Efficacy of sublingual immunotherapy with

house dust mite extract in polyallergen sensitized

patients with allergic rhinitis
Ji-Eun Lee, MD*; Yoon-Seok Choi, MD*; Min-Su Kim, MD*; Doo Hee Han, MD*;
Chae-Seo Rhee, MD*; Chul Hee Lee, MD*; and Dong-Young Kim, MD*

Background: It is suggested that polysensitized patients might not benefit from specific allergic rhinitis immunotherapy as
much as monosensitized patients, although further research on this subject is needed.
Objective: To compare the efficacy of sublingual immunotherapy (SLIT) with standardized house dust mite extract in
monosensitized and polysensitized patients with allergic rhinitis.
Methods: Patients who were sensitized to house dust mites and treated with SLIT for house dust mites for at least 1 year
between November 2007 and March 2010 were studied. The monoallergen sensitized group was defined as patients who were
sensitized to Dermatophagoides pteronyssinus and/or Dermatophagoides farinae (n 70). The polyallergen sensitized group
was defined as patients who were simultaneously sensitized to house dust mites and other allergens (n 64). A standardized
extract of house dust mites was used for immunotherapy. Antiallergic medication and the total nasal symptom score (TNSS),
including rhinorrhea, sneezing, nasal obstruction, and itchy nose, were evaluated before and 1 year after SLIT.
Results: This study enrolled 134 patients. The TNSS improved significantly after SLIT in both groups, whereas the change
in the TNSS did not differ significantly between the groups. The antiallergic medication scores also decreased significantly in
both groups, but there was no significant difference between the groups.
Conclusions: In polysensitized allergic rhinitis patients, SLIT for D pteronyssinus and/or D farinae produced improvements
in both nasal symptoms and rescue medication scores comparable to those in monosensitized patients, regardless of other positive
allergens. SLIT for D pteronyssinus and/or D farinae should be considered in polysensitized allergic rhinitis patients.
Ann Allergy Asthma Immunol. 2011;107:79 84.

INTRODUCTION A recent study showed the effectiveness of monoallergen

Recently, the sublingual administration of allergen extracts
has become popular in many countries, and its efficacy in
allergic rhinitis has been demonstrated.1 Sublingual immuno-
therapy (SLIT) reduces symptoms and the need for medica-
tion.2
Most randomized controlled studies demonstrating the ef-
ficacy of subcutaneous immuneotherapy or SLIT have been
conducted with single-allergen extracts. Recently, the admin-
istration of multiallergen extracts has been recommended.
Some studies have shown that multiple allergen immunother-
apy is effective when administered subcutaneously.35 How-
ever, the limited absorptive capacity of the sublingual mucosa
may make treatment with multiallergen SLIT less effective.6
Affiliations: * Department of Otorhinolaryngology and Research Cen-
ter for Sensory Organs, Seoul National University College of Medicine,
Seoul, Korea.
Disclosures: Authors have nothing to disclose.
The English in this document has been checked by at least 2 professional
editors, both native speakers of English. For a certificate, see http://
www.textcheck.com/certificate/WMd5j2.
Received for publication December 8, 2010; Received in revised form
February 9, 2011; Accepted for publication March 18, 2011.
2011 American College of Allergy, Asthma & Immunology.
Published by Elsevier Inc. All rights reserved.
doi:10.1016/j.anai.2011.03.012
SLIT with grass pollen extract in polysensitized patients.7
However, to our knowledge, no reported study has compared
the efficacy of SLIT with house dust mite extract between
monosensitized and polysensitized patients with allergic rhi-
nitis. Thus, we compared the efficacy of SLIT with standard-
ized house dust mite extract in monosensitized and polysen-
sitized allergic rhinitis patients.
METHODS
Study Design
This study was a prospective case series conducted at a
tertiary referral center. Allergic rhinitis patients sensitized
only to house dust mites were compared with patients simul-
taneously sensitized to house dust mites and other allergens
after 1 year of SLIT with house dust mite extract. Antiallergic
medication score (AMS) and total nasal symptom score
(TNSS), including rhinorrhea, sneezing, nasal obstruction,
and itchy nose, were evaluated before and 1 year after SLIT.
The institutional review board of the Clinical Research
Institute at Seoul National University Hospital approved this
study protocol. Written consent was obtained from the pa-
tients when they were enrolled. We have registered this study
with a public trials registry (registration NCT01247259).

