r person. Candida skin tests were conducted because, when positive, they confirm that the person can mount a cutaneous hypersensitivity reaction, which clarifies that a simultaneous negative TB skin-test result is likely to be a true negative.
In a randomized double-blind manner, skin-test sites on 1 arm were covered with 1 mL of placebo cream (Aqueous cream BP, Sandoz, Bordon, Hants, UK) and the skin-test sites on the contralateral arm were covered with zinc sulfate (2) dissolved in aqueous cream to a concentration of 1% elemental zinc. Each skin test site was immediately covered with an occlusive dressing (Tegaderm, 3M, London, UK). After 24, 48, and 72 h, the dressing and cream were removed, and the “ball-point-pen” test was used to measure induration. The appropriate cream was reapplied and covered after each measurement.
SPSS version 11.5 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Except where otherwise stated, the results of skin tests are those read after 48 h. Continuous data were all normally distributed (except for food frequencies) and were therefore summarized as means (and standard errors of the mean [SEM]). Groups were compared by using t tests, and associations were tested by using univariate linear regression (p value and standardized coefficient shown) and in a backward multiple linear regression model with the least significant variables sequentially removed, according to the log-likelihood test.
Control TB skin-test areas to which placebo cream had been applied yielded significantly smaller reactions in persons with lower concentrations of plasma zinc (p = 0.03, Table). For example, the quarter of the population with the lowest concentrations had, on average, control TB skin-test reactions that were 14 mm in diameter compared with 27 mm for the quarter of the population with the highest plasma zinc concentrations (p = 0.03). This immunologically significant zinc deficiency was frequent even though only 10% of the study population was underweight (body mass index <20 m2/kg).
The TB skin-test results were read in a blinded manner, and reactions to tests with zinc cream applications were an average of 32% larger than the contralateral control skin test reactions with placebo cream applied (Figure 1; p<0.001). TB skin-test results were considered positive if the average diameter of induration was >10 mm 48 h after injection, according to national policy. Skin tests with zinc applications were significantly more likely to have positive results than the simultaneous contralateral control skin tests with placebo cream applications (94% zinc vs. 76% placebo, p = 0.01). Topical zinc caused greater TB skin-test augmentation in persons with lower plasma zinc concentrations (correlation coefficient [R] = 0.3, p = 0.05), and persons with absolute plasma zinc deficiency (<0.6 mg/L) had significantly greater zinc-mediated augmentation (Figure 2, p = 0.02). Zinc cream had no effect in persons with normal plasma zinc concentrations. Thus, zinc cream significantly augmented TB skin-test reactions only in persons deficient in zinc (Figure 2).
TB skin tests are usually read 48 h after PPD injection; however, in this study, additional readings were done at 24 and 72 h, at which time results, similar to those at 48 h, demonstrated that zinc cream caused larger TB skin-test reactions (both p<0.02) and more positive test results (both p<0.006). Furthermore, at 72 and 48 h, this zinc-mediated augmentation was greater in zinc-deficient persons (p = 0.006), although the similar trend at 24 h was not statistically significant. The magnitude of skin-test augmentation with zinc cream, the plasma zinc concentration, and the anthropometric measures had no significant associations with other studied factors except as noted in the Table.
The effect of zinc on the Candida skin-test results was similar to the effect on the TB skin-test results. Specifically, the Candida skin-test reactions with zinc cream were an average of 23% larger than the contralateral skin-test reactions associated with placebo cream applied i