Review

Allergy Asthma Immunol Res. 2015 May;7(3):221-229.

http://dx.doi.org/10.4168/aair.2015.7.3.221
pISSN 2092-7355 • eISSN 2092-7363

Specific Immunotherapy in Atopic Dermatitis

Jungsoo Lee, Chang Ook Park, Kwang Hoon Lee*

Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits
unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Allergen specific immunotherapy (SIT) using house dust mite (HDM) extracts has been performed mainly with patients of asthma and allergic rhini-
tis. In the meanwhile, there has been a long debate on the efficacy of SIT in atopic dermatitis (AD) with only a few double-blind placebo-controlled
trials. However, several randomized controlled trials of SIT in AD revealed significant improvement of clinical symptoms and also, positive result
was shown by a following meta-analysis study of these trials. In order to predict and evaluate the treatment outcome, finding a biomarker that can
predict treatment responses and treatment end-points is critical but it is very challenging at the same time due to the complexity of causes and
mechanisms of AD. Other considerations including standardization of the easiest and safest treatment protocol and optimizing the treatment prepa-
rations should be studied as well. This review summarizes the basics of SIT in AD including the brief mechanisms, treatment methods and sched-
ules, and also highlights the clinical efficacy of SIT in AD along with mild, controllable adverse reactions. Immunologic effects and studies of various
biomarkers are also introduced and finally, future considerations with upcoming studies on SIT were discussed.
Key Words: Specific immunotherapy; subcutaneous immunotherapy; atopic dermatitis; clinical efficacy; biomarker

INTRODUCTION skin barrier and binds with an epidermal dendritic cell (DC) ex-
pressing FcεRI which plays a role in recruiting cutaneous lym-
Atopic dermatitis and allergen phocyte antigen-bearing T cell to initiate cutaneous inflamma-
Atopic dermatitis (AD) is a chronic, inflammatory skin disease tion13 and activate Th2 polarization.14,15 Also, interleukin (IL)-16
with intractable pruritus. As one of the leading skin diseases in and monocyte chemotactic protein 1 (MCP-1) produced by
Westernized countries, its prevalence is increasing steadily these epidermal DCs induce differentiation of monocytes into
world-wide,1-3 AD affects approximately 20% of pediatrics and inflammatory dendritic epidermal cells (IDECs), which produce
1%-3% of adults,4 and 40%-60% of pediatric AD patients contin- IL-1, IL-6, and tumor necrosis factor α (TNF- α). Other cytokines
ue on as adult-forms later in their lives.1,5,6 Its pathogenesis is in AD pathogenesis such as IL-12 and IL-18 aid in transforma-
multifactorial with roots in a combination of genetic, environ- tion of inflammatory responses from Th2 to Th1/0 and enter
mental, skin barrier, and other immunological factors. Although chronic phase.16 Through above mechanisms, allergens in envi-
there is no single gene responsible for onset of the disease, fam- ronment are important in both acute phase from repetitive ex-
ily history contributes in predicting prognosis of AD along with posure and also in chronic status of disease; hence, it is impera-
interplays between environmental and individual factors. Fur- tive for extrinsic patients who have elevated serum and specific
thermore, abnormalities of the skin barrier have been exten- IgE for allergens to avoid possible exacerbating factors. And one
sively studied in the pathogenesis of AD in several studies,7-12 of the most frequently noted allergens for AD exacerbation is a
and these barrier dysfunctions lead to dry and rough surfaced house dust mite (HDM).
skin of AD patients. Consequently disrupted barrier leads to in-
creased rate of secondary infection and penetration of foreign
antigens through damaged stratum corneum. Correspondence to:  Kwang Hoon Lee, MD, PhD, Department of
AD can be classified into either intrinsic or extrinsic AD de- Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei
University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 120-752,
pending on co-existence with allergic features; barrier dysfunc- Korea.
tion and increased penetration of foreign allergens of food and Tel: +82-2-2228-2080; Fax: +82-2-393-9157; E-mail: [email protected]
environment are closely associated with aggravation of extrinsic Received: February 3, 2014; Revised: April 30, 2014; Accepted: June 30, 2014
AD. In an acute stage, allergen penetrates through damaged •There are no financial or other issues that might lead to conflict of interest.