VOLUME 107, JULY, 2011 79

Patients
Between November 2007 and February 2010, patients who
were sensitized to house dust mites and treated with SLIT for
house dust mites for at least 1 year were consecutively
enrolled. The inclusion criteria were as follows: (1) having
more than 2 allergic rhinitis symptoms, including sneezing,
itching, rhinorrhea, and nasal congestion with or without eye
symptoms8; (2) sensitization to Dermatophagoides pteronys-
sinus and/or Dermatophagoides farinae, defined as a serum
specific IgE level for D pteronyssinus and/or D farinae of
class 2 or higher on multiple allergen simultaneous tests
(Immunosystems, Mountain View, California) or wheal di-
ameters for D pteronyssinus and/or D farinae equal to or
greater than that of positive control (histamine) on skin prick
tests (ratio of the size of the allergen-induced wheal to the
size of the wheal elicited by the histamine solution [A/H
ratio], 1); and (3) SLIT with house dust mite for at least 1
year. The skin prick test included 55 inhalant allergens, which
were divided into 5 groups: mites, molds, animals and in-
sects, pollens (tree, grass, and weed), and others. The reac-
tivity of skin prick test was graded according to the A/H ratio
as follows: 1, 25% to 9%, 2, 50% to 99%, 3, 100% to
199%; and 4, 200% or higher. The reactivity of 3 or
higher (A/H ratio 1) was considered an indication of a
clinically significant positive response. Patients who received
immunotherapy in the preceding 3 years or who had systemic
immunologic disorders were excluded.
A total of 182 patients were enrolled initially; however,
134 patients of 182 (73.6%) continued SLIT for 1 year after
enrollment (Table 1). The monoallergen sensitized group was
defined as the patients who were sensitized only to D ptero-
nyssinus and/or D farinae (n 70). The polyallergen sensi-
tized group was defined as the patients who were simultane-
ously sensitized to house dust mites and other allergens (n
64). The polyallergen sensitized group was divided into 5
subgroups according to other positive allergens, such as an-
imals (n 33), fungi (n 24), tree (n 17), house dust
(n 14), and grass (n 11). The numbers are not mutually
exclusive.
SLIT
Immunotherapy was performed using a standardized extract
of house dust mites (50% D pteronyssinus and/or 50% D
farinae; Pangramin SLIT; ALK-Abell, Madrid, Spain). Dur-
Table 1. Demographics of the Study Patients
Monoallergen Polyallergen
Demographics sensitized sensitized
group group
No. of patients 70 64
Male:female 52:18 42:22
Age, mean (SD), y 14.3 (9.9) 15.3 (10.4)
Duration of symptoms, 6.6 (5.3) 6.9 (6.3)
mean (SD), y
No. (%) with asthma history 11 (15.7) 18 (28.6)
80
ing a 4-week increasing-dose phase, the patients increased the
daily dose from 1 to 5 drops of a 1.6-STU/mL solution from
day 1 to 10, 1 to 5 drops of a 8-STU/mL solution from day 11
to 15, 1 to 5 drops of a 40-STU/mL solution from day 16 to
20, 1 to 5 drops of a 200-STU/mL solution from day 21 to 25,
and 1 to 5 drops of a 1,000-STU/mL solution from day 26 to
30. After reaching the maintenance dose, 5 drops of a 1,000-
STU/mL solution, the patients took the allergen 3 times per
week during the maintenance phase. The patients had to keep
the drops of allergen under the tongue for 2 to 3 minutes
before swallowing. When the symptoms of allergic rhinitis
were aggravated during immunotherapy, patients were al-
lowed to use antihistamines or intranasal steroid.
Outcome Measures
All of the patients were asked to complete a symptom ques-
tionnaire before SLIT and 1 year after receiving SLIT. The
questionnaire included questions on rhinorrhea, sneezing,
nasal obstruction, itchy nose, and eye discomfort. The symp-
tom score was recorded and averaged for 1 week using a
6-point scoring system (0 indicating no symptom; 1, very
mild; 2, mild; 3, moderate; 4, severe; and 5, very severe). The
TNSS was defined as the sum of the scores for 4 nasal
symptoms: rhinorrhea, sneezing, nasal obstruction, and itchy
nose (range, 0 20).
Rescue medication was recorded on diary cards. The pa-
tients were asked to record their uses of antiallergic medica-
tions, such as oral antihistamine and intranasal corticosteroid.
The AMS could be calculated with frequency of use multi-
plied by each medication point. Oral antihistamine was
scored as 1 point, and intranasal corticosteroid was scored as
2 points. The AMS was calculated every 2 months during the
1-year application of SLIT.
Statistical Analyses
Symptoms before and after SLIT were analyzed statistically
using a paired t test. The t test was used to compare the
changes in symptoms and antiallergic medications between
the 2 groups. SPSS statistical software (version 12.0; SPSS
Inc, Chicago, Illinois) was used for statistical analyses. P
.05 (2-sided) was considered the limit of significance in all
analyses.
RESULTS
This study enrolled 134 patients with a mean age of 14.7
years (range, 4 53 years). The duration of allergic rhinitis
symptom averaged 6.6 (range, 0.530) and 6.9 (range, 130)
years in the monoallergen sensitized and polyallergen sensi-
tized groups, respectively.
All allergic symptoms, including rhinorrhea, sneezing, na-
sal obstruction, itchy nose, and eye discomfort, improved
significantly after 1-year application of SLIT in both the
monoallergen sensitized group (Fig 1) and the polyallergen
sensitized group (Fig 2).
The TNSS also improved significantly after SLIT in both
groups, although the change in the TNSS did not differ
significantly between the groups (TNSS change, 5.7 vs 5.6;
ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY
 Figure 1. Allergic symptoms in the monoallergen sensitized group. All allergic symptoms improved in the monoallergen sensitized group after a 1-year
application of sublingual immunotherapy (n 70 for rhinorrhea, sneezing, nasal obstruction, and itchy nose; n 47 for eye discomfort).

