Diagnosing and treating skin disease in pets can be extremely frustrating for vets and nurses as well as owners: finding the root cause can be a lengthy process and in the case of canine atopic dermatitis, it entails lifelong management of the condition instead of a simple cure.
However, outstanding progress in the understanding of canine atopic dermatitis has led to the development of new criteria for diagnosis and ground-breaking therapeutic strategies that can help owners gain answers and see results more rapidly than ever before.
This article outlines the process of establishing a diagnosis of atopic dermatitis and identifying the allergens responsible, and examines immunotherapy as an option to help clinics better manage this debilitating disease.
What is atopic dermatitis?
Canine atopic dermatitis (CAD) has recently been redefined by the International Taskforce on Canine Atopic Dermatitis as “a genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features associated with IgE antibodies most commonly directed against environmental allergens” (Halliwell, 2006; Olivry et al., 2010).
In around 10 percent of cases of classical atopic dermatitis, no IgE is demonstrable: such cases are termed ‘atopic-like dermatitis’
It is also worth noting that in around 10 percent of cases of classical atopic dermatitis, no IgE is demonstrable: such cases are termed “atopic-like dermatitis”, whose definition is: “an inflammatory and pruritic skin disease with clinical features identical to those seen in canine atopic dermatitis in which an IgE response to environmental or other allergens cannot be documented” (Halliwell, 2006; Olivry et al., 2010).
Both conditions are a diagnosis of exclusion, reached via a process of elimination: there is currently no single diagnostic test that can rule on whether a pet has atopic dermatitis.
How to diagnose atopic dermatitis
Favrot et al. (2010) developed a set of criteria for the diagnosis of canine atopic dermatitis which remains extremely useful for guidance.
Pruritic patients may have recurrent skin and outer ear infections, be nibbling at their paws and show signs of saliva staining. In addition, clinical presentation can include self-induced alopecia, erythema and lesion distribution which can help pinpoint the disease, with lesions on the face and the feet, in the armpits and ventrum, in the ears and around the perineum.
Prior to starting allergy testing
Although testing does not offer a diagnosis, it can help to identify the allergen and develop an allergy-specific immunotherapy vaccine or offer ways to avoid the allergen in question in the future.
In all cases, a detailed history should be taken first. Most dogs begin to show allergic signs between six months and three years of age (Olivry et al., 2010); therefore, a full history may reveal subtle signs from earlier years in patients which present later in life. A thorough clinical examination should be performed (both general and dermatological), as well as testing for infections and ectoparasites if necessary.
Although testing does not offer a diagnosis, it can help to identify the allergen and develop an allergy-specific immunotherapy vaccine
Any other skin conditions which can appear similar must first be eliminated from the differential diagnosis. Flea bite hypersensitivity and other parasitic infestations are one of the first options which must be ruled out, along with cutaneous adverse food reactions – this can be done via an elimination diet for a minimum of eight weeks – and microbial or yeast infections (these are generally secondary, often to an underlying allergy).
How to perform testing
Once the diagnosis of atopic dermatitis is established, there are two main testing methods available: intradermal allergen testing (IDAT) or serology.
Tests are looking for the allergen-specific immunoglobulin E (IgE): if using serology, we are looking for the allergen-specific IgE in blood; if using intradermal testing (IDAT), we will be looking for IgE bound to the surface of mast cells within the skin.
IDAT offers the advantage of allowing veterinary professionals to build a more flexible selection of allergens and receive same-day results, but it can be time-consuming and requires sedation. On the other hand, serology can be more convenient and mean less drug intervention and inhibition, but without the same speed of result.
If testing via serology, a monoclonal test to detect IgE is preferable; the latest options on the market include a monoclonal cocktail and tests that include the new generation of CCD blockers.
Carrying out intradermal allergen testing
The IDAT kit consists of a positive control (histamine phosphate) and a negative control (usually buffered saline or another diluting agent used for mixing with the allergens) which will be the first to be administered ahead of the allergens; most come pre-diluted and ready to draw up for the skin test.
