Canine atopic dermatitis represents a major clinical challenge in contemporary veterinary medicine, with a prevalence that continues to increase in urban canine populations. This chronic inflammatory skin condition, characterized by intense pruritus and recurrent cutaneous lesions, significantly affects the quality of life of animals and constitutes a frequent reason for consultation in veterinary dermatology. At the recent NAVDF congress in Orlando, our colleague Rosanna Marsella had the opportunity to provide a comprehensive 2025 update on the etiopathogenesis of Canine Atopic Dermatitis.
The evolution of scientific knowledge over recent decades has transformed our understanding of this complex pathology. While genetic factors remain indisputably involved in the susceptibility to develop this condition, the spectacular increase in its incidence strongly suggests the intervention of modifiable environmental factors. This observation opens promising therapeutic and preventive perspectives, based on the modification of the exposome of companion animals.
Intestinal Microbiota and Atopic Dermatitis: Beyond Simple Dysbiosis
Characterization of intestinal dysbiosis in atopic dogs
Scientific investigations conducted on different canine breeds have revealed substantial alterations of the intestinal microbiome in atopic animals. An initial study conducted on a colony of Shiba Inu, comprising nine atopic dogs and sixteen healthy dogs, demonstrated significant modifications of the oral microbiota in allergic subjects. The latter presented an oral microbial profile evocative of human periodontal disease. This clinical observation was correlated with early and severe periodontal disease in this canine population, appearing as early as six months of age. The accumulation of hair between the teeth, a consequence of compulsive chewing, favored the proliferation of Staphylococcus in the oral cavity. Concerning the intestinal microbiota, although no statistically significant difference was initially identified between allergic and normal dogs, a trend toward dysbiosis and intestinal inflammation was observable in atopic animals.
Subsequent pilot studies confirmed the existence of substantial differences in the intestinal microbiome between allergic and healthy dogs. Nevertheless, these preliminary investigations revealed considerable variability in microbial profiles, limiting the scope of initial conclusions. The hypothesis that this dysbiosis would constitute a characteristic signature of atopic disease was questioned by more in-depth work. A study conducted on forty Shiba Inu, equally divided between healthy and atopic subjects, half of the allergic animals having received prior treatment, provided major clarifications. Simultaneous examination of cutaneous and intestinal microbiota revealed that treatment with oclacitinib, a Janus kinase inhibitor targeting allergic inflammation, favorably modified the microbial composition both cutaneous and intestinal. This partial normalization of dysbiosis under anti-inflammatory treatment strongly suggests that the observed microbial alterations represent more a consequence of chronic inflammation than a primary cause of the pathology.
Detailed analysis of these data reveals that the reduction of Staphylococcus populations occurs independently of any antibiotic therapy, solely through control of the underlying inflammatory process. This fundamental observation challenges previous paradigms that attributed to dysbiosis a primary etiological role in canine atopic dermatitis.
Implications of intestinal dysbiosis
The alteration of the intestinal microbiome in atopic dogs holds considerable pathological importance due to its consequences on the intestinal barrier function. The commensal microbiota plays a fundamental role in maintaining epithelial integrity and local immune regulation. When this microbial ecosystem is unbalanced, intestinal permeability increases, creating increased exposure of the immune system to food and environmental antigens normally excluded. This intestinal hyperpermeability facilitates allergic sensitization, even in the absence of clinically apparent gastrointestinal manifestations.
The mechanisms by which intestinal dysbiosis influences the development and expression of atopic dermatitis involve complex interactions between microbial metabolites, epithelial cells and the mucosal immune system. The composition of the microbiota determines the profile of short-chain fatty acids produced by fermentation, which exert substantial immunomodulatory effects. The decrease in microbial diversity observed in atopic dogs is accompanied by a reduction in the production of anti-inflammatory metabolites and a polarization of the immune response toward a Th2 profile, characteristic of allergic diseases.
It should be emphasized that these alterations of the intestinal microbiota are not limited to quantitative modifications, but also encompass qualitative changes in bacterial populations. Beneficial bacterial species producing butyrate, propionate and acetate see their populations decrease, while certain potentially pro-inflammatory species proliferate. This modification of intestinal microbial ecology affects not only the local barrier function but also exerts systemic effects on the overall immune regulation of the organism.
Temporal relationship between dysbiosis and clinical manifestations
A fundamental question remains the establishment of the precise temporal sequence linking intestinal dysbiosis and development of atopic dermatitis. Longitudinal studies conducted on West Highland White Terriers followed from birth have attempted to elucidate this causal relationship. The results of these investigations reveal the impossibility of predicting, by examination of the early intestinal microbiota, which individuals will subsequently develop clinically manifest atopic dermatitis. This observation strongly suggests that intestinal dysbiosis does not constitute an independent predictive factor for disease development, but rather represents a concomitant or consecutive manifestation of underlying pathological processes.
These data fit into a conceptual paradigm where intestinal dysbiosis, although potentially contributing to the amplification and perpetuation of allergic inflammation once established, does not appear to initiate the pathological process. This distinction holds major therapeutic importance, orienting intervention strategies toward treatment of the primary inflammatory process rather than toward an exclusive focus on microbiota restoration.
Influence of Diet on the Development of Atopic Disease
Dietary regimens and allergic risk: epidemiological data
Canine dietary habits have undergone major transformations over recent decades, evolving from a diversified diet including home-prepared foods toward increasing dependence on ultra-processed commercial foods. This evolution of nutritional practices coincides temporally with the increase in the incidence of allergic diseases, suggesting a potential association.
A case-control study conducted in Sweden on several predisposed breeds investigated risk factors associated with the development of atopic dermatitis, including dietary habits. The results demonstrated that maternal diet comprising homemade regimens, as opposed to exclusive commercial foods, conferred a significant protective effect on the offspring. Puppies whose mothers had been fed with domestic preparations presented a reduced incidence of atopic dermatitis. Conversely, exclusive exposure to commercial diet approximately doubled the risk of allergic development in this studied population.
Transcriptomic investigations conducted on a limited number of atopic and healthy dogs provided mechanistic elements. Animals distributed between heat-treated ultra-processed regimen and raw meat-based diet showed substantial differences in cutaneous gene expression after four months of nutritional intervention. The raw regimen induced increased expression of genes involved in innate immunity, suggesting potential anti-inflammatory properties. Although some initial conclusions concerning complete prevention of allergies by raw feeding appear excessive, a modulatory effect on inflammation seems manifest.
