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Genetic Welfare Problems of Companion Animals

An information resource for prospective pet owners

Labrador Retriever Labrador Retriever

Canine Atopic Dermatitis

Related terms: atopy, atopic dermatitis, atopic disease, atopic dermatitis syndrome, canine atopic-like dermatitis

Outline: Atopic dermatitis is a very common allergic skin disease which affects a significant minority of Labrador retrievers (more than 10%). It causes mild to severe itching which, as a result of scratching or rubbing, often leads to further skin damage, irritation, infection and discomfort.

 


Summary of Information

(for more information click on the links below)

1. Brief description

Canine atopic dermatitis is a genetically-predisposed inflammatory and pruritic (itchy) allergic skin disease with characteristic clinical features. Allergic diseases result from an exaggerated immune system response that causes pathological damage associated with antibodies most commonly directed against environmental allergens such as house dust mites and pollens (Olivry & DeBoer 2001, Loewenstein & Mueller 2009).

The clinical features of atopy are variable but the cardinal feature is itchiness which varies in degree from mild to severe. A dog may be itchy over its whole skin or localised to certain parts of the body.

2. Intensity of welfare impact   

The intensity of the welfare impact varies greatly. The primary itch due to atopy itself varies from mild to severe between individuals. The condition is made worse when secondary skin infections occur and these secondary skin infections also vary in magnitude. Atopy can cause great suffering in moderately-severely affected dogs due to the constant skin itching and irritation and the secondary damage that is done by the dog to its own skin through scratching. Sore inflamed areas that are uncomfortable and possibly painful are created. It can be difficult to control medically leading some atopic dogs to become seriously ill due to the side effects of treatment and dogs to be euthanized because of the condition. This is often because diagnosis and treatment are time-consuming and expensive for owners and reasonable long-term control is often the best that can be achieved. Linek & Favrot (2010) surveyed the owners of dogs with atopic dermatitis. They found that 73% of owners thought that their dogs atopic dermatitis had a major impact on the health-related quality of life of their dogs. They also found that 48% of owners considered their own quality of life was negatively affected by their dog having this condition. There is no hope of cure.

3. Duration of welfare impact

Signs of atopic dermatitis usually start before three years of age. Signs can be seasonal but more usually happen all year round. Affected dogs will have the problem for life although the severity will usually wax and wane. Treatment to control the condition is involved and lifelong. Drugs are used in most dogs and these are often required constantly.

4. Number of animals affected

In general, around 10% of all dogs, whatever the breed, are affected (Scott et al 1995, Lund et al 1999) and there are many pedigree dog breeds that are predisposed to atopic dermatitis (Hillier & Griffin 2001) including the Labrador retriever (eg Griffin 1993, Scott et al 1995, Prelaud and Power 2008). Of the 211 known relatives of a group of Labrador retrievers with atopic dermatitis, 52% had clinically significant atopic dermatitis (Shaw et al. 2004). From data on estimates of total dog population in the UK and on the percentage of all micro-chip registered dogs that are Labrador retrievers (Lucy Asher 2011, personal communication), we estimate that the UK population size of this breed may be around 1 million.

5. Diagnosis

The diagnosis of atopic dermatitis is complicated. There is no specific clinical sign or laboratory test result that enables the diagnosis to be made. The basis of diagnosis is for a veterinary surgeon to assess the dog’s history and clinical signs for typical features and to rule out other possible causes of skin itchiness and infection using a combination of tests and trial treatments. Specialist veterinary dermatologist’s advice may need to be sought.

6. Genetics

Canine atopy is likely to be a polygenetic condition (Shaw et al 2004) but no genes have yet been identified. The heritability of atopic dermatitis was around 0.47 in a group of guide dogs the majority of which were Labrador retrievers (Shaw et al 2004). Another indication that the condition is inherited in this breed is that when two atopic Labrador retrievers are mated, up to 65% of the offspring develop atopic dermatitis. If one parent has atopy then 21-57% of them develop atopic dermatitis and when there are two non-atopic parents 11% of offspring are atopic (Shaw et al 2004).

