Atopic dermatitis (AD) is a common chronic inflammatory skin disease. AD usually begins in childhood, but it can also start at any age. Itching is the hallmark symptom of the disease, often unrelenting in severe cases, and leads to sleep disturbance and excoriated infection-prone skin. The distribution of eczematous lesions varies according to the patient’s age and disease activity. AD negatively affects quality of life, social interactions, and work productivity, with a high annual cost of living [1] .

During infancy, AD is generally more acute and primarily involves the face, the scalp, and the extensor surfaces of the extremities. The diaper area is usually spared. In older children and in those who have long-standing skin disease, the patient develops a chronic form of AD with lichenification and localization of the rash to the flexural folds of the extremities [1] .

The pathology behind atopic dermatitis etiology is the loss of the epidermal barrier, which prevents the production of protein filaggrin that can induce T-cell infiltration and inflammation [2] .

Treatment of AD depends on the severity of the disease. Mild forms of the disease are mainly treated with local therapy, medium forms with phototherapy, most often narrow-band UVB phototherapy, whereas the most severe cases are treated with systemic therapy. Systemic therapy includes conventional drugs such as methotrexate and cyclosporine. The knowledge of the pathogenesis of AD is leading to the development of new drugs, such as dupilumab, a fully human monoclonal antibody targeting the IL-4 receptor alpha subunit and inhibitors of Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway, one of the essential signaling pathways in various inflammatory diseases including AD, such are baricitinib, abrocitinib, upadacitinib. Also, phosphodiesterase 4 (PDE4) inhibitors have been approved for both oral and topical use for inflammatory skin diseases [3] [4] [5] .

Treatment of AD is majorly based on skin barrier repair as well as reducing inflammation and itching. They reduce itching and flare-ups, restore the skin barrier and make the patient feel more comfortable [6] . For decades, topical corticosteroids have been the mainstay of treatment for mild-to-moderate AD. One of the problems is frequent corticophobia in patients with AD and parents of children with AD. Either the severity of AD or parents’ fear of chronic corticosteroid treatment has been found to impair the quality of family life [7] .

Besides topical corticosteroids, there are several remedies available for the treatment of AD, such as Janus kinase inhibitors (dergocitinib, ruxolitinib, tofacitinib), calcineurin inhibitors (tacrolimus, pimecrolimus), and phosphodiesterase-4 inhibitors (crisaborole) [3] [5] [8] [9] .

However, all of the treatments aforementioned report some degree of toxicity. In children, the efficacy and safety of topical drugs have not been studied as they are considered as high-risk population. Therefore, conditions such as atopic dermatitis, “cradle cap” or “nappy rash” are often successfully treated with baby shampoos and creams enriched with emollients and plant oils.

Effective treatment of atopic dermatitis therefore requires the development of novel, effective and reliable therapies. New therapies with functional dermocosmetic treatment schemes to help control inflammatory processes and skin damage as well as AD-associated symptomatology have been developed in recent years. One of these, and the subject of this study, is piroctone olamine [10] [11] [12] [13] . Piroctone olamine has been studied in skin and scalp damage and inflammation processes since the 1970s and has been used in various commercial preparations up to the present day. In 2022, the product Blue Cap, whose main ingredient is activated piroctone olamine (CATALYSIS S.L., Madrid), was evaluated with a high degree of satisfaction with no adverse effects reported in the treatment of symptoms associated with psoriasis and seborrheic dermatitis in patients aged 15 to 60 years [14] .

Thus, due to the results obtained and the safety of this ingredient in pediatrics, in the present study we are going to evaluate the efficacy and safety of the product Blue Cap Foam whose main ingredient is activated piroctone olamine in atopic dermatitis in children between 3 and 18 years of age.

The study included 58 patients with AD. All patients were included in the safety analysis (n = 58) whereas 2 patients were excluded from the efficacy analysis due to follow-up loss. The distribution of patients (safety analysis) regarding general characteristics (anamnestic data) is presented in Table 1. Most participants are females, with normal constitutions for their age. Extremities are the most dominant place of skin changes. Half of the participants were previously treated, dominantly with local corticosteroid therapy.

Most skin signs significantly decreased from the baseline to the end of the study. A significant reduction from baseline to end of study is observed for all clinical signs (all p values are less than 0.001). A significant decrease is observed in visit 2, and from visit 2 significant decreases continue to visit 3. On the last visit, a slight increase in symptoms and signs was observed, but still significantly lower compared with baseline and mostly from visit 2 (Table 2). Statistical comparisons between measurements (before and after) are performed with and without Bonferroni corrections, and both approaches are presented in Tables 2-4, Figure 1 in superscripts, next to percentages.

Most patients had moderate to great disappearance of manifestations, skin quality, and total improvement on the second visit (Table 3). Compared to visit 2, the fading of manifestations and improvement continues in visit 3 where the dominant category is “Great” in all variables. At the end of the study, slight worsening is observed compared to visit 3, but still significantly better compared to visit 2. Most of the participants still have a “Great” grade as the dominant category at the end of the study.

Efficacy and tolerability assessed by the investigator were dominantly graded as very good or good on visit 2. By the end of the study, minor improvement or no improvement was observed in efficacy assessed by the investigator and the patient as well as in tolerability assessed by the investigator and the patient compared to visit 2 (Table 4).

In superscript, the number represents the significant difference between examined visit and number visit in superscript. ^aSignificant difference only without Bonferroni correction (not significant on 0.008 level). ^bCochrane Q test.