This modulation of gene expression by diet extends beyond innate immunity genes alone, also affecting the expression of genes involved in epithelial barrier function, cutaneous lipid metabolism and oxidative stress response. These transcriptomic modifications suggest that diet exerts pleiotropic effects on multiple physiological pathways relevant to the pathogenesis of atopic dermatitis.
Antibiotic use and intestinal dysbiosis
A large-scale Finnish study revealed a worrying correlation between antibiotic exposure and the development of atopic dermatitis. Fifty percent of the allergic dogs studied had received systemic antibiotics, compared to only three percent of control dogs. This association was reinforced by a direct correlation between antibiotic use, the degree of intestinal dysbiosis and the severity of allergic manifestations. Systemic antibiotic therapy also constitutes a recognized risk factor for the development of allergies in human medicine, reinforcing the biological plausibility of this association.
This observation raises a fundamental question concerning the etiology of intestinal dysbiosis observed in atopic dogs. Rather than constituting an intrinsic characteristic of allergic pathology, this microbial alteration could result primarily from the increased exposure to antibiotics that atopic animals frequently receive to treat secondary skin infections, particularly Staphylococcus pseudintermedius pyodermas.
This perspective raises major practical implications concerning antibiotic prescription strategies in veterinary dermatology. The systematic and sometimes excessive use of antibiotics for any pustular skin manifestation, a historically widespread practice, may have inadvertently contributed to the increase in the incidence of atopic dermatitis observed over recent decades. Cephalexin, a widely prescribed first-line antibiotic, although generally effective against staphylococcal infections, can induce lasting disturbances of the intestinal microbiome whose long-term consequences on allergic susceptibility have only recently been appreciated.
Impact of ultra-processed regimens versus diversified diet
Investigations concerning the influence of diet type have compared carbohydrate-rich ultra-processed kibble to protein-rich raw regimens. While diet unquestionably modulates the composition of the intestinal microbiome, establishing a direct and univocal association with the development of atopic dermatitis remains complex. Studies often present numerical imbalances between groups, with a predominance of healthy dogs fed kibble, limiting the statistical power of analyses.
Urban life emerges as a recurrent risk factor in these investigations, independently of observations concerning the intestinal microbiome. This association suggests the intervention of additional, probably multifactorial mechanisms, exceeding simple modulation of intestinal flora by diet. The absence of identification of a specific intestinal microbial signature associated with urban life reinforces this hypothesis of etiological complexity.
Finnish work involving more than eight thousand dogs examined early modifiable factors, from nutrition to environment, likely to influence allergic risk. Exposure to an unprocessed regimen, whether at the prenatal stage or during early life phases, exerted a manifest protective effect. Environmental exposure, notably time spent outdoors on grass, also conferred significant protection. Conversely, white-coated dogs and those fed with carbohydrate-rich ultra-processed regimens presented an increased risk of allergic development.
An extensive study involving more than four thousand dogs investigated the relationship between dietary regimens and atopic dermatitis reported by owners. Animals consuming raw regimens, table scraps or receiving fish oil supplements presented a reduced incidence of atopic dermatitis. Inversely, exposure to heat-treated carbohydrate-rich regimens was associated with increased allergic development.
These converging epidemiological observations, despite their methodological limitations inherent to retrospective studies based on owner questionnaires, strongly suggest the existence of a causal relationship between diet type and risk of developing atopic dermatitis. Nevertheless, elucidation of the biological mechanisms underlying these statistical associations remains incomplete and requires complementary experimental investigations.
Potential explanatory mechanisms
Several mechanistic hypotheses can explain these epidemiological observations. The higher bacterial load of raw regimens could favorably modulate the immune system by stimulating the expression of genes involved in innate immunity and generating anti-inflammatory effects. The substantial biochemical differences between raw and ultra-processed cooked meat could differentially influence intestinal barrier function. Feeding with table scraps offers nutritional diversity absent from monotonous commercial regimens, a potentially protective factor.
Dietary diversity, particularly during early developmental phases, exerts a protective effect against the development of allergies in human medicine. Data suggest that early diversified exposure proves preferable to restrictive avoidance. This dietary diversity maintained throughout life could confer lasting protection. Although no veterinary study has specifically investigated this factor as a primary objective, this avenue deserves thorough scientific attention.
Beyond simple diversity of protein sources, the fatty acid composition of dietary regimens probably plays a significant role. Omega-3 and omega-6 fatty acids, whose ratio varies considerably between raw and processed foods, differentially modulate inflammatory pathways. Regimens rich in omega-3 fatty acids, particularly of marine origin, favor the production of anti-inflammatory lipid mediators such as resolvins and protectins, while regimens unbalanced in favor of omega-6 can promote pro-allergic inflammatory cascades.
Heat transformation of foods also induces structural modifications of proteins by glycation and formation of advanced glycation end products (AGEs), which can alter the immunogenicity of food antigens and potentially favor aberrant immune responses. These Maillard reaction products, formed during prolonged heating of foods, accumulate in ultra-processed regimens and could contribute to the chronic low-grade inflammation characteristic of allergic diseases.
Macronutrient composition and immunological impact
The macronutrient composition of dietary regimens, particularly the relative proportion of carbohydrates, proteins and lipids, profoundly influences host metabolism as well as the composition and metabolic activity of the intestinal microbiota. Commercial ultra-processed regimens generally contain high proportions of carbohydrates, often in the form of starch from cereals or legumes, contrasting with the natural composition of the ancestral carnivorous canine diet.
This high carbohydrate load modifies the intestinal fermentation profile, favoring certain bacterial populations at the expense of others. Regimens rich in fermentable carbohydrates can induce increased production of gas and potentially pro-inflammatory metabolites, while decreasing the production of beneficial short-chain fatty acids like butyrate. These modifications of intestinal microbial metabolism can, in turn, affect intestinal barrier permeability and the reactivity of the mucosal immune system.
Dietary proteins, according to their source and degree of transformation, present variable digestibility and allergenicity profiles. Highly processed proteins can undergo modifications of their tertiary structure, exposing normally cryptic epitopes and potentially increasing their capacity to induce immune responses. Conversely, certain forms of fermentation or enzymatic transformation can reduce protein allergenicity by partial hydrolysis.
Lifestyle-Related Factors: Stress, Obesity and Exercise
Stress and atopic dermatitis: a bidirectional relationship
Investigations in human medicine have established a complex bidirectional relationship between stress and atopic dermatitis. While intense pruritus and cutaneous discomfort unquestionably generate stress in patients, converging data suggest that chronic stress can also constitute a triggering factor for atopic dermatitis. Underlying mechanisms involve cortisol release, a hormone that disrupts cutaneous barrier function by altering the synthesis of epidermal lipids and structural proteins, decreasing stratum corneum hydration and increasing transepidermal water loss.