7. How do you know if an animal is a carrier or likely to become affected?

This has not been scientifically tested. There are no genetic tests to guide us. In common with other polygenetic disorders with important environmental influences, it may be considered that any affected individual, or individual with an affected close relative eg parent or sibling should not be considered for breeding. However, this advice has not been tested and other considerations such as narrowing the gene pool and concurrent genetic diseases, such as hip dysplasia must also be considered.

8. Methods and prospects for elimination of the problem

There are no schemes in place to reduce the incidence of atopy. It is generally considered that atopic animals should not be bred but there are no publications that evaluate this idea.  In breeds, such as the Labrador retriever, in order to significantly reduce the incidence and severity of atopy it may be beneficial to widen the gene pool by introducing genes from other breeds.

 

For further details about this condition, please click on the following:
(these link to items down this page)


1. Clinical and pathological effects

Canine atopic dermatitis is a genetically-predisposed inflammatory and pruritic (itchy) allergic skin disease with characteristic clinical features. Allergic diseases result from an exaggerated immune system response that causes pathological damage.

The immune system in a dog’s body consists of various cells and chemicals which work together to defend the body from invading pathogens (eg bacteria, viruses, fungi or parasites that can do harm if inside the body). Some of the immune cells which help defend the body produce proteins called antibodies when stimulated to do so.  Antibodies help the immune cells get rid of the pathogens invading the body. Anything that stimulates the immune system is called an antigen. Antigens are normally parts of the invading pathogen, but sometimes otherwise harmless substances stimulate an immune response in individuals who are prone to allergies and exaggerated immune responses. Any substance that can stimulate an allergic immune response is called an allergen.

Atopy is associated with the immune system over-producing a type of antibodies called IgE. Most commonly this is directed against environmental allergens such as house dust mites and pollens (Olivry & DeBoer 2001, Loewenstein & Mueller 2009).

The clinical features of atopy are variable but the permanent cardinal feature, always present, is itchiness, which varies in degree from mild to severe. A dog may be itchy over its whole skin but more usually the itchiness is localised. The commonest areas to be affected are the ears, around the eyes, the muzzle, the underside of the neck and abdomen, the inside of the legs, the feet and under the tail (Nuttall et al 2009).

In the early stages of the disease there may just be itchiness, however, redness of the skin will soon be seen. This may be general redness or red spots (papules). Further problems arise either from long-term itchiness and the self harm that is caused from scratching, rubbing and chewing of the itchy area or from the presence of skin infections with bacteria (both abnormally high numbers of normal skin bacteria and infections from bacteria not usually present) and with skin yeasts normally present in low numbers. Atopy itself and the secondary skin changes that occur both make these infections more likely. Infected skin tends to itch and the consequential scratching, rubbing and chewing causes further, secondary skin damage and a vicious circle of itching and scratching and worsening skin damage develops. At the root of all this skin damage in the atopic dog is an allergy to environmental allergens, which means the dog will become itchy whenever it is exposed to the allergen/s it reacts against. For many atopic dogs this means constant itchiness as it is often impossible to avoid constant exposure to its problematic allergen - house dust mite.

Secondary skin changes often seen in atopic dogs include: lichenification (thickening of the skin), a coat that is greasy and scaly (dandruff) and loss of fur (alopecia). Pustules and crusts are seen when there is bacterial infection and, when this is deeper in the skin, nodules with pus draining from sinuses may be seen.

Otitis externa (inflammation of the ear canal) is often seen in atopic dogs and sometimes is the main clinical problem. This follows the same pattern as atopic disease elsewhere – the ear canal is lined with skin. Initially there may just be redness but constant irritation, excess secretions and thickening of the skin with secondary bacterial and yeast infections lead to a vicious cycle until the ear canal becomes irreversibly damaged. The clinical signs include scratching at the ears, head shaking, rubbing the ears on the ground, a smelly discharge from the ears. Severe infections can lead to septicaemia (bacterial infection in the bloodstream).

There are currently two main theories for the pathogenesis of atopy and there is good evidence that both are important.

