**3. Conclusions**

doses in these indications [122, 123]. It can be applied via intravenous or subcutaneous administration. In high intravenous bolus regimen, it has been reported to be highly toxic [121]. IL-2 is a key cytokine for T regulatory (reg) cell differentiation, homeostasis and functions [124]. In AA, an imbalance in the immune state of patients has been detected with altered T-helper cell and Treg cell functions [125, 126]. A study by Shin et al. revealed impaired function of CD4 T reg cells [127]. A study by Castela et al. evaluated the efficacy of low dose recombinant IL-2 treatment on five AA patients. Four of five patients had partial regrowth and the improvement continued up to 6 months after drug cessation. Pre and posttreatment biopsies were taken to compare the level of T reg cells and an increase was detected in posttreatment group [128]. Aldesleukin is now being under investigation and clinical studies with larger samples

are needed to assess the exact efficacy of the drug (ClinicalTrials.gov NCT01840046).

Dupilumab is a fully human monoclonal antibody directed against the α subunit of IL-4 receptor. It blocks the signaling of IL-4 and IL-13, both of which are the key cytokines in Th2 mediated pathways [13, 129]. The efficacy of dupilumab has been studied in atopic dermatitis (AD) and asthma with a rapid, significant clinical improvement [129–133]. Also, decreasing in the levels of serum and skin Th2 markers and Th17/IL-23 associated markers have been

Several studies support a shared genetic background between AA and AD, besides both diseases were shown to have upregulation of Th2 component and an IL-23 [12, 134, 135]. The history of atopy and autoimmune disease was also found to be associated with an increased

Suarez-Farinas et al. reported a study of 22 patients who also had AD. They sought a detailed molecular profile of the lesional and nonlesional AA transcriptomes with AA. A significant upregulation of Th2 cytokine IL-13 was found similar to AD lesions. A possible pathogenic

Fuentes-Duculan et al. studied pre- and posttreatment lesional biopsies of 6 patients with patchy AA and performed immunohistochemistry and gene expression analysis. They found a significant expression of inflammatory markers of IL-2, IL-15, Th1 and Th2 (IL-13, CCL17 and CCL18), IL-12/IL-23p40 before treatment. After treatment with intralesional corticosteroid injection, a significant downregulation was observed in IL-12/IL-23p40, CCL18 [11].

Sharing possible common pathways both in AA and AD make dupilumab also worth triable

Tralokinumab is an IgG4 humanized monoclonal antibody that targets neutralising IL-13 [13, 137]. IL-13 is a Th2 cell cytokine and has an important role in atopy [137]. Tralokinumab is under investigation for asthma and AD (ClinicalTrials.gov NC). As mentioned above,

role of Th2 axis in patients with AA was supported as a result of this study [12].

*2.2.6. Th2 pathway inhibition*

*2.2.6.1. Dupilumab*

304 Hair and Scalp Disorders

demonstrated [129].

risk of AA [2, 16, 136].

in AA.

*2.2.6.2. Tralokinumab*

Currently, many therapies are available and the treatment depends on many factors, such as the severity, extent, duration of the disease, and age of the patient.

Although many treatments are shown to be effective in extensive recalcitrant AA, the most important problems of the present studies include the limited number of randomized controlled studies, lack of evaluating the long-term efficacy and follow-up, small number of participants, and significant disease heterogeneity in patient selection.

Better understandings of the immunopathological mechanisms responsible in AA have led the clinical researches to develop better therapeutic options for AA. However, future larger studies are needed to clarify the immunological pathways responsible in AA, which will lead to further therapeutic developments.
