Introduction
House dust mite (HDM) is the most important indoor allergen and one of the three most relevant aeroallergens responsible for the development of allergic symptoms such as allergic rhinitis or allergic asthma worldwide [
1,
2]. Data about the prevalence of allergy to HDM are inconsistent. The GA
2LEN study elicited relevant regional discrepancies in the prevalence of sensitization to HDM in adults throughout Europe reaching rates from 9.3% in Sweden to 30.6% in Spain [
3]. From a clinician’s point of view, the incidence of allergic rhinitis (AR) upon exposure to HDM is obviously more relevant than clinically silent sensitization. This issue was addressed by the GA
2LEN skin test study II, published by Burbach et al. in which the authors differentiated between silent sensitization and clinically relevant sensitization assessed by experienced allergologists with the skin prick test (SPT), the history and further tests such as provocation testing in different European countries with different inhalant allergens. In case of HDM, they found that at least 80% of the participants with positive SPT reaction had a clinical relevant sensitization to HDM in most investigated countries. Only in France, Finland and Austria they revealed clinically relevant sensitization rates of less than 65% [
4]. These findings were corroborated by a study of Blomme et al. in which the prevalence of silent sensitization and allergy to HDM in an unselected population in Belgium was analyzed by SPT and an interview of the participants about possible allergic symptoms. They found a prevalence of silent sensitization to HDM in 25.9% and symptoms of AR caused by HDM in 17.1% of the participants [
5].
It has been demonstrated that untreated HDM allergy of the upper airway has the risk of transforming into a disease of the lower airways with full symptoms of allergic asthma [
2,
6‐
8]. These results clearly underline the socio-economic impact of HDM allergy as a relevant disease generating high costs for the health care systems and severe complaints for lots of patients.
When diagnosing patients with allergic symptoms, a detailed medical history and thorough physical examination are the important first steps [
9,
10]. This procedure should be followed by SPT [
10]. Patients suffering from one single seasonal allergy, for example to grass pollen, can be diagnosed by history and positive SPT alone in case they report about reproducible allergic symptoms occurring every year at the same specific time [
11]. In contrast, perennial allergens like HDM frequently cause unspecific symptoms throughout the year in divergent intensity [
12]. For this reason it can be difficult to match the patients’ complaints and the exposition to the allergen only based on the history. As a consequence, further diagnostic steps such as determination of specific immunoglobulin E (sIgE) to Der p 1, Der p 2 alone or in combination with SPT might be necessary [
9,
11]. However, both, SPT and sIgE may only detect sensitization, which is not equivalent to a clinically relevant allergy as underlined above. Thus, the German guideline on allergen-specific immunotherapy [
13] in IgE-mediated allergic diseases explicitly recommends provocation testing for perennial inhalant allergens such as HDM before initiating allergen immunotherapy [
13,
14]. In case of AR, this approach usually takes the form of specific nasal provocation testing (NPT) [
15]. As NPT is a relatively complex procedure and most clinicians even do not have the technical option to perform it, an easier way to differentiate between clinically relevant and irrelevant HDM sensitizations is desirable. Although there are several studies analyzing the correlation between NPT and sIgE-serology in HDM sensitization [
16,
17], there is to our knowledge no data in literature on the concordance between anamnestic data and NPT in HDM sensitized patients. Therefore, there is a need of an evidence-based study to confirm the general assumption that medical history is too inconsistent in HDM patients making allergen challenge testing necessary.
Thus, the purpose of our study was to compare the medical history of patients with clinically silent sensitization and those with clinically relevant allergy to HDM. We aimed to identify specific questions, which could facilitate a differentiation of both patient groups based on medical history. This could help to avoid time-consuming and risky procedures like NPT at least in some patients.
Results
Based on the above-mentioned inclusion criteria, the database search yielded 471 patients with proven sensitization to D. pteronyssinus or D. farinae. 90% of patients were sensitized to D. pteronyssinus and 93% were sensitized to D. farinae. 85% were sensitized to both, D. pertonyssinus and D. farinae. Only 6% of the individuals were monosenitized to D. farinae. The study population was divided into two groups: 248 patients with a positive NPT result to D. pteronyssinus or farinae and 223 with a negative NPT result.
Important for statistical analysis, the distribution of mono- (sensitization to one allergen only) and polysensitization (sensitization to more than one allergen) was comparable in both groups. Detailed demographic data of our study population are summarized in Table
1.
