Dust Mite Allergy

Etiology

Dust mite allergy develops in childhood or adolescence, with the majority of symptoms manifesting before age 20. The dust mite's gut contains peptidase 1, which is one of the potent digestive enzymes that persist in their fecal matter and is the major inducer of the allergy. Peptidase 1 exhibits cysteine protease activity. The variants of the allergen include Der p 1 of the European house dust mite, Dermatophagoides pteronyssinus, Der f 1 of the American house dust mite Dermatophagoides farinae, Eur m 1 of the Mayne's house dust mite Euroglyphus maynei.[3] 

These allergens are found in the fecal matter of the mites. Their fecal particles are around 20 pellets per day, surrounded by a peritrophic membrane, are about the size of a pollen grain (10-35 mcg diameter), thus can be easily inhaled. The mite's exoskeleton can also contribute to allergic reactions. These allergens on inhalation cause a sensitization reaction, through epithelial leakage into the respiratory system by cleavage of the tight junctions in between the epithelial cells. This leads to increased epithelial permeability, allowing the movement of house dust mite allergens to dendritic antigen-presenting cells.[4]

The house dust mites do not burrow under the skin and are not parasitic. Dust mites are microscopic bugs about 0.4 millimeters in length, and invisible to the naked eye. They are known to feed on the desquamated dead skin cells of humans and pets. They prefer a warm and moist environment of 70 degrees F and 70 percent humidity. Therefore, bedding, linens, carpeting, furniture linens that trap the moisture and provide the most favorable environment for the dust mites to flourish. House dust mites belong to the family Pyroglyphidae, primarily consisting of Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Euroglyphus maynei.[1][5][6] 

These species constitute 80 to 90 percent of the house dust mites. The most important house dust mite is Dermatophagoides pteronyssinus. In drier areas, D. farinae is commonly found. In tropical and subtropical areas, the storage mite, that is, glycyphagid mite Blomia tropicalis (storage mite), which coexists with D. pteronyssinus, is a major source of allergen. Gylcyphagus and Lepidoglyphus may be found in rural homes.

Epidemiology

Dust mite allergy is a prevalent form of allergy. It affects 20 million people across The United States of America. Being ubiquitous, house dust mites are found all across the world. Around 84 percent of USA households have been detected with the presence of house dust mites.[1] In industrialized areas, like Germany, 1 out of every four people are affected by dust mite allergy. Combined, allergic rhinitis (AR) and asthma affect up to 800 million people worldwide, according to the World Health Organization (WHO).[7] 

Up to two-thirds of children with asthma and up to 1/2 of adults who have asthma also suffer from allergies. Of these patients who suffer from asthma and allergies, about 40%-85% of them are allergic to the HDM, this trend is observed all over America, Europe, south-east Asia, and Australia. Around 5 to 30 percent of the general population show house dust mite sensitivity to skin test reactivity.

Ninety-seven percent of people with dust mite allergy are sensitized to the allergen Der p 1. Der p 11 has been most frequently associated with atopic dermatitis.[3] 70 percent of the people with dust mite allergy have been recently found to be sensitized to Der p 23 allergen.[8] To date, 24 allergens associated with house dust mite have been identified.

Pathophysiology

IgE mediated sensitization is responsible for the pathogenesis of dust mite allergy. This a Type 1 hypersensitivity reaction in which the CD4 + and T helper cells stimulate the B cells to produce IgE antibodies specific to the antigen, which is the house dust mite allergen. The IgE binds onto the FceRI receptors on mast cells and blood basophil cells. The mast cells and basophil cells now get sensitized to the allergen-specific IgE antibodies. On subsequent exposure to the same allergens, there is crosslinking of the bound IgE sensitized cells, leading to their degranulation. The inflammatory mediators are released, causing the clinical manifestation of the dust mite allergy. Sensitizations to the dust mite allergens occur quite early in life and lead to a progression from allergic rhinitis to asthma. This is known as the allergic march.[1] It is a significant risk factor for the development of asthma.[9] 

