Pain and dermal reaction caused by injected glycerin in immunotherapy solutions

Fifty percent glycerin preserves immunotherapy solution potency for at least 3 years but must be diluted before injection to reduce glycerin-induced pain and inflammation. We studied pain, erythema, induration, and bruises caused by glycerin (0% to 30%).

In 15 healthy subjects we compared, in double-blind fashion, pain scores, injection site erythema, induration, and bruising caused by subcutaneous injections in randomized order of 0.1, 0.5, and 1 ml of glycerin 0%, 10%, 20%, and 30%.

Injection volume did not significantly influence pain scores from diluent alone (0% glycerin) (p greater than 0.1). Pain scores of subjects given glycerin (0.1 to 1 ml, 10% to 30%) increased significantly as both injection volume (p less than 0.001) and glycerin concentration (p less than 0.001) increased. Pain scores correlated with total glycerin dose administered (volume x concentration) (rs = 0.67, p less than 0.0005) but varied widely, from minimal to severe, in those given the same dose. Injection site erythema, induration, and bruising occurred in some subjects with significant positive correlations between total glycerin dose and both frequency and diameters of erythema and induration. However, these dermal reactions were of trivial clinical importance.

Injected glycerin produces pain that is proportional to total injected dose of glycerin, but individual variation in perceived discomfort is substantial. Total glycerin doses of less than 0.05 ml rarely produce clinically important pain.