House dust mite allergy

House dust mite
Allergy
Lalita Tearprasert; M.D.

Scope
• Introduction
• HDM allergens and Cross-reactivity
• HDM & Respiratory allergic diseases
• Mechanisms of HDM allergen induced sensitization
• Diagnosis of HDM Allergy
• Preventive and Therapeutic Approaches for HDM Allergy

Introduction
• Major perennial indoor allergen cause Asthma, AR, AD
• 50 – 85% of asthmatics are typically HDM allergic
• Prevalence data for HDM allergen sensitization vary from 65 to130 million
persons (1-2%) in the general population worldwide
• Geographic variation
• In1967, Spieksma and Voorhorst established that the dust mite,
Dermatophagoides pteronyssinus, was an important source of house dust
allergens in the Netherland
Thomas A.E. Plattes-Mills. Middleton's Allergy 8th Edition. 453-469.
Gregory and Lloyd.Trends Immunol. 2011; 32(9): 402–411.

Phylum Arthropoda
Domestic mite:
Any species of mite found in house
Dust mite:
Family Pyroglyphidae
- Dermatophagoides
- Euroglyphus
Storage mite(flour,grain, barn, hay):
Family Acaridae & Glycyphagidae
(Tropical mite : Blomia tropicalis)

J. Portnoy et al. / Ann Allergy Asthma Immunol 111 (2013) 465-507.
Domestic
mite

Family Pyroglyphidae
• Dermatophagoides (Subfamily Dermatophagoidinae)
- Dermatophagoides pteronyssinus (Dp)/ European HDM
- Dermatophagoides farinae (Df)/ American HDM
• Euroglyphus (Subfamily Pyroglyphinae)
- Euroglyphus maynei (Em)
>> England, Europe, the southern United state
>> Em frequently co-inhabits with Dp and Df in some geographical areas
>> Many patients sensitive Dp, Df are also sensitive to Em
>> Extracts of Em for diagnosis and immunotherapy are not
commercially available
House dust mite
The two most common HDM species worldwide : Dp, Df
Fernández-Caldas et al. Chem Immunol Allergy, 2014, vol 100, 234–242.
Morgan S. et al.Int Arch Allergy Immunol 2015;166:267–272.

• D. pteronyssinus (Dp) tends to be most abundant.
• Only a few countries have either predominantly D. pteronyssinus or D. farinae.
- Australia, New Zealand, England and Mauritius have D. pteronyssinus
with few other HDM
- Singapore has a bias to D. pteronyssinus but with B. tropicalis
- Most of South Korea has a bias to D. farinae especially in the northwest
- Italy also has D. farinae -biased
• In Asia; Singapore, Malaysia, Hong Kong and the Phillipines have
D.pteronyssinus as the dominant pyroglyphid HDM.
Thailand and Taiwan and have more D. pteronyssinus than D. farinae
Distribution of Dermatophagoides species
Wayne R Thomas. Asian Pac J Allergy Immunol 2010;28:211-24.

In Thailand
N.Malainual et al. Clinical and Expiramental Allergy ,1995, Volume 25, 554-560.

• Eight-legged, Sightless
• 0.3 mm. in length
• Absorbing water through Hygroscopic substance
extrude from leg joints
• Habitat with 3 key macromolecules derived from
organic debris
- keratin (human skin scales) --> food source
- cellulose (textile fibers)
- chitin (fungal hyphae and mite cuticles)
Caldereon, et al. J Allergy Clin Immunol. July 2015;136:38-48.
• Excrete fecal particles
- contain allergenic digestive enzyme
- chitinous peritrophic membrane (not waterproof)
- size 10-35 micron (similar to pollen grain)
- carry allergen 0.2 ng
- airborne and easily inhaled

Life cycle- Egg to adult : 1 month
- Adult living an additional 1-3 months.
- Adult females lay up to 40-80 eggs

• Temperature : 65-80°F (20-25°C)
• Relative humidity (RH) : 70-75%
>> carpets, sofas, mattresses, or clothing
Optimum growth condition
Thomas A.E. Plattes-Mills.Middleton's Allergy 8th Edition. 453-469.
Yu SJ, et al.Asia Pac Allergy 2014;4:241-252.

• Environmental factors of temperature and RH is reflected in seasonal fluctuations
in dust mite numbers and allergen levels in different parts of the world.
• Summer is warm and dump so mite population can expand.
• The most important facilitative factor for mite growth is RH.
- Once humidity decreases below 50%, mite proliferation and survival
is decreased.
- Mites can survive for weeks before they die.
- As humidity falls, it may take months for mites to die and longer for
allergen levels to decrease in carpets, sofas, or mattresses.
- An elevated RH for as briefly as little as 1.5 hours per day (cooking, bathing),
the mite can survive. 2 to 3 hours per day, mites can reproduce.

