Pollen Allergies in Humans and their Dogs, Cats and Horses: Differences and Similarities

Pollen allergies in dog, cats and horses – seasonality

Generally, clinical signs of pollen allergy in these species tend to worsen seasonally
if combined with other allergies, or in the case of pollen-only allergies, are strictly
seasonal. Depending on the severity of clinical signs, a complete diagnostic work-up
might be performed within the first season. In patients with a suggestive history
and clinical signs of pollen allergy (see below for species-specific differences),
the diagnostic work-up consists of ruling out any other differential diagnoses (e.g.
parasites, flea allergy, food allergy and other species dependent disorders- e.g.
Erythema multiforme in horses with signs of urticaria, or painful disorders in cats
with self induced alopecia of the abdominal skin) (Figure 1). After this work-up, allergy testing using intradermal tests or serology (see below)
is performed. In patients with known seasonal allergic disease in e.g. second season
or even later, allergy testing is usually performed without ruling out other less
probable differentials, such as food allergy.

Pollen allergies in the dog (Canis familiaris)

Pollen hypersensitivity is associated with Canine Atopic Dermatitis (CAD), a disease
associated with high specific IgE against environmental allergens 11]. Generally, pollen sensitization is believed to be of minor impact in allergic dogs
even though classical studies indicated similar nasal congestion symptoms in humans
and dogs, for instance to ragweed pollen exposure 12]. The clinical picture differs from that of human rhinitis patients suffering from
pollen allergy. In studies on nasal discharges in dogs, allergic rhinitis due to pollen
allergens was excluded as a cause 13], rather nasal encounter with molds may play a role 14],15]. Thus according to veterinary practice, the canine allergic patient most often presents
with pruritic allergic dermatitis (Figure 2). Here, differential diagnoses to e.g. food-induced allergic dermatitis have to be
ruled out first. Either (for practical reasons) intradermal tests or determination
of specific serum IgE lead then to the diagnosis of canine atopic dermatitis (Figure 1). Whenever pollen sensitization is diagnosed it may be associated with conjunctivitis
in 21% of the dogs 16] and with rhinitis, but it is not associated with asthma 16],17]. The antigen-driven acute and chronic skin inflammation is usually termed CAD by
the veterinary dermatologist, is seen independent of a true atopic background in the
human sense, but associated with specific IgE 18]. The nomenclature of canine allergic diseases reflects that the skin is the most
prominently affected organ: CAD, food induced allergic dermatitis (FIAD), ALD atopic-like
dermatitis (ALD), or FAD (Flea Allergy Dermatitis); (asthma and anaphylaxis in dogs
are only seen in experimental models, in rare cases anaphylaxis may be drug- or insect
venom-induced). Like in humans sensitizations may be associated with an atopic predisposition,
which in dogs strongly varies depending on the breed. In a US study 9% of 30.000 investigated
dogs showed signs of CAD, among them a series of breeds being at higher risk 19] (Table 1, Figure 3), such as the Labrador 20], Maltese or Shih-Tzu in a Korean study – where in fact sensitizations were mostly
found to indoor but not pollen allergens 21]. In a Swiss study, WHWT (White Wine terrier), boxer, French bulldog, Vizsla, bullterrier
and Rhodesian ridgeback were at higher risk; additionally, pugs and Dalmatians were
over-represented although without significance 22]. Atopic predisposition may also enable early sensitization to outdoor allergens,
as was shown in classical 23] and novel dog models where ragweed exposure lead to an asthmatic phenotype 24].

Figure 2. Typical clinical pictures to illustrate canine atopic dermatitis. In 1: Maltese; 2: periocular dermatitis in Jack Russel terrier; 3: English bulldoge;
4: West Highland White terrier (WHW); 5: Doggo Argentino; 6: Boston terrier; Bottom
panel: atopic pododermatitis in 7: French bulldoge; 8: WHW; 9: English bulldoge; 10:
Pitbull.

