House dust mite allergy

House Dust Mite
Allergy
Kullapornpas Benyajirapach, MD
October 26th, 2018

Scope
• History and Introduction
• HDM Allergen
• Mechanisms of HDM Allergen-Induced Sensitization
• HDM-Associated Allergic Diseases
• Diagnosis of HDM Allergy
• Treatment

History and Introduction
• In 1967, Spieksma and Voorhorst established that the dust mite,
Dermatophagoides pteronyssinus, was an important source of house
dust allergens in the Netherlands
• They developed techniques for growing mite - dust mite extracts
• Child or adult spends at least 23 hours a day indoors—at home, in
school, or at work
Thomas A.E. Platts-Mills. Middleton’s Allergy 8th edition. 453-469.

History and Introduction

Phylum
Arthropoda
• “Domestic mites” –
any species of mite
found in homes
• “Dust mites” –
pyroglyphid mites
• “Storage mites” –
in grain, flour, hay and
straw

House Dust Mite
• Dust mites - approximately 0.3 mm in
length
• Mites are eight-legged and sightless
• Live on host skin scales and other debris
• Not capable of searching source of
moisture or drinking liquids
• Entirely dependent on environment
humidity
• Fairly tight optimal growth temperature
between 65-80°F (18-26°C)

Distribution of
Dermatophagoides Species
• D. farinae grows with RH of 50%
• D. pteronyssinus prefers them over 60%
• D. pteronyssinus tends to be most abundant in regions with high
HDM densities (from its faster growth rate)
• Only a few countries have either predominantly D. pteronyssinus or
D. farinae
Wayne R Thomas. Asian Pac J Allergy Immunol 2010;28:211-24

Distribution of
Dermatophagoides Species
• In Asia; Singapore, Malaysia, Hong Kong and the Phillipines have D.
pteronyssinus dominantly
• Thailand and Taiwan have more D. pteronyssinus than D. farinae
• China and Japan have mixed populations
• South Korea is heavily infested with D. farinae although south and south
western cites have D. pteronyssinus
Wayne R Thomas. Asian Pac J Allergy Immunol 2010;28:211-24

HDM in Thailand
N. Malainual et al. Clinical and Experimental Allergy 1995;25:554-560

Mite Life Cycle
Consists of 5 stages:
- Egg
- Larva
- Protonymph
- Tritonymph
- Adult
- Reach adulthood
within 3-4 weeks
- Adult mite life
expectancy 4-6 weeks
- Lay 40-80 eggs
Caldereon et al. J Allergy Clin Immunol. July 2015;136:38-48.

Mite Life Cycle
• Duration of development influenced by ambient relative humidity
(RH) and temperature
• D pteronyssinus - greatest population growth occurs at 25°C (10°C-
35°C)
• D farinae - complete the life cycle at extreme temperatures of 16°C
and 35°C
• Produce 2-3 eggs/day during an approximate 26- and 34-day
reproductive period for D pteronyssinus and D farinae, respectively,
at 23°C and 75% RH
Larry G. Arlian et al. J Allergy Clin Immunol. March 2001;107:406–413.

Mite Life Cycle **
• The lowest RH water balance can be maintained (critical humidity)
for D farinae = 55%-73% for temperatures 15-35°C
• Mites gradually dehydrate and die when continuously exposed to
prolonged periods of RH below the critical humidity level
• Isolated adult male and female D farinae and D pteronyssinus mites
die in 5 to 11 days when continuously exposed to 40% RH at 25°C to
34°C
• Too much moist air can inhibit mite growth
Larry G. Arlian et al. J Allergy Clin Immunol. Jan 2001;107(1):99-104.

Seasonal Variations in Mites
• Humidity within carpets, sofas, mattresses, or clothing
• As humidity falls, mites will withdraw from the surface
• It may take months for mites to die and longer for allergen
levels to decrease

Mite Fecal Particles
• Mites excrete partially digested food mixed with digestive enzymes
as fecal particles surrounded by a chitinous peritrophic
membrane
• Fecal particles represent a major form in which mite allergens
accumulate in house dust
• Peritrophic membrane - particles remain intact, but not waterproof
• Under aqueous conditions - allergens rapidly elute
• Mite fecal pellets - similar to pollen grains in size (10 to 35 μm in
diameter), in the quantity of allergen they carry (approximately 0.2
ng), and in their rapid release of proteins

