Continuing Education Activity

Dust mite allergy is an IgE mediated Type 1 hypersensitivity reaction to dust mite allergens, commonly found in household dust. The prevalence of atopic diseases like allergic rhinitis and asthma with house dust mite being the allergen has been increasing. This activity reviews the evaluation and treatment of dust mite allergy and highlights the role of the interprofessional team in improving care for patients with this condition.

Objectives:

• Describe the etiology of dust mite allergy.
• Review the appropriate evaluation of patients with dust mite allergy.
• Outline the management considerations for patients with dust mite allergy.
• Summarize the importance of collaboration and communication amongst the interprofessional team to enhance care coordination for patients with dust mite allergy.

Introduction

Dust mite allergy is an allergic condition that occurs as a reaction to the dust mite allergens that commonly live in household dust. It is also known as house dust allergy. It is sensitization and an allergic reaction to the droppings of the dust mites. The droppings are an indoor aeroallergen, which on inhalation triggers the allergic reaction. The prevalence of atopic diseases like allergic rhinitis and asthma with house dust mite being the allergen has been increasing. House dust allergy was first identified as an allergen around 1920. In 1967, Voorhorst et al. identified  Dermatophagoides pteronyssinus as the causative allergen for house dust allergy.[1] The first mite allergen identified was the cysteine protease Dermatophagoides pteronyssinus allergen I, or Der p 1 in 1980, followed by Der p 2, and homologous Dermatophagoides farinae 1 and 2.

The house dust mite (HDM or DM) is a predominant source of indoor aeroallergens. Some of the allergic diseases that have been associated with the HDM are allergic rhinoconjunctivitis, allergic asthma, and atopic eczema. The best treatment strategy for allergic rhinitis consists of allergen avoidance first, in junction with pharmacotherapy and allergen immunotherapy (AIT).[2] The appropriate pharmacotherapy consists of antihistamines, leukotriene receptor antagonists, and inhaled or intranasal corticosteroids (ICS). All these treatments are effective and safe, but unfortunately, haven't proved to change the course of HDM related allergic diseases.

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]

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]

• 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:

• 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]

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.

Deterrence and Patient Education

Education involving the patient, their families, and the public, in general, is necessary to ensure the best patient outcomes. The potential severity of dust mite allergy is often underestimated, leading to failure to seek medical therapy. The annual direct medical costs due to dust mite allergy might be substantial, however loss of work productivity leads to higher indirect costs, mainly due to asthmatic symptoms.[35] It is a frequent cause of increased office visits.[36] Handouts, internet sources, and media can help to spread awareness regarding the potential sources of dust mite allergens and the interventions that can be done for allergen avoidance. Proper education on the technique of using nasal sprays and sublingual immunotherapy must be emphasized.

Enhancing Healthcare Team Outcomes

Dust mite allergy is a frequently underdiagnosed, misdiagnosed, and mistreated condition. It leads to detrimental effects on health and life quality as well as increased societal costs. The primary responsibility of diagnosing the condition, educating the patient and their family, management of symptoms to achieve an improved quality of life lies in the hands of primary clinicians. It is vital to consult the interprofessional team of immunologists, otolaryngologists, pulmonologists, primary clinicians, and the patients themselves. Nurses and pharmacists play a significant role in the education of the public as well as ensuring long term benefits to the patients and their families.

The social worker helps to assess the house to look for allergen sources and provides suggestions and resources that can help to remove the allergens. With the vast array of in-vivo and in-vitro diagnostic tests available for dust mite allergy, the role of the laboratory and the laboratory personnel cannot be underestimated. The outcome of dust mite allergy depends on the ability to identify dust mites as the source of the allergic manifestations. However, to improve outcomes, prompt consultation with an interprofessional group of specialists combined with the individual's self-motivation is recommended.

Review Questions

• Access free multiple choice questions on this topic.
• Click here for a simplified version.
• Comment on this article.