Atopic individuals have an abnormal immune response. Allergens are detected in the skin by the immune system. In atopic individuals there is an imbalance of two types of immune cell ie more T helper 2 lymphocytes and fewer T helper 1 lymphocytes. This imbalance leads to other changes in the immune system, which make it respond excessively to small amounts of allergen in the future, easily generating skin inflammation. Excessive amounts of an antibody type (IgE) are present in the body. Excessive skin sensitivity also leads to the skin becoming inflamed much more easily by such things as infection, trauma, drying or heat (Prelaud & Power 2008). A second fundamental abnormality seen in atopic individuals is that they have a skin barrier defect. Their skin suffers from increased water loss and foreign substances such as allergens, bacteria and yeast can penetrate more easily than normal. This allows more contact of the allergens with the immune system (see above). It also allows greater adherence of Staphylococci bacteria and Malassezia yeasts and is part of the reason that atopics are prone to these skin infections (Prelaud & Power 2008).

Recently, reviewers have assessed evidence for which allergens may be the most important in canine atopy (Prelaud & Power 2008, Loewenstein & Mueller 2009). Allergens from the house dust mite Dermatophagoides farina are the most important. Allergies to other mites such as Dermatophagoides pteronyssinus, Euroglyphus maynei, Acarus siro and Tyrophagus putrescentiae are either less common or may be largely due to cross reaction with D. farinae. Cross-reactions occur when a test detects one substance rather than another. D. farina lives in carpets and soft furnishings and dogs that live indoors are constantly exposed to its allergens. Sensitivity to pollens can certainly be important but are usually seasonal in the UK. Many types of tree pollens are involved in canine atopy, and grass pollens are commonly involved. There are also many weeds implicated in canine atopy eg ragweed, plantain and mugwort. The importance of mould allergens in canine atopy is uncertain. Other allergens which have been considered of importance in the past, but which are no longer, include cockroach and other insects, house dust, fabrics such as cotton, wool and linen. The importance of “danders” such as human or animal skin extracts is unproven. 

An important concept in the pathogenesis of canine atopic dermatitis is that of the pruritic threshold. An individual may not be itchy just because it is atopic eg if it is mildly atopic. It may need another factor to combine with the atopy to tip it over the threshold of having clinical signs. So, various factors that can cause itchy skin may combine. In some dogs, just having one or two of these factors may not cause a problem but if a third or fourth occurs then disease will follow. An inherited atopic state is an important predisposing factor in many animals and a leading cause of welfare problems in dogs. Other factors may include inherited defects and abnormalities such as forms of seborrhoea (abnormal greasy/scaly skin), excessive skin folds, abnormal ear canals (pendulous ears or narrow ear canals) and inherited susceptibilities to bacterial infections. They may also include environmental factors such as flea infestation or a dry climate.

One important environmental influence may be the degree of early exposure to allergens for genetically predisposed individuals. There is evidence that prolonged and more intensive exposure to allergens in early life makes atopic dermatitis more likely and also that it is more likely to be severe. This is the case both for house dust mite allergens (de Weck 1995, de Weck et al 1997) and for pollens; pollen allergies may be more common in puppies born during the pollen season (Halliwell 1990).

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2. Intensity of welfare impact

The intensity of the welfare impact varies greatly (Linek & Favrot 2010). The primary itch due to atopy itself varies from mild to severe between individuals. It may also vary according to the season and environment that the dog is experiencing ie whether it is housed indoors or outside and where it is exercising, for example a dog allergic mostly to grasses may be better at the seaside than walking through meadows. Skin infections worsen the condition and their severity can vary. It has been reported that 68% of dogs with atopic dermatitis have had at least one skin infection by the time that the diagnosis is made (Griffin 1993). Atopy can cause great suffering in moderately-severely affected dogs due to the constant skin itching and irritation and the secondary damage that is done by the dog to its skin creating sore inflamed areas that are uncomfortable and possibly painful.  Owners reported that having atopy negative affected their dogs’ life in that it interrupted and interfered with normal activities such as playing, walking, sleeping and sometimes eating (Linek & Favrot 2010). Atopy can be difficult to control medically and suffering can be difficult to avoid during the time when a diagnosis of atopic dermatitis is being confirmed. This can be a prolonged and involved procedure (see below).