House Dust Mite

HDM Allergen
• First major mite allergen purified = D. pteronyssinus allergen I
(Der p 1)
• 24-kD glycoprotein has both sequence homology with cysteine
proteinases and functional enzymatic activity
• Second major allergen identified using polyclonal sera, and mAb
assays allowed purification and subsequent cloning of the protein
Der p 2
• Homologous cross-reacting allergens are produced by D. farinae
• Mite allergens referred to as group 1 (Der p 1 and Der f 1) and group
2 (Der p 2 and Der f 2)
Thomas A.E. Platts-Mills. Middleton’s Allergy 8th edition. 453-469

HDM Allergen

HDM Allergen
• Mite allergens - in the form of fecal particles
• Contain mite-derived proteins and
endotoxin derived from bacteria, mite
DNA, and bacterial DNA (unmethylated)
• Endotoxin - potent TLR-4 agonist
• Unmethylated DNA - activate TLR-9
• Peritrophic membrane of the particle - made of
chitin
• Chitin and its breakdown products - act on
TLR-2 and dectin-1

Gregory and Lloyd. Trends Immunol. 2011;32(9):402-411.
HDM Allergen

M. Raulf et al. Allergo J Int 2015;24:68-80.
Mite Allergen Groups
Major Allergens:
Group 1, Group 2
Der p 1 and Der p 2
strongly associated
with asthma, rhinitis

Der p 11 - more
common in sera from
patients with Atopic
Dermatitis

Der p 23, major
allergen
associated with
asthma

Mite Allergens
Functional Overview
Functions of allergens
• Proteases - Der p 1, 3, 6, 9, 20
• Lipid-binding proteins - Der p 2, 7, 13, 14
• Contractile proteins - Der p 10, 11, 16, 17, 24
• Glycosidases and carbohydratebinding proteins Der f 4, 12,
15, 18, 23
• Der p 5, 19, 21, and 22 - unidentified as to function
J. Portnoy et al. Ann Allergy Asthma Immunol 2013;111(6):465-507.

Mite Allergens – Protease
• Intestinal tract of mite
• Der p 1 - cleave CD23 IgE receptor from human B-cell
membranes → ablating the feedback inhibitory mechanism that
normally limits IgE synthesis
• Der p 1 - cleave CD25 subunit of the T-cell interluekin-2
receptor → promote TH2 responses
• Der p 1, 3, 6, 9, and 20 - degrade tight junctions in lung
epithelium → release of proinflammatory cytokines from bronchial
epithelial cells, mast cells, eosinophils, and basophils

Mite Allergens –
Lipid-binding Proteins
• Der p 2, 7, 13, and 14 - lipid-transfer or lipid-carrying proteins
• Der p 2 - related to lymphocyte antigen 96 (MD-2 protein) that
allows toll-like receptor 4 to bind to endotoxin
• Der p 2 - related to the activation of innate immunologic
mechanisms → TH2 immunolgic responses.

Mite Allergens – Glycosidases
and CHO-binding Proteins **
• Der p 4 – α-amylase
• Der p 15 and 18 – chitinases
• Der p 20 - arginine kinase, binds chitin
• Chitin fragments - immunomodulator
• Chitinases → facilitate their production
from plants, fungi, and insects → induce TH2
responses

Mite Allergens – Muscle, Cytoskeleton, Ca2+-
binding proteins
• Der f 10, 11, 16, 17, and 24 - tropomyosin, paramyosin, gelsolin,
Ca2+-binding protein, and troponin C respectively
• Involved in structural aspects of cells: cytoskeleton organization,
membrane trafficking, and lipid signaling (regulation of
diacylglycerol and phosphatidylinositol 4,5-bisphosphate signaling
pathways)

Mite Allergens – Muscle, Cytoskeleton, Ca2+-
binding proteins
• Der p 10 - tropomyosin that shares more than 65% of
residues with other invertebrate
• Recombinant allergen cross-reacts with shrimp
tropomyosin
• Tropomyosin - responsible for clinical cross-reactivity
between dust mites and seafood (shellfish,
crustaceans)
• In a study of dust mite–allergic patients from
southern Bavaria, IgE antibodies to Der p 10 were
found in 4 of 93 sera (4.3%)
• Two of these patients had oral symptoms accompanied
by bronchospasm after consumption of shrimp

Mechanisms of HDM Allergen-Induced Sensitization

Gregory and Lloyd. Trends Immunol. 2011;32(9):402-411.

Caldereon et al. J Allergy Clin Immunol. July 2015;136:38-48.