When the house dust mite fecal pellets are inhaled, they contact the airway epithelium and become hydrated and discharge their allergenic contents onto a mucosal barrier. For interaction with dendritic antigen-presenting cells, potential allergens must cross this protective epithelium. The tight junctions are the route for their entry. The allergens, predominantly, Der p 1 disrupt these tight junctions by either of the following two processes:

1. Proteolytic cleavage of protease-sensitive receptors on the epithelial barrier of respiratory epithelium cells, leading to access of allergens to the antigen-presenting cells, mainly the dendritic cells. The dendritic cells give these allergens to the T helper-2 cells, which respond by the release of cytokines, mainly granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-6 (IL-6) and interleukin-8 (IL-8) that attract the inflammatory cells to the airway. The T helper 2 cells activate the B cells to produce IgE, which are produced in large numbers in subsequent allergen exposure. When the individual is exposed to house dust mite allergen again, the allergens bind to the IgE, and the IgE binds to the mast cells and basophils, causing their degranulation and causes the release of histamine and leukotrienes, from bronchial epithelial cells, mast cells, and basophils. The proteases also lead to changes in the concentration of intracellular calcium and increased expression of Interleukin-6 mRNA.[10]
2. Activation of transduction signaling pathways that lead to the release of chemokines.[4]

Two major groups of allergens from mites of the genus Dermatophagoides have been identified.[11]

• Group I. These allergens are glycoproteins that demonstrate both structural homology and cross-reactivity. An example of this group of allergen is Der p 1.
• Group II. These show a closer homology and cross-reactivity.

The common house dust mites and their allergens are listed as follows:

• Der p 1, house dust mite Dermatophagoides pteronyssinus allergens
• Der p 2, house dust mite Dermatophagoides pteronyssinus allergens
• Der p 23, house dust mite Dermatophagoides pteronyssinus allergens
• Der f 1, house dust mite Dermatophagoides farinae allergens
• Der f 2, house dust mite Dermatophagoides farinae allergens

Der p 1, being the major cause of dust mite allergy, is responsible for triggering the IgE binding levels of 80 to 90 percent. It targets CD23 and CD25, which cleaves these receptors from the surface of the active B and T cells, respectively, triggering the further release of IgE.[12] Der p 1 catalytically inactivates the alpha antitrypsin, thus making the lower respiratory tract vulnerable to damage by proteinases, promoting airway inflammation and asthma.[13] There is a quantitative relationship between house dust mite allergen exposure and the development of sensitization and, consequently, asthma. Studies have shown that 2 micrograms of Der p 1 per one gram of house dust, that is 100 house dust mites per one gram house dust, potentially lead to sensitization and development of asthma. 10 micrograms of Der p 1 per one gram of house dust that is 500 house dust mites per one gram of house dust lead to acute asthma in individuals who are allergic to house dust mites.[14][15][16]

Asthma usually develops as a result of combined environmental and genetic factors. Dust mite allergy leads to the development of atopic asthma, which is a predisposition to the development of hypersensitivity Type 1 reactions.

House dust mite allergy plays a role in the development or exacerbation of atopic dermatitis. The house dust mite allergens activate the pattern activation receptors that include toll-like receptor 1, toll-like receptor 6, and toll-like receptor 9 and nucleotide-binding oligomerization domain 2. This leads to a release of innate proallergic cytokines, namely interleukin-25 and interleukin-33, in epidermal keratinocytes, causing the activation of the innate immune system in the keratinocytes.[17]

History and Physical

Dust mite allergy leads to perennial allergic rhinitis; that is, the symptoms of dust mite allergies occur throughout the year. Symptoms are more likely to occur while sleeping at night and early in the morning on waking up because the dust mites inhabit the pillows, bedcovers, mattresses, and blankets. Common dust mite allergy symptoms include:  

