The primary aim of our study was to assess the validity of topical immunotherapy in a population of 252 patients with AA.
The main result was satisfactory with 44.05% of patients experiencing at least 50% of terminal hair regrowth.
The evidence-based results of topical immunotherapy confirm the theory that AA is related to an autoimmune etiology. The mechanism that is operative in this therapy is mainly due to local immunomodulation through two components: the synthetic antigen acts in a competitive way with the antigen involved in pathogenesis of AA and consequently represents an alternative target for the immune system. Moreover, because of a prolonged immune stimulation in treated patients, we can observe an increase of Treg lymphocytes which contrast the immune reaction towards the follicle [17, 18].
The average of success rates coming out of our data are in line with those reported in other studies in the literature. A 2010 meta-analysis, reported a mean efficacy of topical immunotherapy in up to 50–60% of patients with a range from 9% to 87% . The great variability of success rates, even using the same standard protocol, can be explained by different experimental designs, inclusion and exclusion criteria, and duration of treatment in the single study.
In our population, no statistically significant difference (p > 0.05) was observed in success rates between different sensitizers: 50.98% of patients responded to DNCB, 45.71% responded to SADBE, and 34.43% responded to DPCP. These data can be explained because the sensitizing agents share the same mechanism of action: they all trigger a local allergic reaction that induces regression of the active phase of the disease and the progressive disappearance of alopecia patches.
The only exceptions are patients with AL with more than 30% involvement of the scalp. In this subpopulation, the sensitizer that seems to work best is DNCB with a success rate of 83.33% (p < 0.001); however, this agent today is almost disused because it was found to be mutagenic with the Ames genotoxicity test since it leads to an increase in the exchange of chromosomal material between the sister chromatids in human skin fibroblasts. On the contrary, in this subpopulation, the sensitizer with the worst outcomes was DPCP, since not one of the patients had hair regrowth. This is in contrast to what is reported in the literature and is likely to be attributed, rather than to a real ineffectiveness of this immunosensitizer, to the individual variables related to the small number of subjects in this group (6 patients). In this group SADBE has shown an intermediate result with a response rate of 51.72% and, despite there being no statistically significant difference in success rate between DNCB and SADBE, the p value is “borderline”, i.e., close to 0.05.
Some evidence on the similar efficacy of DPCP and SADBE was provided by Ohlmeier et al. who initially treated 142 patients with DPCP; after 6 months of therapy “non-responder” patients were treated using SADBE as sensitizer with the same standard protocol of application of therapy and, even changing the sensitizing agent, immunotherapy was not effective in this group of patients .
The secondary goal of our study was to define some possible prognostic factors that may affect the treatments success. During our experience, the most important independent prognostic factors on clinical outcomes were:
The extension of scalp involvement.
The duration of the disease and the duration of the current acute attack of AA before the beginning of the therapy.
The presence of atopy, mainly of eczema.
The early development of allergic contact dermatitis to sensitizers.
In our cohort, we registered better clinical results in patients with AL, in all cases with a short time between the onset of alopecia and the beginning of the therapy, and in the people who developed allergic dermatitis early and with low concentrations of the sensitizing agent.
The statistical analysis of our data revealed a close correlation between the extension of AA before the therapy and the clinical outcome. The success rate in patients with AL was statistically significantly higher than in patients with AT or AU. At the same time, the average success rate in patients with AT was statistically significantly higher than in patients with AU. The same comparison made between AL subclasses has not shown statistically significant differences in treatment response. These data are in line with the literature; in fact several studies have demonstrated how the extension of AA is one of the main clinical prognostic factors. Ohlmeier et al. identified the severity of hair loss extension as the only prognostic factor, whereas Weise et al.’s population found the worst response to the immunotherapy in patients with AT or AU [19, 20] rather than in patients with AL. However, discordant data came from Gordon et al. and Firooz et al. who did not found any correlation between the extension of the hair loss and the response to treatment [21, 22].
As in our cohort of patients, other studies found a correlation between duration of AA and response to treatment [20, 21, 23], while other authors did not come to the same conclusions [22, 24].
Another important prognostic factor in our analysis was the presence of atopy. Allergic patients had worse outcomes; however, the role of atopy as a prognostic factor is still highly debated. Results similar to our data have been described by several authors [20, 21, 23], but on the other hand, some works showed the opposite results [19, 22, 24].
Other parameters that did not influence clinical outcomes in our investigation, unlike what we expected from literature data, were:
Age of onset
Overuse of topical immunotherapy
In our population, 34 out of 252 patients (13.49%) had a positive family history of AA; this evidence supports the hypothesis that the disease has a genetic component. Moreover, some authors also reported that a positive family history is associated with a worse prognosis with poor response to therapy  but, among the patients examined in our work, we did not found this correlation.
The major weakness of this study is the lack of a control group: this could have allowed the observers to conclude that any changes in the “active treatment group” were due to the treatment studied rather than to other factors.
One other limitation of the study is the relatively small numbers of subjects in the group with AL that represents the most common type of AA (140 patients; 55% of the total population).
Furthermore, in the subgroup of patients with AL and more than 30% scalp involvement, only six patients were treated with DPCP, making the analysis of the data in this subpopulation not really statistically significant, because of the individual variables related to the small number of subjects in the group.