HDM allergens
• Mite allergens are present in mite bodies, secretion and excretion
• Fecal particles contain the greatest proportion of mite allergen

• Airborne mite allergen is detected only during or shortly after
disturbance of dust. Fell rapidly after disturbance.
• Little or no airborne allergen (e.g., less than 1 ng/m3) is
present in undisturbed conditions.
• Indicate that mite allergen is predominantly airborne on
particles greater than 10 µm in diameter.
• Fecal particles become airborne and easily inhaled.

• Exposure to mite allergens is in the form of fecal particles contain
- Mite-derived proteins
- Endotoxin derived from bacteria >> potent TLR-4 agonist
- Mite DNA and bacterial DNA (unmethylated) >> activate TLR-9.
- Chitin peritrophic membrane >> Chitin and its breakdown products can act on
TLR-2 and dectin-1
Potential adjuvants

Mite Allergen Group
M. RAULF et al. Allergo J Int 2015; 24: 68–80. Fernández-Caldas et al.
Chem Immunol Allergy, 2014, vol 100, 234–242.
33 groups
Major allergens (frequency of patients sensitized and amount of specific IgE)
- Group 1 (Der p 1 and Der f 1)
- Group 2 (Der p 2 and Der f 2)

• Allergens from mites include commonly encountered functions
of allergens from a wide variety of sources
- Proteases (Group1, 3, 6, 9, 20)
- Lipid-binding proteins (Group 2, 7, 13, 14)
- Contractile proteins (Group 10, 11, 16, 17, 24)
- Glycosidases and carbohydrate-binding proteins (Group 4, 12, 15, 18, 23)
- Glutathione S-transferase (Group 8)
- Unidentified function
• Most mite allergens are enzymes
Rubaba Hamid Shafique, M.Phil et al. Allergy Rhinol 3: 74–90, 2012.
Mite Allergen functions

Group 1
Caldereon, et al. J Allergy Clin Immunol. July 2015; 38-48
Schulz O. et al. J. Exp. Med. 1998, 271-275
Cysteine proteases
- Destroy the epithelial tight junctions
- Innate immune response :recognized by
PAR-2 and TLRs --> PAMPs
- Adaptive immune : Promote Th2
- Activating mast cells independently of IgE
• Glycoprotein 25 kDa, Heat-labile
• Peptidase enzyme/ Proteolytic enzyme
(Identity with plant enzyme papain)
• Location: Gut
• Der p1, Der f1
• Der p 1: significant role in IgE antibody responses
1.) Cleavage of CD23 (FCeRII on B cells) ----> IgE
2.) Cleavage of CD25 (IL-2R on T cells) ----> Th2 response

• Group 3 : Trypsin-like enzyme
- also found in insect venoms
- Der p 3 quite similar to the cockroach Bla g 10
• Group 6 : Chymotrypsin
• Group 9 : Collagenolytic serine protease
Group 3,6,9
Serine proteases
• Trypsin
- Destroy the epithelial tight junctions
- Trigger PAR-2 ---> results in the initiation of multiple G-protein
coupled signaling cascades
- Promote Th2

• Innate immune: TLR4 (on DCs, airway
epithelium, and airway smooth muscle cells)
bind endotoxin
• Adaptive immune: Promotion of TH2
polarization and inflammatory cell recruitment
Group 2
• Glycoprotein 15 kDa, Heat-stable
• Molecular mimicry of MD-2 protein
(lymphocyte antigen 96)
• Lipid-transfer or lipid-carrying proteins
• Location: Intracellular
• Der p2, Der f2
MD-2 like
lipid-binding protein
Caldereon, et al. J Allergy Clin Immunol. July 2015; 38-48.
Associated with Oral mite syndrome

• Occurs because of shared similar or identical IgE-binding epitopes
• Der p highly cross-reactivity with Der f
- Group 2 allergens are very similar to each other in structure,
with greater than 90% sequence homology, indeed,
no mAb assays currently available can distinguish Der p 2 from Der f 2
• B. tropicalis cross-react partially with other dust mites
>> designated Blo t 5 because it has sequence homology with Der p 5
G. Reese et al.Int Arch Allergy Immunol 1999;119:247–258.
Cross-reactivity