• Sneezing
• Rhinorrhea
• Allergic conjunctivitis
• Nasal stuffiness
• Itchy nose, mouth or throat
• Itchy skin
• Postnasal drip
• Cough
• Coughing bouts that may be exacerbated by a viral infection
• Lethargy, malaise
• Impaired sleep caused by shortness of breath, coughing or wheezing

If dust mite allergy triggers asthma, the following may also present:

• Dyspnea
• Chest tightness or discomfort
• Wheezing on exhalation

The following risk factors predispose an individual to develop dust mite allergy:

• Childhood or adolescence
• Family history of allergies
• Exposure to a high level of dust mites

The development of allergies to certain foods like shellfish or mollusks can also occur as a result of cross-reactivity.

Evaluation

Present symptoms, past medical history of allergic manifestations, home environment, and circumstances prompt the clinician to carry out further tests for the diagnosis of dust mite allergy.

In vivo techniques 

• Skin prick test. It has high sensitivity and is preferred as the first-line test for the detection of sensitization of dust mite allergy. It is a convenient, inexpensive test that yields results within 20 minutes. However, it may produce a high number of false-positive results owing to cross-reactivity. It is not indicated in people with dermatitis or those using antihistamines.
• Atopic patch tests. It detects the T cell-mediated reaction in the allergy.[18]
• Basophil activation test (BAT). It is a quantitative test that detects the activation markers on the basophil surface in whole blood. This test can be performed in patients who are already taking antihistamines. It also demonstrates a functional response. However, inconsistent results may be present because of the different varieties of commercial testing kits and varied protocols used.[19]
• Nasal provocation test. It identifies and quantifies the clinical relevance of dust mite allergen. The respiratory mucosa is exposed to the dust mite allergen, and the consequent clinical reactions are monitored. Anterior rhinomanometry and acoustic rhinometry are then used for the graphical display of the changes in nasal airflow and patency.[20]
• IgE blood test

In vitro techniques

• Enzyme-linked immunosorbent assay (ELISA). It can detect both total and selective IgE levels. Taking cross-reactivity of IgE into consideration, competitive ELISA can be used. The disadvantage is that ELISA cannot be used for a thorough analysis of multiple allergens.
• Radio allergen sorbent test (RAST). It is an in vitro test for the detection of IgE levels. The serum IgE of the patient bound to the allergen is immobilized on a solid substrate, and then these are detected using radiolabelled anti-IgE antibodies. Its use has become limited due to the availability of better techniques like ELISA.[21]
• Microarrays. It can be used to detect multiple antigens on a single slide. It includes single-plex (ImmunoCAP) and multiplex (ImmunoCAP ISAC) assays. One commercially available microarray is ImmunoCAP immunosorbent allergen chip (ISAC) that is used to define an individual's complete allergen sensitivity profile. A better available microarray is a MeDALL chip that can be used to monitor IgE and IgG reactivity profiles toward more than 170 allergens, but this is still under evaluation. These assays are expensive and available in large hospitals, thus cannot be used to detect dust mite allergy sensitization at the primary point of care.[22]
• Fluoroenzyme immunoassays

Diagnosis of asthma. Over time dust mite allergy culminates into asthma or may lead to exacerbation of asthma.

• Peak expiratory flow rate (PEFR). In mild asthma, PEFR is more than or equal to 200 L per minute, with moderate asthma, PEFR is 80 to 200 L per minute, in severe asthma PEFR is less than 80 L per minute.
• Spirometry. The methacholine challenge test is used when there is no acute asthma. A fall of FEV1 of less than 20 percent after administering methacholine is diagnostic for asthma. During acute asthma, inhaled beta-agonists like salbutamol can be administered. A rise of FEV1 by 12 percent or more is diagnostic of asthma. Asthmatics sensitized to house dust mites have lower FEV1/FVC ratio as compared to asthmatics without the sensitization.[23]

The quantification of dust mite allergens from the house can be done through immunochemical assays, namely, RAST inhibition technique, sandwich radio or enzyme immunoassays, or MAb assays. However, their use is limited due to the requirement of trained laboratory personal and sophisticated equipment.