References

1.

Biagtan M, Viswanathan R, Bush RK. Immunotherapy for house dust mite sensitivity: where are the knowledge gaps? Curr Allergy Asthma Rep. 2014 Dec;14(12):482. [PMC free article: PMC5034865] [PubMed: 25354663]

2.

Yang L, Zhu R. Immunotherapy of house dust mite allergy. Hum Vaccin Immunother. 2017 Oct 03;13(10):2390-2396. [PMC free article: PMC5647988] [PubMed: 28853977]

3.

Banerjee S, Resch Y, Chen KW, Swoboda I, Focke-Tejkl M, Blatt K, Novak N, Wickman M, van Hage M, Ferrara R, Mari A, Purohit A, Pauli G, Sibanda EN, Ndlovu P, Thomas WR, Krzyzanek V, Tacke S, Malkus U, Valent P, Valenta R, Vrtala S. Der p 11 is a major allergen for house dust mite-allergic patients suffering from atopic dermatitis. J Invest Dermatol. 2015 Jan;135(1):102-109. [PMC free article: PMC4636057] [PubMed: 24999597]

4.

Wan H, Winton HL, Soeller C, Tovey ER, Gruenert DC, Thompson PJ, Stewart GA, Taylor GW, Garrod DR, Cannell MB, Robinson C. Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions. J Clin Invest. 1999 Jul;104(1):123-33. [PMC free article: PMC408401] [PubMed: 10393706]

5.

Blythe ME, Williams JD, Smith JM. Distribution of pyroglyphid mites in Birmingham with particular reference to Euroglyphus maynei. Clin Allergy. 1974 Mar;4(1):25-33. [PubMed: 4824570]

6.

Thomas WR, Smith WA, Hales BJ. The allergenic specificities of the house dust mite. Chang Gung Med J. 2004 Aug;27(8):563-9. [PubMed: 15553602]

7.

Bousquet J, Dahl R, Khaltaev N. Global Alliance against Chronic Respiratory Diseases. Eur Respir J. 2007 Feb;29(2):233-9. [PubMed: 17264322]

8.

Weghofer M, Grote M, Resch Y, Casset A, Kneidinger M, Kopec J, Thomas WR, Fernández-Caldas E, Kabesch M, Ferrara R, Mari A, Purohit A, Pauli G, Horak F, Keller W, Valent P, Valenta R, Vrtala S. Identification of Der p 23, a peritrophin-like protein, as a new major Dermatophagoides pteronyssinus allergen associated with the peritrophic matrix of mite fecal pellets. J Immunol. 2013 Apr 01;190(7):3059-67. [PMC free article: PMC4582595] [PubMed: 23460742]

9.

Sears MR, Herbison GP, Holdaway MD, Hewitt CJ, Flannery EM, Silva PA. The relative risks of sensitivity to grass pollen, house dust mite and cat dander in the development of childhood asthma. Clin Exp Allergy. 1989 Jul;19(4):419-24. [PubMed: 2758355]

10.

King C, Brennan S, Thompson PJ, Stewart GA. Dust mite proteolytic allergens induce cytokine release from cultured airway epithelium. J Immunol. 1998 Oct 01;161(7):3645-51. [PubMed: 9759888]

11.

International Workshop Report. Dust mite allergens and asthma: a worldwide problem. International Workshop report. Bull World Health Organ. 1988;66(6):769-80. [PMC free article: PMC2491145] [PubMed: 3069235]

12.

Chapman MD, Wünschmann S, Pomés A. Proteases as Th2 adjuvants. Curr Allergy Asthma Rep. 2007 Sep;7(5):363-7. [PubMed: 17697645]

13.

Kalsheker NA, Deam S, Chambers L, Sreedharan S, Brocklehurst K, Lomas DA. The house dust mite allergen Der p1 catalytically inactivates alpha 1-antitrypsin by specific reactive centre loop cleavage: a mechanism that promotes airway inflammation and asthma. Biochem Biophys Res Commun. 1996 Apr 05;221(1):59-61. [PubMed: 8660343]

14.