Treatment of atopic dermatitis usually involves drugs. The most effective treatments are based on corticosteroids or ciclosporin, both of which can have significant side effects with their own welfare issues. Some atopic dogs become seriously ill due to the side effects of treatment. Frequent shampooing is often required which may be unpleasant for some dogs. Owners report that their dogs’ quality of life suffered not only from the disease but also the treatments, even though they considered these treatments helpful (Linek & Favrot 2010). Dogs are euthanized because of atopic dermatitis. This is often because diagnosis and treatment are time-consuming and expensive for owners and reasonable long-term control is often the best that can be achieved rather than there being any hope of cure.

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3. Duration of welfare impact

Signs of atopy can be seen in some individuals from the age of 2-3 months. More usually signs start between the ages of 6-18 months. It is unusual for signs to start after three years. Some dogs have seasonal problems (when its pollen allergens that they are allergic to) but often dogs that had seasonal problems when younger will develop problems lasting all year round when they are older. Without treatment affected dogs will have the problem for life although the severity will usually wax and wane according to the amount of allergens they are exposed to at any given time, secondary infections, any exacerbating factors such as catching fleas and the weather, and the success of treatments.

Treatment of atopic dermatitis is involved and lifelong. Drugs are used in most dogs and these are often required constantly.

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4. Number of animals affected

In general, around 10% of all dogs, whatever their breed, are affected (Scott et al 1995, Lund et al 1999) and there are many pedigree dogs that are predisposed to atopic dermatitis (Hillier & Griffin 2001). Labrador retrievers feature in most lists of predisposed breeds (eg Griffin 1993, Scott et al 1995, Prelaud & Power 2008) and there is evidence of a breed predisposition from Schick & Fadok (1986) and Carlotti & Costargent (1994). A study by Shaw et al (2004) investigated the pedigrees of dogs used as guide dogs for the blind that had been diagnosed with clinically significant atopic dermatitis. Of the 211 relatives traced in this retrospective study of Labrador retrievers, 109/211 (52%) could be said to have had clinically significant atopic dermatitis. From data on estimates of total dog population in the UK and on the percentage of all micro-chip registered dogs that are Labrador retrievers (Lucy Asher, 2011, personal communication), we estimate that the UK population size of this breed may be around 1 million.

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5. Diagnosis

The diagnosis of atopic dermatitis is complicated. There is no characteristic clinical sign or laboratory test result that enables the diagnosis to be made. The basis of diagnosis is for a veterinary surgeon to assess the dog’s history and clinical signs and to rule out other possible causes of the signs using a combination of tests and trial treatments. Over the years there have been various attempts to create formal schemes to aid this process (Willemse 1986, Prelaud et al 1998). The currently favoured scheme was created and tested by Favrot et al (2010) and its use clarified by Olivry (2010).

The 2010 Favrot diagnostic criteria for canine atopic dermatitis - used alongside the elimination of other possible causes of the signs (see below).

  • Onset of signs under three years of age
  • Dog mostly living indoors
  • Glucocorticoid-responsive pruritus (itchiness that decreases when the dog is given glucorticoid drugs)
  • Pruritus (itchiness) without skin lesions at onset
  • Affected front feet
  • Affected pinnae (ear flaps)
  • Non-affected ear margins (the edges of the ear flaps are not affected)
  • Non-affected dorso-lumbar area (back)

If five criteria are met there is a sensitivity of 85% and specificity of 79% for a diagnosis of canine atopic dermatitis. This means that if 100 dogs were diagnosed, using this scheme alone, then 21 of this 100 would have the wrong diagnosis – they actually have another cause of their disease, not atopy. Furthermore, there would have been another 15 dogs that actually do have atopy but had been excluded because the five criteria needed have not been found. For these reasons the scheme can not be used alone. 

