A randomised, controlled trial of a 4% cutaneous emulsion of sodium cromoglicate in treatment of atopic dermatitis in children.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease. Sodium cromoglicate (SCG) is a chromone with anti-inflammatory, anti-itch and anti-allergic activity. This trial is a 12-week comparison (RCT) of a 4% SCG cutaneous emulsion with its vehicle in AD. MATERIALS AND METHODS: 208 children aged 2-12 years participated, 104 in each group. The primary endpoint was change in SCORAD score. Secondary endpoints included SASSAD score, topical steroid usage and global assessments. RESULTS: SCORAD was reduced by 28% (SCG group) and by 19% (vehicle): difference was statistically significant (p = 0.03) after 8 weeks and nearly significant (p = 0.09) after 12. A similar result occurred in SASSAD (p = 0.001 at 8 weeks). In subjects without major protocol deviations (SCG-64, vehicle-63), difference in SCORAD remained significant at 12 weeks (p = 0.04). Weight of topical steroids reduced in both groups: -0.60 ± 1.3 g/day (35%), SCG and -0.05 ± 1.1 g/day vehicle (p = 0.04). Treatment success, defined as investigator global opinion graded very or moderately effective, was significantly more frequent in SCG group (p = 0.025). Application site discomfort reported by 12.5% of subjects in SCG group and 16.5% in vehicle group. CONCLUSIONS: SCG 4% cutaneous emulsion provides an effective, well-tolerated, steroid-sparing treatment for AD in children.

The effect of 4% sodium cromoglicate cutaneous emulsion compared to vehicle in atopic dermatitis in children--A meta-analysis of total SCORAD scores.

An emulsion containing 4% sodium cromoglicate (4% SCG emulsion) has been developed for the treatment of atopic dermatitis in children. We have conducted a meta-analysis of the primary outcome measure (the change in SCORAD score) used in randomized clinical trials (RCTs) with this product. We conducted a search of standard using the keywords, sodium cromoglicate, cromolyn sodium, topical, atopic dermatitis, clinical trial. We identified 19 clinical studies of which 3 used this 4% SCG emulsion formulation, one was a RCT using the change in SCORAD score. We were given access to two further unpublished RCTs, with this measure. The RCTs included 490 subjects (mean age 5.3 years). Each RCT was multicentre of 12 weeks duration, comparing 4% SCG emulsion with the vehicle in which the SCG was dissolved. Using study as the unit and the fixed effect model, the mean difference (95% CI) in the change in SCORAD score was -2.82 (-5.36; -0.29), p = 0.03. Using centre as the unit, and the fixed effect model, the mean difference (95% CI) in the change in SCORAD score was -2.82 (-5.82; -0.46), p = 0.02. These results support the efficacy of this new topical treatment in children with atopic dermatitis.

Chromones.

The chromones are a class of chemical compounds characterised by the presence of the structure 5:6 benz-1:4-pyrone in their chemical make-up. The first chromone in clinical use, khellin, was extracted from the seeds of the plant Ammi visnaga, and had been used for centuries as a diuretic and as a smooth muscle relaxant. Its use in bronchial asthma was reported in 1947. In the 1950s, Benger's Laboratories embarked on a research programme to synthesise and develop modifications of khellin for the treatment of asthma. New compounds were screened using animal models to test the ability of the compound to prevent the anaphylactic release of histamine and SRS-A (leukotrienes) from sensitised guinea pig lung, and a human model to check the ability to reduce the bronchoconstriction induced by inhaled antigen bronchial challenge. For initial screening the human work was undertaken by Dr. R.E.C. Altounyan, who suffered from allergic bronchial asthma and was employed by Benger's Laboratories. After 8 years and more than 600 challenges using over 200 compounds, in 1965 Altounyan arrived at disodium cromoglycate (DSCG), the chromone that met the criteria of providing more than 6 h of protection. DSCG is still used today as a mast cell stabiliser.

The effects of topical sodium cromoglicate on itch and flare in human skin induced by intradermal histamine: a randomised double-blind vehicle controlled intra-subject design trial.

BACKGROUND: Itch is a prominent feature of many skin diseases, particularly atopic dermatitis and cutaneous mastocytosis. Sodium cromoglicate (SCG), a chromone developed for the treatment of allergic disease has been shown to reduce the severity of itch when applied topically to subjects with atopic dermatitis. The aim of this study was to investigate whether topical sodium cromoglicate can reduce the severity of itch induced by intradermal histamine. METHODS: SCG was introduced into the skin of healthy volunteers both by iontophoresis and by topical application using a new 4% cutaneous emulsion (Altoderm™). The skin was then challenged with intradermal histamine. Measurements were made of severity of itch, size of wheal and flare and change in blood flux RESULTS: SCG significantly reduced the severity of itch (P = 0.0045) and flare (P = 0.0143) when delivered by iontophoresis. SCG 4% cutaneous emulsion significantly reduced severity of itch (P = 0.024) and flare (P = 0.015) in atopic subjects. Trend analysis showed increasing effect on itch with increased concentrations of SCG, which was significant (P = 0.046). There were no effects on wheal or blood flux. CONCLUSIONS: Topically applied SCG, administered in a new cutaneous emulsion base, significantly reduced the itch and flare caused by intradermal histamine. The effect was greatest in atopic subjects and increased with the concentration of SCG in the emulsion. TRIAL REGISTRATION: ISRCTN35671014.

Oral and inhaled sodium cromoglicate in the management of systemic mastocytosis: a case report.

INTRODUCTION: Mastocytosis is a rare disease consisting of a group of disorders characterized by a pathologic increase in the number of mast cells in one or more organ system. Treatment is symptomatic. Oral sodium cromoglicate (SCG) is the only treatment licensed for the treatment of mastocytosis. In this case we report how in a mastocytosis patient being treated with H1 and H2 antihistamines, and oral sodium cromoglicate, the addition of inhaled sodium cromoglicate resulted in further improvement. This is the first report of this use of the drug in this disease. CASE PRESENTATION: The subject is a Caucasian woman aged 40 years. Symptoms of mastocytosis began when she was aged 13 years, but the diagnosis was not made until after her first pregnancy aged 33 years. Symptoms improved with H1 and H2 antihistamines, and oral sodium cromoglicate, but it required the addition of inhaled sodium cromoglicate to produce further improvement, specifically in the symptoms of bone pain, fatigue and headache. Doses of oral sodium cromoglicate had to be increased if challenged with a food to which the subject was sensitive. Doses of inhaled sodium cromoglicate had to be increased during the menstrual period. CONCLUSIONS: Patients suffering from the rare disease of mastocytosis have symptoms affecting many body systems. Symptoms result from the release of inflammatory mediators from mast cells. Sodium cromoglicate, a drug that reduces the release of mediators from mast cells, is effective in controlling gastrointestinal symptoms, but less effective in those affecting other body systems. In this case report we have shown that the addition of inhaled sodium cromoglicate controls the symptoms of bone pain, fatigue and headache and also that the doses have to be increased during the menstrual period.