Furry animals allergy (Dogs and Cats)

Furry animals allergy
(Dogs & Cats)
Lalita Tearprasert; M.D.

Scope
Introduction
Prevalence
Cats & Dogs allergens
Clinical effects of allergen exposure
Diagnosis
Environment control

Most persons in Western societies spend more than 90%
of their lives in indoor environments, it is not surprising that
indoor allergens play an important role in allergic sensitization
and symptoms
American Pet Products Manufacturers Association survey from 2010
- 93.6 million cat owners in the United States
- 77.5 million dog owners in the United States
Indoor exposures are of great importance in relation to asthma
Konradsen et al. J Allergy Clin Immunol 2015;135:616-25.
Salo et al. J Allergy Clin Immunol 2008;121:678-84.
Environmental assessment and exposure control 2012 : a practice parameter—furry animals
Introduction

Rönmark et al. J Allergy Clin Immunol. 2009 August ; 124(2): 357–6415.

‣ Germany, Data were collected from 2003 to 2006
‣ 17,641 children and adolescents
Schmitz et al. Int Arch Allergy Immunol 2013;162:263–270.

Gent et al. Environ Res. Author manuscript; available in PMC 2013 October 01.

Pumhirun et al. Asian Pasific Journal Of Allergy And Immunology (1997) 15: 183-185.
100 cases
female: 59, male: 41
aged between 10-59 years,
mean age 27.9 years
who were diagnosed with AR
by history and clinical presentation
underwent a prick skin test
with 30 aeroallergens
THAILAND

Paskorn et al. Asian Pasific Journal Of Allergy And Immunology (2009) 22: 91-95.
THAILAND3-15 years

Bunnag et al. Asian Pasific Journal Of Allergy And Immunology (2009) 27: 79-86.
Percentage of positive skin prick test
- house-dust mite 64.7%
- house dust 64%
- Bermuda grass 52.3%
- cockroach 49.8%
- para grass 49.4%
- sedge 45.9%
- careless weed 45.4%
- dog 44.2%
- cat 39.3%
- Cladosporium 38%
Common causative allergens in AR between 2002 and 2004
at ENT Allergy Clinic at Siriraj Hospital : 736 patients
THAILAND

Cat & Dog allergen : Small particles 2-15 micron
( Mites 10-40 micron, Cockroachs > 10 micron )
The primary source of cat and dog allergens is dander coming off the skin
Airborne : becomes airborne with minimal disturbance, remains airborne for
a long time (many hours)
Approximately 60% of airborne Fel d 1 settles out within 2 days of
disturbance, leaving smaller particles that can remain airborne for up
to 14 days or longer
Erwin EA. et al. Immunol Allergy Clin N Am. 2003; 23:469-81.
The effects of cats/ dogs in the home

Middleton's 8th edition
Can be inhaled into the smaller airways more easily than larger particles,
such as mite feces or pollen grains
The presence of a cat can increase airborne Fel d 1 within 30 minutes
Factors that lead to increase cat allergen concentrations (Fel d1) in house
1.) Increasing numbers of cats in the home
2.) Low ventilation rate
3.) Presence of upholstered furnishings
4.) Carpeting
(Other characteristics of cats, such as length of cat hair, cat sex,
reproductive status, and time spent indoors, were not associated
with levels of Fel d 1)

Airborne allergen was being carried on smaller particles
(less than 5 µm in diameter)
1.) Small particles fall slowly and can be kept airborne by any
movement in the house
2.) Increased ventilation helps to remove small particles from a house
3.) Air filtration with a room air cleaner may be a useful method of
reducing exposure to allergen on small particles
Airborne allergen
Remains airborne (higher total quantity inhaled) : Cat, Dog, Rodent
Transiently airborne : Mite, Cockroach

The particles of dander carrying cat allergens appear to be “sticky” ,
which means that they are consistently carried on clothing from
houses with an animal to other buildings
Possible to measure cat allergen airborne in many homes without a
cat
Sensitization to cats can occur without direct exposure to the
animals
75% of the children who are allergic to cats have never lived in a
house with a cat
Passive transfer of allergens

http://www.asthmacenter.com/index.php/news/details/pet_allergy/
Carpets (Rugs) : Major reservoirs

Major allergens

Lipocalins
More than 50% of the
furry animal allergens

Small, secreted proteins
A group of proteins involved as ligand transport proteins with
enzymatic activity, participating in cell homeostasis
Found in dander, saliva, and urine; sticky particles
Share sequence identities of only 20% to 30%
Some lipocalins display much higher sequence identities
(about 60%) and cross-react : Can f 6, Equ c 1, and Fel d 4
W. Smith et al. Clin Exp Allergy 2004; 34:1732–1738.