The difficulties arise because all the clinical signs of atopic dermatitis are also seen in other common skin diseases. In order to make any of these schemes more reliable they have to be combined with tests that seek to excluded these other conditions. Mange (mite infestations), and bacterial and yeast infections are ruled out by examinations of skin samples and trial treatments. Contact irritation and allergy is ruled out by avoidance of potential causes. Cutaneous (skin) adverse food reactions (food allergy/hypersensitivity) are ruled out by a two month long food exclusion trial. Fleas are ruled out by trial treatment. Some rarer skin diseases may need to be ruled out by skin biopsy.

Tests can be performed to identify which allergens are involved for a particular atopic dog. Unfortunately, these tests are not reliable in determining whether a dog is atopic or not and results of these tests are not used in making the diagnosis (Favrot et al 2010). Allergy testing can be performed using blood tests or intra-dermal (into the skin) injections.

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6. Genetics

That canine atopic dermatitis has a strong inherited component has long been assumed based on its similarity to human atopic syndromes and observations that canine breed and family predispositions are common (Sousa & Marsella 2001, Prelaud & Power 2008). 

The heritability of atopy has been studied by Shaw et al (2004). When considering guide dogs as a whole, a heritability of 0.47 was found. The majority of these dogs were Labrador retrievers but Golden retrievers and Labrador-Golden retriever crosses were also represented. Given that all these puppies were raised in similar conditions it is reasonable to say that about half of the factors that caused them to have clinical atopic dermatitis were genetic and half were environmental. When individual matings were investigated, atopic dermatitis had been diagnosed in 65% of the offspring from the mating of two dogs with atopic dermatitis, 21% to 57% of the offspring from the mating of one dog with atopic dermatitis and one non atopic dog, and 11% of the offspring from the mating of two non atopic dogs.

Canine atopic dermatitis is likely to be one manifestation of canine atopy. As in humans, canine atopy is likely to be a polygenetic condition (Happle & Schnyder 1982, Shaw et al 2004). There is evidence for an important dominant gene; at least in one line of Beagles (de Weck 1995, de Weck et al 1997). A start has been made to investigate specific genes involved in several breeds, including the Labrador retriever but, as yet, there are few publications available (Wood et al 2009).

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7. How do you know if an animal is a carrier or likely to become affected?

This has not been scientifically tested. There are no genetic tests to guide us. In common with other polygenetic disorders with important environmental influences, it may be considered that any affected individual or an individual with an affected close relative (parent or sibling) should not be considered for breeding. However, this advice has not been tested and other considerations such as narrowing the gene pool and concurrent genetic diseases, such as hip dysplasia must also be considered.

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8. Methods and prospects for elimination of the problem

It may be considered that individuals with atopic dermatitis should not be used for breeding. This would include any affected individual, even if only mildly affected. This is because environmental factors are certainly important in whether an atopic individual has clinical signs and how bad they are. So, a mildly affected individual does not necessarily have “better” genes than a severely affected one. Not breeding from animals with a close relative that has suffered from any degree of atopic dermatitis would also be recommended, based on general information given for reducing disease resulting from polygenetic conditions (Bell 2005). But considerations should be given to not overbreed from individuals that are healthy, as far as atopy goes, which could have other problems as this could have unintended and undesirable genetic consequences (Oberbauer 2005). In breeds, such as the Labrador retriever, it may be necessary to widen the gene pool by introducing genes from other breeds.

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9. Acknowledgements

UFAW is grateful to Rosie Godfrey BVetMed MRCVS and David Godfrey BVetMed FRCVS for their work in compiling this section.