Stress also induces the release of substance P and nerve growth factor, mediators involved in inflammation and pruritus. This neurochemical cascade establishes a self-perpetuating vicious circle where inflammation and stress mutually reinforce each other. Canine studies have demonstrated a synchronization of chronic stress between owners and dogs, suggesting a transmission of emotional state. Owner personality traits exert a measurable effect on cortisol levels detectable in canine hair, reflecting long-term hormonal impregnation.
Dogs with atopic dermatitis present higher hair cortisol concentrations than healthy controls, correlated with disease severity. Nevertheless, the distinction between cause and consequence remains problematic. Elevated cortisol could result from stress induced by chronic pruritus rather than constitute a primary etiological factor. This causal ambiguity requires prospective longitudinal studies to elucidate the temporal sequence of events.
Beyond the direct effects of cortisol on cutaneous barrier function, chronic stress exerts systemic immunomodulatory effects. Prolonged activation of the hypothalamic-pituitary-adrenal axis induces dysregulation of the balance between Th1 and Th2 type immune responses, with a tendency toward Th2 polarization characteristic of allergic diseases. Chronic stress also alters regulatory T cell function, compromising immune tolerance mechanisms and favoring excessive inflammatory responses to environmental antigens.
The neuroendocrine mechanisms linking stress and cutaneous inflammation also involve the peripheral cutaneous nervous system. Dense innervation of the skin by sensory nerve fibers producing neuropeptides establishes bidirectional communication between the nervous system and cutaneous immune system. Local release of substance P, calcitonin gene-related peptide (CGRP) and other neuropeptides in response to stress activates mast cells, keratinocytes and resident immune cells, amplifying the cutaneous inflammatory response.
Obesity and systemic inflammation
Canine obesity, whose prevalence increases parallel to that observed in owners, establishes a complex relationship with atopic dermatitis. In human medicine, a bidirectional association between obesity and atopic dermatitis is documented. While intense pruritus and cutaneous discomfort limit physical activity and favor weight gain, obesity itself increases the risk of developing atopic dermatitis through systemic inflammatory mechanisms.
Hypertrophic adipocytes characteristic of obesity secrete reduced quantities of adiponectin, a hormone with anti-inflammatory properties, while releasing pro-inflammatory cytokines including interleukin-6 and tumor necrosis factor alpha. These mediators favor polarization of the immune response toward a Th2 profile, characteristic of allergic diseases. Obesity thus induces a chronic low-grade inflammatory state, favorable ground for the development of allergic pathologies.
Beyond immunological mechanisms, obesity modifies the physical structure of the skin and compromises cutaneous barrier function through mechanical and metabolic mechanisms. The observed correlation between owner obesity and canine obesity probably reflects shared lifestyle choices concerning diet and physical activity.
Adipose tissue, long considered a simple energy reservoir, is now recognized as an active endocrine organ secreting multiple adipokines with pro- and anti-inflammatory effects. In obesity, the balance between these mediators is disrupted in favor of a pro-inflammatory profile. Leptin, an adipokine whose circulating concentrations are proportional to adipose mass, exerts pro-inflammatory effects and stimulates T lymphocyte proliferation and activation, notably Th1 and Th17 populations. Adiponectin, inversely correlated with adiposity, possesses anti-inflammatory and insulin-sensitizing properties whose decrease in obesity contributes to metabolic and immune dysfunction.
Systemic low-grade inflammation associated with obesity also affects the composition and diversity of the intestinal microbiome. Microbiota modifications induced by obesity, characterized by decreased diversity and alterations in Firmicutes/Bacteroidetes ratios, can contribute to increased intestinal permeability and metabolic endotoxemia, further amplifying systemic inflammation and creating favorable ground for the development of allergic diseases.
Physical exercise and allergic protection
Epidemiological data have demonstrated that regular outdoor exercise exerts a substantial protective effect against allergies, both in dogs and their owners. This observation reinforces the concept of shared exposome between humans and companion animals. Underlying mechanisms probably remain multifactorial, involving diversified environmental exposure, metabolic benefits of physical activity and favorable modulation of the microbiome through interaction with the outdoor environment.
Regular physical exercise exerts well-documented systemic anti-inflammatory effects, mediated by the release of anti-inflammatory myokines by contractile skeletal muscle tissue. Interleukin-6 produced by muscles during exercise, distinct from adipocyte-derived IL-6 in obesity, exerts beneficial metabolic effects and stimulates the production of other anti-inflammatory cytokines like IL-10. Exercise also improves insulin sensitivity, reduces visceral adiposity and favorably modulates the circulating lipid profile, all factors contributing to reduction of systemic inflammation.
Exposure to diversified outdoor environments during exercise favors contact with a variety of beneficial environmental microorganisms. This microbial exposure contributes to the education and maturation of the immune system, favoring the development of regulatory and tolerant responses rather than excessive allergic responses. Time spent on grass and in natural environments allows the acquisition of a more diversified cutaneous and respiratory microbiome, a protective factor against the development of allergies according to the biodiversity hypothesis.
Epithelial Barrier Theory and Chemical Exposome
Conceptual foundations of the epithelial barrier theory
Formulated around 2020, the epithelial barrier theory proposes a unified conceptual framework to explain the increase in allergic diseases in modernized environments. This theory postulates that collective exposure to various pollutants and environmental chemical substances disrupts the integrity of epithelial barriers, whether cutaneous, intestinal or respiratory, thus initiating an inflammatory cascade favoring allergic development.
The central mechanism involves physical and chemical disruption of epithelia by ubiquitous environmental pollutants, leading to chronic inflammation. This inflammation further alters barrier function, establishing a self-perpetuating vicious cycle. Inflammation and dysbiosis progress together, increased permeability favoring dysbiosis which amplifies inflammation. This immune disruption favors polarization toward a Th2 response, characteristic of allergies, increasing allergic sensitization.
Investigations have demonstrated an association between air pollution and increased cutaneous transepidermal water loss, independently of individual genotype. This alteration of the cutaneous barrier results exclusively from environmental factors. The authors of this theory suggest that this mechanism could extend beyond allergies to chronic inflammatory diseases in general, all initiated by increased permeability of epithelial barriers induced by chronic exposure to low doses of environmental pollutants.
This theory unifies several apparently disparate observations concerning the increase in allergic and chronic inflammatory diseases in industrialized societies. It explains why individuals without manifest genetic predisposition can develop allergic diseases when exposed to certain environments, and why migration of populations from rural areas to urban environments is accompanied by an increase in allergic incidence independently of genetic changes.
