Discussion
TAA, transient burning or painful sensations, OLP
Tacrolimus in an oral patch carrier system was compared to both tacrolimus gel and corticosteroid gel as standard of care for the management of OLP. A placebo patch as a negative control intervention would not have been applicable due to ethical standards for managing symptomatic lesions. Moreover, the patch was applied only 2 times/day because its release profile ranged from 10 to 12 h and the patch disintegration time was 30–45 min with minimal salivary washout compared to oral gel [The study demonstrated that both tacrolimus and triamcinolone, regardless of carrier system, showed significant reductions in all clinical parameters after treatment termination. However, there was no significant difference between groups. These results were consistent with other studies comparing corticosteroids with calcineurin inhibitors [Topical application of tacrolimus could initially stimulate sensory neurons through substance P release. This would explain the transient burning or painful sensations documented in tacrolimus groups. However, the calcium influx provoked by the neuron activation probably led to a depletion of phosphatidylinositol 4,5-bisphosphate (PIP2) and subsequent inactivation of the calcium channels [Siponen et al. showed that tacrolimus and triamcinolone acetonide 0.1% ointment had a great reduction in clinical score at 9 weeks of treatment with percent change of 37% and 32% respectively with no statistically significant difference between them [Tacrolimus patch and gel showed better initial reduction in TAA compared with triamcinolone 0.1% Group III with significant reduction starting from the fourth week till the end of the follow-up period, and these results were consistent with Laeijendecker et al. (2006) who reported that topical tacrolimus 0.1% ointment induced a better initial therapeutic response than triamcinolone acetonide 0.1% ointment. However, relapses occurred frequently within 3–9 weeks of the cessation of treatment [The previous interpretation was documented in the recent meta-analysis by Zhangci et al. (2022), which reported that there was no difference in clinical resolutions between tacrolimus and corticosteroids and recommended the use of mucoadhesive carrier systems with a sustained release profile for improving the clinical outcomes [Caspase-3 expression decreased in epithelium and increased in connective tissue after treatment in both tacrolimus groups, whereas corticosteroid treatment increased in both epithelium and connective tissue. This could be justified by the fact that, tacrolimus is more selective for lymphocytes, and hence fewer lymphocytes expected to express caspase-3. Furthermore, the anti-inflammatory tacrolimus effect is not exclusively through apoptosis but through inhibition of T-cell activation from the start [Generally, this study showed that topical tacrolimus patch had superior and initial rapid clinical effect with higher patient compliance than tacrolimus and triamcinolone acetonide gel, although statistically insignificant. These findings may be attributed to a reduction in the number of T-lymphocyte cells and caspase-3 expression within the basal epithelium. The study was limited by the short follow-up, precluding the opportunity to evaluate the relapse rate and highlighted the need to assess treatment durability with further clinical trials.