Table 1
Demographic data of patients allergic to HDM and patients with clinically silent sensitization
Gender | | | | 0.701 |
Male | 131 (59%) | 150 (61%) | 281 (60%) | |
Female | 92 (41%) | 98 (40%) | 190 (40%) | |
Age | 34 (16; 6–74) | 29 (14; 5–81) | 32 (17; 5–81) | 0.610 |
Sensitization | | | | 0.717 |
Monosensitized to HDM | 57 (27%) | 61 (26%) | 118 (26%) | |
Polysensitized | 153 (73%) | 177 (74%) | 330 (74%) | |
Time of presentation | | | | 0.326 |
Winter (October–March) | 105 (47%) | 128 (52%) | 233 (50%) | |
Summer (April–September) | 118 (53%) | 120 (48%) | 238 (50%) | |
We found a trend that patients allergic to HDM complain more often about perennial symptoms than subjects with clinically silent sensitization (34% vs. 30%, p = 0.374).
Concerning nasal symptoms, as reported by patients in the questionnaire recording medical history, rates of nasal airway obstruction were comparable in both groups (66% vs. 69%, p = 0.630). Patients allergic to HDM tend to suffer more often from nasal secretion (45% vs. 37%, p = 0.244) but significantly less from nasal dryness (34% vs. 46%, p = 0.046).
With regard to ocular complaints, significantly more patients only sensitized to HDM reported about red eyes than patients with positive NPT to HDM (13% vs. 4%, p = 0.008). Moreover, within the group of polysensitized participants, significantly more patients with negative NPT to HDM suffered from red eyes (14% vs. 4%, p = 0.017). The rate of ocular itching was comparable in both groups (39% vs. 40%, p = 0.834). However we observed the trend that patients in the monosensitized subgroup with positive NPT reported more often about this condition (28% vs. 20%, p = 0.357).
Concerning atopic co-morbidities, the prevalence of self-reported asthma was comparable in both groups (20% vs. 19%, p = 0.851). However, in the subgroup of monosensitized patients, individuals allergic to HDM complained more frequently about asthma (0% vs. 5%, p = 0.061), whereas there was no single asthmatic person among patients with a clinically silent monosensitization to HDM. Patients in the positive NPT group suffered significantly more often from atopic dermatitis (14% vs. 7%, p = 0.046).
With regard to sleep quality, patients with clinically silent sensitization to HDM tended to be more often affected by un-restorative sleep (44% vs. 38%,
p = 0.293). Symptoms in the morning were comparable between both patient groups: only slightly more patients allergic to HSM complained about symptoms in the morning (51% vs. 49%,
p = 0.724). Markedly, but not significantly more patients with silent sensitization reported about snoring (33% vs. 23%,
p = 0.072). However, the number of patients reporting about a dry mouth at night or in the morning was equal (44% vs. 40%,
p = 0.563). All clinical data of the study population obtained are summarized in Table
2.
Table 2
Clinical data of patients allergic to HDM and patients with clinically silent sensitization (data
taken from questionnaire recording medical history)
Perennial complaints | 66 (30%) | 83 (34%) | 146 (32%) | 0.374 |
Location-dependent symptoms | 60 (31%) | 76 (39%) | 136 (35%) | 0.090 |
Nasal complaints |
Nasal airway obstruction | 102 (69%) | 108 (66%) | 210 (68%) | 0.630 |
Nasal secretion | 53 (37%) | 73 (45%) | 126 (41%) | 0.244 |
Nasal dryness | 67 (46%) | 54 (34%) | 121 (40%) | 0.046 |
Ocular complaints |
Red eye | 17 (13%) | 6 (4%) | 23 (8%) | 0.008 |
Monosensitized to HDM | 2 (8%) | 1 (3%) | 3 (5%) | 0.556 |
Polysensitized | 15 (14%) | 5 (4%) | 20 (9%) | 0.017 |
Itching | 73 (40%) | 78 (39%) | 151 (39%) | 0.834 |
Monosensitized to HDM | 10 (20%) | 14 (28%) | 24 (23%) | 0.357 |
Polysensitized | 63 (48%) | 64 (42%) | 127 (45%) | 0.339 |
Atopic dermatitis | 8 (7%) | 20 (14%) | 28 (11%) | 0.046 |
Asthma | 14 (19%) | 22 (20%) | 36 (19%) | 0.851 |
Monosensitized to HDM | 0 (0%) | 5 (17%) | 5 (9%) | 0.061 |
Polysensitized | 14 (26%) | 17 (21%) | 31 (23%) | 0.541 |
Sleep quality |
Un-restorative sleep | 62 (44%) | 61 (38%) | 123 (41%) | 0.293 |
Dry mouth at night | 58 (40%) | 70 (44%) | 128 (42%) | 0.563 |
Snoring | 46 (33%) | 38 (23%) | 84 (28%) | 0.072 |
In Table
3, additional information about the patients’ home environment is listed. Patients allergic to HDM seem to have suffered more often from location-dependent symptoms than subjects with clinically silent sensitization (39% vs. 31%,
p = 0.090). While the age of the mattresses used by the patients of both main groups was comparable (39% vs. 37%,
p = 0.723), patients allergic to HDM used encasings for their mattresses and pillows (23% vs. 18%,
p = 0.127) more frequently. In Table
4, laboratory characteristics are listed.