© Copyright The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease http://e-aair.org   221
Lee et al. Volume 7, Number 3, May 2015

Pyroglyphidae Dermatophagoides farinae (Der f), Derma- ripheral allergen-specific Tregs through similar mechanisms for
tophagoides pteronyssinus (Der p) and Euroglyphus maynei are inducing T-cell tolerance, inhibitory functions of IL-10, TGF-β,
the most common types of HDM. The antigenically active parti- and reduction of mast cell and eosinophil. However, in early
cles contain high enzymatic activity and act through destroying stages of treatment, expression of Treg, reduction in IgE or in-
tight junction of epidermis, enhancing penetration of allergens crease in IgG4 might not be evident in SLIT compared to SCIT.24
deep into the skin.17,18 One of enzymes that HDM possesses is The most important factor to consider while choosing candi-
serine cysteine proteinase, and these enzymes are able to acti- dates for immunotherapy is finding those who are actually sen-
vate proteinase-activated receptors (PARs). Among many PARs, sitized to HDM. Therefore, majority of previously reported
PAR-1, and PAR-2 are known to be most populated in respirato- studies also enroll patients who have positive allergen sensiti-
ry, gastrointestinal systems and skin.19 When PAR is activated, zation to HDM. Standards for choosing candidates for SIT in
various inflammatory mediators such as IL-6 and IL-8 are se- our institution is first selecting extrinsic AD patients with serum
creted, leading to increase vascular permeability, infiltration of total IgE above 150, and then additionally selecting only those
leukocytes, increased airway hypersensitivity, and other effects who have positive reactions (over 3+) to HDM on CAP-test or
by HDM that preceded clinical symptoms of allergic diseases.20 skin prick test. We initially start the therapy in weekly regimen
for 16-18 weeks as initial build-up phase and slowly escalates
Allergen specific immunotherapy (SIT) dosage of HDM extract, and when the maintenance dosage is
Mechanisms of allergen SIT reached, the patient visits the clinic biweekly for four times. Af-
HDM avoidance has been practiced as a part of lifestyle modi- terwards, the monthly regimen can be installed. Depending on
fication with extrinsic AD patients for quite a period. Yet as a clinical response, the patient can continue on with the treat-
more active treatment modality, SIT is receiving more attention. ment for 3 to 6 years.
SIT was initially practiced in allergic rhinitis or asthma patients. There is no exact consensus for treatment period, interval
Up until now, SIT is the only disease-specific treatment modali- time between treatments, and follow-up period after termina-
ty that suppresses allergic responses for a long period of time. tion of SIT, but most literature generally agree upon 3 years as
SIT aims to induce allergen-specific tolerance otherwise known an ideal treatment period.25 Our institution also maintains one
as allergen vaccination21 through acquiring immune tolerance year of treatment for all those started on SIT, and continues for
with induction of allergen-specific regulatory T cells (Tregs). 3 years unless complete remission is reached.
The acute phase of AD is closely associated with production
of Th2 cytokines and commonly observed Th2-biased profiles Clinical efficacy of allergen SIT in AD
are suggested to be results of increased clonal expansion or dif- Efficacy of SIT with HDM in AD
ferentiation of Th2 cells or increased tendency to activation and In the past, there has been a lack of evidence of SIT in AD
apoptosis of high IFN-γ producing Th1 cells.22 These Th1 cells compared to that in asthma or allergic rhinitis. However, with
are known to be involved in apoptosis of epithelium in AD. increasing reports of comparable efficacy and safety of SIT in
Thus, induction of Treg cells during the SIT consequently in- AD, researches are actively seeking into the field of SIT in AD as
creases suppression of allergen-induced T-cell proliferation, well. Recently published meta-analysis on 8 different random-
and Th1 and Th2 cytokines.23 Thereby, we may observe clinical ized controlled trials of SIT on AD showed excellent results of
improvement of AD as a result of skin inflammation reduction the therapy, strengthening rationale for the treatment.26
and a diminution in epithelium apoptosis. Results from previously performed randomized controlled SIT
Tregs involved in mechanisms of SIT express IL-10, trans- are summarized in Table 1. First, in Kaufman and Roth’s study in
forming growth factor β (TGF-β) to elicit early phase desensiti- 1974 (United States), quasi-randomized controlled study was
zation of mast cell, basophil, and eosinophil. These allergen- performed among total of 52 adult and pediatric AD patients.27
specific Tregs also suppress Th2 cells, thereby inhibiting IgE A total of 26 patients completed the SCIT trial for a period of 2
production, while at the same time stimulating expression of years, and significant clinical improvement was seen in 81% of
IgG4, a non-inflammatory immunoglobulin isotype. Also, cyto- the treatment group and 40% of the placebo group. Warner et
kines such as IL-3, IL-4, IL-5, IL-9, and IL-13 that are expressed al.28 conducted randomized, double-blind, placebo-controlled
from Th2 play an important role in survival, activation, and dif- study for children with asthma (United Kingdom) and among
ferentiation of mast cells, basophil, and eosinophils, but SIT 20 children who possessed additional atopic features, there was
suppresses cytokine axes as well. subjective improvement of clinical eczema features as judged by
the patients and parents in active treatment group (77.8%) com-
Treatment methods and schedules pared to minimal improvement in the placebo group (27.3%) af-
SIT can be divided into 2 major groups depending on the route ter 1 year of treatment. Later, Glover and Atherton performed
of administration: sublingual (SLIT) and subcutaneous (SCIT) randomized, double-blind, placebo-controlled trials for HDM
methods. While the routes may differ, both equally affect pe- SCIT for 24 pediatric AD patients.29 The first study did not reveal

