Atopic Dermatitis Atopic Dermatitis Atopic

Atopic Dermatitis

1. Atopic Dermatitis(eczema):
Pathogenesis, clinical manifestations, and diagnosis

2. Definiton
atopic dermatitis is a chronic, pruritic, inflammatory skin
disease that occurs most frequently in children but also affects
adults.
Atopic dermatitis is often associated with an elevated serum
level of immunoglobulin E (IgE) and a personal or family history
of atopy, which describes a group of disorders that includes
eczema, asthma, and allergic rhinitis .
Although sensitization to environmental or food allergens is
clearly associated with the atopic dermatitis phenotype, it does
not seem to be a causative factor but may be a contributory
factor in a subgroup of patients with severe disease

3. EPIDEMIOLOGY
Prevalence and incidence—Atopic dermatitis affects
approximately 5 to over 20 percent of children worldwide,
with large variations among countries and ethnic groups
[4,5]. Countries in Africa, Oceania, and the Asia-Pacific
region have higher rates of atopic dermatitis than
countries in the Indian subcontinent and Northern/Eastern
Europe [5]. In the United States, the overall prevalence is
approximately 16 percent, with the highest rates reported
in African American children (19 percent
Data on the prevalence of atopic dermatitis in adults are
limited.

4. Risk factors
multiple genetic and environmental factors:
●Genetic risk factors–A family history of atopy(eczema, asthma, or
allergic rhinitis) is the strongest risk factor for atopic dermatitis
Approximately 70 percent of patients have a positive family history of
atopic diseases. Children with one atopic parent have a two-to
threefold increased risk of developing atopic dermatitis, and the risk
increases to three-to fivefold if both parents are atopic [Loss-of-
function variants in theFLGgene, resulting in defective epidermal
barrier, are a major risk factor for atopic dermatitis and other skin and
allergic diseases, including allergic contact dermatitis, asthma, and
food allergy. Multiple other genes have been proposed as potential
contributors to the risk of atopic dermatitis, including genes involved
in the regulation of innate host defenses and T cell function [21]

5. ●Environmental exposures-Environmental factors, including
climate, urban versus rural setting, air pollution, early exposure to
nonpathogen microorganisms, and water hardness, may influence
the risk of atopic dermatitis
•The "hygiene hypothesis-Two systematic reviews provided
evidence to support an inverse relationship between atopic
dermatitis and exposure to endotoxin, early daycare, helminth
infestation, number of siblings, farm animals, and pet dogs in early
life .There was no protective effect associated with viral or
bacterial infec
Water hardness-–Epidemiologic evidence from ecologic studies
linked high hardness (high levels ofcalcium carbonate) of domestic
water with increased prevalence of atopic dermatitis in children

6. PATHOPHYSIOLOGY
A multiplicity of mechanisms are involved in the
pathogenesis of atopic dermatitis, including epidermal
barrier dysfunction, genetic factors, Th2 cell-skewed
immune dysregulation, altered skin microbiome, and
environmental triggers of inflammation .

7. PathoPHiziology
Epidermal barrier dysfunction—The epidermal barrier
function primarily resides in the stratum corneum,
which consists of vertical stacks of anucleate
corneocytes packed with keratin filaments embedded in
a matrix of filaggrin breakdown products, ceramides,
cholesterol, and free fatty acids.
Filaggrin–Filaggrin deficiency is a major determinant
of defective barrier functionIt is associated with
disruption of keratinocyte differentiation, impaired
corneocyte integrity and cohesion, impaired tight
junction formation, decreased water retention, altered
lipid formation, and enhanced susceptibility to
cutaneous infection.