Cat lipocalin
1.) Fel d 4
2.) Fel d 7
Dog lipocalin
1.) Can f 1
2.) Can f 2
3.) Can f 4
4.) Can f 6
Lipid-binding activity of the lipocalins may
be a factor that promotes the induction
of allergic responses (Th2)

Albumins

Minor allergens
Fel d2 : Pork-cat syndrome
(associated with allergic symptoms on
eating pork but might not be an
inhalant allergen)
Cat lipocalin
1.) Fel d 2
Dog lipocalin
1.) Can f 3

Cats allergens
Middleton's 8th edition.
The major cat allergen is Fel d 1
Purification of Fel d 1 by Ohman et al. in 1974
More than 90% of all people who have respiratory tract symptoms
(Asthma, Rhinitis) related to cat exposure have IgE antibodies
specific for Fel d 1

Fel d 1 (Secretoglobin)
Major cat allergen : up to 95% of all patients with cat allergy react to Fel d 1
Size 14 kDa
Appears to be a unique marker for the presence of cats
All natural breeds of cat produce Fel d 1
Males producing a larger amount than females
Primarily produced in sebaceous, anal, and salivary glands
Mainly present in the epidermis and fur (root > tip)
The highest concentrations being found on hair from the neck

No important cross-reactivities with other mammalian
Spread to the environment through airborne dander
The biological role of secretoglobin is unknown
Allergenicity of inhaled Fel d 1 can be increased by its binding to
the mannose receptor on dendritic cells, thereby initiating the process of
internalization and the production of Fel d 1–specific IgE and IgG1

Fel d 2 (Albumin)
All cats have this allergen
Size : relatively large (62-kD) protein
Target of IgE antibodies in approximately 10% of cat-allergic subjects
Cross-reacts immunologically with several different mammalian
albumins, including those of dog, pork, and beef
>> Pork-cat syndrome

PORK- CAT SYNDROME
Primary sensitization is related to environmental exposure to cat albumin
Cross-reactivity between cat and pork albumin
Can affect children and adults. Majority being adults or teens
Presenting with food-related or idiopathic urticarial
or anaphylactic symptoms : Allergic reactions to pork
Both pork–cat and alpha-gal food allergies are IgE-mediated,
and can show similar responses with certain skin tests and immunoassays
Commins and Platts-Mills. Curr Allergy Asthma Rep. 2013 February ; 13(1): 72–77.

Occur within 30–45 min and can occur as rapidly as oral itching during the
meal
Onset of a “new” food allergy in an older child or adult may merit
consideration of pork–cat syndrome as a diagnosis, especially if a
history of tick bites is absent
Most of these patients report reactions to pork
10% to 20%, report reactions to beef
No cases with reactions to cow's milk have been reported

Fel d 4 (Lipocalin)
Found primarily in cat saliva
It is an important cause of allergic sensitization in part because of
extensive allergen cross-reactivity with horse (Equ c 1), mouse (MUP1),
rat (Rat n 1), and dog (Can f 2, Can f 6)
Cross-reactivity of Fel d 4 with dog allergen suggests a role in
cosensitization between cat- and dog-allergic patients
Highly homologous to the major horse allergen Equ c 1
Fel d 4 >> Can f 2, Can f 6, Equ c 1

Fel d 5 (Cat IgA)
Major IgE binding epitope on cat IgA is "Alpha-gal"
which is associated with delayed anaphylaxis to red meat
IgE to alpha-gal is not associated with rhinitis or asthma
Main source of cat IgA is saliva

Saleh et al. Clinical and Molecular Allergy 2012, 10:5.
Alpha-gal is an oligosaccharide : galactose-alpha-1,3-galactose
- IgE antibodies will bind to any proteins that carry this oligosaccharide
- found in mammalian cells of non-primates
- present in beef, pork, lamb and cat dander
- absent in chicken and fish
Symptoms : 2 distinct forms of anaphylaxis
1.) Immediate onset anaphylaxis during first exposure to IV cetuximab
2.) Delayed onset anaphylaxis 3–6 h after ingestion of mammalian
food products (e.g., beef and pork) >> Red meat syndrome
ALPHA-GAL ALLERGY