P .94; Fig 3A). The AMSs were decreased significantly
after SLIT in both the monoallergen sensitized and polyal-
lergen sensitized groups but did not differ significantly be-
tween the 2 groups (54.1 vs 46.1, P .56; Fig 3B).
In the 5 polyallergen sensitized subgroups, the changes in
the TNSS did not differ significantly compared with that in
the monoallergen sensitized group (Fig 4). The 5 subgroups
did not differ significantly in the change in AMS compared
with the monoallergen sensitized group (Fig 5).
The incidence of adverse events of SLIT was 22.9% during
the 1-year follow-up period. Aggravation of allergic rhinitis
symptoms was the most common adverse event (41.8%),
followed by itching sense of the oral cavity (16.2%), itching
sense or discomfort of the eye (13.5%), skin itching or rash
(6.7%), breathing discomfort (4%), and wheezing (1.3%).
However, these adverse events, including wheezing and
breathing discomfort, were temporary and subsided spon-
taneously without medication. None of the patients needed

Figure 2. Allergic symptoms in the polyallergen sensitized group. All allergic symptoms improved in the polyallergen sensitized group after a 1-year
application of sublingual immunotherapy (n 64 for rhinorrhea, sneezing, and nasal obstruction; n 63 for itchy nose; n 35 for eye discomfort).

VOLUME 107, JULY, 2011 81

 Figure 3. Comparison of changes in total nasal symptom score (TNSS) and antiallergic medication score (AMS) between the 2 groups. A, TNSS in the
monoallergy sensitized group (Mgr) and polyallergen sensitized group (Pgr). Change in TNSS did not differ significantly between the 2 groups (TNSS change,
5.7 vs 5.6; P .94). B, Antiallergic medication score (AMS) in the Mgr and Pgr. Change in AMS did not differ significantly between the 2 groups (AMS change,
54.1 vs 46.1; P .56).

to visit an emergency department because of adverse
events.
DISCUSSION
A double-blind, placebo-controlled study showed that SLIT
with house dust mite extract in perennial allergic rhinitis was
well tolerated, although it was reported that the improvement
in the TNSS was not significant compared with the placebo
group.9 Conversely, a meta-analysis found promising evi-
dence of the efficacy of SLIT using house dust mite extract.10
Other retrospective studies of SLIT with house dust mite
extracts in monosensitized patients claimed that SLIT was an
effective treatment modality.11,12 Previously, we also reported
a randomized study that showed that SLIT significantly im-
proved the symptoms and medication scores in Korean pa-
tients with allergic rhinitis to house dust mites.13
House dust mite is the most common allergen to provoke
allergic rhinitis in Korea. It is known to be a perennial

Figure 4. Changes in total nasal symptom score (TNSS) in the subgroups of the polyallergen sensitized group. Change in TNSS did not differ significantly
in the 5 subgroups compared with the monoallergen sensitized group (Mgr).