Exposure to surfactants and detergents
Companion animals, due to their proximity to the ground, undergo increased exposure to chemical products used for domestic cleaning. Surfactants and detergents present in the majority of commercial animal shampoos can, during frequent use, alter the cutaneous barrier. The epidemiological observation of an association between excessive washing and increased risk of atopic dermatitis thus finds a plausible mechanistic explanation.
This chronic chemical exposure, even at low concentrations, can cumulatively disrupt cutaneous homeostasis, compromising barrier function and favoring allergen penetration. The question arises whether certain veterinary practices, initially intended to help atopic animals through frequent therapeutic baths, could paradoxically contribute to chronic alteration of the cutaneous barrier when implemented long-term with products containing aggressive surfactants.
Surfactants act by solubilizing surface lipids, including epidermal lipids essential to cutaneous barrier function. Ceramides, cholesterol and free fatty acids constituting the intercellular lipid mortar of the stratum corneum can be extracted by surfactants, compromising the lamellar organization of this hydrophobic barrier. Repeated use of surfactants, even those considered mild, can induce cumulative depletion of these essential lipids, increasing transepidermal water loss and permeability to allergens and irritants.
Beyond lipid extraction, certain surfactants can also denature structural proteins of the epidermis, including filaggrin and intercorneocyte tight junction proteins. These protein alterations further compromise the structural integrity of the cutaneous barrier. Elevation of cutaneous pH induced by many alkaline cleaning products also disrupts the activity of enzymes involved in barrier maturation and favors proliferation of certain pathogenic bacterial species.
Food emulsifiers and intestinal permeability
Food emulsifiers, ubiquitous additives in processed human and canine foods, have been associated in human medicine with metabolic syndrome and intestinal dysbiosis. Substances such as carrageenan and guar gum, commonly identifiable on labels of commercial dog foods, serve to create experimental models of inflammatory bowel diseases in laboratory rodents. These agents experimentally disrupt the intestinal epithelial barrier and induce dysbiosis.
Chronic exposure to commercial foods containing these additives could progressively alter canine intestinal permeability, favoring dysbiosis and a low-grade inflammatory state. This mechanistic hypothesis could constitute the missing link explaining the epidemiological association between ultra-processed regimens and atopic dermatitis, beyond simple differences in macronutrient composition. In-depth investigations remain necessary to validate this hypothesis in canine populations.
Emulsifiers like carboxymethylcellulose and polysorbate-80 have demonstrated, in murine models, their capacity to induce low-grade intestinal inflammation, alteration of microbiota composition with decreased diversity, and increased intestinal permeability allowing bacterial translocation. These effects occur at exposure concentrations comparable to those resulting from consumption of processed foods containing these additives.
The mechanism by which emulsifiers alter the intestinal barrier involves their interaction with the protective mucus layer covering the intestinal epithelium. This bilayer mucus layer constitutes a first line of defense, maintaining commensal bacteria at a distance from the epithelium while allowing nutrient absorption. Emulsifiers, due to their amphiphilic properties, can disrupt the structural organization of this mucus layer, allowing increased contact between bacteria and intestinal epithelium, thus triggering a local inflammatory response.
Air pollution and canine atopic dermatitis
Atmospheric fine particles, classified according to their diameter (PM2.5 for particles less than 2.5 micrometers, PM10 for those less than 10 micrometers), penetrate deeply into the respiratory tract and deposit on cutaneous surfaces. These particles are considerably smaller than traditional allergens like pollen (approximately 30 micrometers) or mites (approximately 20 micrometers), conferring superior tissue penetration properties.
Studies have established an association between exposure to passive smoking and development of atopic dermatitis in dogs. The investigation differentiated exposure to airborne secondhand smoke and tertiary smoking, consisting of fine particles deposited on domestic surfaces. A significant association was identified between high exposure to passive smoking and presence of atopic dermatitis.
Comparative investigations between allergic and normal dogs revealed that atopic animals came from environments presenting higher atmospheric concentrations of fine particles PM2.5 and PM10. A direct correlation between fine particle levels and severity of atopic dermatitis was documented. This pollutant exposure was also associated with an increase in transepidermal water loss, evidencing an alteration of cutaneous barrier function.
Fine particles constitute a complex mixture of organic and inorganic components, including polycyclic aromatic hydrocarbons, heavy metals, volatile organic compounds and elemental carbon. These constituents exert multiple toxic effects on epithelial tissues. Polycyclic aromatic hydrocarbons bind to the aryl hydrocarbon receptor (AhR) expressed by keratinocytes and cutaneous immune cells, activating pro-inflammatory signaling pathways and disrupting normal epidermal differentiation.
Reactive oxygen species generated by metallic components of fine particles induce oxidative stress in cutaneous and respiratory tissues. This oxidative stress damages membrane lipids by peroxidation, proteins by carbonylation and DNA by adduct formation, triggering inflammatory responses and compromising barrier function. Increased levels of malondialdehyde, a marker of lipid peroxidation, in the plasma of atopic dogs correlates with dermatitis severity and suggests a role of oxidative stress in disease pathogenesis.
Epigenetic modifications induced by pollutants
Beyond direct alteration of the cutaneous barrier, environmental pollutants can induce epigenetic modifications altering gene expression without DNA sequence mutation. These epigenetic changes, resulting from exposure to environmental toxins, affect the manner in which genes are expressed. Although potentially reversible, these modifications can also be transmitted to subsequent generations through mechanisms including DNA methylation.
Veterinary investigations have demonstrated that increased exposure to fine particles in atopic dogs was accompanied by epigenetic modifications. These changes induced a decrease in the expression of genes coding for anti-inflammatory and regulatory mediators, like TGF-β, parallel to an increase in the expression of pro-inflammatory genes. These alterations of gene expression favor an immunological environment conducive to allergic development, independently of inherited genetic mutations.
The epigenetic mechanisms involved include DNA methylation at the level of CpG islands in gene promoter regions, post-translational modifications of histones (acetylation, methylation, phosphorylation) affecting chromatin accessibility, and regulation by non-coding RNAs including microRNAs. These modifications can be induced by exposure to environmental pollutants and persist long after cessation of exposure, or even be transmitted to offspring through transgenerational epigenetic inheritance.
Air pollutants, notably polycyclic aromatic hydrocarbons and heavy metals, can induce modifications of DNA methylation patterns in genes regulating immune response and epithelial barrier function. Hypermethylation of promoters of anti-inflammatory genes like FOXP3 (regulatory T lymphocyte transcription factor) or IL10 can reduce their expression, compromising immune tolerance mechanisms. Conversely, hypomethylation of promoters of pro-inflammatory genes can increase their expression, favoring a chronic inflammatory state.