Delayed anaphylaxis to red meat 3-6 hr. after ingestion
- identified IgE antibodies to the oligosaccharide
galactose-α-1,3-galactose (“alpha-gal”)
Majority of children with this syndrome present with urticaria rather
than acute episodes of delayed anaphylaxis
First report that tick bites could give rise to allergic reactions to meat
was made by Dr. Sheryl Nunen to the Sydney Allergy Society in 2006
>> published in 2009 >> In 2012 confirmed in Australia and Europe
(other tick species)
RED MEAT SYNDROME

Loan Star Tick (USA)
- most in Southern
Amblyomma americanum

European Castor bean Tick (Europe)
Paralysis Tick (Australia)
Ixodes holocyclus

Cause
Alpha-gal is not naturally present in humans, but is all other mammals
Primary exposure causing sensitization to alpha-gal is from tick bites
(Tick feed on another mammal, alpha-gal will remain in its alimentary tract)
Tick bite will inject the alpha-gal into host
Release IgE antibodies to foreign carbohydrate

Diagnosis : A detailed history can help in achieving diagnosis
- type of ingested foods
- time to onset of symptoms
- the geographic area of residence as well as history of tick bites
Investigations
- sIgE to pork, beef, cat albumin,
alpha-gal

IgE responses to different cat components can be induced through
different routes of exposure and are associated with either inhalant symptoms
or 2 forms of food allergy
Pork-cat syndrome
Red meat
syndrome
Fel d 4 (Lipocalin)
cross-react with
Can f 6, Equ c 1

Dogs allergens
Dog allergy appears to be less common than cat allergy as a
cause of asthma
Airborne
Small particles tend to remain airborne for long periods and,
when inhaled, can penetrate into the lower airways and trigger
asthma symptoms

Can f 1 (Lipocalin)
Major dog allergen
Size 23-25 kDa
Secreted from canine Von Ebner's glands
Found in dog hair, dander, and saliva
Detectable in all homes with a dog and in 1/3 of homes without dogs
50-90% of patients sensitized to dog have antibodies to Can f 1

288 healthy dogs
Levels of Can f 1 on fur vary between
breeds, gender, hormonal status,
hair length, and according to the
presence of seborrhea
Ramadour et al. Allergy 2005: 60: 1060–1064.

Breeds (Labrador retriever), sex and seborrhea seem to influence
the levels of Can f 1 on fur
Ramadour et al. Allergy 2005: 60: 1060–1064.

Can f 2 (Lipocalin)
Found in dander and saliva
IgE cross-reactivity was demonstrated between Can f 2 and
the cat allergen Fel d 4, although they share less than
22% sequence identity >> observed cosensitization to cats
and dogs in some individuals

Can f 3 (Albumin)
Albumin seems to be a common cross-sensitizing allergenic
component
Obviously found in all dogs >> makes it impossible for there
to be a completely nonallergenic dog

Can f 5 (Kallikrein)
Similar to prostatic kallikrein
Found in up to 70% of patients with dog allergy
No patterns of cross-reactivity to allergens from other furry animals
Cross-reactivity to human prostate-specific antigen, the major
allergen in seminal plasma, has been reported, which suggests
that sensitization to Can f 5 could be relevant to seminal fluid allergy

Sensitization (Development of allergen specific IgE) in
susceptible individuals
If the exposure persists, often leading to manifestations of
diseases, such as asthma and rhinitis.
Continued exposure to the allergens is likely to exacerbate
symptoms and lead to poorer outcomes
Clinical effects of
allergen exposure

Threshold level for allergen exposure
Cats Dogs
Sensitization level
(mcg/g.)
1 2
Theshold level
(mcg/g.)
8
(Fel d 1)
10
(Can d 1)
Almqvist. Clinical Reviews in Allergy & Immunology. Volume 28. 2005.
Measurement of cat allergens in settled dust should not be used
as a surrogate for airborne exposure (C)

For many years, it was assumed that living in a house with a cat
increased the risk of allergy
In 1999, Hesselmar et al. reported that children who lived in a house
with a cat were less likely to be sensitized to cat allergens
Individual differences will affect the response to animal exposure,
2 very different mechanisms
1.) IgG4 production : Allergen-specific tolerance
2.) Increased endotoxin or increased bacterial diversity in the home
>> effects on the microbiome of the child : not allergen-specific

Chen et al. J Allergy Clin Immunol 2007;119:1148-55.