Table 1. Like atopic humans some domestic animals may have a higher genetic risk to develop
allergies

Figure 3. Illustration of the most important breeds of dogs, cats and horses that were described
to have a higher risk for atopic/allergic diseases (accessory toTable 1). 1. Labrador Retriever: ©Michael Bernkopf. 2. Golden Retriever: from Pixabay. 3. Setter: from Pixabay. 4. Sealyham Terrier: ©Michael Bernkopf. 5. West Highland White Terrier (WHW): © Michael Bernkopf. 6. English Bulldog: from Pixabay. 7. Boxer: from Pixabay. 8. Cocker Spaniel: from Pixabay. 9. Collie: from Pixabay. 10. Foxhound: from Pixabay. 11. Dalmatian: from Pixabay. 12. Lhasa apso: from Lhasaapso (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons. http://commons.wikimedia.org/wiki/File%3ALhasaapso.jpg. 13. Maltese: from Pixabay. 14 A Miniatur Schnauzer: from Pixabay. B Schnauzer from Pixabay. 15. Pug: from Pixabay. 16. Rhodesian Ridgeback: from Pixabay. 17. Shi-TZU: from Pixabay. 18. Shar peis: from Flickr: M.Peinado Commons: M.Peinado (originally posted to Flickr as Gorda –
100) [CC BY 2.0 (http://creativecommons.org/licenses/by/2.0)], via Wikimedia Commons. http://commons.wikimedia.org/wiki/File%3AGorda_-_100.jpg. 19. Vizsla: from Noveczki Katalin (own work) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons. http://commons.wikimedia.org/wiki/File%3AVizsla_r%C3%A1h%C3%BAz_a_vadra.jpg. 20. Abyssinian cat: from Pixabay. 21. A Devon cat: Fergie, kindy provided by Sybille Greff. B Devon cat: Lakritze, kindy provided by Sybille Greff. 22. Dutch warmblood: “Ubility” by Remy Overkempe – originally posted to Flickr as Ubility. Licensed under
CC BY-SA 2.0 via Wikimedia Commons – http://commons.wikimedia.org/wiki/File:Ubility.jpg#mediaviewer/File:Ubility.jpg. 23. Silver Morgan: By Laura Behning. [CC BY 2.0 (http://creativecommons.org/licenses/by/2.0)], via Wikimedia Commons. http://commons.wikimedia.org/wiki/File%3ASilverMorgan.jpg. 24. Swedish Warmblood: By Jenny Dybedahl (Own work) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons. http://commons.wikimedia.org/wiki/File%3AFoal-three-hours-old.jpeg. 25. Oldenburg horse: By Martin Bahmann (Own work) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons. http://commons.wikimedia.org/wiki/File%3ABess2.jpg. 26. Hackney Pony: by Heather Moreton from Louisville, KY, USA (Hackney Pony Uploaded by Princess Mérida)
[CC BY 2.0 (http://creativecommons.org/licenses/by/2.0)], via Wikimedia Commons. http://commons.wikimedia.org/wiki/File%3AHackney_Pony_(7714709846).jpg. 27. Paso Fino: by Arsdelicata (Own work) [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. http://commons.wikimedia.org/wiki/File%3APuerto_rican-Paso-Fino-Horse-chestnut.jpg. 28. Polish Arabian: by Alina-Arabians (own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0) oder GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons. http://commons.wikimedia.org/wiki/File%3APoster_(Ekstern_x_Parella_-_Arbil).jpg29. Arab, Mare: by Pixabay. 30. Saddlebred American: by Heather Moreton from Louisville, KY, USA [CC BY 2.0 (http://creativecommons.org/licenses/by/2.0)], via Wikimedia Commons http://commons.wikimedia.org/wiki/File%3AFive_Gaited_American_Saddlebred_(3007248363).jpg.

Pollen allergen sensitization in dogs is evaluated by intradermal skin testing (IDT),
injecting the allergen extracts into the shaved skin of the lateral thorax or abdomen
25]. Usually, the animals have therefore to be sedated or anesthetized. Reddishness,
wheal and flare reactions of half of the size of the positive control (histamine)
are interpreted as specific reaction. Generally, dogs react to pollen from grasses,
trees and weeds (Table 2). The results of our literature research show a high variability in prevalence, probably
caused by different geographic regions and lifestyle; insufficient data were found
for cats and horses.