Table 3
Additional information about patients’ home environment
Location-dependent symptoms | 60 (31%) | 76 (39%) | 136 (35%) | 0.090 |
New mattress (≤ 2 years) | 54 (37%) | 61 (39%) | 115 (38%) | 0.723 |
Encasings | 36 (18%) | 53 (23%) | 89 (21%) | 0.127 |
Table 4
Laboratory characteristics
Total IgE (kU/L) | 320.98 (573.89) | 284.66 (423.42) | 303.72 (507.78) |
D. pter |
CAP class | 2.80 (1.40) | 1.84 (1.34) | 2.33 (1.45) |
Serum IgE (kU/L) | 16.56 (24.94) | 6.91 (17.11) | 12.06 (22.15) |
D. far |
CAP class | 2.70 (1.57) | 1.63 (1.45) | 2.17 (1.60) |
Serum IgE (kU/L) | 18.89 (29.21) | 6.60 (16.20) | 13.13 (24.79) |
Discussion
Taking a detailed patients’ history is a crucial part of the process of finding the correct diagnosis in allergic diseases [
10]. In case of allergy to HDM, experts in the field of allergy and immunology recommend additional NPT besides the common practice of taking medical history and evaluating the SPT and/or specific IgE level before starting allergy immunotherapy [
13,
28]. A significant reason for this recommendation is that contrary to other aeroallergens such as pollen or pets, the symptoms patients allergic to HDM report of are considered as inconsistent. However, NPT has several disadvantages like time costs and induction of potentially harmful allergic reactions. In contrast to many evidence-based approaches in the field of allergy and immunology, to our knowledge, it has not been evaluated so far if it is possible to diagnose allergy against HDM based on the history only. Thus, the aim of this study was to evaluate retrospectively if the application of a standardized questionnaire alone—addressing the most relevant symptoms of AR—would be able to identify individuals with clinical relevant allergy to HDM.
Sensitization can be differentiated into monosensitization (sensitization against a single allergen) and polysensitization (sensitization against at least two allergens) [
8]. In our study, sensitization was indicated either by a positive reaction on standardized SPT or positive serum sIgE-levels or both. According to epidemiological studies, polysensitization is more common than monosensitization [
29,
30]. This was also the case in our preselected cohort, since only 26% of all participants were monosensitized to HSM.
Encasings were prescribed for patients with positive a NPT result. Other typical measures against HSM (including removal of carpets and indoor plants) were recommended. In case they had no contraindications, patients were treated with a nasal cortisol spray. All patients were asked to make another appointment in our department after three months to reevaluate their complaints. In case no sufficient improvement with above-mentioned therapy measures was seen and patients had no contraindications, allergen immunotherapy was recommended.
Perennial rhinitis, which is a typical characteristic of HDM allergy, is most often defined by the persistence of at least two of the following symptoms over nine months: serous or seromucous hypersecretion, nasal blockage caused by a swollen nasal mucosa, or sneezing paroxysms. Nasal congestion and mucous production (postnasal drip) are also predominant in most patients, while sneezing, itching, and watery rhinorrhea may be minimal [
31,
32].
Although nasal obstruction is one of the main symptoms affecting the quality of life of adolescents [
33] and adults [
34] suffering from perennial AR, we found no relevant difference in the degree of nasal obstruction reported by the participants of both groups. Nasal secretion, however, was a little bit more pronounced in our patients with positive NPT (45% vs. 37%). Accordingly, nasal dryness was reduced within this group (34% vs. 46%). Nasal operations might influence nasal symptoms, especially nasal obstruction. In the presented study, we excluded patients with a history of nasal surgery less than 2 months prior to their presentation at our department. However, even earlier operations might have an impact on nasal symptoms. This might be a disadvantage of the study. Nevertheless, we assume that the influence of these operations on our data may be neglected, as we as we included a relatively large number of patients in both subgroups.
Our participants were also asked about their ocular complaints, comprising symptoms of bilateral red eyes but also itching and tearing of their eyes in general. Didier et al. reported in their cross-sectional observational survey about AR-associated ocular symptoms in 19% of the overall study population and 52% in the AR population of adults. Interestingly, HDM sensitization was one of the most important trigger factors of ocular symptoms (35%) identified in this study [
35]. Another cross-sectional study demonstrated that a physician diagnosis of conjunctivitis was in 16% of 1549 asthmatic children (mean age 4.3 years). 44% of these children had at least one ocular symptom (itching, lacrimation or redness) suggesting ocular allergy. Again, HDM were with 71.4% one of the most common sensitizing agents [
36]. Interestingly, in our study significantly more patients with silent sensitization against HDM reported about symptoms of conjunctivitis than individuals with clinically relevant allergy (13% vs. 4%). This effect was especially pronounced in the polysensitized group (14% vs. 4%). A possible explanation for this finding might be, that polysensitized patients suffered from red eyes because of other allergens. However, the rate of ocular itching was comparable in both groups (39% vs. 40%).
