d1 House dust mite

Dermatophagoides pteronyssinus is one of a group of mites originally found in house dust. These domestic mites, comprising both house dust mites and storage mites, contain species that are highly allergenic. Atopic reactivity to their products is one of the most common causes of allergic disease in the world, affecting the upper and lower airways, eyes, skin, and less frequently, the gastrointestinal tract and subsequent systemic exposure, inducing anaphylaxis. (1)

Living environment

Within any given geographical region, dust mites vary in their distribution among specific locations and with the seasons. The highest mite numbers are found in private homes, and higher mite allergen exposure correlates with higher education, higher household income, and lower population density in the home (16).

Mite allergen levels are higher in older homes and non-air-conditioned dwellings (17). Apartments in the inner city have low dust mite levels, with mouse and cockroach allergens predominating. (18)

Worldwide distribution

There is good evidence that dramatically decreasing exposure to dust mite allergens can reduce symptoms related to dust mites in patients with already established asthma and rhinitis. This evidence comes from controlled trials of avoidance and from confining patients to a sanatorium or to a hospital-based allergen “free” unit. (5-8)

High altitude is generally not hospitable to dust mites, which may part of the explanation that before the discovery of dust mites, sanitaria for asthma and other respiratory diseases were often built at high altitudes, e.g., the Alps in Europe and Denver, CO, in the USA. Dust mite growth (9) and sensitization (10) are much lower in the Alps than at sea level, the apparent result of the lower indoor humidity at high altitude.

Some of the most impressive results have come from Sanatoria at high altitudes in the Alps, but these studies are complicated to interpret because such confinement will also reduce exposure to animal dander and fungi, as well as mites (5, 11, 12).

Dust mites are found worldwide except in the Arctic and Antarctica. D. pteronyssinus tends to be more abundant in Europe than in the United States.

As a source of sensitizing allergens, mites dominate in environments with temperate climates, damp and humid dwellings and most families live in separate homes (New Zealand, Australia, Europe (West and Central) England, Scotland, areas of the United States and South America where homes are both warm and damp. In contrast, in northern areas of Europe where the climate is extremely dry mites cannot survive the winter. (13)

D. pteronyssinus dominates in the UK, and New Zealand, while D. farinae is more prevalent in some areas of the United States, and Blomia tropicalis is dominant in areas of South America and other tropical areas. (14, 15)

Main

Dust mite allergen exposure as a trigger to exacerbate existing asthma has been clearly and repeatedly demonstrated (1). The inhalation of dust mite allergen can have effects beyond bronchospasm, decreasing mucociliary clearance and thus increasing the deposition of other inhaled particles. Dust mite allergen avoidance has been found to improve the broncho-dilating effect of deep inhalation in asthmatic children. (19, 20)

Allergic rhinitis

The link between allergen sensitization and symptoms can be demonstrated using nasal challenge with mite allergen, which produces obstruction and rhinorrhea that correlate with mite skin test reactivity(21). Significant proportions of the allergic rhinitis patients and chronic rhinosinusitis patients with allergy are sensitized to house dust mites. (22)

The management of mite-induced rhinitis and asthma includes allergen avoidance, plus treatment of symptoms with medication. In eligible patients, specific allergen immunotherapy (SIT) is given to reduce symptoms; in some cases, SIT may produce long-lasting clinical benefit. (1)

Information on the occurrence of ocular symptoms in association with allergic rhinitis is sparse, but one study of patients with allergic rhinitis to a variety of allergens including dust mites found that most individuals also had ocular involvement with symptoms of pruritus, tearing conjunctival injection, and eyelid edema. (23)

Asthma

Rhinitis and asthma run together (“United Airways Disease”) - Patients with allergic mite sensitive asthma also have symptoms of allergic rhinitis, supporting the “unified airway” concept that asthma and allergic rhinitis may not be separate entities but rather linked manifestations of allergic inflammation occurring throughout both upper and lower airways. (24)

Mites as a cause of allergic asthma

Dust mites including D pteronyssinus are one of the most frequent causes of respiratory allergies and mite exposure is a very important factor eliciting exacerbations of asthma (2).  However, many patients are unaware that dust mites are a trigger for their asthma, yet report symptoms of sneezing, wheezing or eye irritation during activities which render the mite fecal particles airborne, such as house cleaning, or disturbing bedding upon awakening (13)

IgE to mites in early childhood predisposes to asthma - Mite allergy is a major risk factor for asthma and mite sensitization early in life has a significant impact on subsequent pulmonary function. One multicenter, birth cohort study followed 1314 children from birth to 13 years of age  (25). Asthma symptoms and lung function, specific IgE, and perennial allergen exposure (mite, cat, and dog dander) were assessed at regular intervals. The great majority (90%) of children with wheeze but no sensitization had lost their symptoms by school-age and retained normal lung function at puberty. In contrast, sensitization to perennial allergens including mite, which developed in the first 3 years of life was correlated with compromised lung function at school age.  Sensitization and exposure occurring later than 3 years of age resulted in much weaker effects on lung function, and sensitization to seasonal allergens such as pollens had no effect on subsequent lung function (25).

Exposure

Dust mite allergen exposure as a trigger to exacerbate existing asthma has been clearly and repeatedly demonstrated (1). The inhalation of dust mite allergen can have effects beyond bronchospasm, decreasing mucociliary clearance, and thus increasing the deposition of other inhaled particles.  Dust mite allergen avoidance has been found to improve the broncho-dilating effect of deep inhalation in asthmatic children. (19, 20)

Respiratory viruses

Mites synergize with respiratory viruses in causing asthma - Sensitization to Dermatophagoides mites also appears to exacerbate asthma attacks in children suffering from rhinovirus infections (26). The addition of viral infection to allergen exposure in mite-sensitized individuals results in more severe attacks with acute wheezing (26) and hospitalization (27, 28).

Atopic Dermatitis

The prevalence of sensitization to mites can be very high in patients with atopic dermatitis. The increase in the permeability of atopic skin and the ability of mite proteases to decrease skin barrier function may allow more effective sensitization with aeroallergens, initiating a vicious cycle of inflammation and further allergen exposure (1)

Mite molecules relevant in AD

The anti-mite IgE in patients with respiratory allergic disease is directed mainly to the major allergen components found in fecal particles (Der p 1, Der p 2, Der p 23, Der p 4, Der p 5, Der p 7, der p 21). In contrast, patients with atopic dermatitis were found to be sensitized to a broader range of major and minor allergenic mite components, including allergens occurring mainly in mite bodies (Der p 10, Der p 11, Der p 14, Der p 18) as well as those in mite feces (Der p 1, Der p 2, Der p 5, Der p 7, Der p 21, Der p 23). This suggests that in atopic dermatitis the principal route of exposure is direct contact of the mite body and feces with the skin of the patient rather than via inhalation. Some studies also reported sensitization to a broader range of minor allergen components of Dermatophagoides farinae Der f 11, Der f 13, Der f 14, Der f 32 and Der f Alt a 10. (29)

The important role of paramyosin (Der p 11) in AD- Der p 11 was defined several years ago and is distinctive because of the high molecular weight i.e. ~95-100 kDa (30). Thus, sensitization to this allergen may reflect the fact that the eczematous skin allows easy penetration of allergens even with molecular weight as high as 100,000 (55).  However, in 2014, it was reported that IgE antibodies to Der p 11 are more common in sera from patients with Atopic Dermatitis (AD). Group 11 allergens (Der p 11, Der f 11) should be included among allergen components routinely tested in the clinical laboratory as they are considered major allergen molecules in patients with AD and sensitization to HDM. (31)

Other diseases

In mite-sensitized individuals, allergic symptoms following exposure via the oral/gastrointestinal route can occur in two situations: A) food colonized by mites; B) food containing tropomyosins.

Mites as food allergens-Allergic reactions to foods colonized by mites

Systemic allergic symptoms, sometimes severe, can occur after inadvertent ingestion of dust mites present in a food that has been colonized by mites, referred to as oral mite anaphylaxis. This was first reported in 1993, in a patient who ate a fried pastry made from flour that had been contaminated with D. farinae mites (32). Subsequently, multiple cases of systemic allergy have been reported in mite sensitized patients who ate a variety of foods made with mite-contaminated foods including pancakes (33), wheat and cornflour(34, 35), and grits (36). Mite sensitive patients are thus well advised to store any opened packages of baked goods mixes, grains, or flour in a refrigerator to prevent the growth of mite populations.

In-vitro diagnostics

Mite allergy diagnosis is based on a clinical history to identify associations between mite exposure and symptoms, plus confirmation of the relevant allergens for each patient by in vitro testing or by skin prick testing in the patient. A diagnostic algorithm integrating allergenic molecules has been drawn in 2016 when the role of Der p 23 as a major allergenic protein was still unknown. (13)

Individual allergen components are useful, especially if the molecule in question is important but absent or present in small quantities in extracts – for instance, if it is labile.  However, not all components are commercially available as singleplex tests. The use of component resolved diagnosis could be useful in special circumstances where genuine sensitization is not clear and has to be defined. A combination of results obtained from the extract and individual allergen tests can be used to select optimal specific immunotherapy (2, 13, 37). IgE tests have been also applied to Nasal secretions, sIgE level in nasal secretions of subjects with rhinitis is a reliable noninvasive alternative to serum sIgE for diagnosis of allergic rhinitis. (38)

IgE tests have been also applied to nasal secretions, sIgE level in nasal secretions of subjects with rhinitis is a reliable noninvasive alternative to serum sIgE for diagnosis of allergic rhinitis. (38) A recent study demonstrated local nasal IgE production of mite specific IgE in a large subset of allergic subjects and found that allergic asthmatics with local IgE are more likely to develop an asthma exacerbation when infected with rhinovirus. ​(39)

A minimally invasive method has been used for direct detection of IgE in patients with local allergic (LAR) rhinitis to Dermatophagoides pteronyssinus using an automated immunoassay. According to receiver operating characteristic (ROC) curve analysis, NsIgE ≥0.1450 kU/L, was the optimal cutoff point, obtaining in LAR patients 42.86% sensitivity with the highest specificity (100%), and 75% sensitivity and 100% specificity for AR. Then, the detection of NsIgE to HDM in LAR by using a simple, commercial device with high specificity. ​(40)

A number of molecules recognized by IgE and risk of asthma - Sensitization to mites often starts at an early age (39) and early sensitization to Der p 1, 2, and 23 is associated with asthma development. Asthmatic atopic patients are also sensitized to a wider range of mite components than atopic patients without asthma and have higher levels of IgE specific for each allergen component. (41)

Skin prick test

Extracts of D pteronyssinus from differing sources often show great variability regarding allergen composition and may lack important individual allergen molecules altogether (42, 43).  Some of these missing molecules may be essential for a diagnosis. On the other hand, extract-based reagents contain a much greater range of different molecules than those included in currently available allergen microarrays or singleplex catalogs.

The current study evaluates sixteen commercially available Dermatophagoides pteronyssinus and Blomia tropicalis extracts for allergy diagnosis from different European manufacturers regarding allergen composition and content and whether these differences could influence their biological activity. Results: Mite extracts showed a 10-60 fold variation regarding the total protein content. The contents of the major allergens of D. pteronyssinus and B. tropicalis differed considerably (30-53 fold change) among the extracts. Blo t 5 was quantitatively present in < 50% of the of the B. tropicalis reagents and could not be clearly detected by immunoblotting in the majority of the B. tropicalis commercial extracts. Conclusions: Certain natural D. pteronyssinus and B. tropicalis extracts lack important allergens showing a considerable variability in composition and content. Closer collaboration among clinicians, allergen manufacturing companies, and regulatory agencies to improve the quality and consistency of D. pteronyssinus and B. tropicalis extracts are warranted to achieve a more precise diagnosis and treatment of house dust mite allergy. (44)

Allergen immunotherapy

sIgG4 to Der p 1 and Der p 2 reflect the change in immunological reactivity during AIT and can be useful to confirm successful immunological stimulation against these molecules (45). Moreover, delivery of AIT earlier in life may be associated with a greater increase in sIgG4 against Der p 1 and Der p 2 after 36-month treatment. However, currently available SCIT reagents induce different levels of specific IgG4, IgE/IgG4 ratio, and IgE-blocking factor to different molecules. (46)

In asymptomatic pre-school children with sensitization to house dust mite, preventive sublingual immunotherapy‐treated patients showed significantly higher IgG epitope diversity to HDM allergens compared to placebo‐treated individuals after 24 months of treatment while no increase in IgE epitope diversity was seen. These findings suggest that preventive sublingual immunotherapy at a molecular level has a beneficial effect by favoring a broader repertoire of blocking IgG and an inhibition of molecular spreading. ​(47)

The patterns of IgE reactivity to HDM allergens seem to be similar in adults and 5- to 17-year-old children living in the USA, Canada, Europe, and Japan. Therefore, mite specific AIT should rely upon a mixture of D. pteronyssinus and D. farinae extracts, manufactured from both feces and bodies. Such a combination was reported to be appropriate to treat children and adult Dermatophagoides-allergic patients from Asia, Europe, and North America. (48)

Identification of human IgE Ab binding epitopes can be used for the rational design of allergens with reduced IgE reactivity for therapy.  Mutagenesis of a Der p 2 epitope defined by x-ray crystallography revealed an IgE Ab binding site that will be considered for the design of hypoallergenic for immunotherapy (49). The aim of this study was to design and obtain a hybrid protein (DPx4) containing antigenic regions of allergens Der p 1, Der p 2, Der p 7, and Der p 10 from this mite. (50)

Prevention strategies

Avoidance

Reducing exposure to mites to fight asthma in mite-allergic children - In mite-sensitized asthmatic patients, bronchospasm and bronchial hyper-reactivity are exacerbated upon exposure to mites but ameliorated in a mite-allergen-free environment (51). Mite allergen levels in the domestic environment have been shown to correlate with asthma symptoms in dust mite sensitive asthmatic children, and with abnormal pulmonary function and bronchial reactivity in mite-sensitive adult asthmatics. Seasonal fluctuations in mite numbers and corresponding variations in allergen exposure are reflected in seasonal increases and decreases in bronchial hyper-reactivity.

The combination of mite sensitization and mite exposure together correlate with the severity of asthma symptoms (52), with increased exhaled nitric oxide and bronchial hyper-reactivity (53), and with acute exacerbations resulting in admission to hospital (54).

Effect of environmental conditions on mite survival and growth ​

Mites thrive in environments averaging 68 to 77 degrees Fahrenheit (20 to 25 degrees Celsius) with relatively high humidity levels between 70 and 80 percent and will die in low humidity and extreme temperatures. Dust mites are photophobic, they live deep inside soft substrates (carpet, pillows, mattresses, clothing). These environments help to minimize fluctuations in humidity and help the mites to retain water. Mites absorb moisture from their environment and are therefore absolutely dependent on the level of humidity in their immediate surroundings. (13)

More than 80% of mite allergen is on particles >10 μ, and is undetectable in the air of undisturbed rooms, becoming airborne only after the disturbance of the soft substrates in which the allergen was produced.

Allergenic molecules

Der p 1 and Der p 2

Together Der p 1 and Der p 2 will identify between 63 and 97% of patients sensitized to Der p extracts  (55, 56). Results from a recent European study demonstrates that the two major allergens Der p 1 and Der p 2 appear to be sufficient for the diagnosis of more than 97 % of D pteronyssinus allergic patients, but in other atopic populations a significant proportion (up to 37%) of house dust mite sensitized patients may be missed by the use of only group 1 and group 2 specific IgE component tests (57). The use of Der p 1 and Der p 2 sIgE in the diagnosis of D. pteronyssinus allergy is supported by several studies. Both displayed good diagnostic performance and would be useful in a clinical setting in the accurate diagnosis of dust mite allergy Der p 2 and Der f 2. ​(57)

The group 2 allergens from D pteronyssinus and D. farinae, Der p 2 and Der f 2 have been reported to have almost complete cross reactivity (58). Der p 1 and Der p 2 are major allergens in D pteronyssinus. Der p 2, is a heat and pH stable protein of 14 kDa, belonging to the group 2 mite allergen.  So far over 30 house dust mite allergens has been described. It seems that the IgE binding frequency of individual allergens may show high variability in certain populations. (59)

Der p 23​

Der p 23 has recently been identified as another major dust mite allergen present on the surface of mite fecal particles, which are the major airborne form of mite allergens (4). It is present in low levels in mite extract (21, 27, 53). Der p 23 appears highly clinically relevant (54) and early sensitization in children to Der p 23 is associated with asthma development (29). Sensitization to Der p 1 and Der p 23 before the age of five was predictive of asthma at school-age (30). The prevalence and amount of specific IgE to Der p 23 and Der p 2 are disproportionately high compared to the expression of other Dermatophagoides allergens. (54) At present, 32 of the 37 internationally recognized HDM allergen groups have been identified in Dermatophagoides farinae. Der f 23 is also a major HDM allergen with predominantly conformational sIgE binding epitopes. (58) (59)

Other molecules

Der p3, p6 and p9, which are serine proteases (61). Der p11, another muscle allergen, has an unusually high molecular weight of 100 kDa, has homology with the paramyosin proteins found in invertebrates, is present in dust mite bodies rather than feces, and is the significant dust mite allergen in atopic dermatitis. (30)

The key to accurate management of mite allergy is knowing the patient’s sensitization profile at the molecular level. To date, a total of 38 allergens for D. pteronyssinus have been identified and formally named. (http://www.allergen.org).

Recently discovered allergens were identified using new techniques of transcriptome and proteome analysis (60). The four molecules with the highest clinical relevance are also available for singleplex IgE tests. They include the three major allergenic proteins: Der p 1, Der p 2, and Der p 23, and the panallergen Der p 10, a tropomyosin.  Other molecules are listed in the following table.

Reviewer: Dr. Christian Fischer

Last reviewed: October  2020