance. The response was maintained in 52 by continuous therapy, for a mean of 16 months at the time of reporting. The reported duration of remission following cessation of hydroxyurea has varied from 24 hours9 to several months3-5 . Rebound of psoriasis after discontinuation has been reported occasionally6-8.

Generalised pustular psoriasis: Stein et al. reported 4 patients with generalised pustular psoriasis who responded to hydroxyurea 1 - 2 g daily9. Somewhat less consistent results were obtained by Lingren and Groth, who treated 12 episodes of generalised pustular psoriasis in 6 patients, and induced remission in six episodes using hydroxyurea 1.5 - 2 g daily10.

Synergy of Hydroxyurea Treatment For Psoriasis with other treatments

There has been a single report on treatment of 14 patients with severe psoriasis using a combination of hydroxyurea (500 mg daily) with methotrexate (12.5 - 15mg weekly)11 . An adequate response was obtained in 13 patients, and the hydroxyurea appeared to reduce the quantity of methotrexate required.

Safety, side-effects and patient acceptability of Hydroxyurea Treatment For Psoriasis

The main concern regarding toxicity of hydroxyurea has been over myelosuppression which may manifest as megaloblastic anaemia, thrombocytopenia or leukopenia 1,6,8,10,12 . Haematological abnormalities are particularly frequent with this drug. Layton et al reported significant blood changes in 35% of their patients 8 and, in one report, macrocytosis and a reduced red cell count, although not anaemia, were seen in 4 of 5 patients treated 13. These side effects may develop after several months of treatment6 . They have generally been reversible after discontinuation of the drug. Since hydroxyurea is largely excreted in the urine, extra caution is required if renal function is impaired. It may occasionally cause fever6,14. Cutaneous side effects of hydroxyurea include partial alopecia, increased pigmentation, scaling, atrophy, nail changes, erythema of the face and hands, and a lichenoid eruption15. Hydroxyurea is a cytotoxic drug with potential for teratogenic effects and is best avoided in women of child-bearing age.

Monitoring: As in the case of azathioprine, it is recommended that patients should have their full blood count, including platelet count and differential white cell count, checked prior to commencing the drug and, at least, weekly intervals for at least the first six weeks. Subsequently, the intervals between haematological assessments may be gradually extended, provided there is no cause for concern. The maximal interval should not exceed three months. Serum creatinine and liver function tests should also be monitored. It would also seem prudent to examine patients every six months for evidence of malignancy and to advise females to attend, when called, for routine cervical smears.

Cost implications of using Hydroxyurea Treatment For Psoriasis

In a published cost analysis of psoriasis treatment hydroxyurea had the distinction of being the cheapest treatment16.

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Diprolene AF : This medication is used to treat swelling, inflammation, or itching of skin conditions such as eczema, dermatitis, rashes, insect bites, poison ivy, allergies and other irritations.

Dovonex : This medication is a form of vitamin D. It is used on the skin to treat psoriasis.

Elidel : Pimecrolimus is used to treat certain skin conditions such as eczema (atopic dermatitis), in people who have not responded well to, or who should not use other eczema medications (e.g., topical steroids). Atopic dermatitis is an allergic-type condition that causes red, irritated, and itchy skin.

Kenalog : This medication is used to treat swelling, inflammation, or itching of skin conditions such as eczema, dermatitis, rashes, insect bites, poison ivy, allergies and other irritations.

Lamisil : This medication is an antifungal used on the skin to treat skin infections such as athlete's foot, jock itch or ringworm.

Protopic : This medicine is an immunosuppressant used topically to treat itching and swelling associated with a certain skin condition (atopic dermatitis).

Selsun : This medication is used to treat dandruff; a certain scalp infection (seborrheic dermatitis); and for a condition that discolors the skin (tinea versicolor).

Synalar : This medication is used to treat swelling, inflammation, or itching of skin conditions such as eczema, dermatitis, rashes, insect bites, poison ivy, allergies and other irritations.

Ultravate : This medication is used to treat swelling, inflammation, or itching of skin conditions such as eczema, dermatitis, rashes, insect bites, poison ivy, allergies and other irritations.

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