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Veterinary Focus

Issue number 31.2 Other Scientific

The diagnostic challenges of canine atopic dermatitis

Published 30/09/2021

Written by Ana Rostaher

Also available in Français , Deutsch , Italiano and Español

Clinicians face a challenge when confronted with a possible case of canine atopic dermatitis; Ana Rostaher reviews the diagnostic options and offers some practical tips. 

The reactions are read after 15 minutes; here four of the allergens produced positive erythema and wheal formation (arrowed) comparable to the positive (+) control (score = 4).

Key points

The diagnosis of canine atopic dermatitis is problematic, as there is currently no reliable biomarker that can distinguish the disease from other dermatological disorders.


When faced with a possible atopic dog, the clinician must interpret and consider various aspects, including the patient’s history, characteristic clinical features and exclusion of other differential dermatoses.


Intradermal testing (IDT) is the preferred diagnostic method among dermatologists to identify canine atopic dermatitis and ascertain the causal allergens.


Allergen-specific IgE serology offers several advantages over IDT and is often used as an alternative for canine atopic dermatitis diagnosis, but there are also disadvantages, with false positives being a potential risk.


 

Introduction

Canine atopic dermatitis (CAD) is a common inflammatory skin disease, affecting up to 15% of the global dog population 1. The pathogenesis of the disease is multifactorial, with both skin barrier dysfunction and immunological dysregulation known to have central roles, and both may be influenced by genetic and environmental factors. IgE and non-IgE mediated immunological events are key features in the pathogenesis, with allergens constituting the main triggering factors 2. The most commonly associated laboratory feature in CAD is the allergen-specific serum IgE levels, but (in contrast to humans) elevated total IgE levels do not assist in the diagnosis of CAD. Dogs are reported to have much higher levels of IgE than humans, probably as a result of their more frequent exposure to parasite infestation 3

There are two major risk factors for atopic dermatitis; breed predisposition (e.g., 50% of West Highland White terriers may be affected) and a familial history of CAD 4. However, since both genetic and environmental factors are involved, the phenotypic manifestation of the disease is highly variable – not only between different breeds, but also among individual dogs of the same breed. Given that CAD is both a complex disease with multiple facets and that other skin conditions may mimic the condition, a definitive clinical diagnosis is considered challenging. 

 

Diagnostic considerations

Because there is currently no reliable biomarker that can distinguish CAD from other dermatological disorders, the diagnosis of CAD remains clinical, and hence the clinician must interpret and consider various aspects, including the patient’s history, characteristic clinical features and exclusion of other differential dermatoses. Figure 1 offers a workflow for the diagnosis of CAD. The first step is to rule out other CAD-mimicking diseases, because although pruritus is the most consistent finding, it is by no means exclusive for CAD, and other differentials should be considered. Ectoparasite infestations or bacterial or yeast infections, secondary to a non-pruritic disorder (e.g., endocrinopathies, sebaceous adenitis), or less frequently neoplastic disease (e.g., cutaneous lymphoma, though more commonly seen in older patients), should be ruled out during the initial workup phase on the basis of the signalment, history or additional targeted tests (Table 1). It is worth noting that one aspect very typical for CAD may be observed at the onset, when pruritus may be alesional or associated with primary skin lesions such as erythema and sometimes papules. With progression over time and additional secondary infections, signs such as pustules, alopecia, excoriations, lichenification, crusting and seborrhea may develop. The face, inner aspect of the pinnae, axillae, abdominal, inguinal and/or perineal areas and distal extremities are typical predilection sites in most dogs with CAD (Figure 2), although the affected body areas may vary with breed 5

Table 1. Additional testing methods used in a CAD work-up to assess for any concomitant or atopic dermatitis-resembling  disease, in addition to an elimination diet trial.
Flea combing Fleas
Skin cytology
Malassezia dermatitis
Bacterial dermatitis
 
Skin scrapes/
hair plucking/
tape stripping
 
Scabies 
Other ectoparasites: Demodex spp., Cheyletiella spp., Neotrombicula autumnalis 
Dermatophytosis
 
Fungal culture Dermatophytosis
Skin biopsy
Sebaceous adenitis
Cutaneous lymphoma
 

 

Once other potential etiologies have been ruled out, the standardized clinical criteria for CAD (“Favrot’s criteria”) can be applied to aid interpretation of the clinical findings in a pruritic dog (Table 2). These should not be employed before this point, because whilst ~80% of dogs that fulfil five of these criteria will have CAD, the remaining 20% will have another disease. Conversely, around 20% of dogs that do have CAD will not demonstrate at least five of these factors. 