In summary, our questionnaire revealed no suitable differences in nasal or ocular symptoms between subjects with relevant allergy against HDM and individuals with silent sensitization, even though these findings are known to belong to the key symptoms of AR. Concerning the temporal and regional occurrence of allergic symptoms, we did not observe significant differences (see Table
2).
We also detected no difference in the prevalence of self-reported asthma between the two groups (20% vs. 19%). Overall, this is a much higher prevalence compared to the prevalence of asthma in Germany, reported to be 6.2% [
37], which is in line with the fact that asthma is more frequently seen in patients with allergen sensitization. In the monosensitized subgroup, there was no patient with asthma in the silent sensitization group, but five patients with asthma and allergy to HSM (0% vs. 17%). This finding shows that there is a connection between allergy to HDM and asthma.
Besides causing allergic rhinitis and asthma, dust mite allergens are known to induce further atopic diseases such as atopic dermatitis (AD) [
38]. AD is characterized by pruritus and chronic or relapsing eczematous lesions with typical morphology and distribution [
39]. Several studies demonstrated a relationship between the exposure to high levels of HDM allergens in babyhood and the development of asthma [
7,
40] and atopy [
41] in childhood. Accordingly, Zureik et al. found in a huge cross-sectional study a positive association between sensitization to HDM and the severity of asthma [
42]. Besides inhalation, a possible route of exposure to HDM allergens is direct contact with the skin [
43,
44]. Consequently, it is not surprising that significantly more patients of our cohort, allergic to HDM, suffered from these atopic diseases in contrast to the control group of sensitized only patients (14% vs. 7%), underlining some representative character of our study population. The differences between the two groups were statistically significant but these items of our questionnaire alone are not useful for the differentiation between clinical relevant HDM allergy and pure sensitization.
A further part of the questionnaire deals with the possible impact of AR on different facets of sleep, comprising interruption of the sleep, un-restorative sleep, snoring, and dry mouth at night or in the morning. It is known that AR negatively affects sleep in many ways. This was confirmed by a meta-analysis of observational studies [
45]. Nasal congestion, which is a typical symptom of AR, is a known risk factor for sleep-disordered breathing and snoring [
46‐
48]. Thus, application of nasal corticosteroids positively affects sleep quality in patients with AR [
49,
50]. In contrast, in the presented study, there were no significant differences in the severity of symptoms related to sleep between the patients with HDM allergy and those with sensitization. Regarding some aspects (un-restorative sleep and snoring) individuals with silent sensitization tended to suffer slightly more often from reduced sleep quality. Other diseases also might influence sleep quality. These were not excluded in this study, which might influence the presented data. However, as we included a relatively large number of patients in both subgroups, we assume that this effect can be neglected.
The last part of our questionnaires addresses the home environment of the participants. This is especially important in case of HDM allergy because the bed and the mattresses are essential habitats for mites [
2,
51]. Factors shown to decrease HDM concentrations in the home include use of newer mattresses and mite-impermeable mattress covers [
52,
53]. Interestingly, more patients allergic to HDM reported about location-dependent complaints (39% vs. 31%) and more often used encasings for their beds (23% vs. 18%). In contrast, the age of the mattresses possessed by both groups was comparable. One could speculate that the individuals affected by HDM allergy have already investigated their symptoms and tried to start action against them thereby emphasizing the pre-selection of the cohort presenting at a center of maximum care as our university hospital.
There are several discrepancies between the findings presented in this study and the cited results found in the literature. Some of this could be explained by different inclusion criteria and initial questions. Moreover, our study has a pre-selection bias, as all patients presented at a specialized university clinic due to upper airway complaints. Thereby this cohort is not representing the general population. However, patients presenting to a specialist in allergy and clinical immunology would have similar characteristics, underlining the importance of the questions we address. Besides this main limitation, slight additional drawbacks of our study have to be addressed. First, our questionnaire was adapted from the RQLQ [
20,
21]. It is a standardized but not a validated tool. Furthermore, some items are related to the last 7 days, which may lead to false negative results, for example if patients do not present in the main allergy season. Moreover, the questionnaire addressed subjective symptoms. Objective data, for example pulmonary function tests, was not collected. Last, all data were evaluated retrospectively. In spite of these limitations, the presented study shows important data on the concordance between anamnestic data and NPT in HDM sensitized patients. It confirms the current opinion that clinical data in HDM sensitized patients is insufficient for initiating allergen-specific immunotherapy.
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