Higher cat allergen exposures from both parent and children mattresses
significantly increased the risk of the development of cat sensitization when the
children were 2 years old but showed no effect when the children were 6 years old

Age and parental history of allergy were significant risk factors for
the development of cat sensitization during childhood.

Pets and Asthma. PLoS One. 2012;7(8):e43214.

Finland
All children aged 1–4 yr (N = 4779)
Born between 2001 and 2005
Cross-sectional questionnaire data on pet exposure in infancy and
physician-diagnosed pet allergies
Longitudinally accumulated data on sIgE and skin prick tests
indicating allergic sensitization
Pyrhonen et al. Pediatr Allergy Immunol 2015: 26: 247–255.

Independently of allergic family history,
the incidence of a positive test for
either dog or cat allergens was higher
and started to rise earlier in children
exposed to respective pet allergens
at home compared with non-exposed
Pyrhonen et al. Pediatr Allergy Immunol 2015: 26: 247–255.
Early exposure to dog and cat at home is strongly associated with
respective pet allergy and IgE-mediated sensitization to respective
pet allergens during the first 4 years of life

1.) Although exposure to elevated cat allergen Fel d 1
concentrations before 3 months of age may reduce the
likelihood of developing cat sensitization, the risk reduction is
not sufficient to justify a decision to get a cat to avoid IgE
sensitization. (C)
2.) Although exposure to elevated dog allergen Can f 1
concentrations before 3 months of age may reduce the
likelihood of developing dog sensitization, the risk reduction is
not sufficient to justify a decision to get a dog to avoid IgE
sensitization. (C)
Primary prevention

Hypoallergenic pets
In 2004, Allerca Lifestyle Pets, a company based out of San Diego,
California, began to market “hypoallergenic” cats and dogs
Allerca does not claim a 100% success rate for all customers
Claims their pets produce lower allergenic quantities of pet dander
(eg, Fel d 1 and Can d 1 from cats and dogs, respectively)
through gene mutations
Eg. Mindeelyn Siberian Cats, Siberian Cat Breeder, Allerca Lifestyle
Pets, Kitails Siberian Cattery
A. Butt et al. / Ann Allergy Asthma Immunol 108 (2012) 74–76.

“ There was no evidence for differential shedding of allergen
by dogs grouped as hypoallergenic ”
Nicholas E. et al. Am J Rhinol Allergy 25, 252–256, 2011.

Because 1 or more cat/ dog allergens are present
in all cats/ dogs, patients should not be advised that
it is safe to obtain a nonallergenic cat/ dog (C)
>> No studies have shown conclusively that cats
can be hypoallergenic
>> Hypoallergenic dogs were no less allergenic
than regular breeds

Diagnosis
History of pet exposure
Skin prick test / Specific IgE
Challenge/ provocation test
Wood et al. J Allergy Clin Immunol 1999;103:773-9.

Dog epithelium
1:20 (W/V)
Cat hair
10,000 BAU/ml

This study clearly supports the value of SPTs and RASTs
in the diagnosis of cat allergy. Although not perfect,
a positive result with these 2 tests is most often indicative
of a true cat allergy; a negative result, especially for SPTs,
rules out most cases of cat allergy.
IDSTs appear considerably less diagnostically useful.

1.) Avoidance/ Removing pets from home
Avoidance is the most effective way to manage cat and dog allergy.
Patients should be advised to consider removing the cat or dog from
the environment, if present, to improve respiratory health. (A)

By the 20 th week after cat removal,
levels 8/15 homes were within or
very close to the upper
95% confidence limit of the
18 control homes without cats
Median Fel d 1 content reached
that level at approximately 23 weeks
after cat removal
20-24 weeks

2.) Reduce exposure to allergens
To reduce exposure to cat allergens with the cat still living
in the house, a combination of measures, such as removing
reservoirs, keeping the cat out of the bedroom, washing the
cat, air cleaning with a HEPA room air cleaner, improving
ventilation, and mattress and pillow covers, may be helpful. (C)

2.1) Removing reservoirs
Carpeting and bedding serve as significant reservoirs, frequent vacuuming
or ideally carpet removal should be considered (C)
To reduce transport of cat allergen, people should consider changing their
clothes when traveling from a high cat allergen environment to
a low cat allergen environment (C)
Long-term regular use of high-efficiency or central vacuum cleaners
is associated with reduced exposure to Fel d 1 and Can f 1 in homes
with cats or dogs living in them, although the health effects are uncertain. (B)

Mattress encasings
- Some woven microfiber bed encasings, generally those with a mean
pore size of 6 micron or less, block cat allergen from penetrating the
fabric though the respiratory health benefit from their use is unclear. (C)
- Nonwoven microfiber encasings collect allergen on their surface
over time, including cat and mite allergens. Because they cannot be
washed, they are unsuitable for allergen avoidance. (C)

2.2) Removing allergens from pets
Washing cats or dogs at least weekly can reduce airborne
cat Fel d 1 or dog Can f 1; however, the clinical benefit is yet to
be proven and the effect of washing is not sustained. (B)

Suggested that cats should be bathed in tap water or pet shampoo
for at least 3 minutes to solubilize Fel d 1
Avner et at. J Allergy Clin Immunol 1997;100:307-12.

Immersion of cats in water for 3 minutes produced a highly significant
reduction in airborne allergen 3 hours later, but the quantity of allergen
becoming airborne from the cat did not remain low 1 week later
Avner et at. J Allergy Clin Immunol 1997;100:307-12.

HEPA air cleaners run continuously over time can reduce
exposure to dog and cat allergen concentrations, but the clinical
benefits are unknown. (B)
2.3) Air filtration
2.4) Use of dry heat
Dog and cat allergens are relatively stable to dry heat so dry
heat should not be used specifically to reduce exposure. (C)

2.5) Chemical treatments
Chemical treatments, such as tannic acid, can be applied to
carpet to give short-term reduction of cat allergen, but this is not
sustained and there is no evidence that it improves respiratory
health. (C)
Use of hypochlorite bleach to denature indoor allergens can
reduce allergen exposure, improve quality of life, and reduce the
likelihood of developing atopy, but it can also lead to increased
respiratory symptoms in individuals using it. (C)

Sufficient control of exposure to cat allergens to improve
health requires a combination of measures, such as removing
reservoirs, keeping the cat out of the bedroom, washing the cat,
air cleaning with a HEPA room air cleaner, improving ventilation,
and mattress and pillow covers. (C)
Combination measures

SHARMA et al. Pediatr Clin N Am 54 (2007) 103–120.

Cat hair extracted for 3 minutes with tap water or pet shampoo
for 3 minutes can remove a mean of 200 g of Fel d 1 per gram of hair

Exposure to both dog and cat allergen has been shown to be ubiquitous
and can occur even without an animal in the home, making avoidance
even more difficult
The major allergen content of cat extracts is relatively low, requiring
larger amounts to be given than for pollens or house dust mite
The major allergen content of most dog extracts is too low
to allow effective dosing, even with undiluted manufacturers' extracts
Allergen immunotherapy 2011 : a practice parameter third update

The first randomized double-blind placebo-controlled trial using SCIT
for cat-induced asthma was reported in 1984.
- received SCIT with purified cat pelt allergen : 9 patients
received placebo : 8 patients
Results : The treatment group was shown
- delayed onset of ocular and respiratory symptoms with cat exposure
- decreased magnitude of SPT reactivity to cats
- decreased methacholine responsiveness
- increased serum IgG to cat allergen
Ohman JL Jr , et al. J Allergy Clin Immunol 74:230 –239, 1984.

Lilja et al. J Allergy Clin Immunol 1989;83 :37-44.

Alvarez-Cuesta et al. J Allergy Clin Immunol 1994;93:556-66.
" Standardized cat extract IT "

Allergen immunotherapy 2011 : a practice parameter third update

SCIT has shown real benefit in cat-allergic patients with
allergic asthma and allergic rhinoconjunctivitis. The data
for dog are less robust
SLIT remain experimental
Morris Ling, et al.Allergy Asthma Proc 31:385–391, 2010.
Dog epithelium
1:10 (W/V)
Cat hair
10,000 BAU/ml

Furry animals allergy (Dogs and Cats)

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Furry animals allergy (Dogs and Cats)

Similar to Furry animals allergy (Dogs and Cats) (20)

More from Chulalongkorn Allergy and Clinical Immunology Research Group

More from Chulalongkorn Allergy and Clinical Immunology Research Group (20)

Recently uploaded

Recently uploaded (20)

Furry animals allergy (Dogs and Cats)