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  • Review
  • Open Access

Atopic dermatitis in cats and dogs: a difficult disease for animals and owners

  • 1Email author and
  • 1
Clinical and Translational Allergy20188:41

https://doi.org/10.1186/s13601-018-0228-5

  • Received: 2 July 2018
  • Accepted: 10 September 2018
  • Published:

Abstract

The purpose of this review article is to give an overview of atopic dermatitis in companion animals and of recent developments including knowledge on immunological background, novel treatment options and difficulties in disease management. The prevalence of hypersensitivities seems to be increasing. The pathogenetic mechanisms are not fully understood, yet multiple gene abnormalities and altered immunological processes are involved. In dogs and cats, the diagnosis of atopic dermatitis is based on history, clinical examination and exclusion of other differential diagnoses. Intradermal testing or testing for serum allergen-specific Immunoglobulin E is only used to identify allergens for inclusion in the extract for allergen immunotherapy. Symptomatic therapy includes glucocorticoids, ciclosporin, essential fatty acids and antihistamines. A selective janus kinase 1 inhibitor and a caninized monoclonal interleukin-31 antibody are the newest options for symptomatic treatment, although longterm effects still need to be assessed. The chronic and often severe nature of the disease, the costly diagnostic workup, frequent clinical flares and lifelong treatment are challenging for owners, pets and veterinarians. Patience and excellent communication skills are needed to achieve a good owner compliance and satisfactory clinical outcome for the animal.

Keywords

  • Allergy
  • Canine
  • Feline
  • Atopy-like dermatitis
  • Adverse food reaction
  • IL-31
  • Lokivetmab
  • Immunotherapy

Background

Atopic dermatitis (AD) is a common skin disease in dogs and cats. Its clinical, immunological, histological and pathological features in dogs are so similar to the human counterpart, that canine atopic dermatitis has been suggested as an animal model for human AD [1, 2]. In Table 1 some of the similarities and differences are summarized. Much less is known on the pathogenesis in cats, but the clinical findings are different to those seen in humans and dogs.
Table 1

Similarities and differences of AD in dogs and humans

 

Dogs

Humans

Pathogenesis

Th2 immune response

Skin barrier damage

Allergic inflammation

[18, 19, 153]

Th2 immune response

Skin barrier damage

Allergic inflammation

[154]

IL-4 and IL-13

Pruritus, acute inflammation [155]

Pruritus, acute inflammation [156, 157]

Periostin (PO) expression

Increased expression, related to the chronicity of skin lesions [158]

Increased expression, related to the chronicity of skin lesions [159, 160]

Histologic pattern

Spongiotic, hyperplastic dermatitis with mononuclear infiltrate; predominantely T-lymphocytes [153, 161]

Spongiotic, hyperplastic dermatitis with mononuclear infiltrate; predominantely T-lymphocytes [162, 163]

Dysbiosis

Reduced microbiome diversity [164] and fungal dysbiosis [165]

Reduced microbiome diversity and fungal dysbiosis [166]

Clinical signs

Eczematous skin lesions with no progression of clinical signs e.g. no development of asthma [2, 44]

Atopic march

Allergy testing

Intradermal testing without high risk of anaphylactic reactions [69]

Skin prick testing

Immunotherapy

Accelerated immunotherapy without increased risk for anaphylactic reactions [76, 78, 79]

Standard AIT

Canine atopic dermatitis

Canine AD is a multifactorial disease process. It is defined as a “genetically predisposed inflammatory and pruritic allergic skin disease often associated with a production of immunoglobulin (Ig) E against environmental allergens” [3]. The estimated prevalence of AD in the dog is approximately 10–15% [4]. Although the pathogenesis is not completely understood, there is evidence for genetic abnormalities, an altered immune system with cutaneous inflammation and a skin barrier defect [5, 6].

Genetic background

Multiple gene expressions involved in skin barrier function and cutaneous inflammation have been described as down- or upregulated in the skin of privately owned atopic dogs [79] as well as in a canine model of AD [10]. In the latter study, 361 genes relevant for inflammation, wound healing or immune response processes showed an increased expression, whereas 226 genes associated with differentiation and skin barrier function showed decreased mRNA concentrations in allergen-treated skin of sensitized dogs [10]. In atopic German shepherds a significant association with chromosome 27 was determined, especially with genes that had a connection to plakophilin 2 production [11]. Plakophilin 2 is an important structural protein, which is expressed in epithelial and immune cells [11, 12]. The predisposition of German shepherds for AD is likely due to a risk haplotype in combination with multiple variants resulting in a changed expression of the plakophilin 2 gene and nearby genes [11]. In the United Kingdom the risk of Labrador and Golden retrievers to develop AD was almost 50% due to the genetic background [13, 14]. Multiple breeds including Boxer, Westhighland White Terrier, French bulldog, Bullterrier, American cocker spaniel, English springer spaniel, Poodle, Chinese Sharpei, Dachshund, Collie, Miniature schnauzer, Lhasa apso, Pug and Rhodesian ridgeback are also predisposed [15, 16] and breed predispositions vary with geographic location [17].

Immunologic alterations

In acute lesions, allergic inflammation triggers the release of cytokines such as interleukin (IL-) 4 and IL-13, which induce a T helper 2 (Th2) response [1, 18, 19]. In more chronic skin lesions, CD4+ and CD8+ skin-associated T lymphocytes additionally stimulate the production of various cytokines such as IL-13, IL-22 and IFN-γ [20]. Recent findings on cytokines and specific cell types in atopic dogs are listed in Table 2.
Table 2

Recent findings on T cells and cytokines in canine atopic dermatitis

Cytokine/cell

Function

IL-31

Important role in atopic pruritus [167]. Its serum concentration correlates with the severity of active skin lesions [168]

IL-13

Induces production of PO in keratinocytes and fibroblasts, associated with chronicity of skin lesions and their deterioration [1]

IL-25

Increased in PO-stimulated keratinocytes [1], clinical relevance unclear. In a murine asthma model relevant for Th2-mediated immunity, contributes to a decreased epidermal barrier function in human AD [169171]

IL-33

Upregulated in chronic lesional skin, similar to atopic humans [172]

CD 34+ cells

Increase in peripheral blood, unclear clinical relevance [173]

CD4+ CD25+ FoxP3+ cells

Significantly higher percentage in peripheral blood and correlated with severity of AD [174]

Skin barrier defects

According to the “outside-in” theory an impaired epidermis leads to an increased allergen penetration and hence a higher allergen exposure of epidermal immune cells [21]. This skin barrier defect may be due to decreased filaggrin concentrations [22]. Caspase 14 is involved in the breakdown of filaggrin into natural moisturizing factors such as free amino acids and small peptides and altered concentrations might influence the skin barrier function and hydration of the stratum corneum [23, 24]. Conflicting results regarding the filaggrin metabolism in atopic dogs have been published with lower [22] and higher caspase 14 concentrations [24]. Changes in the ceramide composition of lesional canine atopic skin have been described [25, 26] contributing to disorganisation of the lipid envelope and hence disruption of the epidermal barrier. Ceramide profiles of atopic dog skin contained lower amounts of CER [EOS], CER [EOP] and CER [NP] [27], similar to what is seen in humans. A decreased relative content of ceramides in atopic dogs might be one reason for the increased transepithelial water loss observed in both lesional and non-lesional skin [28]. Moreover, house dust mite allergens can alter the expression and possibly also the function of corneodesmosomal and tight junction proteins through proteolytic digestion and/or allergic inflammation, facilitating a higher allergen penetration through the epidermis [29].

Feline atopy-like dermatitis

The function of IgE in the cat is not completely clarified, consequently the term “feline atopic dermatitis” is not ideal [30, 31], but rather it is refered to as “feline atopy-like dermatitis”. The pathogenesis of feline atopy-like dermatitis is not completely elucidated. Data on genetic alterations and skin barrier abnormalities as reported in human and canine AD are rare.

Genetic background

In a large study evaluating allergic cats, pure-bred cats were overrepresented in the group of cats with atopy-like dermatitis compared to cats with flea allergy, but the study lacked a non-allergic control group [32]. In this study, Abyssinians were only affected by atopy-like dermatitis and not flea allergy. A predisposition for Devon rex, Abyssinian and domestic shorthaired cats was reported in another study [33]. A case report of three littermates with clinical signs and history consistent with atopy was described implying a heritable factor [34], however more detailed genetic studies are lacking [31].

Immunologic and skin barrier alterations

In cats, histopathologic features of atopy-like dermatitis include perivascular to diffuse dermal infiltration of T lymphocytes, activated antigen presenting cells, eosinophils, macrophages and high numbers of mast cells [35]. A significant increase of CD4+ T cells, IL-4 and CD1a+ dentritic cells was found in the skin of cats with atopy-like dermatitis, pointing to a Th2-mediated immune dysfunction [33, 36], although cytokine pathways have not been investigated [37]. Comparable to humans and dogs [38] a fungal dysbiosis was found with next generation sequencing of skin swabs taken from healthy and allergic cats [39]. Skin hydration as a measure of the skin barrier did not always correlate with clinical scoring indicating that a barrier defect may not be as relevant in cats [40].