Table 2. Overview of types of pollen causing atopic/allergic diseases in domestic animals and
respective references *)

In contrast, a human allergist may get the impression that in veterinary practices
IgE testing has a lower impact, due to a lack of standardized allergen extracts or
reliable anti-dog IgE reagents. Interestingly, the human alpha chain of the high affinity
receptor Fc?RI is used in a commercial test for the detection of e.g. canine IgE 26]. This is possible due to a 54% amino acid identity and 68% similarity among the human
and canine alpha chain and precise knowledge of the amino acids involved in the IgE
binding 27]. To the best of our knowledge, the ISAC microarray testing has not been introduced
into veterinary allergy diagnosis so far.

Specific sensitizations to pollen in canine versus human studies

In more than 1000 atopic dogs in Australia, a 10 to 25% sensitization to pollen of
any kind (grass, tree, weed) was determined by intradermal tests 25]. A more recent cross-sectional study in 651 atopic dogs indicated that sensitization
between tree, weed and grass pollen, but not to other allergen sources, were in 94%
of cases statistically associated 28]. The authors pointed out that sensitization must clearly be distinguished from clinically
relevant sensitization leading to symptoms.

No seasonal, sex or age dependent risk factors were observed in a recent comprehensive
study of canine grass pollen sensitization in Western France 29]. Importantly, like in humans, a significant increase in the number of dogs sensitized
to grass pollen was observed, namely 14,4% between 1999 and 2002, and 27,7% between
2007 and 2010. More than 80% of the 262 tests were positive for one allergen out of
20-38 extracts tested (among them 4 grass pollen, 8 weed pollen and 17 tree pollen)
and 21% for at least one pollen allergen. The diagnosis of the genuine sensitizing
allergen may be complicated by cross reactivities. Müller et al. proposed that, although
positive reactions among botanically closely related plant allergens may be significantly
more common than those among nonrelated allergens, cross reactivity in 30% of the
tested dogs was not pronounced enough to warrant testing and desensitization using
allergen mixes 25],30].

Exposure to pollen depends on the local plant species, thus geographical differences
enable distinct sensitizations. Masuda et al tested 42 Japanese atopic dogs by IDT
and determined specific IgE using 26 allergen extracts from 8 allergen sources 31]. Japanese cedar (Cryptomeria japonica) pollen, after house dust mites, was the second most important allergen in this area,
with a sensitization prevalence of 50% and a positive IgE reactivity of 16,7% of tested
pet dogs. The same sensitization pattern was seen in the Japanese human patients 32], where besides house dust mites, cedar pollen has become an important health challenge
33]. In a more recent approach, the sensitization to single allergen molecules from Japanese
cedar pollen were evaluated more precisely in a component-resolved manner in 15 dogs.
Besides IgE to Japanese cedar molecules Cry j 1 and Cry j 3, 76% of tested dogs showed
IgE to Cry j 6, hence identifying a new major canine allergen 34]. Interestingly, in canine pollen allergy, an oral allergy syndrome to related foods
can occur likely due to cross reactivity between cedar pollen and tomato 35], although this has only been reported sporadically. The results from a study in the
Bangkok area used a mix of 24 different pollen types in 114 atopic dogs 36], but in this population pollen allergens seem to play a minor role as compared to
dust mite, cockroach, ant and other insect allergens. This mirrors the situation in
Thai children where the prevalence of grass pollen allergy was below 5% as compared
to 50% house dust mite and 23% cockroach sensitization 37].

Clinical treatment: SIT

Interestingly, CAD is regularly and with significant success treated by the veterinary
dermatologist through allergen immunotherapy 38]. In fact, the International Task Force on Canine Atopic Dermatitis recommends offering
SIT to each canine patient sensitized to environmental allergens including pollen
39]. In human atopic eczema treatment SIT is a controversial topic, but here as well
it may improve allergic symptoms even in settings of atopic predisposition 40]. Generally, the dose and frequency of injections in allergic dogs were, at least
in 2001, less harmonized than in human allergology 41] and were more recently compared in 42].