Dust mite allergens and asthma--a worldwide problem. J Allergy Clin Immunol. 1989 Feb;83(2 Pt 1):416-27. [PubMed: 2645343]

15.

Custovic A, Taggart SC, Francis HC, Chapman MD, Woodcock A. Exposure to house dust mite allergens and the clinical activity of asthma. J Allergy Clin Immunol. 1996 Jul;98(1):64-72. [PubMed: 8765819]

16.

Custovic A, Chapman M. Risk levels for mite allergens. Are they meaningful? Allergy. 1998;53(48 Suppl):71-6. [PubMed: 10096813]

17.

Jang YH, Choi JK, Jin M, Choi YA, Ryoo ZY, Lee HS, Park PH, Kim SU, Kwon TK, Jang MH, Im SH, Moon SY, Lee WJ, Lee SJ, Kim DW, Kim SH. House Dust Mite Increases pro-Th2 Cytokines IL-25 and IL-33 via the Activation of TLR1/6 Signaling. J Invest Dermatol. 2017 Nov;137(11):2354-2361. [PubMed: 28684329]

18.

Turjanmaa K, Darsow U, Niggemann B, Rancé F, Vanto T, Werfel T. EAACI/GA2LEN position paper: present status of the atopy patch test. Allergy. 2006 Dec;61(12):1377-84. [PubMed: 17073865]

19.

Sturm GJ, Kranzelbinder B, Sturm EM, Heinemann A, Groselj-Strele A, Aberer W. The basophil activation test in the diagnosis of allergy: technical issues and critical factors. Allergy. 2009 Sep;64(9):1319-26. [PubMed: 19243362]

20.

Gosepath J, Amedee RG, Mann WJ. Nasal provocation testing as an international standard for evaluation of allergic and nonallergic rhinitis. Laryngoscope. 2005 Mar;115(3):512-6. [PubMed: 15744168]

21.

Li L, Qian J, Zhou Y, Cui Y. Domestic mite-induced allergy: Causes, diagnosis, and future prospects. Int J Immunopathol Pharmacol. 2018 Jan-Dec;32:2058738418804095. [PMC free article: PMC6201173] [PubMed: 30350752]

22.

Kazemi-Shirazi L, Niederberger V, Linhart B, Lidholm J, Kraft D, Valenta R. Recombinant marker allergens: diagnostic gatekeepers for the treatment of allergy. Int Arch Allergy Immunol. 2002 Apr;127(4):259-68. [PubMed: 12021544]

23.

Jaén A, Sunyer J, Basagaña X, Chinn S, Zock JP, Antó JM, Burney P., European Community Respiratory Health Survey. Specific sensitization to common allergens and pulmonary function in the European Community Respiratory Health Survey. Clin Exp Allergy. 2002 Dec;32(12):1713-9. [PubMed: 12653161]

24.

Wilson JM, Platts-Mills TAE. Home Environmental Interventions for House Dust Mite. J Allergy Clin Immunol Pract. 2018 Jan-Feb;6(1):1-7. [PMC free article: PMC6474366] [PubMed: 29310755]

25.

Li CL, Lin HC, Lin CY, Hsu TF. Effectiveness of Hypertonic Saline Nasal Irrigation for Alleviating Allergic Rhinitis in Children: A Systematic Review and Meta-Analysis. J Clin Med. 2019 Jan 09;8(1) [PMC free article: PMC6352276] [PubMed: 30634447]

26.

Nelson HS. New forms of allergy immunotherapy for rhinitis and asthma. Allergy Asthma Proc. 2014 Jul-Aug;35(4):271-7. [PubMed: 24992546]

27.