Atopic Dermatitis as a Systemic Disease: The Role of Lipid Metabolism
Beyond cutaneous disease: a systemic perspective
The evolution of scientific knowledge progressively reveals that atopic dermatitis largely transcends a simple localized cutaneous pathology. Growing evidence, initially documented in human medicine then confirmed in dogs, suggests that it is a systemic inflammatory disease with predominant but non-exclusive manifestations at the cutaneous level.
Alterations of lipid metabolism have been identified both at the cutaneous and blood level in atopic individuals, human and canine. These modifications of the lipid profile correlate with disease severity and occur independently of local inflammation and mechanical trauma induced by scratching. This observation suggests fundamental metabolic disruptions rather than simple consequences of chronic cutaneous inflammation.
Phospholipid alterations in canine atopic dermatitis
Glycerophospholipids, fundamental constituents of cell membranes, ensure their stability and functional dynamics. Investigations have revealed that phospholipids are increased in the skin but reduced in the blood of dogs with atopic dermatitis. These systemic modifications of lipid composition affect epidermal barrier function.
Experimental work has identified a set of cutaneous lipid characteristics allowing classification of samples as controls or atopic with 95% accuracy. Blood lipids discriminated between control and atopic dogs with 90% accuracy. These data suggest that canine atopic dermatitis constitutes a systemic disease and support the use of rapid lipid profiling to identify new diagnostic and prognostic biomarkers.
In-depth lipidomic analysis reveals specific alterations of particular lipid classes. Ceramides, essential components of the intercellular lipid barrier of the stratum corneum, present both quantitative and qualitative abnormalities in atopic skin. Certain ceramide subclasses, notably very long chain ceramides crucial for optimal lamellar organization of the barrier, are deficient. This deficiency in specific ceramides compromises the formation of organized lipid structures necessary for effective cutaneous barrier function.
Circulating phospholipids, particularly lysophospholipids and certain phosphatidylcholine species, show altered profiles in atopic dogs. These modifications could reflect disturbances of systemic lipid metabolism affecting the availability of lipid precursors necessary for synthesis of cutaneous barrier lipids. Enzymes involved in lipid metabolism, including phospholipases, sphingomyelinases and ceramidases, could present dysfunctions contributing to the observed lipid abnormalities.
Historical implications and future perspectives
Retrospectively, similar observations had been reported in horses affected by summer eczema during the 1980s. These animals presented altered lipid profiles, observations that had not been fully exploited for lack of an appropriate conceptual framework. These contradictory reports had been progressively abandoned, researchers not having tools to interpret these systemic circulating lipid abnormalities in the context of a pathology then considered exclusively cutaneous.
This historical perspective raises the possibility that these investigators had identified early a marker of systemic inflammation whose relevance has only recently been recognized. Blood lipid composition currently differentiates normal dogs from allergic dogs, potentially constituting a marker of systemic inflammation rather than a primary cause of the disease. These observations reinforce the emerging concept of atopic dermatitis as a cutaneous manifestation of systemic metabolic and inflammatory dysregulation.
The implications of this systemic perspective extend to therapeutic strategies. If atopic dermatitis indeed represents a systemic metabolic disease with predominant cutaneous manifestations, therapeutic approaches should perhaps target not only local cutaneous inflammation but also underlying systemic metabolic disturbances. Supplementation with specific lipid precursors, optimization of essential fatty acid metabolism and correction of enzymatic dysfunctions of lipid metabolism could constitute therapeutic strategies complementary to conventional anti-inflammatory treatments.
Comorbidities and extracutaneous manifestations
Recognition of atopic dermatitis as a systemic disease also opens perspectives concerning comorbidities observed in atopic patients. In human medicine, patients with severe atopic dermatitis present an increased risk of developing various chronic inflammatory conditions, including cardiovascular diseases, metabolic disorders and neuropsychiatric affections like anxiety and depression.
Although data concerning systemic comorbidities of canine atopic dermatitis remain limited, anecdotal observations suggest the existence of extracutaneous manifestations. Some atopic dogs develop chronic allergic bronchitis or present intermittent gastrointestinal symptoms, suggesting multi-organ involvement consistent with the concept of systemic disease. Reported improvement of chronic gastrointestinal symptoms in dogs treated with allergen-specific immunotherapy for their atopic dermatitis supports this systemic perspective.
Clinical Implications and Therapeutic Perspectives
Rethinking antibiotic use in veterinary dermatology
Epidemiological data concerning the association between antibiotic therapy and increased risk of atopic dermatitis impose a critical reevaluation of prescriptive practices in veterinary dermatology. Historically, systematic prescription of antibiotics, notably cephalexin, for any pustular cutaneous manifestation constituted common practice. This reflex therapeutic approach has progressively been questioned, initially due to concerns about bacterial resistance.
Current data suggest that the consequences of excessive antibiotic therapy far exceed the question of microbial resistance. Lasting alteration of the intestinal microbiome induced by systemic antibiotics could contribute long-term to allergic predisposition. This perspective imposes a more conservative approach, favoring topical treatments, antiseptics and targeted anti-inflammatory therapies when appropriate, reserving systemic antibiotic therapy for documented and clinically significant infections.
The optimal strategy should involve systematic cytological evaluation to objectively document the presence and density of bacteria before initiating antibiotic therapy. Localized superficial infections can often be controlled by topical antiseptic treatments (chlorhexidine, benzoyl peroxide) without recourse to systemic antibiotics. When systemic antibiotic therapy proves necessary for deep or extensive pyodermas, selection of narrow-spectrum antibiotics specifically targeting Staphylococcus pseudintermedius should be favored to minimize impact on the commensal microbiome.
Dietary diversity versus nutritional monotony
Traditional recommendations in veterinary dermatology advocated a single and constant diet for animals predisposed to allergies, with the perspective of preserving options for subsequent diagnostic food elimination trials. This restrictive approach contrasts radically with data in human medicine demonstrating the benefits of early dietary diversity in allergy prevention.
The therapeutic paradigm could evolve toward encouraging diversified food exposure rather than toward preventive avoidance. Alternation between different dietary regimens could favor a more resilient and diversified intestinal microbiome. Incorporation of fresh unprocessed ingredients in addition to a commercial food base could offer an acceptable compromise between practicality and nutritional diversity. These recommendations remain however speculative in the absence of prospective interventional studies in canine populations.
Early and progressive exposure to a variety of food proteins during critical phases of immune development could promote the development of oral tolerance rather than allergic sensitization. This approach contrasts with historical recommendations of preventive avoidance but aligns with human pediatric data demonstrating that early introduction of potential food allergens reduces the risk of developing food allergies.