Practical approach

Clinical features

The following three main allergy categories can be distinguished in cats and dogs: flea (and other insect bite) hypersensitivities, cutaneous adverse food reaction (AFR) and AD due to environmental allergens. The clinical signs in the atopic dog are mostly distinct when compared to the atopic cat. A short overview of the main clinical features, diagnosis and treatment options in companion animals is given in Table 3.
Table 3

Clinical features, diagnosis and treatments of atopic dermatitis for small animals

 

Dog

References

Cat

References

Age

Commonly 6 months to 3 years

[41]

Commonly < 3 years

[31, 32]

Clinical symptoms

Pruritus

 

Eosinophilic granuloma complex (indolent eosinophilic ulcer, eosinophilic granulomas, eosinophilic plaques)

[32, 46, 47]

Inflammation (Erythema, self-induced alopecia, excoriation) secondary infection

[41, 42]

Head and neck pruritus

Miliary dermatitis

Self-induced alopecia

Affected body part

Ear pinnae, axillae, ventral abdomen, extremities, paws, inguinal, lips, perianal region

[42, 43]

Head, mouth, neck, abdomen, trunk

 

Diagnosis

Exclusion diagnosis (rule out differential diagnosis, compatible history and clinical signs

 

Exclusion diagnosis (rule out differential diagnosis, compatible history and clinical signs

 

Therapy

Allergen contact avoidance

[71]

Allergen contact avoidance

 

Specific targeted: Allergen-specific immunotherapy

[70, 7279, 81, 82]

Specific targeted: Allergen specific immunotherapy

[33]

Untargeted, symptomatic:

 

Untargeted, symptomatic:

 

 Glucocorticoids

[85]

 Glucocorticoids

 

 Ciclosporin

[86, 87, 89]

 Ciclosporin

[88, 90, 91]

 Oclacitinib

[9295]

 Oclacitinib

[96]

 Lokivetmab

[83, 84]

  

 Antihistamines

[97100, 103105]

 Antihistamines

[33, 106]

Topical:

 

Topical:

 

 Shampoos

[113, 114]

 

[110]

 Hydrocortisone-aceponate

[108, 109]

 Hydrocortisone-aceponate

 

 Tacrolimus

[111, 112]

  

Supportive dietary interventions

Essential fatty acids

[116119]

Essential fatty acids

[115]

Probiotics

[124, 125]

  

Cholecalciferol

[129]

  

Clinical features of canine AD

In dogs, clinical signs of an environmental allergy mainly develop between 6 months and 3 years of age [41]. Erythema is a primary lesion of canine AD; pruritus and inflammation can result in self-induced alopecia, excoriation and secondary infections with papules, pustules and crusts [41, 42]. Axillae, ventral abdomen, distal extremities, inner pinnae and periocular, perioral and perianal regions are commonly affected [42]. Otitis externa is present in half of the dogs with AD. Predilection sites differ from breed to breed [43]. Even though dogs can have multiple target organs for hypersensitivities (including gut and respiratory) [44], the contact with environmental allergens predominantly induces skin lesions in this species [45]. There is no evidence for the progression of initially exclusive cutaneous lesions to respiratory signs and systemic hypersensitivities comparable to the “atopic march” in humans [44]. In contrast to the cat, clinical examination in the dog frequently provides clues on the pathogenesis of the pruritus as to the presence of flea bite hypersensitivity versus environmentally-induced atopy or AFR. The former is characterized by pruritus focused on the dorsal lumbosacral area, ventral abdomen, tailbase and thighs.

Clinical features of feline atopy-like dermatitis

The manifestation of specific cutaneous reaction patterns [46] can indicate an allergic primary cause in cats. These involve head and neck pruritus, miliary dermatitis characterised by small crusted papules, self-induced alopecia without any other clinical lesions and eosinophilic lesions such as eosinophilic indolent ulcers, eosinophilic granulomas and eosinophilic plaques [32, 47]. In rare cases, untypical AD symptoms such as plasma-cell pododermatitis, seborrhoea, ceruminous otitis, facial erythema and exfoliative dermatitis were reported [31, 48]. Additionally noncutaneous signs such as sneezing, coughing, conjunctivitis, diarrhoea or vomiting can be presented in affected cats [32]. The disease onset can vary, but commonly it is under 3 years [31, 32], whereas the mean age for AFR is slightly higher (approximately 4–5 years) with a range from 3 months to 11 years [48]. In contrast to the dog, flea-bite hypersensitivity and environmentally induced and AFR look much more similar in the cat [32].

Diagnosis

A differential diagnosis of AD is based on age of onset, breed and clinical signs. Other differential diagnoses such as ectoparasites and flea bite hypersensitivity must be ruled out by a consequent ectoparasite control. There is no single test differentiating the atopic from the non-atopic dog or cat [49].

It is not possible to distinguish clinical signs of AD caused by perennial environmental allergens from AFR [16, 50, 51]. Hence an elimination diet followed by a provocation with the original food should be performed in any dog or cat with non-seasonal AD [52], particularly those with a long history of pruritus and/or gastrointestinal signs [51, 53]. A diet length of 6–8 weeks is recommended, as 90% of the dogs with AFR show some improvement during this time period [54]. Every food can potentially result in an AFR [55]. The most common reported causative allergens for canine AFR are beef, dairy products, chicken, wheat, and lamb [56]. However, soy, corn, egg, pork, fish and rice have also been reported as offending allergens [56]. The food sources most frequently causing AFR in cats were beef, fish, and chicken [58]. Wheat, corn, dairy products, lamb, egg, barley and rabbit were also reported as offending allergens in individual cats. The selection of appropriate protein and carbohydrate sources for an elimination diet can be challenging. It is important to use a protein and carbohydrate source, which the dog or cat has never received before [52], thus a detailed food history needs to be obtained by the veterinarian. Multiple studies have shown that various commercial special diets with only one protein source on their label were contaminated and contained substances not listed on the label [5760]. Highly hydrolysed food is an alternative, but some dogs allergic to chicken also react to diets containing hydrolysed chicken protein [61]. Therefore a home cooked diet by the owner is considered as diagnostic gold standard [52], where instead of commercial dry or canned food the owner purchases one type of meat and one carbohydrate source and prepares those him-/herself for the pet. As cats are obligate carnivores, the use of a carbohydrate source is optional in the short term and indeed may reduce palatability. Currently there is no reliable alternative test for diagnosing food allergy [62]. There is only poor correlation between IgE- and IgG-antibodies in the serum and clinical food reactions [53, 63]. A patch test can be used for the selection of the elimination diet food source if the food history is unknown. This test has a poor positive predictability, but a high negative predictability [53]. A lymphocyte proliferation test was able to detect a type IV hypersensitivity in the blood [6466] by measuring activated T-helper lymphocytes under food allergen stimulation with flow-cytometry [66]. In 49 of 54 AFR dogs this test accurately provided positive reactions against one or more food allergens [66], however this test is not commercially available at this time.

AD in animals is diagnosed by history, clinical examination and exclusion of all differential diagnoses. Positive reactions are frequently seen in healthy dogs on both intradermal tests [67] and serum tests for allergen-specific IgE [68]. The total serum IgE concentrations seem to have no clinical relevance in the dog [44]. Once AD is diagnosed in an animal, testing can be used in combination with clinical historical information to choose which allergens should be selected for allergen immunotherapy. Serum tests for allergen-specific IgE and intradermal tests are equally useful and both are still performed with allergen extracts in animals, in contrast to component-resolved tests such as single molecule CAP testing or ImmunoCAP ISAC 112 microarray in human medicine [45]. Prick puncture testing is not performed routinely in veterinary medicine, as intradermal testing is an established and safe diagnostic tool with a very low risk of adverse effects [69].

Treatment of atopic dermatitis in small animals

Therapy selection depends on the pet’s condition, especially the severity of the lesions and degree of pruritus and owner preference and especially in cats—on the ability to medicate. The therapy needs to be reassessed regularly and adapted to the individual [70]. With the exception of avoidance of the causative allergen [71], in general there are two different treatment approaches: specific with allergen immunotherapy or symptomatic with a variety of drugs. The combination of various drugs can increase the chance of remission [70].

Specific allergen-targeted therapy

Allergen immunotherapy (AIT) is the only possibly curative treatment option [70]. In approximately 50–75% of the atopic animals desensitization is effective [7276]. In those animals, it is often recommended to continue the treatment lifelong [70, 77]. In contrast to human medicine where accelerated immunotherapy (“rush”) is only advised in selected patients, due to the high frequency of systemic adverse reactions, in dogs rush-immunotherapy is effective and safe with no reported increased risk of adverse reactions [76, 78, 79]. Intralymphatic desensitization (ILIT) in humans was reported to reduce the therapeutic interval from 3 years to 8 weeks with less severe adverse effects [80]. ILIT is also used in veterinary medicine, but with less predictable success than in humans and a recent report showed the need for ongoing immunotherapy at regular intervals [81]. Sublingual immunotherapy (SLIT) was introduced to veterinary medicine some years ago, but so far limited published data is available [82].

Biologicals

Monoclonal antibodies are a focus of research in human medicine. They target specific receptors or cytokines and are highly specific and effective in blocking their target molecule. Lokivetmab is a monoclonal caninised anti-IL-31 antibody, that was recently approved for the use in atopic dogs. It significantly decreased pruritus for at least 4 weeks [83]. Its efficacy is comparable to oral prednisolone. Lokivetmab is regarded as safe without any immediate hypersensitivity reactions. Adverse reactions were similar in dogs treated with lokivetmab to those treated with placebo [84]. In the treatment group, 2.5% of the dogs produced antibodies against lokivetmab [84] but their clinical significance is unclear at this point. To date no other therapeutic monoclonal antibody exists in veterinary medicine.

General anti-inflammatory and anti-pruritic treatment

In severely affected dogs and cats, glucocorticoids, ciclosporin, oclacitinib or lokivetmab are used for symptomatic therapy due to their clinical efficacy and high success rates of 70–80% [85].

Glucocorticoids are inexpensive, universally available and have been the mainstay of treatment for allergic pets for many years. However, the potentially severe adverse effects of oral and particularly injectable depot glucocorticoids such as polyuria and polydipsia, polyphagia, muscle atrophy, secondary skin infections, calcinosis cutis and others have led to the development of alternative drugs for dogs and cats.

Ciclosporin, a calcineurin inhibitor, is highly effective in dogs and cats with comparable results to glucocorticoids [8688]. The initial daily dosage can be reduced in the majority of animals to every other day or twice weekly [86, 87]. Mild gastrointestinal symptoms (e.g. diarrhoea and vomiting) frequently occur at the beginning of treatment but usually resolve during continued administration [89]. Hirsutism, gingival hyperplasia and hyperplastic dermatitis are reported adverse effects which typically resolve with dose reduction or discontinuation [87]. Sporadic case reports exist of immunologically naive cats newly infected with Toxoplasma gondii, developing systemic and even fatal clinical signs [90, 91]. It is recommended to evaluate anti-toxoplasma antibodies in outdoor cats and cats fed raw meat prior to initiating cyclosporine therapy.