8. PathoPHiziology
Other factors that can result in skin barrier
breakdown include:
Imbalance between stratum corneum protease
(eg, kallikrein, stratum corneum chymotryptic
enzyme) and antiprotease activity (eg,
lymphoepithelial Kazal-type related inhibitor
[LEKTI]).
•Abnormalities of the tight junction function.
Tight junctions are located in the granular layer of
the epidermis below the stratum corneum
and are thought to seal the intercellular space to
prevent the free diffusion of macromolecules .
Defective tight junctions may contribute to skin
barrier impairment.
•Microbial colonization and release of
proinflammatory cytokines
•Inflammatory cytokines, such as interleukin (IL)
4, IL-13, IL-17A, IL-22, IL-25, and IL-31, have also

9. Genetic factors—A genetic basis for atopic dermatitis
was initially suggested by twin studies that found
concordance rates of 80 percent for monozygotic twins
compared with 20 percent for dizygotic twins
FLG variants—Loss-of-function variants inFLG, located
in the epidermal differentiation complex on
chromosome 1q23.3 and encoding profilaggrin, cause
ichthyosis vulgaris , the most common single-gene,
inherited disorder of keratinization and are also the
strongest genetic risk factor for atopic dermatitis.

10. Immune dysregulation and inflammation-Both the
innate and acquired immune responses have a role in
the pathogenesis of type 2 inflammation in atopic
dermatitis.Keratinocytes and antigen-presenting cells
in the skin express a number of innate immune
receptors called pattern recognition receptors, which
include toll-like receptors (TLRs)

11. CLINICAL MANIFESTATIONS
Common features—Dry skin and severe pruritus are
the cardinal signs of atopic dermatitis. However, the
clinical presentation is highly variable, depending upon
the patient's age, ethnicity, and disease activity

12. CLINICAL MANIFESTATIONS
Acute eczema is characterized by
intensely pruritic, erythematous papules
and vesicles with exudation and crusting
,whereas subacute or chronic lesions
present as dry, scaly, or excoriated,
erythematous papules. Skin thickening
from chronic scratching (lichenification)
and fissuring may develop over time . In
many patients, lesions in different stages
may be present at the same time.

13. CLINICAL MANIFESTATIONS
In children and adults with deeply pigmented skin,
erythema may appear dark brown or violaceousinstead
of pink or red, as typically seen in patients with lighter
complexions. The typical erythematous and scaly lesions
of eczema may appear as lesions with a grayish,
violaceous, or dark brown hue . Dry skin may have a
whitish or ashy color and a reduction in skin shininess .
Lichenifiedareas typically appear hyperpigmented.
Postinflammatoryhyper-and hypopigmentation are also
common
Atopic dermatitis occurs in the first year of life in 60
percent of cases and by the age of five years in nearly
85 percent of cases. The clinical presentation at various
ages is outlined below

16. CLINICAL MANIFESTATIONS
in infants and young children (zero to two years), atopic
dermatitis typically presents with pruritic, red, scaly,
and crusted lesions on the extensor surfaces and cheeks
or scalp (picture 4A-E) but may be diffuse (picture 4A,
4F). There is usually sparing of the diaper area (picture
5) [78]. Acute lesions can include vesicles, and there
can be serous exudates and crusting in severe cases.

17. CLINICAL MANIFESTATIONS
In older children and adolescents (2 to 16 years), atopic
dermatitis is characterized by less exudation and often
demonstrates lichenified plaques in a flexural
distribution, especially of the antecubital and popliteal
fossae, volar aspect of the wrists, ankles, and neck (
The sides of the neck may show a reticulate
pigmentation, the so-called "atopic dirty neck

18. CLINICAL MANIFESTATIONS
●In adults, atopic dermatitis is considerably more
localized and lichenified. The areas involved are, in
most cases, the skin flexures .Less frequently, the
dermatitis may involve the face, neck

20. Associated features
-Patients with atopic dermatitis may present a variety of
cutaneous findings, so-called "atopic stigmata," which include:
Centrofacialpallor
●White dermographism
●Keratosis pilaris
●Palmar hyperlinearity
●Pityriasisalba
●Periorbitaldarkening ("allergic shiners") and Dennie-Morgan
infraorbitalfolds
●Thinning or absence of the lateral portion of the eyebrows
(Hertoghe'ssign)
●Infra-auricular and retroauricularfissuring
●Nipple eczema