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AAIR Specific Immunotherapy in Atopic Dermatitis

Table 1. Summary of characteristics and results from randomized controlled trials included in this review
Total number of Total
Year Study Type of Type of
Study Country patients duration Improvement Reference
published design SIT allergens
(treatment, placebo) (months)
Kaufman and Roth 1974 US qRCT DB PC 52 (26, 26) SCIT dander, HDM 24 (+) by physician 27
molds, pollen
Warner et al. 1978 England RCT DB PC 20 (9, 11) SCIT HDM 12 (+) by patients 28
Glover and Atherton 1992 England RCT DB PC 24 (13, 11) SCIT HDM 8 (+) by patients 29
Silny and Czarnecka-Operacz 2006 Poland RCT DB PC 20 (10, 10) SCIT dander, HDM 12 (+) by physician 30
pollen
Pajno et al. 2007 Italy RCT DB PC 56 (28, 28) SLIT HDM 18 (+) by physician 31
Novak et al. 2012 Germany RCT DB PC 168 (112, 56) SCIT HDM 18 (+) by physician 32
Qin et al. 2013 China RCT DB PC 107 (58, 49) SLIT HDM 12 (+) by physician 33
SIT, specific immunotherapy; qRCT, quasi-randomized controlled trial; DB PC, double-blind placebo-controlled; SCIT, subcutaneous immunotherapy; SLIT, sublingual
immunotherapy; HDM, house-dust mite; (+), Presence.

any statistical difference between the treatment and placebo (53.85%), treatment group (77.78%) showed improvement in
groups. The second study was conducted with patients who un- symptoms. SIT for AD patients are practiced in Korea as well.
derwent active treatment in the first study and found greater But only little clinical studies have been conducted. There was
clinical improvement, suggesting that long-term treatment for one pilot study of SIT published by Nahm et al.34 Even though
at least 1 year is necessary. Persistent efforts of SIT in AD contin- 20 AD patients showed significant decreased in SCORAD score
ued, and a double-blind, placebo-controlled trial was conduct- with noticeable clinical improvement after 12 months, since it
ed, for 20 adult and pediatric AD patients.30 They used W- was modified treatment methods combining SIT and hista-
Atopowe zapalenie skóry (W-AZS), a Polish acronym for atopic mine-immunoglobulin complex treatment, it was difficult to
dermatitis severity score to assess the extent and severity of skin see the sole and exclusive efficacy of SIT. Our institution per-
inflammation index in AD patients concerning pruritus, sleep formed retrospective review on patients who underwent at least
disturbances and extent and severity of skin inflammation, to 3 years of HDM SIT for 217 extrinsic AD patients selected
evaluate the clinical efficacy. There was a significant decrease in through total IgE and CAP test or skin prick test with hypersen-
clinical score of W-AZS index after a period of 12 months, sup- sitivity to HDM.35 Clinical improvement was judged based on
porting growing number of evidence for efficacy. A random- investigator global assessment (IGA) and patients’ subjective
ized, double-blind, placebo-controlled trial was performed assessment of symptoms. In overall, 88.4% of patients showed
among a larger population of pediatric patients31 as a sublingual clinical improvement and among these patients, 63.9% patients
method for 18 months. Scoring atopic dermatitis (SCORAD) showed complete or near-complete remission. Pruritus and
showed a dramatic decrease 9 months after the treatment and loss of sleep was also significantly reduced with 87.2% of pa-
disease-control medication for treatment of AD was significant- tients reporting improvement in pruritus, and 92.7% of patients
ly reduced in treatment group compared to placebo group. In with only mild or no disturbance of sleep. Hence, although the
addition, compared to baseline, visual analogue scale (VAS) efficacy of SIT for extrinsic AD patients with positive reactions
showed tendency to decrease only in the treatment group, al- to HDM was believed to have controversial results for patients
though did not show statistical significance. Another random- in the past, there is a growing trend of thought through many
ized double-blind placebo-controlled trial by Novak et al.32 was double-blind placebo-controlled trials and meta-analysis, that
conducted with 168 adult AD patients for 18 months. Even SIT is indeed an efficient and safe treatment modality for AD
though, the study did not reveal the efficacy in overall AD pa- patients. While 3 to 6 years of treatment period is generally rec-
tients, SIT showed statistical significance of SCORAD reduction ommended in literature, there is no set evidence stating long-
in subgroup of severe AD patients with SCORAD >50. Median term efficacy for AD patients receiving SIT for more than 3
reduction of total SCORAD of 18% was observed. The best out- years. Yet retrospective review from our institution support the
come was shown during September to February, due to the use long term efficacy of SIT indicating clinical improvements are
of indoor heating and subsequent high HDM exposure. The ef- most significant when the treatment is continued for a mini-
ficacy was more pronounced with longer duration. Lastly, most mum of 3 years.
recent randomized control trial carried out by Qin et al.33 ana-
lyzed 107 patients undergoing SLIT for 12 months. A total of 84 Side-effects and complications
patients finished the trial, compared to the placebo group Both local and systemic complications can occur due to SIT.

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Lee et al. Volume 7, Number 3, May 2015