Oclacitinib is a selective inhibitor of janus kinase 1. Janus kinase 1 is involved in the signaling pathways of the receptors for IL-2, IL-4, IL-6, IL-13 and IL-31 [92], and thus aims at blocking the Th2 pathway. It is administered to dogs at a dose of 0.4–0.6 mg/kg twice daily for 2 weeks and then daily at that dose is reported to be as effective as glucocorticoids [93, 94]. In comparison to cyclosporine, oclacitinib has a more rapid effect and gastrointestinal adverse effects are less frequently observed [95]. Skin infections and histiocytomas were reported with increased frequency in dogs on longer term oclacitinib therapy [93]. Oclacitinib given to a small number of cats with atopy-like dermatitis over a 4 week period was effective [96], however the dose required was higher than for dogs, the period of monitoring was short and both more and larger studies are needed before it can be recommended as standard therapy.

Different antihistamines are associated anecdotally with individual responses, therefore a trial therapy with various antihistamines over 7–14 days is recommended [97, 98]. Histamine binds to four receptor subtypes (H1to H4) which are expressed in different tissues [99]. Its interaction with the high-affinity H1 receptor is known to cause cutaneous vasodilatation, oedema, and wheal formation. Histamine can also attract effector cells such as eosinophils to the region of inflammation [99]. Antihistamines targeting the cutaneous H1 receptors block the binding of histamine and are used most frequently in order to reduce the pruritus in atopic dogs [100]. Antihistamines binding to the H4 receptor showed an anti-inflammatory and anti-pruritic effect in mice [101, 102]. However, they did not prevent the development of acute skin lesions in a canine atopic model [103]. A double blinded, placebo-controlled, cross-over study evaluated the efficacy of dimetindene and a combination of hydroxyzine and chlorpheniramine in 19 atopic dogs and concluded that in both groups a limited, but significant improvement on pruritus was achieved, nevertheless other drugs might additionally be needed [104]. Many owners consider antihistamines useful therapeutic agents for their pets’ allergy [105]. The recommended dosage of antihistamines is much higher in cats and dogs than in humans. Dogs can rapidly metabolise hydroxyzine to cetirizine and need twice daily hydroxyzine orally at 2.0 mg/kg [99]. In one study a positive effect of antihistamines, mainly loratadine and cetirizine, was shown in 67% of 31 atopic cats [33]. In contrast, in another study, cats with allergic dermatitis treated with cetirizine hydrochloride showed no significant differences in lesion- and pruritus-scores to those treated with placebo [106].

A future non-specific treatment alternative might be the subcutaneous injection of cytosine-phosphate guanine oligodeoxynucleotides bound to gelatine nanoparticles (CpG GNPs). This therapy resulted in decreased lesions and pruritus in ≥ 50% of atopic dogs, similar to what is seen with AIT and the mRNA expression of IL-4 was also decreased in those dogs [107]. However, this treatment is currently not commercially available.

Due to their hair coat and compliance issues, topical treatment of dogs and cats can be difficult for owners and therefore it is less frequently used than in humans [44]. Topical glucocorticoid ointments can be used for localised skin lesions in sparsely haired areas, but prolonged application may result in skin atrophy [98]. Topical hydrocortisone aceponate was effective for canine AD [108, 109] and feline atopy-like dermatitis [110]. Topical calcineurin inhibitors such as tacrolimus have been used successfully in localized lesions of canine AD [111, 112]. Atopic dogs may benefit from shampoo therapy [113, 114].

Adding dietary supplementations such as essential fatty acids (EFA), probiotics or vitamins can have a positive benefit for atopic animals. EFA are used to treat AD in cats [115] and dogs [116]. Oral EFA can improve the coat quality, strengthen the skin barrier and reduce the transepidermal water loss [117]. Moreover EFA can lower the amount of glucocorticoids and cyclosporine needed to control clinical signs of canine AD [118, 119].

Probiotics are microorganisms that are claimed to provide health benefits when consumed [120, 121]. Their mechanism is not completely elucidated, but may involve binding Toll-like receptors and downregulate the allergic predominately TH2-mediated response [122, 123]. Lactobacillus paracasei K71 given orally to atopic dogs led only to a slight improvement of lesion- and pruritus-score [124]. However, the medication score was reduced significantly indicating a potential benefit as a complementary therapy [124]. Lactobacillus rhamnosus GG given to puppies led to a reduction of immunologic indicators of AD, even though no significant clinical improvement was observed [125].

In human studies a positive impact of cholecalciferol on AD was detected [126128]. Similarly, systemic cholecalciferol reduced pruritus and lesion scores in dogs with AD [129].

How to diagnose and manage AD in the difficult animal and its owner

Both diagnosis and therapy of AD in cats and dogs requires patience, time and effort. An appropriate diagnostic work-up will ensure the correct diagnosis of the disease and concurrent flare factors and usually includes an elimination diet and ectoparasite control as well as cutaneous cytology to rule out secondary infections. It is not uncommon for dogs and cats with environmental allergies to be affected by flea bite hypersensitivity or AFR concurrently [32, 50] and it can be difficult to determine how much of the symptomatology is due to which type of antigen. In those animals, the diagnostic work-up may require an elimination diet with several provocation trials and an extensive flea control in addition to repeated examinations of the animal in order to ensure adequate resolution of secondary infections and concurrent flea bite hypersensitivity. Many owners do not believe that their dog or cats’ problem is food triggered and are reluctant to limit their pet’s food intake to one protein and one carbohydrate source. AFR is not necessarily related to a recent diet change and in one report most of the dogs with AFR received the same food for 2 years or longer before symptoms arose [130]. An elimination diet with restriction to one food source in outdoor or free-roaming cats, dogs living on a farm or in a household with small children is difficult to impossible. Cats should ideally be kept inside for the diet period [131] and some dogs need to wear a muzzle during walks to prevent the rapid gobbling down of potentially allergenic food stuff [51, 132]. Throughout the diagnostic process owner noncompliance can be an issue, because of high costs, continuous drug administration and the organisational and emotional problems associated with feeding a limited elimination diet. Thorough and repeated client education and support contribute to good owner compliance [133]. A diary for the owners to record the daily pruritus, drug side effects or pitfalls during the elimination diet can increase their motivation [131]. Low palatability, refusal of the diet (particularly in cats) or gastrointestinal symptoms such as diarrhoea or constipation can decrease compliance [134]. A gradual change to the “new” food can minimise those problems. In contrast to dogs it is not an option to allow cats to “starve for a few days” while offering the new diet, as a negative energy balance due to anorexia can initiate hepatic lipidosis [135]. Owners may need to be made aware of the “traps” of an elimination diet [131], for example tooth paste and medications for pets are frequently flavoured with animal proteins and thus will interfere with the elimination diet. Chewable drugs or drugs in gelatin capsules need to be avoided [131] as it was shown that dogs allergic to corn and soy showed cutaneous flares after receiving chewable capsules containing pig protein, soy and milbemycin [132]. Similarly many owners do not consider treats “food” and rely on those for dog training. Those treats need to be replaced with one made of the protein used in the diet to optimise outcome. Secondary infections, most often Malassezia spp. in dogs [117, 136] and staphylococci in dogs and cats [137140] may mimic the clinical signs of allergy and require investigation of other possible causes for the infection. After establishing the diagnosis, it is important to explain to the owner that an allergy is a lifelong disease and thus will usually require lifelong management. Multiple adaptations of therapy may be needed depending on the individual animal’s condition and flare factors. Treatment options, their costs, efficacy and safety need to be discussed with the owners in detail. Some may prefer a rapid clinical improvement with a potent systemic drug, whereas others may not want to risk this drug’s side effects. Short-term relief can lead to a higher owner compliance. The emotional relationship between owner and animal should not be underestimated. Often owners suffer with their animal and sleepless nights of the owners are the consequence of a highly pruritic animal.

Unmet needs and research

At this point, the pathogenesis of AD in dogs and cats is not fully elucidated. Multiple genes are implicated [14]. However, further genomic studies and investigations on breed differences may allow a better understanding of the heritability. Research on the role of CD25+ FoxP3+ T cells is ongoing [20]. In human medicine the hygiene hypothesis ascribes the increasing allergy risk to a modern environment and life style with less pathogen exposure [141, 142]. This might apply to animals in the same way as the prevalence of AD seems to be lower in dogs living in rural areas [143]. More studies are needed to evaluate environmental influence on AD in dogs and cats, possibly enabling prophylactic measures in the future. Allergen-specific IgE can be measured, but a correlation of the results with clinical signs is not always present [144]. Multiple serum allergy tests are offered, but cannot be used to diagnose AD. Additionally, inter- and intralaboratory variability of some of those tests is high [145148]. With regard to treatment for AD the first monoclonal antibody for atopic dogs, an anti-IL-31-antibody, is available with promising clinical results, but the consequences of a long-term blockade of IL-31 are unknown at this point [84]. Individual phenotypes of AD in dogs and cats may respond better to specific drugs than others. More studies and pooling of data to obtain numbers to achieve significance are needed to evaluate the efficacy of specific drugs in specific breeds and pheno- as well as genotypes to allow tailored patient-oriented therapy in veterinary medicine. AIT is typically administered via subcutaneous injections in both dogs and cats, there is however a lack of well-powered dose-finding studies in animals. Further and comparative studies are also needed to investigate which alternative application route is most suitable in which clinical situation. Using recombinant allergens such as Dermatophagoides farinae allergen (Der f 2) [149, 150] may result in more reproducible results and a higher success rate compared to standard AIT and ILIT [151]. Modified allergen preparations such as allergoids, allergen peptides as well as alteration with adjuvants may decrease the risk of adverse effects and increase efficacy [152]. First studies evaluated bacterial oligodeoxynucleotides in canine AD [79, 107] with promising results.

