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.