Eifan AO, Akkoc T, Yildiz A, Keles S, Ozdemir C, Bahceciler NN, Barlan IB. Clinical efficacy and immunological mechanisms of sublingual and subcutaneous immunotherapy in asthmatic/rhinitis children sensitized to house dust mite: an open randomized controlled trial. Clin Exp Allergy. 2010 Jun;40(6):922-32. [PubMed: 20100188]

28.

Calderón MA, Simons FE, Malling HJ, Lockey RF, Moingeon P, Demoly P. Sublingual allergen immunotherapy: mode of action and its relationship with the safety profile. Allergy. 2012 Mar;67(3):302-11. [PubMed: 22150126]

29.

Pajno GB, Caminiti L, Vita D, Barberio G, Salzano G, Lombardo F, Canonica GW, Passalacqua G. Sublingual immunotherapy in mite-sensitized children with atopic dermatitis: a randomized, double-blind, placebo-controlled study. J Allergy Clin Immunol. 2007 Jul;120(1):164-70. [PubMed: 17543376]

30.

Vrtala S, Huber H, Thomas WR. Recombinant house dust mite allergens. Methods. 2014 Mar 01;66(1):67-74. [PMC free article: PMC4582397] [PubMed: 23911838]

31.

Araki A, Ait Bamai Y, Ketema RM, Kishi R. [House Dust and Its Adverse Health Effects]. Nihon Eiseigaku Zasshi. 2018;73(2):130-137. [PubMed: 29848863]

32.

Settipane RA, Kaliner MA. Chapter 14: Nonallergic rhinitis. Am J Rhinol Allergy. 2013 May-Jun;27 Suppl 1:S48-51. [PubMed: 23711042]

33.

Huang FL, Liao EC, Yu SJ. House dust mite allergy: Its innate immune response and immunotherapy. Immunobiology. 2018 Mar;223(3):300-302. [PubMed: 29079219]

34.

Kim J, Lee S, Woo SY, Han Y, Lee JH, Lee IY, Lim IS, Choi ES, Choi BW, Cheong HK, Lee SI, Ahn K. The indoor level of house dust mite allergen is associated with severity of atopic dermatitis in children. J Korean Med Sci. 2013 Jan;28(1):74-9. [PMC free article: PMC3546108] [PubMed: 23341715]

35.

Greiner AN, Hellings PW, Rotiroti G, Scadding GK. Allergic rhinitis. Lancet. 2011 Dec 17;378(9809):2112-22. [PubMed: 21783242]

36.

Brożek JL, Bousquet J, Agache I, Agarwal A, Bachert C, Bosnic-Anticevich S, Brignardello-Petersen R, Canonica GW, Casale T, Chavannes NH, Correia de Sousa J, Cruz AA, Cuello-Garcia CA, Demoly P, Dykewicz M, Etxeandia-Ikobaltzeta I, Florez ID, Fokkens W, Fonseca J, Hellings PW, Klimek L, Kowalski S, Kuna P, Laisaar KT, Larenas-Linnemann DE, Lødrup Carlsen KC, Manning PJ, Meltzer E, Mullol J, Muraro A, O'Hehir R, Ohta K, Panzner P, Papadopoulos N, Park HS, Passalacqua G, Pawankar R, Price D, Riva JJ, Roldán Y, Ryan D, Sadeghirad B, Samolinski B, Schmid-Grendelmeier P, Sheikh A, Togias A, Valero A, Valiulis A, Valovirta E, Ventresca M, Wallace D, Waserman S, Wickman M, Wiercioch W, Yepes-Nuñez JJ, Zhang L, Zhang Y, Zidarn M, Zuberbier T, Schünemann HJ. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision. J Allergy Clin Immunol. 2017 Oct;140(4):950-958. [PubMed: 28602936]

Disclosure: Pearl Aggarwal declares no relevant financial relationships with ineligible companies.

Disclosure: S Senthilkumaran declares no relevant financial relationships with ineligible companies.