House Dust Mite Associated
Allergic Diseases

Relevance of HDM to Allergic
Diseases
• Chronic rhinitis, asthma, and atopic dermatitis
• Rarely conjunctivitis, urticaria, and anaphylaxis
• Atopic dermatitis - almost all on dust mite sensitization
• High titer of IgE antibody to dust mite (i.e., greater than 30 IU/mL)
was very strongly associated with atopic dermatitis (odds ratio [OR],
20 or greater)

Sensitization or Disease
• Sensitization threshold level
= 2-μg group 1 mite allergen, or about 100 mites/g of dust
• But “threshold” for sensitization of nonallergic children
∼20 μg/g or higher
• Threshold level for developing symptoms in sensitized individuals
= 10 μg/g of dust
• In a prospective study, exposure to high levels of allergen at age 1
year → ↑ risk for development of asthma by the age of 10 years and
related to early onset of asthma
• In addition, studies in children older than 3 years of age hospitalized
for asthma exacerbations in England showed that 80% were both
sensitized and exposed to high levels of relevant allergen at home.

Indoor Allergen Exposure and
Sensitization or Disease

• 85% of patients sensitive to house dust
mites were positive to both D.
pteronyssinus and D. farinae,
indicating substantial cross-reactivity
• House dust mite and the cockroach are
important aeroallergen sensitizers
among Thai population
• More than half patients were skin-test
positive to the house dust mite and the
cockroach
Pumhirun et al. Asian Pac J Allergy Immunol 1997;15:183-185.

Sritipsukho P. Asian Pac J Allergy Immunol 2002;22:91-95.

Sporik R et al. N Engl J Med 1990;323:502-7.

• A positive SPT to HDM at age 1 or 2 years predicted wheeze at age 12 years (adjusted odds ratio: 1 year, 3.31
[95% CI 1.59-6.91]; 2 years, 6.37 [95% CI, 3.48-11.66])
• Among wheezy 1-year-olds, those who were HDM sensitized had a 75% (95% CI, 51-%) probability of wheeze at
age 12 years compared with a 36% (95% CI, 23-50%) probability among those not sensitized
• Among eczematous 1-year-olds, those who were HDM sensitized had a 67% (95% CI, 45-84%) probability of
wheeze at age 12 years compared with a 35% (95% CI, 25-45%) probability among those not sensitized
• Among 1-year-old children with both eczema and wheeze, the probability of wheeze at age 12 years was
64% (95% CI, 35-87%) if HDM sensitized and 50% (95% CI, 26-74%) if not
• HDM sensitization at age 1 or 2 years in wheezing and eczematous children at increased familial allergy risk
predicts asthma
Lodge et al. J Allergy Clin Immunol 2011;128:782-8.

• rDer p 11 allergen was localized in the
muscle beneath the skin of mite bodies
but not in feces
• Der p 11 - major allergen for patients
suffering from atopic dermatitis (AD),
whereas it is only a minor allergen for
patients suffering from respiratory forms
• rDer p 11 might be a useful serological
marker allergen for the identification of a
subgroup of HDM-allergic patients
suffering from HDM-associated AD
Banerjee et al. J Invest Dermatol. 2015 January;135(1):102–109.

Diagnosis
• Skin prick testing
• Specific IgE
• Nasal provocation testing (NPT) - in perennial allergic rhinitis (AR)
due to house dust mites when inconclusive history information
• Absolute contraindications to NPT:
 Acute inflammatory diseases of the nose or paranasal sinuses
 Procedures in nasal cavity or paranasal sinuses < 8 weeks in the past

HDM Allergen Extracts
• Quantity of dust mite allergen in house dust extracts varied widely,
0.05 - 2.0 μg/mL of Der p 1
• Dust mite extracts made either from whole-mite culture or from
isolated mite bodies → different ratios of group 1 to group 2
allergens
• Extracts made from bodies of D. pteronyssinus - 40 μg/mL of Der p 1
and 30 μg/mL of Der p 2
• Wholeculture extract - at least 10 times more group 1 than group 2
• In the United States, all extracts made from isolated mite bodies
• In Europe, both types of extracts available

Avoidance Measures

Environmental Assessment and Exposure
Control of Dust Mites:
Practice Parameter 2013
• 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, primary prevention might not be possible to achieve in
regions where mite exposure is prevalent.
(Strength of recommendation: strong, A evidence)
• Minimize exposure of dust mite–sensitized children to dust
mite allergens to decrease their risk of developing asthma and
possibly rhinitis.