Conclusion

AD in pets is diagnosed by history, clinical signs and the ruling out of differential diagnoses. Allergy tests (intradermal tests and serum tests for allergen-specific IgE) cannot be used as a diagnostic tool for AD, but rather in association with clinical history permit the selection of relevant allergens for immunotherapy. Multiple flare factors such as additional flea-bite hypersensitivity and AFR and secondary bacterial or yeast infections can complicate AD in the dog and cat and need to be identified, prevented and/or treated. Intensive and regular communication with the pet owner and a diagnostic work-up and treatment tailored to the individual pet and owner’s needs is essential for a good compliance and optimal outcome.

Abbreviations

AD: 

atopic dermatitis

Ig: 

immunoglobulin

IL: 

interleukin

Th2: 

T helper 2

PO: 

periostin

AFR: 

adverse food reaction

AIT: 

allergen immunotherapy

ILIT: 

intralmyphatic immunotherapy

SLIT: 

sublingual immunotherapy

EFA: 

essential fatty acids

CpG GNPs: 

cytosine-phosphateguanine oligodeoxynucleotides bound to gelatine nanoparticles

Der f 2: 

Dermatophagoides farinae allergen

Declarations

Authors’ contributions

Both authors contributed to writing this paper and reviewing the literature. Both authors read and approved the final manuscript.

Acknowledgements

We want to thank the dermatology team of the clinic for their support and critical discussion: Dr. Christoph Klinger, Dr. Laura Udraite, Dr. Teresa Boehm and Amelie von Voigts-Rhetz. We are grateful to Dr. Sonya Bettenay for the revision of the article.

Competing interests

The authors declare that they have no competing interests.

Availability of data and materials

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

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Not applicable.

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Authors’ Affiliations

(1)
Small Animal Medicine Clinic, Centre for Clinical Veterinary Medicine, Ludwig Maximilian University, Veterinaerstraße 13, 80539 Munich, Germany