When selecting the relevant allergens to use, there can be a huge range of potential options. Contacting local veterinary schools or even human dermatologists in the area can help you to narrow down the choices to select those most relevant to your location. These may include tree pollens, moulds or insects, as well as the ubiquitous house dust mites. Bear in mind that the time of year when testing is conducted can be vital: if the patient has a seasonal flare, it is far preferable for the test to be performed at least two weeks into the relevant time period.
To perform IDAT, patients are usually sedated. It is important to avoid ketamine, diazepam, propofol and acepromazine as they have an antihistaminic property which can influence the reaction
To perform IDAT, patients are usually sedated. It is important to avoid ketamine, diazepam, propofol and acepromazine as they have an antihistaminic property which can influence the reaction. Clip a patch on non-lesioned skin over the lateral thorax and place marks for injections on the skin. Then inject allergens intradermally according to the test’s protocol. Be sure to make a note of the start and finish times, and monitor for a reaction.
Interpreting IDAT results
Reactions usually appear within 15 to 20 minutes, meaning it is important to keep the patient sedated and wait the allotted time period (generally 20 minutes).
Look for erythematous, turgid and “wheal and flare” responses. For those less confident in your abilities to visually interpret the reactions, you can measure each to compare with the mean results of both the positive and the negative controls: anything greater than the mean can usually be accepted as a positive result.
Dermal reactions of cats can be more difficult to recognise than dogs; one tip is to use a light to cast a shadow and see the reactions in relief, or simply to feel with the fingertips
Note that the dermal reactions of cats can be more difficult to recognise than dogs; one tip is to use a light to cast a shadow and see the reactions in relief, or simply to feel with the fingertips.
If the concentration is too high, the allergens themselves could be an irritant, and trauma to the test site can also cause a false positive. False negatives may be caused by inhibition from drugs already delivered by well-meaning owners, by out-of-date allergens or by failure to include relevant allergens.
Drugs that can interfere
A number of drugs can compromise IDAT results, including antihistamines, hydrocortisone aceponate and glucocorticoids (whether topical, oral or depository), as well as oclacitinib. Effects of each last for varying lengths of time, ranging from a week for antihistamines to six to eight weeks for depository glucocorticoids to dissipate.
If carrying out serological allergy testing, drugs are less likely to have an effect, but it is always worth checking with your chosen laboratory before submitting a sample.
Drawing a conclusion
It is important to remember that these are not diagnostic tests in their own right: a positive reaction does not mean the allergen in question is causing the clinical signs until all other options are ruled out. Confirm whether the symptoms are year-round or seasonal to help build the wider clinical picture.
If both serology and IDAT are negative, a case of atopic-like dermatitis is the likely option: it presents the same symptoms and signs, but the allergen cannot be documented.
Taking action with tailored treatment
If there is a diagnosis of canine atopic dermatitis, the test results can be used to build the formulation of an allergen-specific immunotherapy (ASIT) vaccine for the patient, as well as advice on how to avoid the particular allergen if relevant (and possible).
ASIT has been reported to reduce symptoms in around two-thirds of patients (Schnabl et al., 2006) and there are a number of options available for delivery: aqueous and alum-precipitated products can be offered via slow subcutaneous injections, or there is the alternative for rush immunotherapy as a method for rapidly desensitising patients. The latest developments on the market also involve sublingual or intra-lymphatic delivery.
ASIT [allergen-specific immunotherapy] has been reported to reduce symptoms in around two-thirds of patients and there are a number of options available for delivery
The slow injection method starts with a low quantity and concentration which is then increased over the course of 12 weeks. Owners can administer this themselves at home after the first few have been performed in the veterinary practice. The rush therapy, which can only be carried out with the aqueous immunotherapy option, delivers the same amount of therapy in one day, with injections given every half-hour under constant supervision.
With both therapies, a response should be seen within six to nine months, but at least 12 months should be given before making a decision on whether the therapy is successful: it is beneficial for owners to keep a diary to track any pruritus so dosages can be adjusted accordingly.
The newest technique of intra-lymphatic immunotherapy sees a small amount injected into either the submandibular or the popliteal lymph nodes, often guided by ultrasound.