21. (picture 7A-B)
(picture 8)

22. Clinical variants
—Regional and morphologic variants of atopic
dermatitis may be the only manifestation of atopic
dermatitis or occur in association with the classic age-
related manifestations. Regional variants include:
●Atopic hand eczema–Atopichand eczema typically
involves the volar wrists and dorsum of the hands (
●Eyelid eczema–Eyelid dermatitis is a common feature
of atopic dermatitis and, in some patients, may be the
only manifestation .It is often associated with
lichenification and presence of Dennie-Morgan lines
●Atopic cheilitis–

23. Clinical variants
Laboratory findings—Up to 80 percent of patients with
atopic dermatitis have increased serum IgE levels, often
with eosinophilia. The IgE level tends to vary with
disease severity, although some patients with severe
disease have normal IgE values.
Most patients with atopic dermatitis have a cutaneous
hyperreactivity to various environmental stimuli,
including exposure to food and inhalant allergens,
irritants, changes in physical environment (including
pollution, humidity, etc), microbial infection, and stress

24. Clinical variants
Clinical course and complications—Atopic dermatitis
follows a chronic, relapsing course over months to
years. Patients with mild disease may experience
intermittent flares with spontaneous remission, but
patients with moderate to severe dermatitis rarely clear
without treatment.

25. Clinical variants
Patients with atopic dermatitis are predisposed to the
development of bacterial and viral skin infections.

26. COMORBIDITIES
Allergic rhinitis, asthma, and food allergy—Patients
with atopic dermatitis and a genetic predisposition to
produce IgE following exposure to allergens may
develop a typical sequence of atopic dermatitis, allergic
rhinitis, asthma, and food allergy at certain ages (the
"atopic march")

27. Diagnosis
History and clinical examination—In the vast majority
of cases, the diagnosis of atopic dermatitis is clinical,
based upon history, morphology and distribution of skin
lesions, and associated clinical signs

29. Diagnostic criteria
The United Kingdom Working Group on atopic dermatitis
criteria include one mandatory and five major criteria but
do not include allergy criteria as originally proposed by
Hanifinand Rajka
Evidence of pruritic skin, including the report by a
parent or caregiver of a child rubbing or scratching
In addition to itchy skin, three or more of the following
are needed to make the diagnosis:
●History of skin creases being involved. These include
antecubitalfossae, popliteal fossae, neck, areas around
eyes, and fronts of ankles.

30. Diagnostic criteria
●History of asthma or hay fever (or history of atopic
disease in a first-degree relative for children <4 years of
age).
●The presence of generally dry skin within the past
year.
●Symptoms beginning in a child before the age of two
years. This criterion is not used to make the diagnosis in
a child who is under four years old.
●Visible dermatitis involving flexural surfaces. For
children under four years of age, this criterion is met by
dermatitis affecting the cheeks or forehead and outer
aspects of the extremities.

31. Diagnostic criteria
The American Academy of Dermatology criteria for the
diagnosis of atopic dermatitis include three sets of
essential, important, and associated features [2]:
●Essential features:
•Pruritus
•Eczema (acute, subacute, chronic) with typical
morphology and age-specific patterns:
-Facial, neck, and extensor involvement in infants and
children
-Current or previous flexural lesions in any age group

32. Diagnostic criteria
-Sparing of the groin and axillary regions
•Chronic or relapsing history

33. Diagnostic criteria
Important features:
•Early age of onset
•Personal and/or family history of atopy, IgEreactivity
•Xerosis
.