References

  1. Mineshige T, Kamiie J, Sugahara G, Shirota K. A study on periostin involvement in the pathophysiology of canine atopic skin. J Vet Med Sci. 2018;80(1):103–11.PubMedView ArticleGoogle Scholar
  2. Marsella R, Girolomoni G. Canine models of atopic dermatitis: a useful tool with untapped potential. J Invest Dermatol. 2009;129(10):2351–7.PubMedView ArticleGoogle Scholar
  3. Halliwell R. Revised nomenclature for veterinary allergy. Vet Immunol Immunopathol. 2006;114(3–4):207–8.PubMedView ArticleGoogle Scholar
  4. Hillier A, Griffin CE. The ACVD task force on canine atopic dermatitis (I): incidence and prevalence. Vet Immunol Immunopathol. 2001;81(3–4):147–51.PubMedView ArticleGoogle Scholar
  5. Marsella R, Olivry T, Carlotti DN. International Task Force on Canine Atopic D. Current evidence of skin barrier dysfunction in human and canine atopic dermatitis. Vet Dermatol. 2011;22(3):239–48.PubMedView ArticleGoogle Scholar
  6. Marsella R, De Benedetto A. Atopic dermatitis in animals and people: an update and comparative review. Vet Sci. 2017;4(3):37.PubMed CentralView ArticlePubMedGoogle Scholar
  7. Merryman-Simpson AE, Wood SH, Fretwell N, Jones PG, McLaren WM, McEwan NA, et al. Gene (mRNA) expression in canine atopic dermatitis: microarray analysis. Vet Dermatol. 2008;19(2):59–66.PubMedView ArticleGoogle Scholar
  8. Wood SH. The genetics of canine atopic dermatitis [Thesis]: Liverpool; 2010.Google Scholar
  9. Plager DA, Torres SM, Koch SN, Kita H. Gene transcription abnormalities in canine atopic dermatitis and related human eosinophilic allergic diseases. Vet Immunol Immunopathol. 2012;149(1–2):136–42.PubMedPubMed CentralView ArticleGoogle Scholar
  10. Schamber P, Schwab-Richards R, Bauersachs S, Mueller RS. Gene expression in the skin of dogs sensitized to the house dust mite Dermatophagoides farinae. G3 (Bethesda). 2014;4(10):1787–95.View ArticleGoogle Scholar
  11. Tengvall K, Kierczak M, Bergvall K, Olsson M, Frankowiack M, Farias FH, et al. Genome-wide analysis in German shepherd dogs reveals association of a locus on CFA 27 with atopic dermatitis. PLoS Genet. 2013;9(5):e1003475.PubMedPubMed CentralView ArticleGoogle Scholar
  12. Ardesjö-Lundgren B, Tengvall K, Bergvall K, Farias FHG, Wang L, Hedhammar A, et al. Comparison of cellular location and expression of Plakophilin-2 in epidermal cells from nonlesional atopic skin and healthy skin in German shepherd dogs. Vet Dermatol. 2017;28(4):377-e88.PubMedPubMed CentralView ArticleGoogle Scholar
  13. Shaw SC, Wood JL, Freeman J, Littlewood JD, Hannant D. Estimation of heritability of atopic dermatitis in Labrador and Golden Retrievers. Am J Vet Res. 2004;65(7):1014–20.PubMedView ArticleGoogle Scholar
  14. Nuttall T. The genomics revolution: will canine atopic dermatitis be predictable and preventable? Vet Dermatol. 2013;24(1):10-8 e3-4.PubMedView ArticleGoogle Scholar
  15. Verlinden A, Hesta M, Millet S, Janssens GP. Food allergy in dogs and cats: a review. Crit Rev Food Sci Nutr. 2006;46(3):259–73.PubMedView ArticleGoogle Scholar
  16. Picco F, Zini E, Nett C, Naegeli C, Bigler B, Rufenacht S, et al. A prospective study on canine atopic dermatitis and food-induced allergic dermatitis in Switzerland. Vet Dermatol. 2008;19(3):150–5.PubMedView ArticleGoogle Scholar
  17. Jaeger K, Linek M, Power HT, Bettenay SV, Zabel S, Rosychuk RA, et al. Breed and site predispositions of dogs with atopic dermatitis: a comparison of five locations in three continents. Vet Dermatol. 2010;21(1):118–22.PubMedView ArticleGoogle Scholar
  18. Olivry T, Dean GA, Tompkins MB, Dow JL, Moore PF. Toward a canine model of atopic dermatitis: amplification of cytokine-gene transcripts in the skin of atopic dogs. Exp Dermatol. 1999;8(3):204–11.PubMedView ArticleGoogle Scholar
  19. Schlotter YM, Rutten VP, Riemers FM, Knol EF, Willemse T. Lesional skin in atopic dogs shows a mixed Type-1 and Type-2 immune responsiveness. Vet Immunol Immunopathol. 2011;143(1–2):20–6.PubMedView ArticleGoogle Scholar
  20. Jassies-van der Lee A, Rutten VP, Bruijn J, Willemse AT, Broere F. CD4+ and CD8+ skin-associated T lymphocytes in canine atopic dermatitis produce interleukin-13, interleukin-22 and interferon-gamma and contain a CD25+ FoxP3+ subset. Vet Dermatol. 2014;25(5):456-e72.PubMedView ArticleGoogle Scholar
  21. Santoro D, Marsella R, Pucheu-Haston CM, Eisenschenk MN, Nuttall T, Bizikova P. Review: pathogenesis of canine atopic dermatitis: skin barrier and host-micro-organism interaction. Vet Dermatol. 2015;26(2):84-e25.PubMedView ArticleGoogle Scholar
  22. Marsella R, Papastavros V, Ahrens K, Santoro D. Decreased expression of caspase-14 in an experimental model of canine atopic dermatitis. Vet J. 2016;209:201–3.PubMedView ArticleGoogle Scholar
  23. List K, Szabo R, Wertz PW, Segre J, Haudenschild CC, Kim SY, et al. Loss of proteolytically processed filaggrin caused by epidermal deletion of Matriptase/MT-SP1. J Cell Biol. 2003;163(4):901–10.PubMedPubMed CentralView ArticleGoogle Scholar
  24. Fanton N, Santoro D, Cornegliani L, Marsella R. Increased filaggrin-metabolizing enzyme activity in atopic skin: a pilot study using a canine model of atopic dermatitis. Vet Dermatol. 2017;28(5):479-e111.PubMedView ArticleGoogle Scholar
  25. Reiter LV, Torres SM, Wertz PW. Characterization and quantification of ceramides in the nonlesional skin of canine patients with atopic dermatitis compared with controls. Vet Dermatol. 2009;20(4):260–6.PubMedView ArticleGoogle Scholar
  26. Chermprapai S, Broere F, Gooris G, Schlotter YM, Rutten V, Bouwstra JA. Altered lipid properties of the stratum corneum in Canine Atopic Dermatitis. Biochim Biophys Acta. 2018;1860(2):526–33.PubMedView ArticleGoogle Scholar
  27. Yoon JS, Nishifuji K, Sasaki A, Ide K, Ishikawa J, Yoshihara T, et al. Alteration of stratum corneum ceramide profiles in spontaneous canine model of atopic dermatitis. Exp Dermatol. 2011;20(9):732–6.PubMedView ArticleGoogle Scholar
  28. Shimada K, Yoon JS, Yoshihara T, Iwasaki T, Nishifuji K. Increased transepidermal water loss and decreased ceramide content in lesional and non-lesional skin of dogs with atopic dermatitis. Vet Dermatol. 2009;20(5–6):541–6.PubMedView ArticleGoogle Scholar
  29. Olivry T, Dunston SM. Expression patterns of superficial epidermal adhesion molecules in an experimental dog model of acute atopic dermatitis skin lesions. Vet Dermatol. 2015;26(1):53-6, e-17-8.PubMedView ArticleGoogle Scholar
  30. Reinero CR, DeClue AE, Rabinowitz P. Asthma in humans and cats: is there a common sensitivity to aeroallegens in shared environments? Environ Res. 2009;109(5):634–40.PubMedView ArticleGoogle Scholar
  31. Favrot C, Rostaher A, Fischer N. Clinical symptomps, diagnosis and therapy of feline allergic dermatitis. Schweiz Arch Tierheilkd. 2014;156(7):327–35.PubMedView ArticleGoogle Scholar
  32. Hobi S, Linek M, Marignac G, Olivry T, Beco L, Nett C, et al. Clinical characteristics and causes of pruritus in cats: a multicentre study on feline hypersensitivity-associated dermatoses. Vet Dermatol. 2011;22(5):406–13.PubMedView ArticleGoogle Scholar
  33. Ravens PA, Xu BJ, Vogelnest LJ. Feline atopic dermatitis: a retrospective study of 45 cases (2001–2012). Vet Dermatol. 2014;25(2):95-102, e27-8.PubMedView ArticleGoogle Scholar
  34. Moriello KA. Feline atopy in three littermates. Vet Dermatol. 2001;12(3):177–81.PubMedView ArticleGoogle Scholar
  35. Roosje PJ, Whitaker-Menezes D, Goldschmidt MH, Moore PF, Willemse T, Murphy GF. Feline atopic dermatitis. A model for Langerhans cell participation in disease pathogenesis. Am J Pathol. 1997;151(4):927–32.PubMedPubMed CentralGoogle Scholar
  36. Roosje PJ, Dean GA, Willemse T, Rutten VP, Thepen T. Interleukin 4-producing CD4+ T cells in the skin of cats with allergic dermatitis. Vet Pathol. 2002;39(2):228–33.PubMedView ArticleGoogle Scholar
  37. Diesel A. Cutaneous hypersensitivity dermatoses in the feline patient: a review of allergic skin disease in cats. Vet Sci. 2017;4(2):25.PubMed CentralView ArticlePubMedGoogle Scholar
  38. Rodrigues Hoffmann A, Patterson AP, Diesel A, Lawhon SD, Ly HJ, Elkins Stephenson C, et al. The skin microbiome in healthy and allergic dogs. PLoS ONE. 2014;9(1):e83197.PubMedPubMed CentralView ArticleGoogle Scholar
  39. Meason-Smith C, Diesel A, Patterson AP, Older CE, Johnson TJ, Mansell JM, et al. Characterization of the cutaneous mycobiota in healthy and allergic cats using next generation sequencing. Vet Dermatol. 2017;28(1):71-e17.PubMedView ArticleGoogle Scholar
  40. Szczepanik MP, Wilkolek PM, Adamek LR, Zajac M, Golynski M, Sitkowski W, et al. Evaluation of the correlation between Scoring Feline Allergic Dermatitis and Feline Extent and Severity Index and skin hydration in atopic cats. Vet Dermatol. 2018;29(1):34-e16.PubMedView ArticleGoogle Scholar
  41. Griffin CE, DeBoer DJ. The ACVD task force on canine atopic dermatitis (XIV): clinical manifestations of canine atopic dermatitis. Vet Immunol Immunopathol. 2001;81(3–4):255–69.PubMedView ArticleGoogle Scholar
  42. Favrot C. Clinical signs and diganosis of canine atopic dermatitis. Eur J Companion Anim Pract. 2009;19(3):219–22.Google Scholar
  43. Wilhem S, Kovalik M, Favrot C. Breed-associated phenotypes in canine atopic dermatitis. Vet Dermatol. 2011;22(2):143–9.PubMedView ArticleGoogle Scholar
  44. Pucheu-Haston CM. Atopic dermatitis in the domestic dog. Clin Dermatol. 2016;34(2):299–303.PubMedView ArticleGoogle Scholar
  45. Jensen-Jarolim E, Einhorn L, Herrmann I, Thalhammer JG, Panakova L. Pollen allergies in humans and their dogs, cats and horses: differences and similarities. Clin Transl Allergy. 2015;5:15.PubMedPubMed CentralView ArticleGoogle Scholar
  46. Diesel A, DeBoer DJ. Serum allergen-specific immunoglobulin E in atopic and healthy cats: comparison of a rapid screening immunoassay and complete-panel analysis. Vet Dermatol. 2011;22(1):39–45.PubMedView ArticleGoogle Scholar