Probiotics: a benign intervention with promising effects
The use of probiotics represents a relatively benign therapeutic and preventive intervention, supported by mechanistic and epidemiological data. Probiotics can favorably modulate the immune response, increase intestinal microbial biodiversity and exert systemic anti-inflammatory effects. Administration of probiotics during gestation and lactation in predisposed bitches could reduce allergic risk of the offspring.
Nevertheless, not all probiotics are equivalent, and selection of specific strains with documented immunomodulatory properties proves crucial. Additional investigations remain necessary to identify optimal strains, determine effective dosages and establish the temporal windows of maximally beneficial intervention.
The mechanisms by which probiotics exert their preventive effects against allergies include production of anti-inflammatory metabolites like short-chain fatty acids, stimulation of production of regulatory cytokines (IL-10, TGF-β) by intestinal dendritic cells, and reinforcement of intestinal barrier function by stimulation of mucus production and improvement of epithelial tight junction integrity. Certain probiotic strains also exert direct antimicrobial effects against intestinal pathogens through bacteriocin production and competition for epithelial adhesion sites.
Modulation of the environmental exposome
Recognition of the role of environmental pollutants in the pathogenesis of atopic dermatitis opens preventive perspectives, although their practical implementation presents considerable challenges. Reduction of exposure to passive smoking constitutes a clear and immediately applicable recommendation. Advice concerning minimization of exposure to urban air pollutants proves more problematic, many owners not having realistic options for modifying their residential environment.
Judicious selection of domestic cleaning products, favoring less aggressive alternatives, could reduce cutaneous exposure of animals to surfactants. Limitation of baths to clinically necessary situations, using products specifically formulated to respect canine cutaneous barrier, represents a practical modification of care routines.
Use of air purifiers equipped with HEPA filters in dwellings could reduce exposure to atmospheric fine particles and airborne allergens, although the efficacy of this intervention to prevent canine atopic dermatitis has not been formally evaluated. Maintenance of optimal ambient humidity (40-60%) contributes to preserving cutaneous hydration and barrier function, particularly in dry climates or during heating seasons.
Stress management and optimal weight maintenance
Although the precise mechanisms linking stress and atopic dermatitis remain partially elucidated, the documented correlation between cortisol levels and disease severity justifies attention to environmental stress management. Environmental enrichment, regular exercise and maintenance of stable routines can contribute to minimizing chronic stress.
Prevention and correction of obesity, through appropriate diet and regular exercise, offer multiple benefits exceeding sole reduction of allergic risk. Outdoor exercise combines the advantages of physical activity, exposure to a biodiversified environment and mental stimulation, constituting a global preventive intervention.
Stress reduction strategies include establishment of predictable routines, provision of secure and quiet spaces, and use of behavioral modification techniques for animals presenting excessive anxiety. Synthetic appeasing pheromones, although their efficacy to prevent or treat atopic dermatitis has not been demonstrated, can contribute to reducing overall stress and improving the well-being of anxious animals.
Etiological Complexity and Challenges of Future Research
Heterogeneity of canine atopic dermatitis
Canine atopic dermatitis does not constitute a single and homogeneous pathological entity, but rather represents a clinical syndrome resulting from multiple convergent etiological pathways. This heterogeneity manifests in the variability of triggers, some animals presenting a predominant food component while others respond primarily to environmental allergens. A subset of animals presents apparently non-IgE-mediated atopic dermatitis, defying classic paradigms of allergic disease.
This etiological complexity partially explains the difficulties encountered in identifying universal biomarkers or diagnostic microbial signatures. Associations identified in certain populations are not systematically confirmed in other cohorts, probably reflecting the existence of distinct pathogenic subtypes under the unifying designation of atopic dermatitis.
Identification of these distinct endotypes, defined by specific pathogenic mechanisms rather than by simple clinical characteristics, represents a major objective of contemporary research. The precision medicine approach, adapting therapeutic strategies to specific pathogenic mechanisms operating in each individual patient, could substantially improve therapeutic efficacy and reduce exposure to ineffective treatments for certain endotypes.
Gene-environment interactions and concept of pathological threshold
Clinical development of atopic dermatitis results from complex interactions between genetic susceptibility and environmental factors. The concept of pathological threshold proposes that risk factors, genetic and environmental, exert additive effects. Individuals progressively accumulate risk factors until crossing a threshold beyond which clinical manifestations become apparent.
This conceptualization explains why all genetically predisposed animals do not necessarily develop the disease, and why environmental modifications can influence clinical expression independently of genotype. It also opens preventive perspectives, suggesting that reduction of exposure to modifiable environmental risk factors could maintain certain individuals below the clinical threshold despite genetic predisposition.
This additive model implies that no single factor, whether genetic or environmental, proves necessary or sufficient for disease development. Rather, various combinations of risk factors can lead to the same clinical phenotype. This perspective explains the variable efficacy of interventions targeting individual factors and underlines the necessity of multimodal approaches integrating simultaneously several intervention axes.
Scientific gaps and research priorities
Despite substantial progress accomplished, many fundamental questions persist. The precise temporal sequence linking dysbiosis, inflammation and barrier alteration remains incompletely elucidated. The distinction between cause and consequence proves particularly problematic concerning cross-sectional observations of dysbiosis in already atopic animals.
Prospective longitudinal studies, following at-risk cohorts from birth, prove necessary to establish causal relationships between early exposures and subsequent disease development. Identification of early biomarkers allowing prediction of future disease development before appearance of clinical manifestations would constitute a major advance, opening windows of preventive intervention.
The precise mechanisms by which food emulsifiers and other chemical additives affect canine intestinal barrier require rigorous experimental investigation. Intervention studies testing the effect of specific dietary modifications on the incidence of atopic dermatitis in at-risk populations remain largely absent from veterinary literature.
Elucidation of epigenetic mechanisms by which exposure to environmental pollutants influences allergic susceptibility represents a promising research domain. Characterization of specific epigenetic modifications induced by different pollutants, their reversibility and their potential for transgenerational transmission require in-depth investigations. The possibility of therapeutic interventions specifically targeting these pathological epigenetic modifications constitutes an innovative therapeutic perspective.
Methodological challenges and translational considerations
Investigations on canine atopic dermatitis encounter substantial methodological challenges. Racial variability, diversity of environments and breeding practices, as well as heterogeneity of dietary regimens complicate epidemiological analyses. Retrospective studies based on owner questionnaires suffer from recall and classification biases, limiting the robustness of conclusions.
