Summary

Dogs have a global distribution and all dogs produce allergens. Allergic sensitization to dogs is considered to be a risk factor for asthma and rhinitis, and has increased significantly over recent decades for both children and adults. Dog allergen particles are tiny so they easily become airborne, disperse effectively, and can enter small bronchioles to reach lower airways. Dog hair and dander extracts contain many antigens, any of which can bind to IgE antibodies and trigger respiratory symptoms in sensitized individuals. Many of these compounds also cross-react with other mammalian allergens, which poses extended diagnostic and therapeutic challenges. Evaluating dog sensitization can be challenging, but the introduction of molecular-based diagnostics has been an important step forwards in the accurate diagnosis of dog allergy.

Epidemiology

Worldwide distribution

A 2016 survey of more than 27,000 internet users from 22 countries reported that one-third (33%) of people have a dog living in their home. Allergy to dogs has been recognized for many years, but the prevalence of dog sensitization varies geographically due to cultural differences, environmental factors and pet ownership. In a large pan-European study of adults referred to allergy testing clinics, approximately 27% (range, 16.1–56.0%) were sensitized to dogs. In Korea, 20.4% of adults assessed for various allergic diseases were sensitized to dogs, and direct exposure to dogs was an independent risk factor for sensitization to dog allergens.

Allergic sensitization to dog dander was reported by nearly one in ten (9.7%) German children aged 3–17 years, and the prevalence of sensitization increased with the age of the child. Two large population-based surveys have demonstrated how sensitization to dog allergens has increased significantly over time for both children (Brazil: 8.1% in 2004 to 40.3% in 2016; p<0.001) and adults (Sweden: 13% in 1994 to 25% in 2009; p<0.001), which may be due to the hygiene hypothesis, changes in the manufacturing of agricultural products, and increased urban living with sedentary indoor lifestyle behaviors. Of note, adults are more likely than children to be mono-sensitized to animal allergen components.

These recent surges in sensitization are of concern because allergic sensitization to dogs may be a risk factor for asthma and rhinitis. Regardless of dog ownership, a Japanese study reported that more children with asthma were sensitized to dog allergens before they developed respiratory symptoms than non-asthma children.

Clinical Relevance

Asthma and allergic rhinitis

Sensitization to dog allergen in early life is a strong predictor of the development of childhood asthma. Furthermore, the probability of remission of childhood asthma in later adolescence is reduced if the individual is sensitized to furry animals such as dogs. Contact with an allergen source can cause not only immediate symptoms but also a prolonged period of bronchial hyperreactivity which can last for several weeks.

In the UK, dog-sensitized children aged three years who were exposed to high levels of dog allergen had significantly poorer lung function compared to sensitized children who were not exposed (p=0.005). A large population-based survey in the US similarly reported an increased prevalence of asthma and emergency care visits among dog-sensitized individuals exposed to elevated levels of allergens, and attributed 44.2% of asthma attacks to high levels of dog allergen in the bedroom. Projection of these results to the entire US population indicated more than one million increased asthma attacks per year for dog-sensitive and exposed individuals.

Other topics

Interestingly, approximately half (51%) of patients with severe asthma in Germany, who were previously considered nonatopic on the basis of non-standardized allergy testing, demonstrated allergic sensitization when tested against an extended panel of aeroallergens including dog dander.

Diagnostics

Environmental source

The dog allergens (Canis familiaris allergens, e.g. Can f 1, Can f 2, Can f 4, and Can f 6) are ubiquitous and found in dog hair, dander and saliva,. Can f 3 is also present in serum and Can f 5 in non-neutered male urine.

Can f 1 levels are not affected by the number of dogs in the home, but are significantly related to the amount of time a dog is kept indoors. Dog gender and breed may affect shedding of allergens and endotoxins into the environment. For instance, Can f 5 is only present in significant quantities in intact male dogs, which may help explain why children exposed to female dogs have a lower risk of asthma compared to those exposed to male dogs. While certain breeds may be marketed as “hypoallergenic” due to reduced shedding or a compact coat, two separate studies failed to show any difference in allergen shedding between dog breed groups.

Skin prick tests

Diagnosis of dog allergy can be difficult: many patients are misclassified due to self-reporting and even structured allergy history assessments can produce high levels (i.e. 27%) of false-positive rates for dog allergy. Serum IgE to dog epithelium has a poor correlation to skin testing with only 52.2% agreement and a correlation coefficient r=0.37. Academic studies utilizing component resolved diagnostics have reported only 64% of sensitized adults have IgE reactive to Can f 1, while only one-third (32%) of those individuals are mono-sensitized to Can f 1. This suggests clinicians relying on these tests may be falsely assuming these patients are not dog-sensitized.

Evaluating dog sensitization is significantly more challenging and complex than it is for cats, and there remains a great difficulty in using skin prick tests (SPT) for detecting dog-allergic patients. Commercially-available dog extracts used in skin testing are composed of multiple proteins which vary by up to 1,000-fold in potency. The amounts of identified allergens in each extract are unclear as crude dog extracts are not standardized, and considerable variation in SPT results can also depend on the source of the extract used (e.g. liver, serum, salivary gland or keratinocyte). This extensive variation in the allergen composition of commercial SPT solutions results in a patient-dependent ability to activate basophils. Contamination of the extract by non-dog allergens can cause false positives during testing, which also severely limits the utility of crude dog extracts in SPT to accurately identify sensitized individuals.

Prevention And Therapy

Prevention strategies

The effect of dog ownership on the development of asthma is inconclusive. Overall, dog ownership at an early age has either been demonstrated to reduce the risk of asthma at a later age, or increase the risk of asthma and wheezing (e.g. systematic reviews by and). However, ownership of two or more dogs during the first year of life has been specifically associated with reduced risks of atopy, seroatopy and asthma in children by the time they reached six or seven years of age, versus children who were exposed to no dogs or just one dog. The true picture of the relationship between risk and dog ownership is complicated by differences in study design and selection bias, as well as age-related heterogeneity.

While certain breeds may be marketed as “hypoallergenic” due to reduced shedding or a compact coat, studies have failed to show any difference in allergen shedding between dog breed groups. Washing a dog at least twice a week significantly reduces recoverable Can f 1 in hair and dander samples, and moderately reduces airborne Can f 1. Effective cleaning of floors and seats, as well as the use of uncovered versus covered seats, has been shown to lower the levels of animal allergens in public environments.

Cross-Reactivity

Co-sensitization between dog, cat and horse is frequently observed. Cross-reactivity between Can f 1 and Fel d 7 (a lipocalin allergy found in cats) is likely as the proteins share 62% sequence identity. Can f 2 has homology with the allergen mouse urinary protein (MUP), but shows limited patient-dependent cross-reactivity (22%) with Fel d 4. Can f 4 displays 38% sequence identity to bovine and porcine odorant-binding proteins, and between 25–29% identity to several known mammalian allergens including Equ c 1, Mus m 1, Rat n 1, and Fel d 4. Despite belonging to the same lipocalin protein family, Can f 4 shows only about 25% sequence identity to Can f 1 and Can f 2. Can f 6 has shown extensive cross-reactivity with both horse and cat lipocalins and may contribute with these homologous allergens to multi-sensitization and symptoms in individuals allergic to mammals.

Mono-sensitization to Can f 3 appears to be very rare, and this albumin has high sequence homology with albumins from many other mammals including human, pig, cattle, cat, sheep, mouse and rat. Can f 5 cross-reacts with prostate-specific antigen (PSA) of human seminal plasma (HSP), which can be significant for patients with anaphylactic HSP allergies.