  47. Favrot C, Steffan J, Seewald W, Hobi S, Linek M, Marignac G, et al. Establishment of diagnostic criteria for feline nonflea-induced hypersensitivity dermatitis. Vet Dermatol. 2012;23(1):45-50, e11.PubMedView ArticleGoogle Scholar
  48. Bryan J, Frank LA. Food allergy in the cat: a diagnosis by elimination. J Feline Med Surg. 2010;12(11):861–6.PubMedView ArticleGoogle Scholar
  49. DeBoer DJ, Hillier A. The ACVD task force on canine atopic dermatitis (XV): fundamental concepts in clinical diagnosis. Vet Immunol Immunopathol. 2001;81(3–4):271–6.PubMedView ArticleGoogle Scholar
  50. Olivry T, Deboer DJ, Prelaud P, Bensignor E. International task force on canine atopic D. Food for thought: pondering the relationship between canine atopic dermatitis and cutaneous adverse food reactions. Vet Dermatol. 2007;18(6):390–1.PubMedView ArticleGoogle Scholar
  51. Hensel P, Santoro D, Favrot C, Hill P, Griffin C. Canine atopic dermatitis: detailed guidelines for diagnosis and allergen identification. BMC Vet Res. 2015;11:196.PubMedPubMed CentralView ArticleGoogle Scholar
  52. Kennis RA. Food allergies: update of pathogenesis, diagnoses, and management. Vet Clin North Am Small Anim Pract. 2006;36(1):175-84, vii-viii.PubMedView ArticleGoogle Scholar
  53. Bethlehem S, Bexley J, Mueller RS. Patch testing and allergen-specific serum IgE and IgG antibodies in the diagnosis of canine adverse food reactions. Vet Immunol Immunopathol. 2012;145(3–4):582–9.PubMedView ArticleGoogle Scholar
  54. Olivry T, Mueller RS, Prelaud P. Critically appraised topic on adverse food reactions of companion animals (1): duration of elimination diets. BMC Vet Res. 2015;11:225.PubMedPubMed CentralView ArticleGoogle Scholar
  55. Martin A, Sierra MP, Gonzalez JL, Arevalo MA. Identification of allergens responsible for canine cutaneous adverse food reactions to lamb, beef and cow’s milk. Vet Dermatol. 2004;15(6):349–56.PubMedView ArticleGoogle Scholar
  56. Mueller RS, Olivry T, Prelaud P. Critically appraised topic on adverse food reactions of companion animals (2): common food allergen sources in dogs and cats. BMC Vet Res. 2016;12:9.PubMedPubMed CentralView ArticleGoogle Scholar
  57. Raditic DM, Remillard RL, Tater KC. ELISA testing for common food antigens in four dry dog foods used in dietary elimination trials. J Anim Physiol Anim Nutr (Berl). 2011;95(1):90–7.View ArticleGoogle Scholar
  58. Ricci R, Granato A, Vascellari M, Boscarato M, Palagiano C, Andrighetto I, et al. Identification of undeclared sources of animal origin in canine dry foods used in dietary elimination trials. J Anim Physiol Anim Nutr (Berl). 2013;97(Suppl 1):32–8.View ArticleGoogle Scholar
  59. Willis-Mahn C, Remillard R, Tater K. ELISA testing for soy antigens in dry dog foods used in dietary elimination trials. J Am Anim Hosp Assoc. 2014;50(6):383–9.PubMedView ArticleGoogle Scholar
  60. Horvath-Ungerboeck C, Widmann K, Handl S. Detection of DNA from undeclared animal species in commercial elimination diets for dogs using PCR. Vet Dermatol. 2017;28(4):373-e86.PubMedView ArticleGoogle Scholar
  61. Jackson HA, Jackson MW, Coblentz L, Hammerberg B. Evaluation of the clinical and allergen specific serum immunoglobulin E responses to oral challenge with cornstarch, corn, soy and a soy hydrolysate diet in dogs with spontaneous food allergy. Vet Dermatol. 2003;14(4):181–7.PubMedView ArticleGoogle Scholar
  62. Mueller RS, Olivry T. Critically appraised topic on adverse food reactions of companion animals (4): can we diagnose adverse food reactions in dogs and cats with in vivo or in vitro tests? BMC Vet Res. 2017;13(1):275.PubMedPubMed CentralView ArticleGoogle Scholar
  63. Jeffers J, Shanley K, Meyer E. Diagnostic testing of dogs for food hypersensitivity. J Am Vet Med Assoc. 1991;198:245–50.PubMedGoogle Scholar
  64. Fujimura M, Masuda K, Hayashiya M, Okayama T. Flow cytometric analysis of lymphocyte proliferative responses to food allergens in dogs with food allergy. J Vet Med Sci. 2011;73(10):1309–17.PubMedView ArticleGoogle Scholar
  65. Okayama T, Matsuno Y, Yasuda N, Tsukui T, Suzuta Y, Koyanagi M, et al. Establishment of a quantitative ELISA for the measurement of allergen-specific IgE in dogs using anti-IgE antibody cross-reactive to mouse and dog IgE. Vet Immunol Immunopathol. 2011;139(2–4):99–106.PubMedView ArticleGoogle Scholar
  66. Suto A, Suto Y, Onohara N, Tomizawa Y, Yamamoto-Sugawara Y, Okayama T, et al. Food allergens inducing a lymphocyte-mediated immunological reaction in canine atopic-like dermatitis. J Vet Med Sci. 2015;77(2):251–4.PubMedView ArticleGoogle Scholar
  67. Mueller RS, Fieseler KV, Rosychuk RA, Greenwalt T. Intradermal testing with the storage mite Tyrophagus putrescentiae in normal dogs and dogs with atopic dermatitis in Colorado. Vet Dermatol. 2005;16(1):27–31.PubMedView ArticleGoogle Scholar
  68. Lian TM, Halliwell RE. Allergen-specific IgE and IgGd antibodies in atopic and normal dogs. Vet Immunol Immunopathol. 1998;66(3–4):203–23.PubMedView ArticleGoogle Scholar
  69. Hillier A, DeBoer DJ. The ACVD task force on canine atopic dermatitis (XVII): intradermal testing. Vet Immunol Immunopathol. 2001;81(3–4):289–304.PubMedView ArticleGoogle Scholar
  70. Saridomichelakis MN, Olivry T. An update on the treatment of canine atopic dermatitis. Vet J. 2016;207:29–37.PubMedView ArticleGoogle Scholar
  71. Olivry T, Mueller RS. International task force on canine atopic D. Evidence-based veterinary dermatology: a systematic review of the pharmacotherapy of canine atopic dermatitis. Vet Dermatol. 2003;14(3):121–46.PubMedView ArticleGoogle Scholar
  72. Loewenstein C, Mueller RS. A review of allergen-specific immunotherapy in human and veterinary medicine. Vet Dermatol. 2009;20(2):84–98.PubMedView ArticleGoogle Scholar
  73. Fischer N, Rostaher A, Favrot C. Intralymphatic immunotherapy: an effective and safe alternative route for canine atopic dermatitis. Schweiz Arch Tierheilkd. 2016;158(9):646–52.PubMedView ArticleGoogle Scholar
  74. Willemse A, Van den Brom WE, Rijnberk A. Effect of hyposensitization on atopic dermatitis in dogs. J Am Vet Med Assoc. 1984;184(10):1277–80.PubMedGoogle Scholar
  75. Schnabl B, Bettenay SV, Dow K, Mueller RS. Results of allergen-specific immunotherapy in 117 dogs with atopic dermatitis. Vet Rec. 2006;158(3):81–5.PubMedView ArticleGoogle Scholar
  76. Hobi S, Mueller RS. Efficacy and safety of rush immunotherapy with alum-precipitated allergens in canine atopic dermatitis. Tierarztl Prax Ausg K Kleintiere Heimtiere. 2014;42(3):167–73.PubMedGoogle Scholar
  77. Griffin CE, Hillier A. The ACVD task force on canine atopic dermatitis (XXIV): allergen-specific immunotherapy. Vet Immunol Immunopathol. 2001;81(3–4):363–83.PubMedView ArticleGoogle Scholar
  78. Mueller RS, Bettenay SV. Evaluation of the safety of an abbreviated course of injections of allergen extracts (rush immunotherapy) for the treatment of dogs with atopic dermatitis. Am J Vet Res. 2001;62(3):307–10.PubMedView ArticleGoogle Scholar
  79. Mueller RS, Veir J, Fieseler KV, Dow SW. Use of immunostimulatory liposome-nucleic acid complexes in allergen-specific immunotherapy of dogs with refractory atopic dermatitis—a pilot study. Vet Dermatol. 2005;16(1):61–8.PubMedView ArticleGoogle Scholar
  80. Senti G, Johansen P, Kundig TM. Intralymphatic immunotherapy. Curr Opin Allergy Clin Immunol. 2009;9(6):537–43.PubMedView ArticleGoogle Scholar
  81. Timm K, Mueller RS, Nett-Mettler CS. Long-term effects of intralymphatic immunotherapy (ILIT) on canine atopic dermatitis. Vet Dermatol. 2018;29(2):123-e49.PubMedView ArticleGoogle Scholar
  82. DeBoer DJ, Verbrugge M, Morris M. Clinical and immunological responses of dust mite sensitive, atopic dogs to treatment with sublingual immunotherapy (SLIT). Vet Dermatol. 2016;27(2):82-7e23.PubMedView ArticleGoogle Scholar
  83. Michels GM, Ramsey DS, Walsh KF, Martinon OM, Mahabir SP, Hoevers JD, et al. A blinded, randomized, placebo-controlled, dose determination trial of lokivetmab (ZTS-00103289), a caninized, anti-canine IL-31 monoclonal antibody in client owned dogs with atopic dermatitis. Vet Dermatol. 2016;27(6):478-e129.PubMedGoogle Scholar
  84. Michels GM, Walsh KF, Kryda KA, Mahabir SP, Walters RR, Hoevers JD, et al. A blinded, randomized, placebo-controlled trial of the safety of lokivetmab (ZTS-00103289), a caninized anti-canine IL-31 monoclonal antibody in client-owned dogs with atopic dermatitis. Vet Dermatol. 2016;27(6):505-e136.PubMedGoogle Scholar
  85. Olivry T, Foster AP, Mueller RS, McEwan NA, Chesney C, Williams HC. Interventions for atopic dermatitis in dogs: a systematic review of randomized controlled trials. Vet Dermatol. 2010;21(1):4–22.PubMedView ArticleGoogle Scholar
  86. Steffan J, Parks C, Seewald W. North American Veterinary Dermatology Cyclosporine Study G. Clinical trial evaluating the efficacy and safety of cyclosporine in dogs with atopic dermatitis. J Am Vet Med Assoc. 2005;226(11):1855–63.PubMedView ArticleGoogle Scholar
  87. Nuttall T, Reece D, Roberts E. Life-long diseases need life-long treatment: long-term safety of ciclosporin in canine atopic dermatitis. Vet Rec. 2014;174(Suppl 2):3–12.PubMedPubMed CentralView ArticleGoogle Scholar
  88. Roberts ES, Speranza C, Friberg C, Griffin C, Steffan J, Roycroft L, et al. Confirmatory field study for the evaluation of ciclosporin at a target dose of 7.0 mg/kg (3.2 mg/lb) in the control of feline hypersensitivity dermatitis. J Feline Med Surg. 2016;18(11):889–97.PubMedView ArticleGoogle Scholar
  89. Kovalik M, Thoday KL, van den Broek AH. The use of ciclosporin A in veterinary dermatology. Vet J. 2012;193(2):317–25.PubMedView ArticleGoogle Scholar
