In a recent study published in the March 11 issue of the New England Journal of Medicine, a group of investigators from the United Kingdom, Ireland, France, and Israel have shown that oral ivermectin is more effective than topical malathion. A total of 812 children were recruited for the study, they were predominantly females (86.9%), with a median age of 10 years. There were two treatment groups. One received ivermectin at a dose of 400 μg per kg in two doses on day 1 and 8. The other group was treated with malathion lotion. The children were examined on day 15 for evidence of head lice. The researchers found that 95 percent of those treated with ivermectin were lice-free after two weeks compared to 85 percent of those using malathion.

The investigators recommend that ivermectin should be used in cases were first-line topical treatments fail, in order to avoid head lice resistances to ivermectin.

Oral Ivermectin versus Malathion Lotion for Difficult-to-Treat Head Lice

Chosidow O, et al.

N Engl J Med 2010; 362:896-905.

Background

Head-lice infestation is prevalent worldwide, especially in children 3 to 11 years old.  Topical insecticides (i.e., pyrethroids and malathion) used as a lotion, applied twice at an interval of 7 to 11 days, are typically used for treatment. Resistance of lice to insecticides, particularly pyrethroids, results in treatment failure. The efficacy of alternative agents is controversial.

Methods

We conducted a multicenter, cluster-randomized, double-blind, double-dummy, controlled trial comparing oral ivermectin (at a dose of 400 μg per kilogram of body weight) with 0.5% malathion lotion, each given on days 1 and 8, for patients with live lice not eradicated by topical insecticide used 2 to 6 weeks before enrollment. The cluster was defined as the household. Infestation was confirmed and monitored by means of fine-toothed combing. Patients were at least 2 years of age and weighed at least 15 kg; all were treated at the study sites. The primary end point was the absence of head lice on day 15.

Results

A total of 812 patients from 376 households were randomly assigned to receive either ivermectin or malathion. In the intention-to-treat population, 95.2% of patients receiving ivermectin were lice-free on day 15, as compared with 85.0% of those receiving malathion (absolute difference, 10.2 percentage points; 95% confidence interval [CI], 4.6 to 15.7; P<0.001). In the per-protocol population, 97.1% of patients in the ivermectin group were lice-free on day 15, as compared with 89.8% of those in the malathion group (absolute difference, 7.3 percentage points; 95% CI, 2.8 to 11.8; P = 0.002). There were no significant differences in the frequencies of adverse events between the two treatment groups.

Conclusions

For difficult-to-treat head-lice infestation, oral ivermectin, given twice at a 7-day interval, had superior efficacy as compared with topical 0.5% malathion lotion, a finding that suggests that it could be an alternative treatment. (ClinicalTrials.gov number, NCT00819520.)

This study is very interesting as chronic urticaria is a very freqüent  disease. Many patient do not respond readily to traditional therapies with antihistamines, and therefore there is a need for new treatments. The present study shows positive results in steroid-dependent patients, and so it would be predictable that results can be even better in patients with cronic urticaria that are not steroid-dependent.

Methotrexate: a useful steroid-sparing agent in recalcitrant chronic urticaria

Perez A, Woods A, and Grattan CEH

Br J Dermatol 2010; 162: 191-194

Background. Reports of methotrexate for chronic urticaria are anecdotal.

Objectives To assess the effectiveness of methotrexate in steroid-dependent chronic urticaria, its impact on steroid reduction and any differences in response between patients with and without functional autoantibodies.

Methods A retrospective case-note review of 16 patients with steroid-dependent chronic urticaria treated with methotrexate was carried out. Ten patients had chronic ordinary/spontaneous urticaria (CU), including three with associated delayed-pressure urticaria; four patients had normocomplementaemic urticarial vasculitis (UV); and two patients had idiopathic angio-oedema without weals. Median disease duration before methotrexate was 48·5 months (range 12–164). All were unresponsive to antihistamines and second-line agents, except prednisolone. Eleven were assessed for autoimmune urticaria with the basophil histamine release assay (n = 5), autologous serum skin test (n = 5) or both (n = 1). Response to methotrexate was scored: no benefit; some benefit (fewer weals and symptomatic improvement but no steroid reduction); considerable benefit (improvement with steroid reduction); or clear (no symptoms, off steroids but on antihistamines).

Results Twelve of 16 patients (eight CU, three UV, one idiopathic angio-oedema) responded. Three showed some benefit, seven considerable benefit and two cleared. Four of eight responders and three out of three nonresponders showed evidence of functional autoantibodies. The dose to achieve a steroid-sparing effect was 10–15 mg weekly (cumulative dose range 15–600 mg, median 135 mg). Methotrexate was well tolerated.

Conclusions Methotrexate may be a useful treatment for steroid-dependent chronic urticaria. Functional autoantibodies do not correlate with response. The beneficial effects of methotrexate may be anti-inflammatory and immunosuppressive. It may therefore benefit chronic urticaria independently of the pathogenic mechanism, whether autoimmune or not.