furry animals allergy (dogs and cats)

Furry animals allergy

(Dogs & Cats)

Lalita Tearprasert; M.D.

Scope

IntroductionPrevalenceCats & Dogs allergensClinical effects of allergen exposureDiagnosisEnvironment 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

Prevalence

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 yearswho were diagnosed with AR

by history and clinical presentationunderwent 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 2004at ENT Allergy Clinic at Siriraj Hospital : 736 patients

THAILAND

Cat & Dog allergens

Taxonomy

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 longerKonradsen et al. J Allergy Clin Immunol 2015;135:616-25.

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

http://www.asthmacenter.com/index.php/news/details/pet_allergy/


Major allergens

Lipocalins


More than 50% of thefurry animal allergens

Small, secreted proteinsA group of proteins involved as ligand transport proteins with

enzymatic activity, participating in cell homeostasisFound in dander, saliva, and urine; sticky particlesShare 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 allergensFel 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 1Purification of Fel d 1 by Ohman et al. in 1974More 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 1Size 14 kDaAppears to be a unique marker for the presence of catsAll natural breeds of cat produce Fel d 1Males producing a larger amount than femalesPrimarily produced in sebaceous, anal, and salivary glandsMainly present in the epidermis and fur (root > tip) The highest concentrations being found on hair from the neck




No important cross-reactivities with other mammalianSpread to the environment through airborne danderThe biological role of secretoglobin is unknownAllergenicity 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 allergenSize : relatively large (62-kD) proteinTarget of IgE antibodies in approximately 10% of cat-allergic subjectsCross-reacts immunologically with several different mammalian

albumins, including those of dog, pork, and beef >> Pork-cat syndrome

PORK- CAT SYNDROMEPrimary sensitization is related to environmental exposure to cat albuminCross-reactivity between cat and pork albuminCan affect children and adults. Majority being adults or teensPresenting with food-related or idiopathic urticarial

or anaphylactic symptoms : Allergic reactions to porkBoth 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 mealOnset 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 salivaIt 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 asthmaMain 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


CauseAlpha-gal is not naturally present in humans, but is all other mammalsPrimary 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

AirborneSmall 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 allergenSize 23-25 kDaSecreted 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 dogs50-90% of patients sensitized to dog have antibodies to Can f 1



288 healthy dogsLevels 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 salivaIgE 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 kallikreinFound in up to 70% of patients with dog allergyNo patterns of cross-reactivity to allergens from other furry animalsCross-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)


Early exposure Good or bad ??

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.

FinlandAll 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 allergiesLongitudinally 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) Environmental assessment and exposure control 2012 : a practice parameter—furry animals

Primary prevention

Hypoallergenic petsIn 2004, Allerca Lifestyle Pets, a company based out of San Diego,

California, began to market “hypoallergenic” cats and dogsAllerca does not claim a 100% success rate for all customersClaims 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 exposureSkin prick test / Specific IgEChallenge/ provocation test

Environmental assessment and exposure control 2012 : a practice parameter—furry animalsWood et al. J Allergy Clin Immunol 1999;103:773-9.


Dog epithelium1:20 (W/V)

Cat hair10,000 BAU/ml

Wood et al. J Allergy Clin Immunol 1999;103:773-9.

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.


Environment control


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

Immunotherapy

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 epithelium1:10 (W/V)

Cat hair10,000 BAU/ml

Thank you

furry animals allergy (dogs and cats)

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