In superscript, the number represents the significant difference between examined visit and number visit in superscript. ^cFriedman test.

In superscript, the number represents the significant difference between examined visit and number visit in superscript; ^aSignificant difference only without Bonferroni correction (not significant on 0.016 level). ^cFriedman test.

The distribution of patients regarding the activated piroctone olamine (APO) during the trial, assessed by the patient, is presented in Table 5. Very good and good are dominant or only categories, both on visit 2, visit 3, and at the end of the study. Improvement from visit 2 to the end of the study is small and even overall statistical significance is present in feeling on the skin and staining after application, post hoc analysis revealed no significant differences between measurements with and without p-value correction. The change between visits 2, 3, and 4, even if significant, is clinically small. The overall variability might be different, but comparing each measurement reveals no statistical significance.

In the final assessment (Table 6), the grading of the treatment revealed significant healing and reduction of manifestations, nearly 50% reduction at the end of the study. Three patients had adverse effects, all at the beginning of the study (all had a burning sensation). Tolerability assessed by the patient and investigator revealed very good and good results at the beginning of the study and by the end of the study with no significant difference from visit 2 to the end. Therapy success assessed by the investigator and patient was dominantly graded as excellent and very good, both on visit 2 and at the end of the study (Table 4, Figure 1).

Scoring range from 1—insufficient to 6—very good; No significant differences between measurements in posthoc analysis have been observed and no superscript numbers are presented. ^cFriedman test. ^dCochrane Q test.

In superscript, the number represents the significant difference between examined visit and number visit in superscript; ^aSignificant difference only without Bonferroni correction (not significant on 0.016 level). ^cFriedman test. ^dCochrane Q test.

Piroctone olamine (PO)—the main chemical ingredient of Blue Cap—has been widely used in the treatment of facial and hair seborrheic dermatitis. The action mechanism of PO consists of selective inhibition in the cellular uptake of essential substances for the metabolism and development of fungal cells such as potassium ions, phosphates, and amino acids. Also, PO is concentrated inside the fungal cell where it binds irreversibly to certain structures and organs such as the cell wall and membrane, mitochondria, ribosomes, and microsomes fortifying its fungistatic effect [15] [16] .

Besides its fungistatic effect, PO expresses anti-inflammatory properties by lowering free radical concentration, as well as inhibiting the WTN signaling pathway which leads to lower cell differentiation, migration, and hyperplasia [17] .

Through these properties PO has been proven efficacious in the treatment of seborrheic dermatitis as well as positive adjuvant effects in the treatment of psoriasis [18] , its effect has not been investigated in the treatment of atopic dermatitis yet.

First-line therapy for acute management of AD includes topical therapies such as corticosteroids, calcineurin inhibitors, and phosphodiesterase inhibitor crisaborole, as well as a tendency to explore the efficacy and safety of topical JAK inhibitors. Topical agents have remained the mainstay therapy for decades. However, there has been a longstanding need for topical therapies with high efficacy and low risk of adverse effects with long-term use [19] .

Evidence shows that 42.5% of the caregivers of children with atopic dermatitis had used alternative therapies, most commonly due to fears of topical steroid side effects and dissatisfaction with conventional treatment [20] .

Our results show that patients treated twice daily with only Blue Cap foam had a significant improvement in skin lesions as well as subjective symptoms of their AD. In the examined group during the first month of the study, none of the patients had the necessity of additional application of topical steroids, and most of them reported high tolerability of the applied product.

Upon cessation of application of the investigated product (Blue Cap foam), a significant percentage of patients experienced a relapse of AD, nevertheless in most cases not in the severity before the study inclusion. Given the high tolerability and efficacy during the application phase, these findings endorse the investigation of continuous and frequent use of Blue Cap foam as a non-steroidal alternative topical treatment of AD.

The Blue Cap foam represents a unique product, that accentuates the antioxidative and anti-inflammatory effects of piroctone olamine by distributing it in its activated form. With this method, we are strengthening the antioxidant potential of molecules, and therefore we can donate more electrons and neutralize a larger number of free radicals, prevent and reduce the risk of developing an acute disease, or stabilize a chronic disease.

In this study, we demonstrated that Blue Cap foam is a safe and effective treatment option for pediatric patients with AD, who desire an alternative treatment approach or who are unable to use standard treatment. Since the incidence rise of this global disease and an increase of patients and parents/caregivers that insist on a non-steroidal topical treatment, such product should be evaluated in further large and placebo-controlled studies and potentially find itself in future treatment protocols.

Mirjana Gajić-Veljić and Jovan Lalošević: Crucial contribution to the article conception. Obtaining and interpretation of results. Design and review of manuscript. Final revision of the manuscript, being prepared for publication. All others: Obtaining and interpretation of results.

This research was partly funded by Catalysis, S.L. (Madrid, Spain).

The authors declare no conflicts of interest. The authors alone are responsible for the content and writing of the article. The funders had no role in the study design, data collection and analysis, nor any decision on manuscript publishment or preparation.

Gajić-Veljić, M., Marenović, B., Mijušković, M., Reljić, V., Tiodorović, D., Popović, D., Zorić-Blagojević, S., Vučinić, M., Marquez-Soriano, D. and Lalošević, J. (2024) Blue Cap Is Effective and Safe for the Treatment of Atopic Dermatitis in Children. Open Journal of Pediatrics, 14, 609-622. https://doi.org/10.4236/ojped.2024.143059