82 ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY

 Figure 5. Changes in antiallergic medication scores in the subgroups of the polyallergen sensitized group. Change in AMS did not differ significantly in the
5 subgroups compared with the monoallergen sensitized group (Mgr).
allergen that does not have seasonal variations, unlike pol-
len allergens. It is reported that the density of mite is lowest
in May, but it is a sufficient amount to evoke the allergic
symptoms. Thus, it is believed that there were no differences
in exposure level to house dust mites throughout the year.
It is often suggested that polysensitized patients might not
benefit from specific immunotherapy as much as monosen-
sitized patients, although further research on this subject is
needed, as indicated in a previous study.14 A randomized
controlled trial of SLIT with timothy extract alone and mul-
tiple pollen extracts reported that SLIT with timothy extract
alone was effective and showed significant improvements in
immunologic outcomes, in contrast to SLIT with multiple
pollen extracts. Therefore, it raised questions regarding the
use of multiple allergen mixes for SLIT because multiple
pollen extracts showed a limited response.7 Another study
examined the efficacy of SLIT in polysensitized patients to
grass and birch and reported that SLIT with birch only or
grass only also conferred a measurable improvement.15 In our
study, we used only house dust mite extract for polysensitized
patients regardless of other positive allergens and found that
the nasal symptoms and rescue medication scores improved
significantly in all polyallergen sensitized group subgroups. It
is assumed that because house dust mites play the main role
as a dominant allergen in polysensitized patients, SLIT with
house dust mite extract only in polysensitized patients might
be as effective as that in monosensitized patients. These
results are important clinically because most allergic rhinitis
patients are polysensitized. On the basis of our results, SLIT
can be recommended to more patients with allergic rhinitis
due to house dust mites in countries where its use is currently
restricted to monosensitized patients.16
VOLUME 107, JULY, 2011
Previous studies showed that SLIT induces regulatory T-
cell suppression via interleukin 10 and modulates the aller-
gen-specific T-cell responses in a similar way to subcutane-
ous immunotherapy.17 Regulatory T cells contribute to the
control of immune responses in 5 major ways: (1) suppres-
sion of antigen-presenting cells that support the generation of
effector TH2 and TH1 cells; (2) suppression of TH2 and TH1
cells; (3) reduction of the production of allergen-specific IgE
and induction of IgG4, IgA, or both; (4) reduced activity of
mast cells, basophils, and eosinophils; and (5) interaction
with resident tissue cells and remodeling.18
A retrospective study showed that length of the effect of
SLIT is strictly related to the length of treatment.11 Our
previous study of SLIT with house dust mite extracts for 6
months showed significant improvements in all nasal symp-
toms.19 In addition, our 1-year follow-up results also demon-
strated significant improvements.13 These studies support the
evidence that a 6-month application of SLIT can improve
nasal symptoms and the improvement persists for more than
1 year. During SLIT application, the use of rescue medica-
tions was also reduced significantly, so it is unlikely that
rescue medications enhanced the efficacy.
One of the advantages of SLIT is improved safety. In our
study, only minor adverse effects were reported, and no
systemic allergic reaction, such as anaphylaxis, was seen.
There was no significant difference in the number of adverse
events between the 2 groups. SLIT induces fewer systemic
adverse effects, and most adverse events have been local
reactions in the nose, eye, and oral cavity. Three cases of
anaphylaxis after SLIT were reported in the English litera-
ture. Two of these reports described anaphylaxis that was due
to a mixture of multiple allergens, and the third case was due
83
to latex. However, no anaphylaxis occurred with commer-
cially available allergens.20 22
In this study, we observed that subjective symptoms and
antiallergic medication used decreased significantly with a
1-year application of SLIT with house dust mite extract in
polysensitized patients with house dust mite allergic rhinitis.
However, there are 2 limitations. First, there is no control
group; thus, the placebo effect could not be fully evaluated.
There was a review paper on SLIT for individual allergens in
which SLIT with house dust mite appears to be more effec-
tive than treatment with other types of allergen and even more
effective than treatment with placebo.1 In our study, we
aimed to evaluate the efficacy of house dust mite SLIT in
polyallergen sensitized patients with allergic rhinitis com-
pared with that in the monosensitized group. Therefore, the
monoallergen sensitized group could be considered as a con-
trol group to the polyallergen sensitized group. The second
limitation is the small number of enrolled patient. Consider-
ing the limited number of patients with allergic rhinitis who
are candidates for SLIT and 30% of the mean dropout rate,1
it was almost impossible to get a large sample size in our
study. A further long-term study with a larger number of
patients is needed to evaluate whether the reduced allergic
symptoms persist and whether the symptom-free duration
increased with the duration of SLIT application in polysen-
sitized patients.
In summary, in polysensitized house dust mite allergic
rhinitis patients, SLIT for D pteronyssinus and/or D farinae
demonstrated comparable improvements in both nasal symp-
toms and rescue medication scores to those in monosensitized
patients, regardless of other positive allergens. Thus, SLIT
for D pteronyssinus and/or D farinae should be considered in
polysensitized allergic rhinitis patients.
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Requests for reprints should be addressed to:
Dong-Young Kim, MD, PhD
Department of Otorhinolaryngology
Seoul National University College of Medicine
28 Yongon-dong, Chongno-gu, Seoul, 110-744, Korea
E-mail: dongkim@snu.ac.kr
ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY