Table Of ContentPractical
Insights into
Atopic Dermatitis
Kwang Hoon Lee
Eung Ho Choi
Chang Ook Park
Editors
123
Practical Insights into Atopic Dermatitis
Kwang Hoon Lee • Eung Ho Choi
Chang Ook Park
Editors
Practical Insights
into Atopic Dermatitis
Editors
Kwang Hoon Lee Eung Ho Choi
Department of Dermatology Department of Dermatology
Yonsei University College of Medicine Yonsei University Wonju College
Seoul of Medicine
Korea (Republic of) Wonju
Korea (Republic of)
Chang Ook Park
Department of Dermatology
Yonsei University College of Medicine
Seoul
Korea (Republic of)
ISBN 978-981-15-8158-8 ISBN 978-981-15-8159-5 (eBook)
https://doi.org/10.1007/978-981-15-8159-5
© Springer Nature Singapore Pte Ltd. 2021
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Contents
Part I Introduction
Introduction to Atopic Dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Kwang Hoon Lee
Part II Epidemiology
Epidemiology of Atopic Dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Jaeyong Shin
Part III Clinical Manifestations
Clinical Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Howard Chu, Chang Ook Park, and Kwang Hoon Lee
Pruritus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
Hye One Kim
Part IV Diagnosis
Diagnosis and Severity Assessment of Atopic Dermatitis
(Korean Guideline Included) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Jung Eun Kim and Sang Wook Son
Part V Pathophysiology
Genetics of Atopic Dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Eung Ho Choi
Skin Barrier–Related Pathogenesis of Atopic Dermatitis . . . . . . . . . . 75
Eung Ho Choi
Immune-Meidated Pathogenesis of Atopic Dermatitis . . . . . . . . . . . . 85
Chang Ook Park and Tae-Gyun Kim
Evironmental Factors Related To Atopic Dermatitis . . . . . . . . . . . . . . 101
Jaeyong Shin
v
vi Contents
Food, Inhalant, and Microbial Allergens . . . . . . . . . . . . . . . . . . . . . . . 109
Jung-Won Park
Role of Infection and Microbial Factors . . . . . . . . . . . . . . . . . . . . . . . . 115
Sang Eun Lee
Psychological Stress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
Jung U Shin
Endophenotype and Biomarker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
Kwang Hoon Lee and Chang Ook Park
Part VI Management
Topical Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
Seung-Phil Hong
Systemic Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
Chang Ook Park
Emerging Treatment of AD: Biologics and Small Molecules . . . . . . . 197
Jiyoung Ahn
Phototherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
Sang Ho Oh
Allergen Immunotherapy for Atopic Dermatitis . . . . . . . . . . . . . . . . . 221
Dong-Ho Nahm, Kwang Hoon Lee, and Chang Ook Park
Treatment Algorithms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
Ji Hyun Lee and Joo Young Roh
Part VII Prevention
Prevention of Atopic Dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
Eung Ho Choi
Part I
Introduction
Introduction to Atopic Dermatitis
Kwang Hoon Lee
Atopic dermatitis is one of the most common Patients with chronic and intractable itching,
chronic, recurrent eczematous disorders. It often especially on their faces or hands, would be dif-
begins in infancy or early adolescence, and is ficult to keep social relationships with others.
accompanied by severe itching and various skin Atopic dermatitis not only significantly damages
symptoms. Moreover, there is an increasing num- quality of life by causing sleep deprivation,
ber of atopic dermatitis patients worldwide [1]. fatigue, or decrease in a sense of achievement,
Although atopic dermatitis has various epide- but also put burden on patients themselves and
miological factors, such as region, age, gender, their families. Clinically, its symptoms vary
and sociocultural characteristics, the incidence of depending on the age of patients. The progres-
atopic dermatitis has been increasing all over the sion of atopic dermatitis is classified into three
world due to environmental changes, such as phases based on the patient’s age: infancy, child-
the changes in eating habits, clothing, residential hood, adolescence and adulthood [1, 5, 6].
environment, and urbanization. In case of chil- Infancy is a period that refers to babies from 2 or
dren under 6 years old, the incidence rate of 3 months to 2 years. During childhood, from 3
atopic dermatitis has been reported to be about years to before adolescence, patients experience
3%. Furthermore, its incidence rate has been esti- redness around joint areas of legs, necks, ankles,
mated to be over 20% in children, and 1–3% in and other flexural areas. On these parts of the
adults for the last 20–30 years [2]. The symptoms skin, atopic dermatitis first develops as a form of
usually improve in around the first birthday, kin- acute eczema, which makes skin red, rugged,
dergarten age, or just before puberty; however, flaky, hard. At the same time, skin around the
they may persist until adulthood. According to forehead and eyes becomes red, dark, hard, and
recent clinical studies, there is a steadily increas- flaky. Atopic dermatitis during adolescence and
ing number of adults with acute atopic dermatitis adulthood display symptoms like skin redness
even after their twenties. Since an increasing around the upper part of the body, such as face,
number of adults who experience the develop- neck, head. Then, as in the earlier phases, the
ment of atopic dermatitis for the first time in their affected skin gets dark, swollen, and hard. Various
life, it is likely to be a serious social issue [3, 4]. types of acute or chronic eczema develop around
trunk, hands, feet, arms, legs, and other parts.
It is not difficult for most physicians to
K. H. Lee (*)
Department of Dermatology, Cutaneous Biology diagnose atopic dermatitis; however, it gets
Research Institute, Yonsei University College of sometimes confusing to diagnose because
Medicine, Seoul, Korea (Republic of)
atopic dermatitis is accompanied by various
e-mail: [email protected]
© Springer Nature Singapore Pte Ltd. 2021 3
K. H. Lee et al. (eds.), Practical Insights into Atopic Dermatitis,
https://doi.org/10.1007/978-981-15-8159-5_1
4 K. H. Lee
clinical symptoms and signs [4]. Thus, it Later, Wilson depicted the disease with simi-
becomes complicated to define characteristic lar skin symptoms as infantile eczema. Hebra
clinical symptoms of atopic dermatitis. For also named prurigo, which is considered to be a
example, since skin diseases like psoriasis, subtype of atopic dermatitis nowadays, as “con-
lichen planus, or herpes are distinguish- stitutional prurigo.” Hebra further explained that
able by inspection of primary skin lesions, they the major symptom of prurigo is itching, and pru-
are easy to be diagnosed by doctors, especially rigo is characterized by frequent outbreaks in
by dermatologists. On the other hand, atopic infants, erythematous lesions, papule and lichen-
dermatitis does not provoke prototypical oid lesions increase with age, chronic progressive
eczematous skin lesions in most cases. While course, seasonal fluctuations, and association
the patients scratch their skins, the skin lesions with hay fever and asthma. The concept of con-
are aggravated and resulted in a number of sec- stitution that prurigo begins during early child-
ondary changes. Furthermore, even experts hood and continues to the rest of the life has
have some difficulties in diagnosing atopic become a critical part of dermatology. Brocq
dermatitis due to a lack of definitive examina- later invented the concept of “neurodermatitis”
tions to decide upon. Many physicians also do [6, 12].
not regard this disease as to be curable com- With advancement of immunology and aller-
pletely. Unfortunately, since there are not many gology in the early 1900s, a condition of hyper-
appropriate treatments available for atopic der- sensitivity associated with asthma began to be
matitis, it is liable to abuse alternative thera- referred as ‘atopy’. In 1923, Coca and Cook [13]
pies, resulting in the economic damage to the defined atopy as a tendency to run in families like
atopic dermatitis patients. Recently, numerous hay fever or asthma, and to display hypersensi-
adverse reactions have been reported to occur tive reactions to foreign antigens. The word,
because of prevalent inaccurate and unverified atopy, means “not located in the right place and
information based on personal experiences not in order” in Greek. In 1933, Wise and
throughout the Internet. Sulzberger [5] included development of skin
Even though there were not many basic or symptoms with atopic tendency as a characteris-
clinical studies about atopic dermatitis going on tic of atopic dermatitis and named it atopic der-
actively about 40 years ago, as atopic dermatitis matitis or atopic eczema. Since it has been proved
prevalence rates have been rapidly increasing for that IgE is a mediator of immediate-type hyper-
the past 10 years, now there is a great number of sensitivity by Ishizaka [14], atopy has been
both qualitatively and quantitatively excellent equated with various IgE-mediated diseases by
researches about atopic dermatitis due to a splen- many people. However, it is controversial to sim-
did development in genetics and immunology plify atopic dermatitis as an IgE-mediated dis-
[7–11]. ease, because IgE-mediated penicillin
hypersensitivity or hypersensitive reactions to
insect bites do not often run in families.
History and Definition of Atopic Bruynzeel-Koomen et al. [15] first identified that
Dermatitis Terms IgE is attached to Langerhans cells, which are
antigen-presenting cells, in skin lesions of atopic
The description of atopic eczema is thought to dermatitis patients, and this attachment has been
have started when Robert Willan wrote the term, further verified by other researchers since then.
“eczema,” in 1808. Indeed, the term ‘eczema’ Klubal et al. [16] also observed that these IgE
itself began to be used by the Greek scholar molecules described above adhere to Fc epsilon
Aetios, who used the term as the meaning of boil- RI, a high-affinity receptor for IgE, on the surface
ing and bubbling (eczeo or ekzein = to bubble up) of Langerhans cells in active skin lesions of
in the sixth century AD [6]. atopic dermatitis patients. Consequently, these
Introduction to Atopic Dermatitis 5
results demonstrated that inhalant allergens, such the clinical symptoms when defining atopic der-
as house dust mites, might be able to penetrate matitis [6]. In the light of research and clinical
directly into the skin and cause Th2 immune experiences to date, atopic dermatitis is a disease
responses. that belongs to IgE-mediated diseases from one
In 1983, Wuthrich [17] proposed the classifi- angle of perspectives. On the other hand, it cov-
cation of extrinsic and intrinsic atopy by analogy ers a broader scope. With the above definition, we
with respiratory atopy. However, this classifica- can understand atopic diseases present at both
tion system evoked controversy about nomencla- ends of spectrum, which refer to two phenomena,
ture in around 2000, so it was discussed by the IgE antibody production, and nonspecific
Task Force Teams of the European Academy of immune responses. It is likely to suspect that
Allergology and Clinical Immunology (EAACI) there is atopy disease where the two phenomena
and the World Allergy Organization (WAO) [18]. overlap. However, it may still cause some confu-
Those teams initially described that “atopy sion because there exists a condition that does not
has an individual or familial tendency, and begins have “latent atopy (IgE is detected in blood but
in infancy or adolescence mainly after being does not display clinical symptoms)” or “intrin-
exposed to protein antigens, which are then sen- sic atopy (IgE is not detected but shows clinical
sitized to produce IgE antibodies. As a result, symptoms)” on the margins of the spectrum.
these patients show typical symptoms such as
asthma, rhinitis, or eczema.” Based on the above
definition, if patients have asthma, rhinitis, or Terms of Eczema and Atopic
eczema, which do not have IgE detected, they can Dermatitis
be determined to have no “atopic diseases.” For
that reason, the WAO Task Force Team redefined Being a synonym for various types of dermatitis
“eczema.” Since then, they have confirmed the as well as atopic dermatitis, the term “eczema”
adjective, atopy, only when IgE antigens are has been used historically in numerous
found in patient’s serum. Unfortunately, this clas- regions worldwide by many medical specialties.
sification also led to the division of atopic dis- Eczema means “boiling” in Greek and was intro-
eases into atopic and non-atopic eczema [6]. Up duced in the medical literature to refer to a small
until 50 years ago, many researchers believed group of skin diseases that show vesicular or bul-
that allergies would not be involved in the patho- lous lesions by Robert Wilan [6].
genesis of atopic dermatitis, but rather that dry As mentioned previously, Atopic dermatitis
skin and psychological factors were the main was initially called “porrigo larvalis,” “lichen
causes. Nevertheless, according to the research agrius,” and “prurigo Besnier.” The term “atopy”
results and achievements of all pathophysiologi- itself was introduced by Coca and Cooke [13] in
cal mechanisms or responses to treatments today, 1923, establishing a new definition of hypersen-
atopic dermatitis and allergy are absolutely rele- sitivity, one of the abnormal immunological reac-
vant and inseparable from each other. tions. In 1933, Sulzberger and Wise [5] first
The controversies surrounding this terminol- documented atopic dermatitis in a footnote of
ogy have started with the motivation to under- “1933 Year Book of Dermatology and
stand the etiology of atopic dermatitis. Earlier Syphilogy.” Since then, dermatitis and eczema
terms were based on the clinical studies and have actually been used as synonyms to describe a
symptoms of the disease, whereas the presence of subset of distinct clinical symptoms of patients.
IgE antibodies has become more important when Some doctors also refer general eczema as atopic
defining the term nowadays. According to the dermatitis.
definition made by WAO, WAO initially focused There have been repeated and active discus-
on IgE which is measured in patients, rather than sions for centuries about the accurate meaning of
on visible symptoms. They subsequently included eczema to determine whether eczema