Based on a survey of systemic side-effects occurring SCIT in the An explanation is needed for serum IgE level changes in re-
past 3 years (2008-2011), there were noticeable systemic side- sponse to SIT in regards to highly activated B cells and deregu-
effects in only 0.1% of the total 18.9 million SCIT treatment per- lation of IgE synthesis,41 but there is no clean-cut evidence.
formed, and there was no single case of fatal complications.36 Studies up until now show trend of allergen-specific IgE level
Majority of systemic complications occurred within 30 minutes gradually decreasing after SIT.31,42-46 For total IgE, there was a
of injection, and some of the delayed type response were mild general trend for decrease, but statistically, the results were con-
symptoms such as a flu-like illness.37 flicting with those showing significance31,46 and those that did
Common local side-effects that can occur in SCIT are urticaria not.27,29 Serum IgE begins to change relatively at a slow rate with
or pruritus, but majority of these reactions persist for less than no noticeable drop in its levels; moreover, since there is no evi-
24 hours and are rarely regarded as noticeable complications. dent correlation between clinical improvements after SIT treat-
Comparing with results from our institution and other RCTs ment, it is hard to explain loss or decrease of response to specif-
previously performed, mild urticarial eruptions and pruritus ic allergen only through changes in IgE.47 To many scholars, the
occurred in only <1% of patients.38 Furthermore, in one dou- role of IgE as a measurement of clinical sensitivity remains
ble-blind placebo-controlled trial, incidence of pruritus lasting questionable in reality.43 Other works have stressed a significant
for 1-2 days and discomfort, mild exacerbation of atopic lesions, decrease in Der p-specific IgG4,31,32,45,48,49 and in one pilot study,
urticaria, headaches or rhinitis were almost similar between the treatment with SIT led to decrease in markers of AD activity
treatment and placebo group,26,27,31 leading to a conclusion that such as IL-16 and thymus and activation regulated chemokine
SIT is relatively a safe treatment modality. From RCTs of those (CCL17) in accordance with clinical improvement.44
who underwent SLIT,30,32 fatigue, headache, localized delayed
hyper-responsiveness (>1 hour) occurred in first injection of Examples of biomarker studies
the treatment, and among these side-effects, localized pruritus Although finding a biomarker that can accurately predict
was most common. Other noted side effects were facial edema treatment response is a necessary task, it is a challenging pro-
and gastrointestinal discomfort. Yet most of symptoms were cess considering multifaceted and intricately woven immuno-
mild with spontaneous resolution. There were reports of sud- logic mechanisms and axes involved in allergic patients. Since
den worsening of allergic reactions or generalized pruritus in the late 1990s, there have been many attempts to find biomark-
both placebo and control group, but the patients were all man- er candidates. In the early years, most studies concentrated on
ageable with a brief symptomatic treatment; no other serious endothelial cell adhesion molecules,50-54 and works on chemo-
adverse events were reported.39,40 kines were published in 2000.55-58 Brief summary on history of
According to data collected from our institution, we witnessed biomarker studies are summarized in Table 2. Reviewing stud-
urticaria, localized eruption, pruritus, exacerbation of previous ies on biomarker up until now, there have been reports of aller-
atopic lesions, and relapse of previously known asthma in <1% gen-specific non-IgE antibody increasing through SIT,59 and
of patients. However, the degree of symptoms was very mild, several studies have shown that serum antibodies can reduce in
and the symptoms were all controllable with antihistamines. vitro responses mimicking allergic reactions, such as IgE bind-
We believe that it is actually very difficult to accurately deter- ing to allergen, IgE-facilitated antigen presentation and baso-
mine whether such reactions occur due to SIT or by exposure phil activation.60-62 In a double-blind placebo controlled study
to other exogenous trigger factors. Nevertheless, from evidenc- of grass pollen SIT, there was increase in IgG4, IgE blocking fac-
es collected thus far, SIT is a very safe treatment modality to in- tor along with suppression of facilitated allergen binding.63 The
corporate in a clinic setting. authors stressed that not only IgG4, but combined assessment
of IgG4 and IgE blocking factor can be done in order to more
Biologic effect of allergen SIT in AD comprehensively observe functional and clinical efficacy.
Immunologic effect and other serologic effect Recently, grass pollen SLIT experiment was performed in ex-
There are only few reports on immunological changes ob- perimental exposure chamber, and the results showed comple-
served in serum or skin after SIT since most of studies thus far ment component 1 and the receptor stabilin-1, 2 protein induc-
were concentrated on clinical efficacy and safety. Articles elab- tion from tolerogenic DC also known as regulatory DC has cor-
orating on changes in serum level of IgE and IgG4 are beginning relation with clinical tolerance induced by SIT.64 In addition, the
to appear on surface, but works on variety of cytokines and che- study opened a possibility into readily selecting clinically re-
mokines are lacking. Considering a role of allergen as a potent sponsive and unresponsive group through proteins that are
aggravating factor in AD and complicated axes of immunology easily detected through quantitative polymerase chain reaction
in AD pathomechanism, it is an important task to find efficacy in peripheral blood mononuclear cells, and explained relation-
of inducing immune tolerance through SIT and acquiring data ship of short-term efficacy with regulatory immune response.
that shows intricate interplay of immunologic changes before What exact immunologic mechanisms underlie changes in-
and after treatment. duced in SIT is a field of excitement that raises many questions.