Group10
Tropomyosin
• Muscle protein
• coiled- coil structure, two
parallel alpha-helical
• Location: Muscle
• Der p10, Der f10
• Invertebrates
- Crustaceans (shrimp, lobster,
crab, craw-fish)
- Arachnids (house dust mites)
- Insects (cockroaches)
- Mollusks (e.g. squid)
• 5% to 15% of patients who are
highly sensitized to dust mite also
are sensitized to crustaceans
G. Reese et al.Int Arch Allergy Immunol 1999;119:247–258.
• Found
- Invertebrate >> Allergic
- Vertebrate >> Non-allergic

• Shrimp (Pen i 1, Pen a 1, Met e 1) identity 81-90%
• Cockroachs (Per a 7, Bla g 7) identity 80%
• Other Crustacean
- Crab: Cha f 1
- Lobster: Pan s 1, Hom a 1 identity 81-90%
• Mollusk (Cra g 1, Tur c 1, Tod p 1)
• Helminth (Ascaris, Filaria and Anisakis simplex)
G. Reese et al.Int Arch Allergy Immunol 1999;119:247–258
Tropomyosin
• Der p10, Der f10

Threshold level
• Most studies accept
- Sensitization threshold level 2 μg/g. of dust (100 mites/g.)
- Threshold levels for for developing symptoms
in already sensitized individuals 10 μg/g. of dust (500 mites/g.)
- For nonallergic children higher threshold level 20 μg/g. of dust
World Health Organization (WHO).Bull World Health Organ 1988;66:769-80.
HDM & Respiratory allergic diseases

1. Two-side monoclonal antibody (mAb) based enzyme
immunoassay (ELISA) -- --> Gold standard
- most common available : Der p1, Der f1/ Der p2, Der f2/ Blo t5
2. Guanine (the major nitrogenous excretory product of arachnids)
3. Mite count
Methods of estimating dust-mite allergens
A. Custovic.Allergy 1998; 53 (Suppl 48): 71-76

• Environmental assessment and exposure control of dust mites:
a practice parameter 2013
• Advise patients to minimize exposure of susceptible children to dust mite allergens
to decrease their risk of developing mite-specific IgE. Because intermittent
exposure to mite allergens can lead to sensitization. (Strength of recommendation:
strong, A evidence)
• Advise patients to minimize exposure of dust mite sensitized children to dust mite
allergens to decrease their risk of developing asthma and possibly rhinitis.
(Strength of recommendation: strong, A evidence)
Sensitization & Development respiratory disease

Sporik R et al. N Engl J Med (1990);323: 502-7.
Active asthma was very strongly associated with
both atopy & sensitivity to HDM
Significant relation between high levels of expose
and early onset of wheezing (P=0.001)

Casas et al.European journal of allergy and Clinical Immunology.Allergy 70 (2015); 820-827.
Early life exposure plays a role in the development
of sensitization

Lodge,et al.J Allergy Clin Immunol 2011;128:782-8.
• Birth cohort of 620 children
oversampled for familial allergy
• SPTs to 6 allergens at ages 6, 12, and 24 months
• Wheeze and eczema were recorded during
the first 2 years
• Current wheeze was recorded at age 12 years
• New-onset sensitization by 2 years or sensitization at both 1 and 2 years were both strong predictors
of wheeze at age 12 years

Lodge,et al.J Allergy Clin Immunol 2011;128:782-8.
HDM sensitization was associated with current wheeze at age 12 years

Danansuriya et al. World Allergy Organization Journal (2015) 8:19
• Students with current asthma
were having13 times
higher risk of atopy to HDM
compared to their healthy siblings

• House dust mite and the cockroach are
the most important aeroallergen
sensitizers in Thai allergic rhinitis
patients, since more than half the
patients were skin test positive to the
house dust mite and the cockroach.
• 85% of mite-sensitive patients were
skin test positive to both species of
Dermatophagoides, indicating
substantial cross reactivity.
Pumhirun et al.Asian Pac J Allergy Immunol (1997) 15: 183-185

• 2 Main route
1.) Innate immune system --> Epithelial cells, Dendritic cells
2.) CD4+ TH2 cells induce and IgE-dependent allergic response
Mechanism of HDM allergen induced sensitization
Innate epithelial cytokines
Dendritic cells
Th2

Innate immune system : Epithelial cell
Group 1(cystein protease): PAR-2
Group 2 (MD-2 like LBP): TLR-4
Endotoxin : TLR-4
B-glycan : Dectin-1
Chitin : TLR-2, Dectin-1
Mite&Bac. DNA : TLR-9