Treatment / Management

The most effective intervention for dust mite allergy is primary prevention, that is allergen avoidance. This can be achieved by reducing the levels of mite allergens.

Measures for allergen avoidance in the bedroom

• Covering of mattresses and pillows with fine woven fabric or plastic. These prevent the penetration of the house dust mites.
• Hot washing of bedding, at least once a week in hot water (130 - 140°F), bedding can also be frozen overnight to kill dust mites.
• Removal of carpets and drapes
• Room air cleaner with a high-efficiency particulate air (HEPA) filter. These filters can remove up to  99.7% of particles as small as 0.1 microns.

Measures for allergen avoidance in the whole house

• Humidity control to 45 percent humidity or less
• Vacuum cleaning. They reduce dust disturbances. Dust disturbances include moving furniture, throw pillows, drapes, or bedding that can make mite allergens airborne, thus increasing exposure.
• Cross ventilation
• Use of acaricides, which is a chemical to kill the house dust mites in the house.[11] The disadvantages include short-lived effects and safety concerns for use at home.[24]
(B3)

Over the counter medications. These provide symptomatic relief to the allergic manifestations.

• Antihistamines
• Nasal corticosteroids
• Leukotriene receptor antagonists
• Cromolyn sodium (mast cell stabilizers)
• Decongestants

Nonpharmacological measures. These are safe, effective, and convenient modalities to help manage symptoms of dust mite allergy. Their use as an adjunctive helps to reduce the use of pharmacological drugs.[25](A1)

• Saline nasal irrigation
• Saline nasal sprays

HDM allergen immunotherapy (AIT). This is also known as desensitization. AIT has been in use for achieving clinical tolerance to allergens through the administration of allergen extracts to the sensitized individual. It is effective in the treatment of Type I allergic diseases induced by IgE in terms of alleviating the clinical manifestations of allergic rhinitis and asthma, reducing the use of symptom-relieving medication, and improving the quality of life. It provides an effective improvement in clinical symptoms, reduces the need for rescue medications, improves lung function, and brings about intrinsic disease-modifying effects such that the allergic inception of asthma and new sensitizations can be completely or partially abrogated. The effects persist for years after therapy discontinuation.[26] The following forms of immunotherapy are available:(B3)

• Subcutaneous immunotherapy (SCIT).[27] The house dust mite allergenic extracts are injected in an incrementally increasing dose into the affected individual. The therapeutic dose range of SCIT is between 500 and 2000 AU (activity units) for a targeted maintenance dose of 7 micrograms of Der p 1 and 10 micrograms of Der f 1. The build-up or the induction phase is about 8 - 24 weeks, followed by 3 to 5 years of a monthly maintenance phase. SCIT induces “allergenic tolerance.” The mechanism involves the induction of FOXP3+ CD25+ regulatory T cells (Tregs) specific to such allergens, induction of blocking antibodies such as IgG4 and IgA2, as well as induction of regulatory cytokines such TGF-beta and IL-10  that skew the response from a TH2 to a Treg or TH1 pattern. It provides an effective improvement in clinical symptoms, reduces the need for rescue medications, and improves lung function. 
• Sublingual immunotherapy (SLIT). It is an effective alternative to SCIT. The immune responses include the induction of circulating, allergen-specific Th1, and regulatory CD4+ T cells that lead to clinical tolerance.[28] It can be used for treating extrinsic mild to moderate atopic dermatitis in children who are sensitized to house dust mites.[29]
• Alternative routes include oral, nasal, epicutaneous, bronchial, and intra-lymphatic. Many of these routes have been tried and attempted but abandoned due to increased adverse effects or difficult administration.
• Allergy specific immunotherapy (AIT). This therapy is based on recombinant allergens, rather than on allergen extracts. Modified dust-mite allergens that are hypoallergenic derivatives of group 1 and group 2 have been developed. This is promising towards better efficacy, lesser adverse effects, and better administration, as compared with immunotherapy using allergic extracts. Using a combination of hypoallergenic groups 1 and 2, efforts are being made to develop vaccines.[30]
(B3)