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AAIR Specific Immunotherapy in Atopic Dermatitis

Table 2. Prior studies on biomarker candidates of atopic dermatitis

Candidate marker Action Clinical results Reference
sE-selectin An adhesion molecule on endothelial cells Reflection of disease severity 50,52-54,66,67
sVCAM-1 An adhesion molecule on endothelial cells Not correlated with disease severity 51,52,54,67
sICAM-1 An adhesion molecule on endothelial cells Not correlated with disease severity 52,54
TARC/CCL17 A chemokine that attracts CCR4+ or CCR8+ cells Reflection of disease severity 55,56,58,68-72
MDC/CCL22 A chemokine that attracts CCR4+ cells Reflection of disease severity 56,57,68,69,72,73
CTACK A chemokine that attracts CCR10+ cells Reflection of disease severity 58
IL-13 An inducer of IgE production Reflection of disease severity 74
IgE Primes the IgE-mediated allergic reaction Reflection of disease severity 32,46,68,71,75
No significant result 29,30,72,76
ECP A basic protein located in the eosinophil primary matrix Reflection of disease severity 75,77-80
No significant result 67
TEC Eosinophils control mechanisms associated with allergy Reflection of disease severity 75,79,81
sIL-2R Expressed by antigen-activated T lymphocytes Reflection of disease severity 79-81
IL-16 A chemokine that attracts CD4+ cells Reflection of disease severity 44,73,75
IL-18 An interferon-γ inducing factor Reflection of disease severity 71,82,83
BDNF A peripheral neurotrophin Reflection of disease severity 84,85
NGF A potent mediator in neuroinflammatory processes Reflection of disease severity 86
Positive staining on AD skin only 87
No significant result 88
Substance P A neurotransmitter and a neuromodulator Reflection of disease severity 86
Not correlated with disease severity 89
CCL18 A chemokine that attracts both innate and adaptive immune cells Reflection of disease severity 90
Significantly decreased after Tx 72
MEC/CCL28 A chemokine that attracts CCR3+, CCR10+ cells Reflection of disease severity 91,92
PF-4 A platelet chemokine Reflection of disease severity 93,94
Beta-TG A platelet chemokine Reflection of disease severity 93,94
IL-31 Associated with skin-homing CLA-positive T cells Reflection of disease severity 95
CLSP A modulator of calcium-dependent proteins Positive relation in AEAD skin 96
Der p-specific IgG4 A specific IgG molecule for Der p Reflection of disease severity 32,33,45,48,49
Underlyng bar: studies and results of SIT in AD.
sE-selectin, soluble E-selectin; sICAM-1, soluble intercellular adhesion molecule-1; sVCAM-1, soluble vascular adhesion molecule-1; TARC, thymus and activation-
regulated chemokine; CCL, C-C motif ligand; CCR, chemokine receptor; MDC, macrophage-derived chemokine; CTACK, cutaneous T cell-attracting chemokine; IL-13,
interleukin-13; ECP, eosinophil cationic protein; TEC, total eosinophil count; sIL-2R, soluble IL-2 receptor; BNDF, brain-derived neurotrophic factor; NGF, nerve growth
factor; Tx, treatment; MEC, mucosa-associated epithelial chemokine; PF-4, platelet factor 4; beta-TG, beta-thromboglobulin; CLA, cutaneous lymphocyte antigen;
CLSP, calmodulin-like skin protein; AEAD, acute exacerbated.