Canine experimental models, although valuable for elucidating pathogenic mechanisms, only imperfectly reproduce the complexity of spontaneous disease. Extrapolation of data from other species, notably murine models or human studies, must be performed with caution given substantial physiological and environmental differences.
Development of spontaneous canine atopic dermatitis models, using genetically predisposed breeds raised in controlled environmental conditions, offers opportunities for mechanistic studies while preserving clinical relevance. Establishment of multicentric prospective cohorts, with standardization of diagnostic criteria and data collection protocols, would allow more robust epidemiological analyses.
Interdisciplinary collaboration, integrating dermatologists, immunologists, microbiologists, nutritionists and epidemiologists, proves essential to address the multifactorial complexity of atopic dermatitis. Systems biology approaches, integrating multi-omics data (genomics, transcriptomics, metabolomics, metagenomics), could reveal unsuspected interactions between genetic, metabolic and environmental factors contributing to disease pathogenesis.
Practical Implications for Contemporary Veterinary Medicine
Evolution of diagnostic and therapeutic paradigms
Scientific data accumulated over recent decades impose an evolution of diagnostic and therapeutic paradigms in veterinary dermatology. Recognition of atopic dermatitis as a systemic disease rather than as exclusively cutaneous pathology should influence diagnostic investigation strategies, potentially including evaluation of lipid metabolism and systemic inflammatory markers.
The therapeutic approach could benefit from a more holistic perspective, integrating microbiome modulation, correction of lifestyle factors and reduction of chemical exposome alongside conventional anti-inflammatory treatments. Allergen-specific immunotherapy, intervention fundamentally modulating the immune response rather than symptomatically suppressing inflammation, deserves increased consideration, particularly in young animals.
Emerging therapies targeting specific immune pathways, such as Janus kinase inhibitors (oclacitinib) and anti-IL-31 monoclonal antibodies (lokivetmab), have revolutionized symptomatic management of canine atopic dermatitis. Nevertheless, these agents, although effective in controlling pruritus and inflammation, do not address underlying metabolic and barrier disruptions. Integration of these anti-inflammatory therapies with interventions aimed at restoring barrier function and correcting metabolic dysfunctions could offer synergistic benefits.
Owner education and behavioral modification
Effective implementation of preventive strategies requires active engagement of animal owners. Education concerning the benefits of dietary diversity, importance of regular outdoor exercise, risks associated with exposure to passive smoking and potential impact of excessive use of cleaning products proves crucial. These behavioral modifications, although requiring temporal and sometimes financial investment, offer health benefits far exceeding sole prevention of atopic dermatitis.
Communication of scientific nuances to owners presents considerable challenges. Recommendations must balance available scientific evidence, recognized as provisional and sometimes contradictory, with the need for actionable practical advice. Honest recognition of persistent scientific uncertainties, while providing guidance based on the best available data, constitutes an ethical and pedagogically effective approach.
Owners must understand that prevention of atopic dermatitis relies on a multifactorial approach rather than on a single miracle intervention. Adoption of multiple small lifestyle and environmental modifications can exert substantial cumulative effects on the risk of allergic development. This perspective of multiple modest actions contrasts with the search for a single definitive solution but proves probably more realistic and effective given the multifactorial nature of the pathology.
Professional responsibility and self-reflection
Data concerning the potentially deleterious impact of certain veterinary practices, notably excessive antibiotic prescription and recommendation of monotonous diets, impose professional self-reflection. Evolution of scientific knowledge demands continuous reevaluation of established practices, even when these appeared rational at the time of their adoption.
This professional responsibility extends to active contribution to veterinary research through rigorous documentation of clinical cases, participation in collaborative studies and support for scientific investigations. Evidence-based veterinary medicine requires continuous generation of quality data in real animal populations, complementing controlled experimental models.
The veterinary profession must also recognize that certain historical recommendations, although initially based on apparently solid rationales, have proved counter-productive in light of new knowledge. Scientific humility, recognizing the limits of our current understanding and the necessity to adapt our practices to emerging data, constitutes an essential professional virtue. This intellectual flexibility allows progressive evolution of standards of care in alignment with scientific advances.
One Health approach and comparative health
Atopic dermatitis exemplarily illustrates the One Health concept, recognizing the interconnections between human, animal and environmental health. Dogs, sharing our domestic environments and exposed to the same pollutants and lifestyle factors, serve as sentinels for environmental health risks also affecting human populations. Epidemiological observations of synchronization of allergic diseases between owners and their animals reinforce this shared exposome perspective.
Comparative research on canine and human atopic dermatitis offers mutual benefits. Pathogenic mechanisms elucidated in one species inform understanding of the disease in the other. Dogs, spontaneously developing atopic dermatitis in their natural environment, constitute a translational model superior to experimental murine models for certain research questions. Therapeutic interventions validated in dogs can inform development of human therapies, and reciprocally.
This comparative perspective extends beyond simple mechanistic understanding to encompass public health considerations. Identification of environmental factors contributing to increased atopic dermatitis in urban canine populations signals potential risks for human populations sharing these environments. Interventions aimed at reducing pollutant exposure or promoting healthier lifestyles simultaneously benefit humans and their companion animals.
Conclusion
Canine atopic dermatitis exemplarily illustrates the complexity of multifactorial chronic diseases, resulting from elaborate interactions between genetic predisposition and modifiable environmental factors. Recent scientific advances have considerably enriched our understanding of this pathology, revealing its systemic character and the crucial importance of environmental exposome in its pathogenesis.
The documented increase in the incidence of atopic dermatitis in urban canine populations cannot be explained by rapid genetic modifications, necessarily attributing a major role to contemporary environmental transformations. Exposure to air pollutants, use of domestic chemical substances, consumption of ultra-processed foods, sedentary life and antibiotic exposure constitute as many potentially contributory factors identified by epidemiological and mechanistic investigations.
The epithelial barrier theory offers a unified conceptual framework, proposing that chronic exposure to multiple chemical agents disrupts epithelial integrity, initiating a self-perpetuating inflammatory cascade favoring allergic development. This perspective partially shifts the focus from intrinsic genetic abnormalities toward extrinsic environmental aggressions as primary triggering factors.
The practical implications of these scientific advances remain under development. Lifestyle modifications, including dietary diversification, increased outdoor exercise, reduction of pollutant exposure and judicious use of antibiotics, represent potentially beneficial interventions. Incorporation of probiotics, particularly during early developmental phases, constitutes a promising preventive strategy deserving in-depth investigation.
Recognition of atopic dermatitis as manifestation of systemic metabolic and inflammatory dysregulation, rather than as exclusively cutaneous pathology, opens innovative diagnostic and therapeutic perspectives. Lipid profiling could emerge as a diagnostic and prognostic tool complementary to conventional clinical evaluations.