Treatment of asthma. It depends on the severity of asthma. Short-term relief is provided through short-acting beta-agonists (SABA). The long term relief is provided by anticholinergics, long-acting beta-agonists (LABA), and low dose inhaled corticosteroids. Oral corticosteroids are used in acute exacerbations of asthma. Leukotriene antagonists and mast cell stabilizers may be useful.

Differential Diagnosis

Other than dust mites, house dust allergy can be caused by the following allergen sources:

• Mold. The fungus grows in a humid environment like house basements, kitchens, gardens, and bathrooms. The spores of the mold become airborne, which on inhalation leads to allergic rhinitis.
• Cockroaches. These are found in a variety of environments. The saliva, fecal matter, and shed off parts of cockroaches serve as potential allergens for triggering allergies. Around 68 percent of households in the USA are known to have cockroach allergens. The percentage increases further in urban areas.
• Pollen. Flowers, grass, weeds, and trees are sources of pollens that constitute an essential component of household dust. These are a common cause for triggering allergic reactions.
• Pets. Fur, feathers, animal hair, dander, saliva, and fecal matter all serve as allergens.[31]

Dust mite allergy can be confused with non-allergic forms of rhinitis.[32] These include the following:

• Vasomotor rhinitis. It leads to chronic sneezing and can be triggered by weather change, certain foods or medications, emotions, underlying chronic health problems, or certain odors.
• Rhinitis medicamentosa. It occurs due to the overuse of nasal decongestants and cocaine users.
• Atrophic or senile rhinitis. It occurs due to the hardening and thinning of the nasal turbinates with age or multiple nasal surgeries, making it more susceptible to damage and infection.
• Non-allergic rhinitis with eosinophilia syndrome (NARES)
• Infectious rhinitis. It can be bacterial or viral.
• Chemical rhinitis
• Hormonally induced rhinitis

Prognosis

Minimizing or avoiding the dust mite allergens leads to fewer allergic reactions. However, house dust mite allergy leads to a decreased quality of life in the long run. This can be explained by the following:

• Increased school and work absenteeism
• Decreased concentration leading to poor work performance
• Driving performance, as well as cognitive functions of individuals with a long duration of work, is markedly impaired
• Treatment of allergic symptoms in asthmatics is a substantial economic burden on families
• Disturbed personal relationships
• Decreased daily productivity
• Inability to participate in recreational activities and sports

The cost-benefit analysis demonstrates that immunotherapy is more cost-effective in the long term as compared with symptomatic treatment.[21]

Complications

Persistent exposure to dust mite allergens for a sensitized individual lead to the following complications:

• Sinusitis. The immune response of the body towards continuous exposure to dust mite allergens leads to chronic inflammation of the epithelium lining the sinuses. This obstructs the sinuses and causes increased vulnerability to infection.
• Asthma development. Of the various household allergens, dust mite allergens have the strongest association with the development of asthma.[33]
• Precipitation of acute asthmatic attacks
• Atopic Dermatitis. House dust mite is also a nonspecific allergen as well as an irritant; therefore, it is an aggravating factor for people with atopic dermatitis, regardless of the sensitization to the house dust mite allergen.[34]
• Chronic inflammation and destruction of the respiratory epithelium make the nasal and respiratory passage over-sensitive, leading to an exacerbated reaction to irritants like cigarette smoke, pollution, dry air in heated rooms, as compared with a non sensitized individual.