There still remains a room to search deeper into discovering will be building cornerstone for biomarker discovery.
biomarkers and choose appropriate candidates, mechanism,
treatment response, surrogate end points, and clinical trial for Further considerations and conclusion
new drug development.65 Hence, it will not be an understate- The effectiveness of SIT has been proven through many clini-
ment to say that the new era of AD expects a discovery of bio- cal studies recently published and more studies are expected in
marker that can assess and standardize treatment response. If the future. However, there are still issues that need to be ad-
biologic marker can show clear-cut correlation with clinical dressed before clinically applying SIT in hospital-settings. Stan-
symptoms, it will be an outbreak in the field of science, but con- dardized method in selecting candidate patients should be ap-
sidering variegated clinical pictures and associated immuno- plied for institutions along with objective qualifying criteria.
logical changes, the quest for a search will not be easily an- Also, effective treatment modality for those who are not solely
swered upon. But through future endeavors in creating more sensitized to HDM (polysensitized patients) raises attention.
high-quality standardized experiments that reflect clinical im- There are different routes and schedules for SIT at the moment,
provement and enable predictions of treatment end-points, we and there is rush or ultra-rush protocol besides the well-known

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Lee et al. Volume 7, Number 3, May 2015

conventional protocol. In the future, a development for a safe 132:1130-1.

protocol which enables faster immune reaction is promising. If 11. Sugiura A, Nomura T, Mizuno A, Imokawa G. Reevaluation of the
we can perform further studies to see whether early interven- non-lesional dry skin in atopic dermatitis by acute barrier disrup-
tion: an abnormal permeability barrier homeostasis with defective
tion allows for blocking progression into allergic march, we will
processing to generate ceramide. Arch Dermatol Res 2014;306:427-
be opening many doors into prevention and treatment of vari- 40.
ous allergic diseases. Endeavors in optimizing preparations 12. van Smeden J, Janssens M, Gooris GS, Bouwstra JA. The important
used and improving treatment response with more refined al- role of stratum corneum lipids for the cutaneous barrier function.
lergoids, potent adjuvants, or recombinant vaccine are also Biochim Biophys Acta 2014;1841:295-313.
suggested. Lastly, more work should be done in an attempt to 13. Novak N, Tepel C, Koch S, Brix K, Bieber T, Kraft S. Evidence for a
discover biomarkers for SIT that will allow clinicians to predict differential expression of the FcepsilonRIgamma chain in dendritic
cells of atopic and nonatopic donors. J Clin Invest 2003;111:1047-56.
the outcomes or to judge appropriate treatment duration for
14. Traidl-Hoffmann C, Mariani V, Hochrein H, Karg K, Wagner H,
the patients. Uncovering a new biomarker shall advance the Ring J, et al. Pollen-associated phytoprostanes inhibit dendritic cell
upcoming development and applications of SIT. interleukin-12 production and augment T helper type 2 cell polar-
ization. J Exp Med 2005;201:627-36.
ACKNOWLEDGMENTS 15. Shreffler WG, Castro RR, Kucuk ZY, Charlop-Powers Z, Grishina G,
Yoo S, et al. The major glycoprotein allergen from Arachis hypo-
This study was supported by a grant from the Korean Health gaea, Ara h 1, is a ligand of dendritic cell-specific ICAM-grabbing
nonintegrin and acts as a Th2 adjuvant in vitro. J Immunol 2006;
21 R&D Project, the Ministry of Health & Welfare, Republic of
177:3677-85.
Korea (A111718).
16. Bieber T. Atopic dermatitis. N Engl J Med 2008;358:1483-94.
17. Brown A, Farmer K, MacDonald L, Kalsheker N, Pritchard D, Has-
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