Atopic Dermatitis

Question 1

Xerosis

Answer 1

Dry skin. Represents impaired skin barrier resulting in water loss.

Question 2

Major characteristics of atopic dermatitis

Answer 2

• Xerosis
• Red scaly papules and plaques (eczematous)
• Pruritis
• Chronicity
• Age-dependent morphology and lesion distribution

Question 3

Most common complication of atopic dermatitis

Answer 3

Staphylococcus aureus skin infection

Question 4

Corneocytes

Answer 4

Denucleated keratinocytes of the stratum corneum. Each surrounded by a cornified envelope and connected by corneodesmosomes. The matrix in which these cells reside is called the lipid lamellae and organic acids within this layer make up the acid mantle, maintaining the pH around 5.4-5.9.

Question 5

___ and ___ regulate the shedding of skin.

Answer 5

Proteases (which cleave corneodesmosomes) and protease inhibitors regulate the shedding of skin.

Question 6

Stratum corneum diagram

Answer 6

Question 7

___ in the stratum corneum stimulates protease activation and thus skin shedding.

Answer 7

Increased pH in the stratum corneum stimulates protease activation and thus skin shedding.

Question 8

Most common mutation resulting in atopic dermatitis

Answer 8

Fillagrin. Fillagrin is a component of the cornified envelope. 25-50% of patients with AD have decreased functional fillagrin expression.

Question 9

Total loss of fillagrin results in

Answer 9

Ichthyosis vulgaris

Question 10

Functions of Th2 cells in skin

Answer 10

Question 11

____ decreases the expression of fillagrin in pre-corneocyte keratinocytes and decreases the expression of antimicrobial peptides (cathelicidin and defensins) in the skin.

Answer 11

IL-4 and IL-13 signaling decreases the expression of fillagrin in pre-corneocyte keratinocytes and decreases the expression of antimicrobial peptides (cathelicidin and defensins) in the skin.

Question 12

Inside out vs Outside in hypothesis

Answer 12

Question 13

In humans, the stratum corneum has an average thickness of ___ corneocytes.

Answer 13

In humans, the stratum corneum has an average thickness of 20 corneocytes.

Question 14

The lipid lamellae

Answer 14

The lipid lamellae matrix is a crystalline substance composed of ceramides, cholesterol, fatty acids, and cholesterol esters, and is believed to exist as a single and coherent lamellar gel

Question 15

Natural mositurizing factor

Answer 15

Catabolism product of the amino acids produced by degradation of fillagrin by self proteases. Effectively a buffer consisting of lactic acid, sodium pyrrolidone, carboxylic acid, urocanic acid, and urea.Essential for the retention of waterwithin corneocytes andmaintaining some swellingdue to osmotic pressure, alsoensuring that there are no gaps between swolen corneocytes.

Question 16

Three phases of atopic dermatitis

Answer 16

• Infantile
• Childhood
• Adult

Question 17

Infantile atopic dermatitis

Answer 17

• Manifestations beginning as early as 6 months of age
• Intense pruritis, erythema, papules, vesicles, oozing, crusting
• Usually begins on cheeks, forehead, or scalp in infants (headlight sign), then may extend down trunk
• Usually symmetric
• By 8-10 months extensor surfaces of limbs usually show signs
• Groin and diaper area usually spared in infants
  *

Question 18

Headlight sign

Answer 18

Question 19

Childhood atopic dermatitis

Answer 19

• May follow infantile stage without interruption anywhere between 2 years to puberty
• Characterized less by exudated or crusted lesions and more by chronicity and lichenification, with intense pruritis
• Lesions in this phase often occur as scaly, well circumscribed plaques
• Classically involves wrists, ankles, hands, feet, antecubital, and popliteal regions
• Facial involvement migrates from cheeks and chin to periorbital and perioral
• May display lymphadenopathy, nail pitting or dystrophy, and occasionally staphylococcal or pseudomonal paronychia

Question 20

Paronychia

Answer 20

Infection of the nail bed

Question 21

Adult atopic dermatitis

Answer 21

• Begins during puberty and continues into adulthood
• Classical areas of involvement include face, neck, upper arms, back, dorsal hand aspect, feet, fingers, toes
• Dry, scaling, erythematous papules and plaques, with coalescence of plaques into lichenification from lesional chronicity
• Weeping, crusting, exudation may occur, but usually as a result of secondary staphylococcal infection

Question 22

Prurigo nodularis

Answer 22

Well circumscribed, hyperpigmented, lichenified papules. Appear in adolescent atopic dermatitis, most commonly on lower extremities

Question 23

Regardless of AD phase, ___ may be seen when lesions dissipate.

Answer 23

Regardless of AD phase, post-inflammatory hypopigmentation may be seen when lesions dissipate.

Question 24

Ways S. aureus exacerbates atopic dermatitis

Answer 24

• Superantigens (TSST-1)
• Development of IgE against staphylococcal proteins
• Triggering expression of IL-31, leading to exacerbated pruritis

Question 25

In addition to superantigens causing inflammatory exacerbation in atopic dermatitis, they make treatment less effective by \_\_\_.

Answer 25

In addition to superantigens causing inflammatory exacerbation in atopic dermatitis, they make treatment less effective by **inducing upregulation of an alternative glucocorticoid receptor which does not bind to conventional topical glucocorticoid therapeutics**.

Question 26

Viral complications of atopid dermatitis

Answer 26

* Molluscum contagoisum * Eczema herpeticum

Question 27

The atopic march

Answer 27

Describes long-associated comorbidities including asthma, food allergy, have fever, and atopic dermatitis. Also includes behavioral components like depression and anxiety, though this may be secondary to the weight of having a challenging disease. AD patients lose sleep so inattention at school and fatigue are common. While sleep loss may account for both of these outcomes it is prudent to at least consider a separate diagnosis such as ADHD or anemia.

Question 28

Possible prevention of atopic dermatitis

Answer 28

Rates reduced by 50% in cohort where once daily all over emollient (moisturizer) application was started within 3 weeks of birth

Question 29

Crisaborole

Answer 29

the first of several topical phosphodiesterase inhibitors in development

Question 30

Apremilast

Answer 30

oral small molecule inhibitor of phosphodiesterase 4

Question 31

Dupilumab

Answer 31

A fully human monoclonal antibody that blocks interleukin-4 (IL-4) and interleukin-13 (IL-13)

Question 32

Almost all AD patients experience their first symptoms \_\_\_\_

Answer 32

Almost all AD patients experience their first symptoms **within the first 5 years of life (as many as 60% by age 2)**