Atopic Dermatitis Flashcards
Xerosis
Dry skin. Represents impaired skin barrier resulting in water loss.
Major characteristics of atopic dermatitis
- Xerosis
- Red scaly papules and plaques (eczematous)
- Pruritis
- Chronicity
- Age-dependent morphology and lesion distribution
Most common complication of atopic dermatitis
Staphylococcus aureus skin infection
Corneocytes
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.
___ and ___ regulate the shedding of skin.
Proteases (which cleave corneodesmosomes) and protease inhibitors regulate the shedding of skin.
Stratum corneum diagram
___ in the stratum corneum stimulates protease activation and thus skin shedding.
Increased pH in the stratum corneum stimulates protease activation and thus skin shedding.
Most common mutation resulting in atopic dermatitis
Fillagrin. Fillagrin is a component of the cornified envelope. 25-50% of patients with AD have decreased functional fillagrin expression.
Total loss of fillagrin results in
Ichthyosis vulgaris
Functions of Th2 cells in skin
____ decreases the expression of fillagrin in pre-corneocyte keratinocytes and decreases the expression of antimicrobial peptides (cathelicidin and defensins) in the skin.
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.
Inside out vs Outside in hypothesis
In humans, the stratum corneum has an average thickness of ___ corneocytes.
In humans, the stratum corneum has an average thickness of 20 corneocytes.
The lipid lamellae
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
Natural mositurizing factor
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.
Three phases of atopic dermatitis
- Infantile
- Childhood
- Adult
Infantile atopic dermatitis
- 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
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Headlight sign
Childhood atopic dermatitis
- 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
Paronychia
Infection of the nail bed
Adult atopic dermatitis
- 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
Prurigo nodularis
Well circumscribed, hyperpigmented, lichenified papules. Appear in adolescent atopic dermatitis, most commonly on lower extremities
Regardless of AD phase, ___ may be seen when lesions dissipate.
Regardless of AD phase, post-inflammatory hypopigmentation may be seen when lesions dissipate.
Ways S. aureus exacerbates atopic dermatitis
- Superantigens (TSST-1)
- Development of IgE against staphylococcal proteins
- Triggering expression of IL-31, leading to exacerbated pruritis
In addition to superantigens causing inflammatory exacerbation in atopic dermatitis, they make treatment less effective by ___.
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.
Viral complications of atopid dermatitis
- Molluscum contagoisum
- Eczema herpeticum
The atopic march
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.
Possible prevention of atopic dermatitis
Rates reduced by 50% in cohort where once daily all over emollient (moisturizer) application was started within 3 weeks of birth
Crisaborole
the first of several topical phosphodiesterase inhibitors in development
Apremilast
oral small molecule inhibitor of phosphodiesterase 4
Dupilumab
A fully human monoclonal antibody that blocks interleukin-4 (IL-4) and interleukin-13 (IL-13)
Almost all AD patients experience their first symptoms ____
Almost all AD patients experience their first symptoms within the first 5 years of life (as many as 60% by age 2)
