Preliminary evaluation of a commercial shampoo and fine bubble bathing in the treatment of canine atopic dermatitis: A single-blinded, randomised, controlled study

INTRODUCTION

Canine atopic dermatitis (cAD) is a chronic skin disease characterised by pruritus and inflammation, often associated with elevated levels of immunoglobulin (Ig)E in response to environmental allergens. The condition is further deteriorated by skin barrier function defects and imbalanced microbial flora.¹ All of these factors could lead to secondary bacterial infection and/or Malassezia overgrowth. To address cAD, the 2015 treatment guidelines from the International Committee on Allergic Diseases of Animals (ICADA) recommend various topical therapies.² The aim of these treatment strategies is to target two separate facets of cAD management. First, in cases without apparent infections, the recommendations focus on improving skin barrier function and hygiene. This includes initial options such as applying spot-on essential fatty acids or topical lipid complexes containing ceramides, cholesterol and EFAs, as well as nonirritating shampoos. Secondly, when dealing with secondary bacterial or yeast infections, it is crucial to emphasise the use of gentle, low-irritant antimicrobial shampoos on a weekly basis to restore microbial balance.² This approach serves to reduce the excessive use of systemic antimicrobials, and its effectiveness has been substantiated through several well-executed clinical trials.²

However, it is important to note that topical antimicrobials, especially shampoos, have the potential to induce atopic dermatitis (AD) flare-ups, and treatment should be tailored to each patient.

While the significance of skin hygiene care in managing cAD is widely recognised, there remains a limited range of available options.² Treatment guidelines mention only two specific shampoo products: Allermyl (Virbac) and DOUXO Calm (Ceva Sante Animale).^{3, 4} Nondrug shampoos containing phytosphingosine or ophytrium-based shampoos have shown positive results in clinical evaluations.^{4, 5} Therefore, there is a need to explore new bathing methods for cAD treatment and their efficacy and impact on skin barrier function parameters. Loflath et al. found that the use of ascending bubbles in a whirlpool can effectively lift the hairs, resulting in a more thorough cleansing of the skin surface by removing or diluting dirt, debris and inflammatory mediators. Additionally, this process helps to hydrate the stratum corneum.⁶ A newly developed technological device has the capability to generate fine bubbles (FB), which are defined as bubbles with sizes <100 μm. These FB are divided into ultrafine bubbles (UFB, <1 μm) and microbubbles (MB, 1–100 μm). They are prepared in an FB generator by passing the fluid through its honeycomb structure in a gas–liquid mixer under pressure, creating air-containing FB water. The FB water has been confirmed to possess a potent bactericidal effect on Pseudomonas aeruginosa.⁷ In addition, research demonstrated the beneficial effects of UFB shower on a mouse model of AD.⁸

Skin barrier dysfunction plays a role in the development of AD, with transepidermal water loss (TEWL) and stratum corneum hydration (SSH) serving as key parameters to assess epidermal function in atopic dogs. Numerous studies have showcased increased TEWL and reduced SH in atopic dogs as a result of lower ceramide distribution.^9-11 The objective of this study was to assess the clinical effectiveness of FB therapy compared to the low-irritant shampoo method in dogs with AD. The evaluation included measurements of SSH and TEWL to assess skin barrier function. Furthermore, clinical improvements were recorded using Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04)and a pruritus Visual Analog Scale (PVAS) before and after the treatment.

MATERIALS AND METHODS

Production of FB water

The water containing high-density FB was prepared using the FB shower head (ReFa FINE BUBBLE S MTG Co.; Figure 1) The device uses air supplied to tap water to produce FB with bubble sizes ≥100 μm.

RESULTS

Of 17 dogs, nine were in the FB group and 8 in the control group. The average age of the dogs was 4.5 years (range 1–11 years). The breeds consisted of 8 French bulldogs, 2 each of shiba inu, West Highland white terriers and toy poodles, and 1 each of Yorkshire terrier, Lhasa apso and mixed breed (toy poodle × Maltese terrier).

CADESI and pVAS

Figure 2 presents the mean ± SD (range) of CADESI-04 and PVAS scores at D0 and D28. In the FB group, the mean ± SD (range) of CADESI score decreased significantly from 16.0 ± 3.8 (1–35) at D0 to 9.4 ± 1.8 (3–19) at D28 (paired Student's t-test, p < 0.05). However, in the shampoo group, the mean CADESI score decreased from 24.8 ± 7.2 (6–62) to 19.3 ± 6.3 (7–50), yet the difference was not significant compared to D0 (p = 0.10).

In the FB group, the mean ± SD (range) of PVAS was 3.6 ± 0.7 (2–7) at D0 and reduced to 3.1 ± 0.7 (0–6). In the shampoo group, the mean ± SD of PVAS was 2.5 ± 0.3 (2–4) at D0 and increased to 2.8 ± 0.6 (1–6) at D28. However, there were no significant changes in PVAS in either group (p > 0.05).