• Advise dust mite–sensitized patients with asthma or rhinitis
to minimize exposure to dust mite allergens in addition to
avoiding other relevant allergens to which they are sensitized and
avoiding irritants, to decrease their risk of developing symptoms.
(Strength of recommendation: strong, B evidence for asthma;
strength of recommendation: strong, C evidence for rhinitis)
• Advise patients to minimize exposure of dust mite–sensitized
children with atopic dermatitis to dust mite allergens, to decrease
the symptoms of atopic dermatitis.
(Strength of recommendation: moderate, C evidence)

• Although 5-15% of patients who are highly sensitized to dust mite
also are sensitized to crustaceans, the clinical significance of this is
unknown. For that reason, no recommendation can be made
regarding the need to advise crustacean-naive patients about
their risk of ingestion.
(Strength of recommendation: none, D evidence)
• Evaluate patients who complain of oral symptoms or symptoms
consistent with an IgE-mediated reaction after ingestion of
grain flour for dust mite sensitization regardless of whether
they have wheat-specific IgE.

• Currently there is no evidence supporting routine
measurement of specific IgE to dust mite components,
although such measurements may be considered when necessary,
such as for patients with potential Der p 10 (tropomyosin as found in
cockroach and crustaceans) sensitivity.
(Strength of recommendation: weak, D evidence)

• Encourage dust mite–allergic patients to
obtain and use a hygrometer to measure
humidity in their home.
(Strength of recommendation: strong, D evidence)
• Advise patients that relative humidity in the home should be kept
at 35% to 50% to decrease the growth of dust mites.
(Strength of recommendation: strong, B evidence)

• Do not recommend the use of acaricides to eliminate mite populations
because of their limited efficacy at lowering allergen levels and concerns
about the use of chemical agents in the home. (Strength of
recommendation: moderate, B evidence)
• Tell patients that the use of physical measures to kill mites, such as
heating, freezing, and desiccation, theoretically should be effective;
however, controlled trials have not been performed to demonstrate clinical
benefit when they are used. (Strength of recommendation: weak, D
evidence)

• Bedding should be washed weekly to decrease dust mite
numbers and mite allergen levels, and that high temperature is
not necessary. Home hot water should be kept below the
temperature (120°F) that causes a scalding risk to occupants.

• Recommend regular vacuuming using cleaners
that have high-efficiency particulate air
(HEPA) filtration or with a central vacuum with
adequate filtration or that vents to the outside to
decrease exposure to dust mite allergen-containing
particles.
• Recommend that patients should use mite
allergen–proof mattress, box spring, and
pillow encasings to decrease exposure to mite
allergens.

• Discourage members of families with an atopic background from
sleeping in bunk beds. If bunk sleeping is necessary, the
sensitized person ideally should sleep in the top bed and the top and
bottom mattresses (and any fabric-covered “bunky-boards”) should
be enclosed in allergen-impermeable encasings.
(Strength of recommendation: moderate, B evidence)
• Do not recommend tannic acid for decreasing mite allergens in
carpet dust because it is only marginally effective.

• HEPA filtration alone is of uncertain benefit for patients with mite allergy, although it
can decrease local exposure to airborne mite allergens and to some irritants. If used,
recommend that HEPA cleaners should be placed in areas of mite contamination
where air disturbance is likely to suspend particles so that they are available for removal.
(Strength of recommendation: weak, C evidence)

• Offer subcutaneous immunotherapy to dust mite–allergic
patients with rhinitis or mild to moderate asthma if they meet
the general criteria for receiving allergen immunotherapy
(Strength of recommendation: strong, A evidence for asthma;
strength of recommendation: moderate, B evidence for rhinitis)
• Consider subcutaneous immunotherapy for dust mite–allergic
patients with atopic dermatitis if they meet the general criteria
for receiving allergen immunotherapy; however, possible
exacerbation of the disease during the initial phase of
immunotherapy should be discussed with the patient
(Strength of recommendation: moderate, A evidence)

• Patients receiving immunotherapy for dust mite ideally should
receive a dose that delivers approximately 7 µg of Der p 1 per
injection or 500 to 2,000 AU per injection to obtain an optimal
balance between efficacy and safety.
• US dust mite extracts can be mixed with pollen extracts,
including grass and animal dander extracts. Also at
maintenance immunotherapy concentration, US dust mite
extracts can be mixed with fungal or cockroach extracts when
glycerin content is kept at 10%.
(Strength of recommendation: moderate, LB evidence)

• Recommend 3 to 5 years of immunotherapy to obtain the
maximum benefit from immunotherapy for dust mite–induced
asthma and rhinitis.
(Strength of recommendation: moderate, A evidence)
• Certain protocols and dosages of sublingual immunotherapy have
been shown to be safe and effective for dust mite–allergic patients
with rhinitis, mild to moderate asthma, and/or atopic dermatitis;
however, because there currently is no Food and Drug
Administration–approved product available in the United States, its
use should not be recommended until such a product becomes
available. (Strength of recommendation: moderate, A evidence)

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