Persistent scientific challenges include elucidation of precise causal mechanisms, distinction between etiological factors and epiphenomena, identification of early predictive biomarkers and development of effective preventive strategies validated by rigorous interventional studies. The etiological complexity of atopic dermatitis, manifested by its clinical heterogeneity and variability of therapeutic response, suggests the existence of distinct pathogenic subtypes requiring differentiated diagnostic and therapeutic approaches.
Interdisciplinary collaboration, integrating dermatologists, nutritionists, immunologists, microbiologists and epidemiologists, proves essential to progress in understanding and management of this complex pathology. Comparative veterinary medicine, exploiting similarities between canine and human atopic dermatitis, offers mutually beneficial opportunities for both medical domains.
Ultimately, the objective remains improvement of quality of life of affected animals and reduction of the incidence of this chronic debilitating pathology through scientifically-based preventive strategies. Transformation of our pathogenic understanding into clinically effective interventions constitutes the major challenge for the next decade of research and practice in veterinary dermatology.
The evolution of our conceptual paradigms, from a reductionist vision focused on IgE and mast cells toward a holistic understanding integrating barrier dysfunction, dysbiosis, metabolic disturbances and environmental exposome, reflects the maturation of our discipline. This enlarged perspective, although substantially complexifying our understanding of the pathology, simultaneously offers multiple potential therapeutic and preventive intervention points.
The collective responsibility of the veterinary community consists in translating these scientific advances into accessible practical recommendations and modifications of standards of care. This translation requires a delicate balance between scientific rigor and clinical applicability, recognizing limitations of current evidence while providing the best possible guidance to improve the well-being of atopic patients and prevent disease development in at-risk individuals.
FAQs
1. Do raw regimens truly offer superior protection against atopic dermatitis compared to commercial foods?
Epidemiological data suggest an association between raw diet or home preparations and reduced incidence of atopic dermatitis. This association could be explained by several mechanisms: superior beneficial bacterial load favorably modulating the immune system, increased nutritional diversity, absence of emulsifiers and chemical additives present in processed foods, and preservation of thermolabile bioactive compounds. Nevertheless, available studies present substantial methodological limitations, including small sample sizes and absence of control for multiple confounding factors. Raw regimens also carry documented microbiological risks, notably contamination by Salmonella and other pathogens. An intermediate approach, incorporating fresh unprocessed ingredients in addition to a balanced commercial food base, could offer a reasonable compromise. Prospective randomized interventional studies remain necessary to definitively establish the comparative benefits and risks of different nutritional strategies.
2. Should systematic administration of probiotics to gestating and lactating bitches be recommended to prevent atopic dermatitis in offspring of predisposed breeds?
Experimental data demonstrate that administration of probiotics during gestation and lactation can favorably modulate the immune system of offspring, increase expression of genes involved in innate immunity and reduce susceptibility to allergic sensitization in experimental models. These preventive effects appear more pronounced than therapeutic effects in already atopic animals. Nevertheless, several questions remain unresolved: identification of optimal probiotic strains with documented immunomodulatory properties, determination of effective dosages, establishment of the temporal window of maximally beneficial intervention, and validation of preventive efficacy in prospective clinical studies on predisposed breeds. In the current state of knowledge, probiotic administration constitutes a relatively benign potentially beneficial intervention, justifying particular consideration in bitches of highly predisposed breeds. Standardization of protocols and rigorous efficacy studies remain necessary before establishment of universal recommendations.
3. Does the dysbiosis observed in atopic dogs constitute a cause or consequence of the disease, and does this distinction influence therapeutic strategies?
This fundamental question remains partially unresolved, available data suggesting a complex and probably bidirectional relationship. The impossibility of predicting development of atopic dermatitis by examination of early microbiota suggests that dysbiosis does not constitute a primary causal factor. Partial normalization of dysbiosis under anti-inflammatory treatment, even with agents not exerting direct antimicrobial effects, indicates that inflammation favors dysbiosis. Nevertheless, dysbiosis, once established, can amplify inflammation through production of pro-inflammatory metabolites, epithelial barrier alteration and local immune dysregulation. This circular relationship suggests that intervening on dysbiosis, through probiotics or microbiota transplantation, could theoretically break the inflammatory cycle. Therapeutic strategies should probably combine anti-inflammatory approaches targeting the primary pathological process with interventions aimed at restoring a balanced microbiome, recognizing that dysbiosis, although initially secondary, contributes to perpetuation of chronic inflammation.
4. Are epigenetic modifications induced by pollutant exposure reversible, and how does this influence prognosis and therapeutic strategies?
Epigenetic modifications, unlike permanent genetic mutations, theoretically present potential reversibility following modification of environmental exposure. Nevertheless, the kinetics of this reversion remain incompletely characterized, probably varying according to type of epigenetic modification, duration and intensity of initial exposure, and age during exposure. Exposures during critical periods of development could induce more persistent modifications. The possibility of transgenerational transmission of certain epigenetic modifications further complicates the prognostic picture. On the therapeutic level, this potential reversibility suggests that reduction of pollutant exposure, even after diagnosis of atopic dermatitis, could exert long-term benefits exceeding simple reduction of direct barrier aggression. Investigations on pharmacological agents specifically targeting pathological epigenetic modifications constitute a promising research domain. Identification of temporal windows during which environmental interventions exert maximal epigenetic impact could optimize preventive strategies.
5. How to reconcile traditional recommendations of food avoidance to preserve diagnostic options with emerging data suggesting the benefits of early dietary diversity?
This tension between diagnostic and preventive paradigms requires a nuanced reevaluation of practices. Traditional recommendations of dietary monotony aimed to preserve “virgin” proteins for subsequent diagnostic elimination trials. Nevertheless, this approach did not consider the potentially deleterious long-term consequences of limited food exposure on immune development and intestinal microbiome diversity. Data in human medicine clearly demonstrate that early diversified exposure reduces the risk of developing food allergies, reversing preventive avoidance recommendations. A reasoned approach could involve controlled exposure to a diversity of protein sources and ingredients during critical developmental phases, carefully documenting exposures to guide future diagnostic investigations if necessary. Periodic alternation between different balanced commercial food formulations, supplemented with varied fresh ingredients, could offer nutritional diversity while maintaining adequate traceability. The therapeutic objective should evolve from preservation of future diagnostic options toward primary prevention of allergic development through appropriate diversified immune exposure.
Pathophysiology of Atopic Diseases in Veterinary Medicine (Part 1 and Part 2), Rosanna Marsella, Navdf Orlando, 2025