  90. Last RD, Suzuki Y, Manning T, Lindsay D, Galipeau L, Whitbread TJ. A case of fatal systemic toxoplasmosis in a cat being treated with cyclosporin A for feline atopy. Vet Dermatol. 2004;15(3):194–8.PubMedView ArticleGoogle Scholar
  91. Lappin MR, Roycroft LM. Effect of ciclosporin and methylprednisolone acetate on cats previously infected with feline herpesvirus 1. J Feline Med Surg. 2015;17(4):353–8.PubMedView ArticleGoogle Scholar
  92. Gonzales AJ, Bowman JW, Fici GJ, Zhang M, Mann DW, Mitton-Fry M. Oclacitinib (APOQUEL((R))) is a novel Janus kinase inhibitor with activity against cytokines involved in allergy. J Vet Pharmacol Ther. 2014;37(4):317–24.PubMedPubMed CentralView ArticleGoogle Scholar
  93. Cosgrove SB, Wren JA, Cleaver DM, Walsh KF, Follis SI, King VI, et al. A blinded, randomized, placebo-controlled trial of the efficacy and safety of the Janus kinase inhibitor oclacitinib (Apoquel(R)) in client-owned dogs with atopic dermatitis. Vet Dermatol. 2013;24(6):587-97, e141-2.PubMedView ArticleGoogle Scholar
  94. Cosgrove SB, Cleaver DM, King VL, Gilmer AR, Daniels AE, Wren JA, et al. Long-term compassionate use of oclacitinib in dogs with atopic and allergic skin disease: safety, efficacy and quality of life. Vet Dermatol. 2015;26(3):171-9, e35.PubMedView ArticleGoogle Scholar
  95. Little PR, King VL, Davis KR, Cosgrove SB, Stegemann MR. A blinded, randomized clinical trial comparing the efficacy and safety of oclacitinib and ciclosporin for the control of atopic dermatitis in client-owned dogs. Vet Dermatol. 2015;26(1):23-30, e7-8.PubMedView ArticleGoogle Scholar
  96. Ortalda C, Noli C, Colombo S, Borio S. Oclacitinib in feline nonflea-, nonfood-induced hypersensitivity dermatitis: results of a small prospective pilot study of client-owned cats. Vet Dermatol. 2015;26(4):235-e52.PubMedView ArticleGoogle Scholar
  97. DeBoer DJ, Griffin CE. The ACVD task force on canine atopic dermatitis (XXI): antihistamine pharmacotherapy. Vet Immunol Immunopathol. 2001;81(3–4):323–9.PubMedView ArticleGoogle Scholar
  98. Olivry T, DeBoer DJ, Favrot C, Jackson HA, Mueller RS, Nuttall T, et al. Treatment of canine atopic dermatitis: 2015 updated guidelines from the International Committee on Allergic Diseases of Animals (ICADA). BMC Vet Res. 2015;11:210.PubMedPubMed CentralView ArticleGoogle Scholar
  99. Bizikova P, Papich MG, Olivry T. Hydroxyzine and cetirizine pharmacokinetics and pharmacodynamics after oral and intravenous administration of hydroxyzine to healthy dogs. Vet Dermatol. 2008;19(6):348–57.PubMedView ArticleGoogle Scholar
  100. Eichenseer M. Klinische Wirkung der Antihistaminika Chlorpheniramin/Hydroxyzin (Histacalmine®) und Dimetinden (Fenistil®) bei atopischen Hunden. Munich: Ludwig-Maximilians-University; 2013.Google Scholar
  101. Rossbach K, Wendorff S, Sander K, Stark H, Gutzmer R, Werfel T, et al. Histamine H4 receptor antagonism reduces hapten-induced scratching behaviour but not inflammation. Exp Dermatol. 2009;18(1):57–63.PubMedView ArticleGoogle Scholar
  102. Thurmond RL, Desai PJ, Dunford PJ, Fung-Leung WP, Hofstra CL, Jiang W, et al. A potent and selective histamine H4 receptor antagonist with anti-inflammatory properties. J Pharmacol Exp Ther. 2004;309(1):404–13.PubMedView ArticleGoogle Scholar
  103. Baumer W, Stahl J, Sander K, Petersen LJ, Paps J, Stark H, et al. Lack of preventing effect of systemically and topically administered histamine H(1) or H(4) receptor antagonists in a dog model of acute atopic dermatitis. Exp Dermatol. 2011;20(7):577–81.PubMedView ArticleGoogle Scholar
  104. Eichenseer M, Johansen C, Mueller RS. Efficacy of dimetinden and hydroxyzine/chlorpheniramine in atopic dogs: a randomised, controlled, double-blinded trial. Vet Rec. 2013;173(17):423.PubMedPubMed CentralView ArticleGoogle Scholar
  105. Dell DL, Griffin CE, Thompson LA, Griffies JD. Owner assessment of therapeutic interventions for canine atopic dermatitis: a long-term retrospective analysis. Vet Dermatol. 2012;23(3):228-e47.PubMedView ArticleGoogle Scholar
  106. Wildermuth K, Zabel S, Rosychuk RA. The efficacy of cetirizine hydrochloride on the pruritus of cats with atopic dermatitis: a randomized, double-blind, placebo-controlled, crossover study. Vet Dermatol. 2013;24(6):576-81, e137-8.PubMedView ArticleGoogle Scholar
  107. Wagner I, Geh KJ, Hubert M, Winter G, Weber K, Classen J, et al. Preliminary evaluation of cytosine-phosphate-guanine oligodeoxynucleotides bound to gelatine nanoparticles as immunotherapy for canine atopic dermatitis. Vet Rec. 2017;181(5):118.PubMedView ArticleGoogle Scholar
  108. Nuttall T, Mueller R, Bensignor E, Verde M, Noli C, Schmidt V, et al. Efficacy of a 0.0584% hydrocortisone aceponate spray in the management of canine atopic dermatitis: a randomised, double blind, placebo-controlled trial. Vet Dermatol. 2009;20(3):191–8.PubMedView ArticleGoogle Scholar
  109. Nuttall TJ, McEwan NA, Bensignor E, Cornegliani L, Lowenstein C, Reme CA. Comparable efficacy of a topical 0.0584% hydrocortisone aceponate spray and oral ciclosporin in treating canine atopic dermatitis. Vet Dermatol. 2012;23(1):4-10, e1-2.PubMedView ArticleGoogle Scholar
  110. Schmidt V, Buckley LM, McEwan NA, Reme CA, Nuttall TJ. Efficacy of a 0.0584% hydrocortisone aceponate spray in presumed feline allergic dermatitis: an open label pilot study. Vet Dermatol. 2012;23(1):11-6, e3-4.PubMedView ArticleGoogle Scholar
  111. Marsella R, Nicklin CF, Saglio S, Lopez J. Investigation on the clinical efficacy and safety of 0.1% tacrolimus ointment (Protopic) in canine atopic dermatitis: a randomized, double-blinded, placebo-controlled, cross-over study. Vet Dermatol. 2004;15(5):294–303.PubMedView ArticleGoogle Scholar
  112. Bensignor E, Olivry T. Treatment of localized lesions of canine atopic dermatitis with tacrolimus ointment: a blinded randomized controlled trial. Vet Dermatol. 2005;16(1):52–60.PubMedView ArticleGoogle Scholar
  113. Loflath A, von Voigts-Rhetz A, Jaeger K, Schmid M, Kuechenhoff H, Mueller RS. The efficacy of a commercial shampoo and whirlpooling in the treatment of canine pruritus—a double-blinded, randomized, placebo-controlled study. Vet Dermatol. 2007;18(6):427–31.PubMedView ArticleGoogle Scholar
  114. Schilling J, Mueller RS. Double-blinded, placebo-controlled study to evaluate an antipruritic shampoo for dogs with allergic pruritus. Vet Rec. 2012;171(4):97.PubMedView ArticleGoogle Scholar
  115. Harvey RG. Effect of varying proportions of evening primrose oil and fish oil on cats with crusting dermatosis (‘miliary dermatitis’). Vet Rec. 1993;133(9):208–11.PubMedView ArticleGoogle Scholar
  116. Bond R, Lloyd DH. A double-blind comparison of olive oil and a combination of evening primrose oil and fish oil in the management of canine atopy. Vet Rec. 1992;131(24):558–60.PubMedGoogle Scholar
  117. Olivry T, DeBoer DJ, Favrot C, Jackson HA, Mueller RS, Nuttall T, et al. Treatment of canine atopic dermatitis: 2010 clinical practice guidelines from the International Task Force on Canine Atopic Dermatitis. Vet Dermatol. 2010;21(3):233–48.PubMedView ArticleGoogle Scholar
  118. Saevik BK, Bergvall K, Holm BR, Saijonmaa-Koulumies LE, Hedhammar A, Larsen S, et al. A randomized, controlled study to evaluate the steroid sparing effect of essential fatty acid supplementation in the treatment of canine atopic dermatitis. Vet Dermatol. 2004;15(3):137–45.PubMedView ArticleGoogle Scholar
  119. Muller MR, Linek M, Lowenstein C, Rothig A, Doucette K, Thorstensen K, et al. Evaluation of cyclosporine-sparing effects of polyunsaturated fatty acids in the treatment of canine atopic dermatitis. Vet J. 2016;210:77–81.PubMedView ArticleGoogle Scholar
  120. Ohashi Y, Ushida K. Health-beneficial effects of probiotics: its mode of action. Anim Sci J. 2009;80(4):361–71.PubMedView ArticleGoogle Scholar
  121. Elmadfa I, Klein P, Meyer AL. Immune-stimulating effects of lactic acid bacteria in vivo and in vitro. Proc Nutr Soc. 2010;69(3):416–20.PubMedView ArticleGoogle Scholar
  122. Marsella R, Santoro D, Ahrens K, Thomas AL. Investigation of the effect of probiotic exposure on filaggrin expression in an experimental model of canine atopic dermatitis. Vet Dermatol. 2013;24(2):260-e57.PubMedGoogle Scholar
  123. de Roock S, van Elk M, van Dijk ME, Timmerman HM, Rijkers GT, Prakken BJ, et al. Lactic acid bacteria differ in their ability to induce functional regulatory T cells in humans. Clin Exp Allergy. 2010;40(1):103–10.PubMedGoogle Scholar
  124. Ohshima-Terada Y, Higuchi Y, Kumagai T, Hagihara A, Nagata M. Complementary effect of oral administration of Lactobacillus paracasei K71 on canine atopic dermatitis. Vet Dermatol. 2015;26(5):350-3, e74-5.PubMedView ArticleGoogle Scholar
  125. Marsella R. Evaluation of Lactobacillus rhamnosus strain GG for the prevention of atopic dermatitis in dogs. Am J Vet Res. 2009;70(6):735–40.PubMedView ArticleGoogle Scholar
  126. Camargo CA Jr, Manson JE. Vitamin D supplementation and risk of infectious disease: no easy answers. Am J Clin Nutr. 2014;99(1):3–4.PubMedPubMed CentralView ArticleGoogle Scholar
  127. Di Filippo P, Scaparrotta A, Rapino D, Cingolani A, Attanasi M, Petrosino MI, et al. Vitamin D supplementation modulates the immune system and improves atopic dermatitis in children. Int Arch Allergy Immunol. 2015;166(2):91–6.PubMedView ArticleGoogle Scholar
  128. Udompataikul M, Huajai S, Chalermchai T, Taweechotipatr M, Kamanamool N. The effects of oral vitamin d supplement on atopic dermatitis: a clinical trial with staphylococcus aureus colonization determination. J Med Assoc Thai. 2015;98(Suppl 9):S23–30.PubMedGoogle Scholar
  129. Klinger CJ, Hobi S, Johansen C, Koch HJ, Weber K, Mueller RS. Vitamin D shows in vivo efficacy in a placebo-controlled, double-blinded, randomised clinical trial on canine atopic dermatitis. Vet Rec. 2018;182(14):406.PubMedView ArticleGoogle Scholar