Potential enhancement of the allergic response by
HDM
Caldereon, et al. J Allergy Clin Immunol. July 2015;136:38-48.
Der p 1: significant role in IgE antibody responses
1.) Cleavage of CD23 (FCeRII on B cells) ----> IgE
2.) Cleavage of CD25 (IL-2R on T cells) ----> Th2 response
Group 1(cystein protease): PAR-2
Group 2 (MD-2 like LBP): TLR-4
Endotoxin : TLR-4
B-glycan : Dectin-1
Chitin : TLR-2, Dectin-1
Mite&Bac. DNA : TLR-9

• Skin testing and/or specific IgE
• Nasal provocation testing (NPT) : perennial AR due to HDM when the
patient history provides inconclusive information
Diagnosis of HDM allergy
M. RAULF et al. Allergo J Int 2015; 24: 68–80

• D. farinae ,D. pteronyssinus, Mite mix extracts are standardized.
• Commercially available in many country ex. the United States, Europe, Maxico.
• Content of extracts varies depending on whether purified mite bodies or total spent
culture is used as the source material
- Mite bodies greater than 99% purity and are almost exclusively used in the
United States >> 40 µg/mL of Der p 1 and 30 µg/mL of Der p 2
- Spent cultures containing adult mites, eggs, larvae, fecal particles, and culture
medium are often used in Europe >> at least 10 times more group 1 than group 2
Dust mite extracts

1. ) Environment control
- Recommend avoidance for SPT positive to HDM
2. ) Immunotherapy - Subcutaneous (SCIT), Sublingual (SLIT)
Preventive and Therapeutic Approaches
Fernández-Caldas et al.History of Allergy. Chem Immunol Allergy, 2014, vol 100, 234–242.

Environmental control
Avoidance
1.) Physical
2.) Chemical

• A special mite-impermeable
membrane was used in PE and CE
group
• Regular bedsheets were applied to
all groups
• PE group : mattresses were
encased on tops and sides only
CE group : complete mattress
encasement was undertaken
• Mattress encasing with a special membrane was highly efficacious in the reduction of mite
allergen (90%).
• Complete mattress encasing in a tropical environment does not offer any advantage over
partial encasing in the reduction of mite allergen
Vichyanond et al. Allergy 1999, 54, 736-741.
Cover mattresses and pillows with impermeable cover

• The ideal mite cover should have at least 2
important characteristics
1.) block the leakage of mite
allergens from the inside of the
bedding
2.) prevent mites from penetrating
through the covers in either
direction
Mahakittikun et al. J Allergy Clin Immunol 2006;118:1164-8.

• Environmental assessment and exposure control of dust mites: a
practice parameter 2013
- Woven microfiber fabrics with a mean pore size smaller than 10 micron
can effectively block passage of Der p 1 (Strong, B evidence)
- Dust mite allergens (Der f 1 and Der p 1) were decreased to below
detectable limits by fabrics with a pore size smaller than 10 micron

Remove carpets, stuffed animals, and clutter from bedroom
• Removing carpets is more effective in the long term than any currently available carpet
cleaning measure.
• Designing the house with polished floors and wooden or vinyl or leather furniture, to limit the
sites where mites can grow and to reduce dust collectors so as to make cleaning easier.
• The most effective way to manage reservoirs of mite allergens is to remove them completely
from the environment. That means removing carpets, drapes, and upholstered furniture and
sealing mattresses, box springs, and pillows in mite-impermeable covers

Wash bedding regularly 130° F
• 130°F (55°C) can kill mites and allergen removed by washing generally reappears within 1
month
• Washing bedding at 130°F (55°C) once weekly is effective
• Environmental assessment and exposure control of dust mites: a practice parameter
2013
- Most mites that are killed in the washing process die by drowning. Although higher temperature
kills slightly more mites.
- There is evidence that temperatures lower than 130°F are adequate, high temperature is
not necessary.
- Home hot water should be kept below 120°F prevent danger to children.
- Wash bedding weekly in warm water, without aiming for a specific and potentially dangerous
temperature. This will remove most, not all, mites and mite allergens. Clothing also should be
washed after use. (strong, B evidence)

• Vacuum weekly (wearing a mask) using vacuum cleaner with a double-
thickness bag or a high-efficiency particulate air (HEPA) filter.
• Regular (at least weekly) vacuuming is essential for preventing buildup
of mite allergens in homes with carpets.
• Vacuuming does not remove all live mites, mite allergens in the form of
fecal particles can be removed.
Vacuuming
Vacuuming

Reduce humidity
• Reduce humidity below 45% relative humidity (or 6 g H2O/ kg air)
• Environmental assessment and exposure control of dust mites:
a practice parameter 2013
- Advise patients that relative humidity in the home should be kept
between 35% and 50% to decrease the growth of dust mites (Strong, B evidence)
- Encourage dust mite-allergic patients to obtain and use a hygrometer to
measure humidity in their home. (Strong, D evidence)
J. Portnoy et al. / Ann Allergy Asthma Immunol 111 (2013) 465-507

Reduce humidity
• Remove excessive : Using a dehumidifier and/or air conditioning
- Dehumidifier needs to be emptied regularly or set to drain continuously,
and it should be located in areas where dampness is likely to occur.
- Air conditioners need to run long enough to remove sufficient moisture from
the air to decrease RH.