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10. References

Bell J (2005) Managing polygenic disease: canine hip dysplasia as an example. Tufts’ Canine and Feline Breeding and Genetics Conference, Sturbridge, Massachusetts September 30 – October 1, 2005

Carlotti DN and Costargent F (1994) Analysis of positive skin tests in 449 dogs with allergic dermatitis. European Journal of Companion Animal Practice 4: 42–59

Favrot C, Steffan J, Seewald W and Picco F (2010) A prospective study on the clinical features of chronic canine atopic dermatitis and its diagnosis. Veterinary Dermatology 21: 23-31

Griffin CE (1993) Canine atopic disease. In: Current Veterinary Dermatology. Eds CEGriffin, KW Kwochka JM McDonald. Mosby Year Book, St Louis pp 90-120

Happle R and Schnyder UW (1982) Evidence for the Carter effect in atopy. International Archives of Allergy and Applied Immunology 68: 90–92

Halliwell REW (1990) Clinical and immunological aspects of allergic skin diseases in domestic animals: In: von Tscharner C, Halliwell REW eds. Advances in Veterinary Dermatology I. Balliere-Tindall, Philadelphia 91

Hillier A and Griffin CE (2001) The ACVD task force on canine atopic dermatitis: incidence and prevalence. Veterinary immunology and Immunopathology 81: 147-51

Linek M and Favrot C (2010) Impact of canine atopic dermatitis on the health-related quality of life of affected dogs and quality of life of their owners. Veterinary Dermatology: 216-2

Loewenstein C and Mueller RS (2009) A review of allergen-specific immunotherapy in human and veterinary medicine. Veterinary Dermatology 20: 84-98

Lund EM, Armstrong PJ, Kirk CA, Kolar LM and Klausner JS (1999) Health status and population characteristics of dogs and cats examined at private veterinary practices in the United States. Journal of the American Veterinary Medical Association. 214: 1336-41

Nuttall T, Harvey RG and McKeever PJ (2009) Canine atopic dermatitis. In: A colour handbook of skin diseases of the dog and cat, 2nd ed. p20

Oberbauer A (2005) Strategies for Identifying and Managing Complex Genetic Disorders Tufts’ Canine and Feline Breeding and Genetics Conference, Sturbridge, MassachusettsSeptember 30 – October 1, 2005

Olivry T and DeBoer DJ (2001) The ACVD task force on canine atopic dermatitis: forewords and lexicon. Veterinary immunology and Immunopathology 81: 143-6

Olivry T (2010) New diagnostic criteria for canine atopic dermatitis (Letter to the Editor) Veterinary Dermatology 21: 124-7

Prélaud P, Guaguère E, Alhaidari Z, Faivre N, Héripret D and Gayerie A (1998) Reevaluation des criteres de diagnostic de la dermite atopique canine. Revue de Medecine Veterinaire 149: 1057-64

Prelaud P and Poer HT (2008) Atopic dermatitis syndrome. In A Practical Guide to Canine Dermatology. E. Guaguere, P. Prelaud & J.M. Craig eds. Kalianxis, Italy. pp 229

Scott DW, Miller WH and Griffin CE (1995) Immuological skin diseases. In: Muller & Kirk’s Small Animal Dermatology 5th ed. WB Saunders, Philadelphia. pp 500

Schick RO, and Fadok VA (1986) Responses of atopic dogs to regional allergens: 268 cases (1981–1984). J Am Vet Med Assoc189: 1493–1496

Shaw SC, Wood JLN, Freeman J, Littlewood JD and Hannant D (2004) Estimation of heritability of atopic dermatitis in Labrador and Golden Retrievers. American Journal of Veterinary Research 65: 1014-20

Sousa CA and Marsella R (2001) The ACVD task force on canine atopic dermatitis: genetic factors. Veterinary immunology and Immunopathology 81: 153-7

de Weck AL (1995) What can we learn from the atopic zoo. International Archives of Allergy and Applied Immunology 107: 13-18

de Weck AL, Mayer P, Stumper B, Schiessel B and Pickart L (1997) International Archives of Allergy and Applied Immunology 113: 55-57

Willemse T (1986) Atopic dermatitis: a review and reconsideration of diagnostic criteria. Journal of Small Animal Practice 27: 771-8

Wood SH, Ke X, Nuttall T, McEwan N, Ollier WE and Carter SD (2009) Genome-wide association analysis of canine atopic dermatitis and identification of disease related SNPs. Immunogenetics  61(11-12): 765-72

© UFAW 2011


Credit for main photo above:

By Erikeltic at English Wikipedia [CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons