Clinic and diagnostics of house dust mite allergy

House dust mite allergens are common triggers for allergic rhinoconjunctivitis and allergic asthma; they can aggravate atopic dermatitis and rarely lead to anaphylactic reactions due to dust mite allergens in food. Typical symptoms are nasal obstruction, sneezing, and irritation, and more often than in pollen allergy, allergic asthma also develops. The symptomatology exists in principle throughout the year with maximum complaints in autumn and winter. Of particular importance are sleep disturbances due to nasal obstruction, which lead to restrictions in the quality of life and performance of affected patients. Sensitization can be proven by skin tests and detection of serum allergen-specific IgE antibodies; proof of allergy is achieved by nasal or conjunctival provocation tests. The diagnosis of local allergic rhinitis can only be made by provocation or by determination of allergen-specific IgE antibodies in nasal secretions. The quality of the allergen extract used is essential for all tests; it must contain the allergens to which a patient is sensitized. The concentration of Der p 23 in house dust mite extracts is particularly critical.


Introduction
Due to its frequency and frequent correlation with asthma, the detection of house dust mite allergy is of particular importance. Symptoms occur throughout the year, with nasal obstruction and sneezing in the morning and intensification of symptoms in autumn and winter. Symptoms may be misinterpreted as upper respiratory tract infections, and nasal anomalies such as deviated nasal septum or nasal polyps must also be considered in the differential diagnosis. It has been proven that clinical/anamnestic data do not sufficiently distinguish between clinically irrelevant ("silent") sensitization and clinically relevant allergy due to house dust mites; for a reliable differentiation, nasal or conjunctival provocation with the allergen is necessary [1].

Symptomatology
Like other allergens, house dust mite allergens can trigger rhinoconjunctivitis and asthma in allergic patients, exacerbate atopic dermatitis, and also lead to anaphylaxis when ingested orally. House dust mites, which are ubiquitous, are a predominant indoor allergen source. House dust mite allergens can be detected in high concentrations in the home, particularly in the sleeping environment, and also in upholstered furniture and carpets. The allergen originates mainly from mite feces-a house dust mite excretes about 20 faces particles per day, which are surrounded by a peritrophic membrane-and further from fragments of the house dust mite. With the onset of the heating season and reduced air humidity, the faces disintegrate into small particles (< 10 µm) which are inhaled after being stirred up [1]. In many cases, it is assumed that mite allergen exposure occurs mainly in bed, since patients report complaints especially at night and in the morning. However, it has been shown that pronounced exposure to the allergen also occurs during the day. In a study in which dust collectors were positioned in the shoulder area of test persons, it was shown that about 90% of the exposure takes place during the day [2]. Even after the allergen has been stirred up by vacuuming, bed-making, etc., house dust mite allergen is found in the air only for a relatively short time; unlike cat allergen, for example, house dust mite allergen sediments quickly [3,4]. The clinical symptoms are not the same throughout the year; symptoms are accentuated in autumn and winter [5]. In a multinational observational study conducted over 13 months in patients with self-reported, inadequately controlled house dust mite allergy in France, Italy, and Spain, complaint maxima existed in autumn and late spring [6]. It should be borne in mind that mite allergy sufferers are also usually not monosensitized, but also have allergies to pollen, which can also lead to complaints in spring and summer.
Compared to pollen, mite allergens trigger sleep disturbances in particular, which are responsible for daytime fatigue and reduced performance at school or at work. In a study of 1786 subjects with house dust mite allergy who underwent specific immunotherapy with house dust mite allergen, sleep disorders ranked first among the reasons for which a physician was consulted in adults at 73.5%; in children and adolescents, nasal obstruction ranked first, followed by rhinorrhea, and again sleep disorders in third place at 65.8%. These were poor sleep quality with difficulty falling asleep, nocturnal awakening, early awakening, the feeling of lack of sleep, and also snoring [7].
Among the nasal symptoms triggered by house dust mite allergy, especially nasal obstruction and sneezing besides runny nose, nasal itching and also conjunctival complaints with eye watering and itching in the eye are reported by patients [8]. Nasal obstruction in particular has a negative impact on quality of life [9] and is more difficult to control therapeutically than a running nose. Secondary complaints such as decreased taste sensation and headache are also possible.
The risk of developing allergic asthma is higher for patients suffering from house dust mite-related allergic rhinitis than for patients with allergic rhinitis due to pollen allergy; asthma patients with house dust mite-related allergic rhinitis statistically have worse lung function and are more likely to experience asthma exacerbations than asthmatics without house dust mite-related allergic rhinitis [10]. In fact, 50-85% of asthmatics are sensitized to house dust mite allergen [11].
The triggering or at least worsening of atopic dermatitis due to exposure with house dust mite allergens can be proven by patch tests with house dust mite extracts. In a meta-analysis, a patch test with mite allergens was superior to a prick test to prove the association between atopic dermatitis and house dust mite allergy [12].
Food may be contaminated not only with storage mites but also with house dust mites; reactions of varying severity have been reported, particularly after consumption of products made from contaminated grain/flour [13]. In the literature, there are also case reports in which mite allergic patients suffered from FDEIA (food-dependent exercise-induced anaphylaxis) to mite allergens in food in combination with simultaneous exposure to cofactors, in this case physical exertion [14]. Sensitization to mite tropomyosin (Der p 10), which has cross-reactions to tropomyosin in crustaceans and molluscs (e.g., snail), is also important for food allergies in house dust mite allergic patients [15,16].

Prick test
The prick test with mite extracts is highly sensitive and the preferred test for the detection of house dust mite sensitization. Dermatophagoides pteronyssinus and Dermatophagoides farinae extracts are routinely in the standard prick test [17]. It should be noted that false-negative results may result from the use of medications such as antihistamines, false-positive results are to be expected in urticarial dermographism and may also occur when the test is performed on eczematous skin (especially in atopic dermatitis). In the case of local allergic rhinitis due to house dust mite allergy, the skin test is negative by definition [18].
The test result also depends on the quality of the allergen extract; all relevant components must be present in sufficient concentrations. When 10 house dust mite extracts from different manufacturers were tested, only Der p 1 and Der p 2 were present in all extracts. In some extracts there was a lack especially of Der p 5 and Der p 23 [16]. Der p 23 is localized in the peritrophic membrane of the mite faces particles, from which it can only be eluted by special extraction methods [19]. In patients with dominant or exclusive sensitization to this allergen, the skin test may be negative. Different results for the prick test with house dust mite extracts of different manufacturers have been documented in the literature [20].

In vitro tests (detection of specific IgE antibodies)
The determination of the serum allergen-specific IgE antibodies is established with usual commercial test methods. In the case of suspected local allergic rhinitis, specific IgE can be determined in nasal secretions, but this test has not been validated. Besides Dermatophagoides pteronyssinus and farinae extracts, allergen components are available; currently the major allergens Der p 1 and Der p 2 as well as Der p 23 and Der p 10 (tropomyosin) are available for in vitro testing. In case of sensitization to tropomyosin, at least serological cross-reaction to tropomyosin from crustaceans, cockroaches, molluscs, and worms [16], possibly with correlating symptoms after consumption.
Mite allergic patients show an individual sensitization pattern; most patients are sensitized to several mite allergens, some are exclusively sensitized to 2 Clinic and diagnostics of house dust mite allergy K mini-review a single allergen also to such as Der p 23. For in vitro tests, the quality of allergen extracts is essential; here, too, it must be ensured that all relevant allergens are contained in the extract used for the test. Componentbased diagnostics are also helpful here; specific IgE antibodies in serum can be determined specifically to all major allergens also against Der p 23. Sensitization to Der p 23 is also important because it correlates with a significant risk of asthma symptoms [21].

Provocation test
Skin tests and the detection of allergen-specific IgEantibodies are used to prove sensitization to house dust mite allergens. The term allergy is used when sensitization is clinically relevant, i.e. when symptoms occur during exposure. The presence of an allergy cannot be proven with certainty by the patient history alone; in case of doubt, a nasal or conjunctival provocation must confirm the diagnosis.
Established is the nasal provocation test [22]. According to the European position paper, bilateral provocation is recommended; the allergen is preferably applied as a spray (50 µl per spray puff) with two spray puffs each into both nostrils. A subjective/ semiquantitative symptom score is noted to assess the test result; it is recommended to assess nasal secretion, obstruction, sneezing and itching, and additionally eye symptoms [23]. Anterior rhinomanometry, acoustic rhinometry, 4-phase rhinomanometry, and, as the least complex method, determination of peak nasal inspiratory flow (PNIF) are available as objective measurement methods. Even though systemic reactions can in principle be triggered by a nasal provocation test, the test is safe when performed in a standardized manner and provides reproducible results [24,25].
Conjunctival provocation is also described; the assessment includes visible reactions on the conjunctiva and itching of the eye. The result correlates highly with the result of nasal provocation tests [26].
Bronchial provocation proves bronchial symptoms due to house dust mite exposure, but carries the risk of late reactions and is therefore rarely performed [27].
For a valid test result, it is essential that symptom-suppressing drugs such as antihistamines, antidepressants, systemic but also nasally applied corticosteroids are discontinued sufficiently long before a provocation test. Test standardization includes stable environmental conditions for example room temperature, but also the adaptation of the patient to the room climate, verification of nasal or bronchial hyperreactivity etc. Of crucial importance is also the quality of the allergen extract used, which, as for the other test methods mentioned above, must contain the allergen components relevant for the patient in sufficient concentration [23].
According to guidelines, the indication for allergenspecific immunotherapy requires proof that allergic symptoms are actually triggered by the allergen under discussion [28]. Especially in polysensitized patients, but also in patients with local allergic rhinitis, the provocation test is essential to prove the clinical relevance of house dust mite sensitization. Anamnestically, other year-round indoor allergens such as animal allergens, molds, or possibly plants such as Ficus benjamina may trigger symptoms that can hardly be differentiated anamnestically from a house dust mite allergy. The history alone is often not sufficient to clearly confirm the clinical relevance of mite sensitization [29].

Conclusion
House dust mite extracts are complex mixtures of different allergens, most recently Der p 23 was characterized as a major allergen. Extracts used for skin testing, detection of specific IgE antibodies and provocation tests are heterogeneous; depending on the manufacturer and the raw material used, the allergen composition may differ considerably. A positive test result requires that allergens relevant for a patient are contained in the test extract.
House dust mite allergy sufferers have a typical symptomatology with particularly distressing nocturnal and morning nasal obstruction; however, on the basis of the clinical symptoms alone, it is not possible to distinguish with certainty between clinically silent sensitization and relevant allergy. Provocation, established in particular as a nasal provocation test, is currently the investigative method of choice to prove the clinical relevance of mite allergy. The only treatment with sustained efficacy lasting even after the end of therapy is allergen-specific immunotherapy, whereby an essential prerequisite for the indication is the reliable proof of the connection between symptoms and mite allergy.
Funding Open Access funding enabled and organized by Projekt DEAL.
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