 Table 2. Clinical criteria for diagnosing canine atopic dermatitis.
Favrot’s criteria – the 8 major indicators for CAD 5
History
  • Onset of signs under 3 years of age
  • Dog living mostly indoors
  • Glucocorticoid-responsive pruritus
  • “Alesional” pruritus at onset 
 
Clinical exam
  • Affected front feet
  • Affected inner pinnae
  • Non-affected ear margins
  • Non-affected dorso-lumbar area
 
Specific clinical criteria for CAD
Additional body sites which might be affected: 
  • Lips
  • Eyelids
  • Ears (outside)
  • Dorso-lumbar region
  • Thorax
  • Flexural body regions
 
Recurrent skin/ear infections
 

 

Testing for environmental allergens

Once a clinical diagnosis of CAD has been made, further assessment is indicated, particularly to determine which allergens exacerbate clinical signs. This approach enables both appropriate selection of avoidance measures (especially with food allergens, although some measures can also be taken against house dust mites) and selection of allergens for allergen-specific immunotherapy. In general, if a dog has seasonal CAD, an immediate work-up for environmental allergens is warranted, but for cases with perennial pruritus and/or gastrointestinal clinical signs, food-induced dermatitis should be excluded before testing for environmental causes. An approach often used by the author is to initiate feeding of a commercial hydrolyzed diet using an elimination diet protocol. If the clinical signs of CAD persist despite this, testing for environmental allergens is followed, either by in vivo skin testing (most commonly intradermal testing, or IDT) or in vitro allergen-specific IgE serology (ASIS). Other than a poor response to a dietary trial, factors that would prompt allergy testing would be if a dog has severe clinical signs, where signs persist for more than 3 months each year, or if management with symptomatic therapy is unsuccessful (either because of significant drug side effects or poor owner compliance) 6

It must be stressed that neither IDT or ASIS is a screening test for CAD; they only assist in confirming the clinical diagnosis and identification of allergens. Most dogs with CAD will have allergen-specific IgE to environmental allergens identified on testing, although in some cases IgE levels are not elevated (“atopic-like dermatitis”). 

Both tests have their limitations and advantages, with neither being superior, and since the success rate of allergen-specific immunotherapy (ASIT) suggests that the two methods deliver comparable results 7 they may therefore be regarded as complementary. The author therefore prefers performing both skin testing and ASIS if costs allow, although if the former presents potential risks, or the patient is uncooperative, ASIS should be the initial option. If the two methods produce inconclusive results, the results are combined for ASIT, otherwise the choices for ASIT are generally based on the ASIS results. Importantly, for either method clinically relevant allergens must be chosen, which is very much dependent on the patient history and clinician’s judgement.

In addition, skin prick testing has recently become fashionable again, although as yet it is unvalidated in veterinary medicine. Saliva testing is also becoming commercially available, but at the time of writing it cannot be recommended as a diagnostic tool.

Intradermal testing (IDT)

IDT is an indirect measure of cutaneous mast cell reactivity, based on the presence of allergen-specific IgEs on their surface, and is the preferred diagnostic method among dermatologists, partly because mast cells can bind individual allergen-specific IgE molecules for more than a year 8. Data on the sensitivity and specificity of IDT is scarce, although literature reports suggest it to be 30-90% and > 50-95% respectively 6 9. However, a precise assessment is very difficult due to a large number of both intrinsic factors (e.g., patient immunologic make-up) and extrinsic factors (e.g., allergen quality, skill level in performing IDT, season, medications). 

Allergen selection

The selection of the most relevant allergens to be used for IDT depends on the animal’s geographic location, and may be aided by resources such as specialized veterinary and human clinics, allergy laboratories, textbooks and the relevant national allergy bureau. Nevertheless, the choice should be reviewed periodically, with individual allergens removed or incorporated as appropriate. For example, the author’s initial IDT panel, consisting of 43 allergens, has been reduced to the most frequently found 13 environmental allergens (Box 1), and is aligned with allergens used in the local human dermatology clinic. This revised panel has shown no reduction in the efficacy of ASIT over a seven-year period.

 

Box 1. The author’s current choice of 13 allergens for intradermal testing.
  • House dust mites: Dermatophagoides farinae, Acarus siro
  • Pollens
               Grasses: Phleum pratense, Dactylis glomerata, Secale cereale
               Trees: Fraxinus spp., Betula spp.
               Weeds: Rumex crispus, Chenopodium album, Plantago lanceolata, Ambrosia spp., Artemisia vulgaris
  • Yeasts: Malassezia spp.
 

 

IDT can utilize either lyophilized allergens or pre-diluted aqueous allergens intended for immunotherapy (which usually have a shelf life of at least 6-12 months), with the allergens further diluted as indicated in Table 3. They remain stable for up to 2 weeks if stored at 4°C in plastic syringes, or 8 weeks in glass vials, but otherwise allergen extract potency deteriorates with time 9, dilution and higher temperatures. Glycerinated allergens (usually used for prick tests in humans) should be avoided due to the possible irritative effects of the glycerin preservative. 

 Table 3. Reported allergens and recommended concentrations for canine IDT*.
Allergens  Published concentrations/dilutions
Pollens  1000 to 8000 PNU**/mL
Molds 1000 to 8000 PNU/mL
House dust mites:

     D. pteronyssinus
 
100–200 PNU/mL 
     D. farinae
    Tyrophagus putrescentiae
    Lepidoglyphus destructor
75 PNU/mL
 
     Acarus siro
    Blomia tropicalis
 
 50 PNU/mL
 
Epidermal extracts
At least 1,250 PNU/mL
300 PNU/mL for human dander
Whole flea extract
1:500 w/v

 

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