  130. Day MJ. The canine model of dietary hypersensitivity. Proc Nutr Soc. 2005;64(4):458–64.PubMedView ArticleGoogle Scholar
  131. Gaschen FP, Merchant SR. Adverse food reactions in dogs and cats. Vet Clin North Am Small Anim Pract. 2011;41(2):361–79.PubMedView ArticleGoogle Scholar
  132. Jackson HA, Hammerberg B. The clinical and immunological reaction to a flavoured monthly oral heartworm prophylactic in 12 dogs with spontaneous food allergy. Vet Dermatol. 2002;13(4):218.Google Scholar
  133. Chesney CJ. Food sensitivity in the dog: a quantitative study. J Small Anim Pract. 2002;43(5):203–7.PubMedView ArticleGoogle Scholar
  134. Mueller R, Tsohalis J. Evaluation of serum allergen-specific IgE for the diagnosis of food adverse reactions in the dog. Vet Dermatol. 1998;9:167–71.View ArticleGoogle Scholar
  135. Valtolina C, Favier RP. Feline hepatic lipidosis. Vet Clin North Am Small Anim Pract. 2017;47(3):683–702.PubMedView ArticleGoogle Scholar
  136. DeBoer DJ, Marsella R. The ACVD task force on canine atopic dermatitis (XII): the relationship of cutaneous infections to the pathogenesis and clinical course of canine atopic dermatitis. Vet Immunol Immunopathol. 2001;81(3–4):239–49.PubMedView ArticleGoogle Scholar
  137. Simou C, Thoday KL, Forsythe PJ, Hill PB. Adherence of Staphylococcus intermedius to corneocytes of healthy and atopic dogs: effect of pyoderma, pruritus score, treatment and gender. Vet Dermatol. 2005;16(6):385–91.PubMedView ArticleGoogle Scholar
  138. Wildermuth BE, Griffin CE, Rosenkrantz WS. Feline pyoderma therapy. Clin Tech Small Anim Pract. 2006;21(3):150–6.PubMedView ArticleGoogle Scholar
  139. Fazakerley J, Nuttall T, Sales D, Schmidt V, Carter SD, Hart CA, et al. Staphylococcal colonization of mucosal and lesional skin sites in atopic and healthy dogs. Vet Dermatol. 2009;20(3):179–84.PubMedView ArticleGoogle Scholar
  140. Yu HW, Vogelnest LJ. Feline superficial pyoderma: a retrospective study of 52 cases (2001–2011). Vet Dermatol. 2012;23(5):448-e86.PubMedView ArticleGoogle Scholar
  141. Platts-Mills TA. The allergy epidemics: 1870–2010. J Allergy Clin Immunol. 2015;136(1):3–13.PubMedPubMed CentralView ArticleGoogle Scholar
  142. Pali-Schöll I, De Lucia M, Jackson H, Janda J, Mueller RS, Jensen-Jarolim E. Comparing immediate-type food allergy in humans and companion animals-revealing unmet needs. Allergy. 2017;72(11):1643–56.PubMedView ArticleGoogle Scholar
  143. Meury S, Molitor V, Doherr MG, Roosje P, Leeb T, Hobi S, et al. Role of the environment in the development of canine atopic dermatitis in Labrador and golden retrievers. Vet Dermatol. 2011;22(4):327–34.PubMedView ArticleGoogle Scholar
  144. Pucheu-Haston CM, Bizikova P, Eisenschenk MN, Santoro D, Nuttall T, Marsella R. Review: the role of antibodies, autoantigens and food allergens in canine atopic dermatitis. Vet Dermatol. 2015;26(2):115-e30.PubMedGoogle Scholar
  145. Patterson AP, Schaeffer DJ, Campbell KL. Reproducibility of a commercial in vitro allergen-specific assay for immunoglobulin E in dogs. Vet Re. 2005;157(3):81–5.View ArticleGoogle Scholar
  146. Lee KW, Blankenship KD, McCurry ZM, Esch RE, DeBoer DJ, Marsella R. Performance characteristics of a monoclonal antibody cocktail-based ELISA for detection of allergen-specific IgE in dogs and comparison with a high affinity IgE receptor-based ELISA. Vet Dermatol. 2009;20(3):157–64.PubMedView ArticleGoogle Scholar
  147. Thom N, Favrot C, Failing K, Mueller RS, Neiger R, Linek M. Intra- and interlaboratory variability of allergen-specific IgE levels in atopic dogs in three different laboratories using the Fc-epsilon receptor testing. Vet Immunol Immunopathol. 2010;133(2–4):183–9.PubMedView ArticleGoogle Scholar
  148. Plant JD, Neradelik MB, Polissar NL, Fadok VA, Scott BA. Agreement between allergen-specific IgE assays and ensuing immunotherapy recommendations from four commercial laboratories in the USA. Vet Dermatol. 2014;25(1):15-e6.PubMedPubMed CentralView ArticleGoogle Scholar
  149. Kawano K, Mizuno T. A pilot study of the effect of pullulan-conjugated Der f 2 allergen-specific immunotherapy on canine atopic dermatitis. Vet Dermatol. 2017;28(6):583-e141.PubMedView ArticleGoogle Scholar
  150. Olivry T, Paps JS, Dunston SM. Proof of concept of the preventive efficacy of high-dose recombinant mono-allergen immunotherapy in atopic dogs sensitized to the Dermatophagoides farinae allergen Der f 2. Vet Dermatol. 2017;28(2):183-e40.PubMedGoogle Scholar
  151. Fischer N, Tarpataki N, Leidi F, Rostaher A, Favrot C. An open study on the efficacy of a recombinant Der f 2 (Dermatophagoides farinae) immunotherapy in atopic dogs in Hungary and Switzerland. Vet Dermatol. 2018;14:1.Google Scholar
  152. DeBoer DJ. The future of immunotherapy for canine atopic dermatitis: a review. Vet Dermatol. 2017;28(1):25-e6.PubMedView ArticleGoogle Scholar
  153. Sinke JD, Thepen T, Bihari IC, Rutten VP, Willemse T. Immunophenotyping of skin-infiltrating T-cell subsets in dogs with atopic dermatitis. Vet Immunol Immunopathol. 1997;57(1–2):13–23.PubMedView ArticleGoogle Scholar
  154. Peng W, Novak N. Pathogenesis of atopic dermatitis. Clin Exp Allergy. 2015;45(3):566–74.PubMedView ArticleGoogle Scholar
  155. Olivry T, Mayhew D, Paps JS, Linder KE, Peredo C, Rajpal D, et al. Early activation of Th2/Th22 inflammatory and pruritogenic pathways in acute canine atopic dermatitis skin lesions. J Invest Dermatol. 2016;136(10):1961–9.PubMedView ArticleGoogle Scholar
  156. Lee C-H. Immune regulation in pathophysiology and targeted therapy for itch in atopic dermatitis. Dermatol Sin. 2016;34:1–5.View ArticleGoogle Scholar
  157. Neis MM, Peters B, Dreuw A, Wenzel J, Bieber T, Mauch C, et al. Enhanced expression levels of IL-31 correlate with IL-4 and IL-13 in atopic and allergic contact dermatitis. J Allergy Clin Immunol. 2006;118(4):930–7.PubMedView ArticleGoogle Scholar
  158. Mineshige T, Kamiie J, Sugahara G, Yasuno K, Aihara N, Kawarai S, et al. Expression of periostin in normal, atopic, and nonatopic chronically inflamed canine skin. Vet Pathol. 2015;52(6):1118–26.PubMedView ArticleGoogle Scholar
  159. Izuhara K, Nunomura S, Nanri Y, Ogawa M, Ono J, Mitamura Y, et al. Periostin in inflammation and allergy. Cell Mol Life Sci. 2017;74(23):4293–303.PubMedView ArticleGoogle Scholar
  160. Sung M, Lee KS, Ha EG, Lee SJ, Kim MA, Lee SW, et al. An association of periostin levels with the severity and chronicity of atopic dermatitis in children. Pediatr Allergy Immunol. 2017;28(6):543–50.PubMedView ArticleGoogle Scholar
  161. Olivry T, Hill PB. The ACVD task force on canine atopic dermatitis (XVIII): histopathology of skin lesions. Vet Immunol Immunopathol. 2001;81(3–4):305–9.PubMedView ArticleGoogle Scholar
  162. Correa da Rosa J, Malajian D, Shemer A, Rozenblit M, Dhingra N, Czarnowicki T, et al. Patients with atopic dermatitis have attenuated and distinct contact hypersensitivity responses to common allergens in skin. J Allergy Clin Immunol. 2015;135(3):712–20.PubMedView ArticleGoogle Scholar
  163. Piloto Valdes L, Gomez Echevarria AH, Valdes Sanchez AF, Ochoa Ochoa C, Chong Lopez A, Mier Naranjo G. Atopic dermatitis. Findings of skin biopsies. Allergol Immunopathol (Madr). 1990;18(6):321–4.Google Scholar
  164. Santoro D, Rodrigues Hoffmann A. Canine and human atopic dermatitis: two faces of the same host-microbe interaction. J Invest Dermatol. 2016;136(6):1087–9.PubMedView ArticleGoogle Scholar
  165. Meason-Smith C, Diesel A, Patterson AP, Older CE, Mansell JM, Suchodolski JS, et al. What is living on your dog’s skin? Characterization of the canine cutaneous mycobiota and fungal dysbiosis in canine allergic dermatitis. FEMS Microbiol Ecol. 2015;91(12):v139.View ArticleGoogle Scholar
  166. Bjerre RD, Bandier J, Skov L, Engstrand L, Johansen JD. The role of the skin microbiome in atopic dermatitis: a systematic review. Br J Dermatol. 2017;177(5):1272–8.PubMedView ArticleGoogle Scholar
  167. McCandless EE, Rugg CA, Fici GJ, Messamore JE, Aleo MM, Gonzales AJ. Allergen-induced production of IL-31 by canine Th2 cells and identification of immune, skin, and neuronal target cells. Vet Immunol Immunopathol. 2014;157(1–2):42–8.PubMedView ArticleGoogle Scholar
  168. Marsella R, Ahrens K, Sanford R. Investigation of the correlation of serum IL-31 with severity of dermatitis in an experimental model of canine atopic dermatitis using beagle dogs. Vet Dermatol. 2018;29(1):69-e28.PubMedView ArticleGoogle Scholar
  169. Wang YH, Angkasekwinai P, Lu N, Voo KS, Arima K, Hanabuchi S, et al. IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells. J Exp Med. 2007;204(8):1837–47.PubMedPubMed CentralView ArticleGoogle Scholar
  170. Fort MM, Cheung J, Yen D, Li J, Zurawski SM, Lo S, et al. IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity. 2001;15(6):985–95.PubMedView ArticleGoogle Scholar
  171. Hvid M, Vestergaard C, Kemp K, Christensen GB, Deleuran B, Deleuran M. IL-25 in atopic dermatitis: a possible link between inflammation and skin barrier dysfunction? J Invest Dermatol. 2011;131(1):150–7.PubMedView ArticleGoogle Scholar
  172. Asahina R, Nishida H, Kamishina H, Maeda S. Expression of IL-33 in chronic lesional skin of canine atopic dermatitis. Vet Dermatol. 2018;29:246-e91.PubMedGoogle Scholar
  173. Bruet V, Lieubeau B, Herve J, Roussel A, Imparato L, Desfontis JC, et al. Increased numbers of peripheral blood CD34+ cells in dogs with canine atopic dermatitis. Vet Dermatol. 2015;26(3):160-4, e33.PubMedView ArticleGoogle Scholar
  174. Hauck V, Hugli P, Meli ML, Rostaher A, Fischer N, Hofmann-Lehmann R, et al. Increased numbers of FoxP3-expressing CD4+ CD25+ regulatory T cells in peripheral blood from dogs with atopic dermatitis and its correlation with disease severity. Vet Dermatol. 2016;27(1):26-e9.PubMedView ArticleGoogle Scholar

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