Pollen allergies in Cats (Felis catus domestica)

In a recent retrospective study of 45 Australian cats with atopic dermatitis, strong
intradermal test reactions were most frequently seen to pollen allergens (61%) 43]. In fact, in pollen-allergic cats the skin is most often affected by pruritic allergic
/atopic lesions, but cats may also present with allergic rhinitis, such as the Japanese
cat which was diagnosed with cedar pollinosis 44]. Alternatively, cats with asthma may present with spastic coughing, where bronchoalveolar
lavage as the next diagnostic step may reveal eosinophilic inflammation (Figure 1). Intradermal tests will lead then to the final diagnosis, whereas IgE determination
has a lower impact.

The differential diagnosis in lower airway diseases associated with cough, respiratory
distress, or both may be bronchitis or asthma, pneumonia, or neoplasms 45]. Feline asthma is characterized by eosinophilic inflammation and cats have been used
as animal models for human asthma 46],47]. One study reported that domestic mixed breeds, Abyssinian and Devon rex cats are
predisposed, compared to the population of the dermatology referral service 43]. The comprehensive central registry of all pet animals in Switzerland enabled the
statistical evaluation in this study.

Clinical signs of cutaneous hypersensitivities in cats are not pathognomonic and include
eosinophilic granuloma complex and self-induced hair-loss, and should be scored by
an objective scale (SCORing Feline Allergic Dermatitis; SCORFAD) 48]. The AD in cats is not necessarily connected with the levels of IgE or the diagnosis
of specific IgE antibodies in serum 49]. IgE to environmental allergens including pollen can be even found in pathogen-free
housed cats 50],51]. When two groups of 10 cats each were intradermally tested, immediate reactivity
was reported as IgE- as well as IgG-mediated reaction, but also explained by nonspecific
mast cell degranulation 52]. The authors proposed the prior injection of a fluorescent agent in order to enhance
the fidelity of interpretation, a procedure connected with substantially higher strain
for the animals. Even in early studies specific IgG directed against ryegrass pollen,
in addition to flea and house dust mite allergens, was reported and proposed as the
second Th2 antibody class of relevance in feline allergy 53]. Rather than pollen, house dust mite allergens are found abundantly in the sleeping
places of cats, but are not yet definitely proven to be causative allergens in feline
AD or asthma 51].

Itchy inflammatory allergic skin diseases were successfully treated in 100 cats by
daily oral immunosuppression with Cyclosporine over a six-week period 54]. Generally, allergen immunotherapy is described for cats, but is not yet standard
care in veterinary dermatology. This is possibly due to the fact that the underlying
IgE-based diagnosis for identification of the relevant allergen still lacks sufficient
specificity 55]. Elimination diets, necessary for ruling out food hypersensitivities in cats and
other species with non-seasonal cutaneous hypersensitivities, are usually performed
prior to aeroallergen testing. These diets are more difficult to perform in cats than
in dogs, so the owner often cannot follow through on one important step in diagnosing
allergies. Another reason is that cats usually tolerate glucocorticoids much better
than dogs. As mentioned above, Cyclosporine A is also a very useful drug in feline
allergic dermatitis, since it is effective and achievable treatment option in these
species 56],57].

A study using the human Fc?RI alpha chain for detecting feline IgE 26], which has a 56% amino acid identity and 72% homology, resulted in the conclusion
that IgE detection did not diagnose feline food or environmental allergies, but was
effective in diagnosing insect hypersensitivities 49]. Pilot studies with rush allergen immunotherapy with good tolerability were described
in 4 cats 58]. In 81 cats SIT significantly improved the dermatological conditions between 93.6%
(linear granuloma) and 60% (self-induced hair loss), with an 86.1% improvement in
asthma 59]. Studies on subcutaneous versus mucosal (nasal) allergen immunotherapy or novel adjuvants
were done in feline allergic asthma models, including Bermuda grass pollen. The authors
reported improvement of the asthma, increase of the IL-4:IFN-gamma ratio and decline
of bronchial eosinophils, as well as good tolerability 46]. Reinero et al. reported that in cats allergen immunotherapy may be associated with
induction of T-regulatory cells and IL-10, and also cross-protect to non-related allergens,
such as Bermuda grass to house dust mite allergens 60].

Do horses (Equus caballus domesticus) suffer from pollen allergies?