34. Diagnostic criteria
●Associated features:
•Atypical, vascular responses (eg, facial pallor, white
dermographism, delayed blanch response)
•Keratosis pilaris, pityriasis alba, hyperlinear palms,
ichthyosis
•Periocular changes
•Perioral changes, periauricular lesions
•Perifollicular accentuation, lichenification, prurigo-like
lesions

35. tests
Skin biopsy and laboratory tests—Skin biopsy and
laboratory testing, including IgE levels, arenotused
routinely in the evaluation of patients with suspected
atopic dermatitis and are not recommended

36. DIFFERENTIAL DIAGNOSIS
Allergic or irritant contact dermatitis
●Seborrheicdermatitis–Seborrheicdermatitis is the
most common differential diagnosis in infants. The two
conditions may also coexist. The presence of salmon-
red, erythematous skin patches with greasy scale,
involvement of the scalp, and little or no pruritus
support the diagnosis of seborrheicdermatitis.
●Psoriasis–In contrast with atopic dermatitis, in
infants and young children, psoriasis often involves the
diaper area, with well-demarcated, erythematous
patches with little scale
●Scabies–Scabies may present as a diffuse eruption
mimicking atopic dermatitis The involvement

37. DIFFERENTIAL DIAGNOSIS
●Less common conditions that may be confused with
atopic dermatitis include:
•Drug reactions
•Primary immunodeficiencies, including Wiskott-Aldrich
syndrome
•Nutritional deficiencies
•Netherton syndrome
•Cutaneous T cell lymphoma

38. Treatment and managment
The goals of treatment of atopic dermatitis are
to reduce symptoms (pruritus and dermatitis)
prevent exacerbations, and
minimize therapeutic risks.
Management involves elimination of exacerbating factors,
restoration of the skin barrier function and hydration of the
skin, patient education, and pharmacologic treatment of
skin inflammation e.)

40. Patients with mild to
moderate atopic dermatitis
:
•Topical therapies–Patients with mild to moderate
symptoms are generally managed with topical
therapies. For most patients with atopic dermatitis, we
suggest topical corticosteroids and emollients rather
than other topical anti-inflammatory agents (Grade 2C).
The choice of the corticosteroid potency should be
based upon the patient's age, body area involved, and
degree of skin inflammation

41. Patients with mild to
moderate atopic dermatitis
However, for patients with atopic dermatitis in areas at
high risk of atrophy (eg, face, skin folds), topical
calcineurin inhibitors are an alternative to topical
corticosteroids.

42. Second-line treatment
options include
topicalcrisaborole(adults and children) and
topicalruxolitinib(adults and children older than 12
years

43. Maintenance/proactive
therapy
•–For patients with mild to moderate atopic dermatitis
that responds to continuous topical therapy, we suggest
maintenance/proactive therapy with topical
corticosteroids or topical calcineurin inhibitors to
prevent relapse (Grade 2B). Topical corticosteroids or
topical calcineurin inhibitors are applied once daily for
two to three days per week.

44. Patients with moderate to
severe disease
–an inadequate response to topical therapies
dupilumabortralokinumabrather than other
immunosuppressantsor phototherapy (Grade 2C).
however,abrocitinib, andupadacitinibare newly
approved agents that may be alternative options for
adult patients with inadequate response to dupilumab
or tralokinumab
For adults and adolescents narrowband
ultraviolet B (NBUVB) phototherapy is an alternative
first-line treatment if available and acceptable to the
patient, is usually administered in the office 2 to 3times
per week.

45. REFERENCES
Weidinger S, Novak N. Atopic dermatitis. Lancet 2016; 387:1109.
Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for
the management of atopic dermatitis: section 2. Management and
treatment of atopic dermatitis with topical therapies. J Am Acad
Dermatol 2014; 71:116.
Sidbury R, Davis DM, Cohen DE, et al. Guidelines of care for the
management of atopic dermatitis: section 3. Management and
treatment with phototherapy and systemic agents. J Am Acad
Dermatol 2014; 71:327.
Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for
the management of atopic dermatitis: section 1. Diagnosis and
assessment of atopic dermatitis. J Am Acad Dermatol 2014;

46. Thank you!