TEWL and SSH

The changes of TEWL and SSH before and after the trial, presented as mean ± SD (range), are shown in Figure 3. In the FB group, the TEWL values were 8.6 ± 1.2 (4.6–12.0) at D0 and 7.5 ± 0.7 (4.5–11.0) at D28. In the shampoo group, the TEWL values were 7.0 ± 0.7 (5.0–10.8) at D0 and 7.8 ± 1.5 (3.4–17.5) at D28. The SSH values in the FB were 20.0 ± 2.9 (12.5–39.7) at D0 and 18.0 ± 2.0 (10.0–25.9) at D28. The equivalent values in the shampoo group were 20.7 ± 3.0 (11.4–36.0) and 20.1 ± 4.3 (8.4–46.0), respectively. No significant changes were observed in TEWL and SSH in both groups, and there was no significant difference in improvement rates between the groups (p > 0.05).

DISCUSSION

In this randomised, single-blind, controlled trial, the effects of FB on canine atopy were investigated. The results revealed that dogs with AD that received FB bathing once a week for 4 weeks demonstrated a significant reduction in CADESI-04 scores, and no significant changes in PVAS, TEWL and SSH. However, none of dogs in the group that followed the treatment guidelines from 2015 and underwent shampoo treatment demonstrated a significant improvement.

In the present study, the group that received shampoo (Allermyl; Virbac) treatment did not show a significant improvement in terms of clinical presentation and skin barrier function parameters. This finding contradicts the previous study that used the same shampoo method.⁶ One possible reason for this difference could be attributed to variations in the inclusion criteria. In our study, only cases diagnosed with environmental AD were included, while the previous study included cases with allergic pruritus or pruritus of unknown cause. It has been established that dogs with AD suffer from impaired skin barrier function, and shampoo therapy can potentially alleviate pruritus through short-term skin rehydration and mechanical cleaning.⁶ However, it should be noted that shampooing may contribute to skin dryness, as evidenced by a slight increase in TEWL following the shampoo treatment.² Similar observations have been reported in other studies that utilised emollient bathing or a 2% miconazole/chlorhexadine shampoo administered twice weekly, indicating that even emollient bathing can transiently elevate TEWL.¹⁶ Therefore, it is crucial to carefully adjust the frequency of bathing or select an appropriate bathing method based on the specific condition of the skin and any existing infections. This individualised approach is necessary to avoid exacerbating skin dryness and irritation.

While there is limited research on the cleaning effects of FB in dogs, a study conducted on healthy dogs demonstrated that bathing with MB (diameter range approximately 1–100 μm) for 15 min had a similar cleansing effect to shampooing for 5 min.¹⁷ Additionally, UFB water may possess bactericidal effects on Pseudomonas aeruginosa via damaging the bacterial cell walls, ultimately resulting in cell death.⁷. Although we did not investigate the bactericidal effects in the current study, UFB bathing could potentially be considered as a treatment option for dogs affected by bacterial infections in the future. Another noteworthy point is recent evidence suggesting that bathing with cleansing agents or surfactants, even those containing moisturisers, may still potentially impair the skin barrier function in dogs.¹⁶ Therefore, solely cleaning with FB might provide an alternative option for maintaining skin hygiene. FB bathing has been found to be more effective in cleaning than traditional surfactant-based methods as a consequence of bubble action at the gas/solution interface whereby ascending FB bursts and remove the dirt from the skin surface through negative electrolysis of aqueous solutions.¹⁸ Overall, these findings suggest that FB may achieve the same level of skin hygiene as shampooing or even provide better results.¹⁷ FB has the potential to alleviate clinical signs in dogs with AD by mechanically removing allergens and micro-organisms from the hair coat and skin. These preliminary findings indicate that FB could be a promising approach for managing allergens and controlling micro-organisms in cAD, potentially offering better clinical outcomes compared to conventional shampoo or even antiseptic shampoo. However, further clinical trials are needed to fully understand the mechanisms and confirm the effectiveness of FB in veterinary dermatological practise.

We must acknowledge the few limitations of our study, including the insufficient number of cases included. Although the statistical analysis showed improvement in the FB group, further trials with large sample sizes and longer durations are necessary to fully understand the efficacy of FB. In conclusion, AD is characterised by the presence of allergens adhering to or penetrating the skin barrier, leading to inflammation, itching and potential complications, such as seborrhoea and imbalanced microflora, which can worsen skin clinical signs. Therefore, effectively managing adhering allergens and micro-organisms through proper cleaning and improving skin and coat hygiene is crucial in the treatment of cAD. In our study, there were no significant changes in skin barrier function parameters observed in either group, although TEWL demonstrated a slight decrease in the FB group and a slight increase in the shampoo group. TEWL is a commonly used indicator for assessing skin barrier function and is associated with CADESI in cAD patients.¹⁹ Thus, the main objective of this study was to maintain skin hygiene and minimise damage to the skin barrier function. Based on our findings, FB bathing demonstrated potential as a new cleansing tool with high tolerability and the ability to improve clinical signs in cAD treatment, while having less impact on skin barrier function than frequent shampooing.

AUTHOR CONTRIBUTIONS

Norihito Taguchi: Project administration. Ikki Onishi: Resources. Keita Iyori: Supervision; investigation; funding acquisition; methodology; resources. Yun-Hsia Hsiao: Writing – original draft; writing – review and editing.

ACKNOWLEDGEMENTS

The authors would like to express their gratitude to the owners who dedicated their time to the clinical trial, particularly for participated in the weekly bathing.

FUNDING INFORMATION

This study was partly financially supported by ReFa FINE BUBBLE S MTG Co., which also supplied the fine bubble shower head used in the trial. The funders had no role in study design, data collection and analysis, in writing the manuscript, or decision to publish.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.