In fact, horses do develop respiratory and skin diseases (urticaria, atopic eczema)
due to allergens. Equine IgE can be detected by in vitro diagnosis. In this case the human alpha chain can also be used due to its 64% amino
acid identity and 76% homology to the equine counterpart as evaluated by our own BLAST
search. Moreover, in horses allergen immunotherapy is regularly done 61]. Intradermal allergy tests or serum IgE tests may be chosen for further work-up and
diagnosis for either skin or respiratory allergy (Figure 1).

Again, several breeds can be called atopic and therefore are more prone to allergies;
in one study, Dutch warmbloods, Morgans, Swedish Warmbloods, Oldenburgs, Hackney horses,
Paso finos, Polish Arabians and Arabian/Saddlebred cross were overrepresented 62] (Table 1, Figure 3). In equine allergic respiratory disease the symptoms may range from rhinitis and
asthma to chronic dry cough and emphysema 63], indicating that numerous immediate-type, delayed-immune complex or cellular hyperreactivities
can be causative in acute recurrent airway obstruction (RAO) or chronic obstructive
pulmonary disease (COPD). For diagnosing RAO a lung function test is helpful. Positive
correlations between symptom severity and exogenous factors such as climatic conditions,
rainfall and seasonal pollen counts have been observed 64]. Although recurrent obstruction may be clearly associated with the pollen season,
the terminology is ‘obstructive pulmonary disease’, not asthma 65].

Additionally, pruritic skin diseases as well as recurrent urticaria may be observed
in atopic horses. Furthermore, atopic dermatitis in equines is becoming a more commonly
recognized disease, especially due to newer diagnostic methods and treatment options.
It is interpreted in horses as an inherited predisposition to form specific antibodies
to environmental allergens such as pollens of grasses, weeds and trees, but also to
mold and dust. Clinical signs are pruritus and secondary intense self-trauma, crusting,
alopecia with chronic lesions including lichenification and hyperpigmentation. Affected
areas are often the ears, face, ventrum and legs. The clinical signs are similar to
those caused by insect hypersensitivity and it is extremely common to have both diseases
in the same horse 66].

Diagnosis of hypersensitivity in horses can be made based on clinical symptoms, ruling
out other differential diagnoses (e.g. parasites, food hypersensitivities and insect
hypersensitivities especially in the dermatologic patients), and by serology with
specific IgE diagnosis and intradermal testing (Figure 1). It is substantial to differentiate between asthma and recurrent airway obstruction
(RAO), as for the latter the contribution of IgE or IgG is still a matter of debate.
In a recent study “reaginic” antibodies of the IgE and IgG class were described as
participating in the pathophysiology of asthma and RAO 66], but also delayed type reactions were reported 67]. Equine RAO studies mostly identified Aspergillus as a prominent allergen and include
today component-resolved diagnosis 67],68]. It may be anticipated that a similar pathophysiological principle, IgE and IgG,
will possibly account for pollen allergy. Later studies suggest that better diagnostic
tools could improve the fidelity of equine allergy diagnosis. In an approach with
64 horses specific reactivity could be found to grass pollen allergens when antisera
to peptides from equine IgE were used 69].

Heaves is a recurrent neutrophilic lung disease in horses with clinical similarity
to asthma 70] but likely caused by molds from airborne dust and not by pollen 71]. Interestingly, an enhanced apoptosis rate in CD4 and CD8 T-cells are seen in horses
affected by RAO 72].

SIT can be performed in horses. For instance, 54 horses suffering from atopic skin
diseases including urticaria and pruritus were treated with SIT successfully 62]. Although 75% of horse owners decided to discontinue after a period of between 6
months and 8 years, approximately half of the discontinued horses profited from the
therapy and stayed free from recurrence of clinical signs. The antigens used were
extracts from Arizona cypress pollen, red cedar pollen, in addition to sheep epithelia,
box elder, house dust mix, Dermatophagoides farinae, Dermatophagoides pteronyssinus,
horsefly, flea, Culicoides, black ant, corn, grain mill dust and grain smut. Of the
27 horses that were reported to benefit from SIT, 13 horses had their SIT formulated
based on the results of IDT, nine had their SIT based on a serum test, and five had
both an IDT and a serum test. A chi-square analysis used to compare the success proportions
of SIT between skin tests, serum tests and both showed no statistical difference between
the three groups.