INTRODUCTION
Canine atopic dermatitis (CAD) is one of the most prevalent (20-30%), distressing chronic allergic skin diseases in the developed world, accounting for substantial loss of quality-of-life (QoL)1,2. CAD’s remarkable similarities to its human counterpart make it a suitable animal model for human atopic dermatitis (AD)3. While being a multifactorial disease, its genetic component renders CAD prevalence distinctly high in certain breeds, notably the French bulldog and Labrador retriever4. CAD’s complex and heterogeneous nature is often an obstacle to achieving therapeutic success.
Allergen immunotherapy (AIT) is the only aetiological CAD treatment capable of reversing the long-term syndrome’s pathogenesis, inducing a clinical remission state, and preventing new sensitizations5-10. Ultimately, this targeted therapy aims to improve the patient’s clinical condition and QoL, re-educating the immune system into a desensitised/tolerogenic state that should persist after treatment discontinuation5,6. AIT value for CAD is supported by several studies, reporting success rates between 50% and 80%10,11-18. Moreover, the updated International Committee on Allergic Diseases of Animals’ (ICADA) guidelines for treating CAD recognise AIT as an effective and safe therapy, despite the evidence being based on inconsistent patient-oriented uncontrolled studies19. Among others, AIT’s success depends on the protocol and administration route. Despite the well-established success of subcutaneous immunotherapy (SCIT) for several allergic diseases, human patient and pet-owner compliance is a major challenge5,20-22. The large number of injections and, although rare, the risk of severe systemic reactions due to allergen leakage into the bloodstream account for SCIT dropout5,23,24. Although with still limited evidence and unclear success rate5, sublingual immunotherapy (SLIT) has been seen as a convenient patient-friendly alternative route, as it dismisses the use of needles, facilitates administration, and is associated with fewer systemic reactions5,16,21,22,24-26. Nevertheless, the lengthy treatment time, delay until clinical improvement, perceived investment, and, for SLIT, the required daily administration justifies the low compliance for SCIT and SLIT, reported in both human and veterinary fields5,16,21,22,24-26. There is, therefore, a need to uncover new AIT modalities that address the raised challenges. Accordingly, intralymphatic immunotherapy (ILIT) route has recently emerged for CAD treatment, providing encouraging initial evidence of safety and efficacy11,17,18. However, relapse of CAD clinical signs after ILIT discontinuation is frequent, and its procedure requires trained personnel5,6,10,17.
The skin has become a new direction for vaccination against infectious diseases and cancer in people27-30. As a physiological site of allergen encounter, the skin is endowed with robust immune surveillance provided by a dense population of Langerhans cells (LC) and dermal dendritic cells with unique immunological features30-35. Moreover, as the epidermis is nonvascularised, this route should carry less risk of systemic allergic side-effects20,21,31,32. Epicutaneous immunotherapy (EPIT) has recently regained attention in human medicine as a new promising route of tolerance induction against allergens31,32,35-38. The protolerogenic properties of the skin sophisticated immune network underpin EPIT’s favourable efficacy and safety profile, which is linked to strong patient compliance, even in children and long-term clinical trials31,32,35-38.
To the authors’ knowledge, this is the first clinical trial addressing EPIT for CAD. Our primary aim was to assess EPIT’s feasibility, effectiveness, and safety in dogs with spontaneous, nonseasonal, mite-sensitive CAD over six months. Secondary aims were to ascertain owners’ adherence to therapy and to assess whether there was a breed effect in EPIT efficacy.