• killing mites
• Benzyl benzoate Moist powder and foam.
- The active powder kills 90% of mites in culture within 12 hours
and 100% in 24 hours
- Reapplied at 2-3 month intervals
- Acaricides are not recommended for use on mattresses, particularly
given the likelihood of exposure to the chemical
- Limited efficacy at decreasing allergen levels
(moderate, B evidence)
Acaricides
Ex. Benzyl benzoate,pyrethroids, natamycin (an antifungal), pirimiphosmethyl
Treat carpets with benzyl benzoate or tannic acid

• Protein-denaturing agent
• Reduce allergen levels in house dust : 1% and 3% solutions
• Does not kill mites, so the effect can only be temporary. Reapplied at 1-2 week intervals
• TA was very effective at reducing mite allergen levels in dust, though it required up to 4
hours to exert its full effect.
Tannic acid
Woodfolk et al. Allergy Clin lmmunol. Volume 94, Number 1, 1994, 19-26.
Treat carpets with benzyl benzoate or tannic acid
• Environmental assessment and exposure control of dust mites: a practice
parameter 2013
- Do not recommend tannic acid for decreasing mite allergens in carpet
dust because it is only marginally effective : concentrations of tannic
acid as low as 0.1% were found to inhibit the ELISA assays
(Moderate, C evidence)

Immunotherapy
Akkoc et al. Allergy Asthma Immunol Res. 2011 January;3(1):11-20.

• Recommend 3 to 5 years
• Effective dose
- SCIT : 7 mg of Der p 1 per dose for European extracts
500-2,000 AU per dose for US extracts
(US >> Der p1:Der p2 = 1:1, Europe >> Der p1:Der p2 = 10:1)
- SLIT : 4,200 AU containing approximately 70 mg of Der f 1 given daily
• Frequency of administration once maintenance is reached
- SCIT : Ranged from weekly to monthly
- SLIT : Daily to 3 times per week
• No evidence to support giving lower doses more frequently or higher doses less
frequently to obtain similar efficacy
• Dust mite extracts are compatible with pollen and animal dander extracts and can be
mixed with fungal and cockroach extracts provided they are kept in glycerin at a
concentration of at least 10%
Immunotherapy
Practice parameter 2013

• Retrospective study
• 39 patients (23 boys,16 girls)
• Children with asthma and rhinitis who
were allergic to house dust mite
• 3 years of SLIT with 50 % Der p and
50 % Der f in a standardized extract
Conclusion
• SLIT is effective in children who have
allergic airway disease which cannot be
controlled effectively with allergen
avoidance measures only
Y Nuhoglu, et al. J Investig Allergol Clin Immunol 2007; Vol. 17(6): 375-378.

Cingi C. et al. Eur Arch Otorhinolaryngol. 2014.
• 186 patients with AR who had positive SPT for HDMs
• Administered SLIT using for 1 year
• Evaluation of the patients regarding
- symptom scores
- clinical findings
- Rhinitis Quality of Life Questionnaire (RQLQ)
• At baseline, 6 and 12 months of therapy.

HUI Y. et al. Expiramental and therapeutic medicine 7: 630-634, 2014.
• 90 asthmatic children (with or without
allergic rhinitis) with a mild to moderate
HDM allergy (aged, 5-14 years) were
recruited
• SCIT combined with standardized
management (ICS) for 36 months.
• Suggest that long-term SCIT may
alleviate asthma symptoms and reduce
the required dose of ICS.

In thailand
• A double blind, self-controlled study between the
SMAV and standardized commercial mite allergen
vaccine
• 17 normal Thai adult males and non-pregnant or non-
lactating females aged 18-60 years
Result
- No significant difference in wheal and flare
diameter
- Significant correlation between wheal diameter
- Suggested that SMAV could be used for SPT
instead of using the more expensive imported
commercial vaccine
Visitsunthorn, et al.ASIAN PACIFIC JOURNAL OF ALLERGY AND IMMUNOLOGY (2010) 28: 41-45.

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