Atopic Derm Flashcards
What is the Atopic March?
AD is a complex genetic disease and is often accompanied by other atopic disorders such as allergic rhinoconjunctivitis, asthma, food allergies, and less often eosinophilic esophagitis. These conditions may appear simultaneously or develop in succession. AD and food allergy have a predilection for infants and young children, while asthma favors older children and rhinoconjunctivitis predominates in adolescents. This characteristic age-dependent sequence is referred to as the “atopic march”
Diagnostic features of Atopic Derm
Some Essential features
Some features in early ages/ fam history
Location
Triggers
DIAGNOSTIC FEATURES AND TRIGGERS OF ATOPIC DERMATITIS (AD)Essential features: must be present and are sufficient for diagnosis
Pruritus
Rubbing or scratching can initiate or exacerbate flares (“the itch that rashes”)
Often worse in the evening and triggered by exogenous factors (e.g. sweating, rough clothing)
Typical eczematous morphology and age-specific distribution patterns (see Fig. 12.3)
Face, neck, and extensor extremities in infants and young children
Flexural lesions at any age
Sparing of groin and axillae
Chronic or relapsing course
Important features: seen in most cases, supportive of diagnosis
Onset during infancy or early childhood
Personal and/or family history of atopy (IgE reactivity)
Xerosis
Dry skin with fine scale in areas without clinically apparent inflammation; often leads to pruritus
Associated features: suggestive of the diagnosis, but less specific (see Figs 12.3& 12.14)
Other filaggrin deficiency-associated conditions: keratosis pilaris, hyperlinear palms, ichthyosis vulgaris
Follicular prominence, lichenification, prurigo lesions
Ocular findings: recurrent conjunctivitis, anterior subcapsular cataract; periorbital changes: pleats, darkening
Other regional findings, e.g. perioral or periauricular dermatitis, pityriasis alba
Atypical vascular responses, e.g. midfacial pallor, white dermographism *, delayed blanch
Triggers
- Climate:* extremes of temperature (winter or summer) , low humidity
- Irritants:* wool/rough fabrics, perspiration, detergents, solvents
- Infections:* cutaneous (e.g. Staphylococcus aureus , molluscum contagiosum) or systemic (e.g. URI)
- Environmental allergies:* e.g. to dust mites, pollen, contact allergens
- Food allergies:*
Trigger in small minority of AD patients, e.g. 10–30% of those with moderate to severe, refractory AD
Common allergens: egg > milk, peanuts/tree nuts, (shell)fish, soy, wheat
Detection of allergen-specific IgE (via blood and skin prick tests) does not necessarily mean that allergy is triggering the patient’s AD
In early onset type AD, when does it present and how long does it typically last?
45% of individuals develop within 6 months of age, 60% in first year, 85% before 5 years
60% of these children have remission by age 12
Is a parental history of AD or concurrent asthma/ allergic rhinitis more of a risk factor for AD in the child?
parental history, AD is strongly genetic
The level of _____ in nonlesional skin of children correlates with AD disease severity
Transepidermal water loss
Loss of function mutation of which protein is the strongest known genetic risk factor for AD?
Bonus: which other condition?
Gilaggrin FLG mutations
- Bonus: also thought to be the implicated genetic mutation in Ichthyosis vulgaris*
- FLG mutations are a/w early onset AD, greater severity, persistence into adulthood, increased risk of asthma/ food allergy*
- FLG* mutations cause issues with lipid organization/ processing in stratum corneum
Lesional skin in AD demonstrates elevated levels of ________
Endogenous serine proteases
- Bonus: enzymes SPINK5 polymorphisms/ LEKTI deficiency mutations*
- Other factors that enhance proteolysis*
- increased skin surface pH
- exogenous proteases from allergens
Lesional skin in AD has increased predominance of ____ cytokines
TH2 cytokines, however chronic phase shows increases in Th1 and Th22 cytokines
Which cytokines are seen in acute phase of AD
IL4, IL5, IL13, eosinophilic activation/ mast cells
Which cytokine is the “master switch of allergic inflammtion”
TSLP (thymic stromal lymphopoietin) is an IL7 like cytokine that evokes a TH2 response via DC activation
highly expressed in lesional AD skin
Which Cytokine has a key role in driving Th2 differentiation, IgE production and eosinophilic recruitment?
Which biologic targets this
IL4/ IL13
Dupilumab (Targets IL4alpha)
Three major pathology categories of AD:
- epidermal barrier dysfunction
- immune dysregulation
- alteration of the microbiome
Due to filaggrin mutations, there is (increased/decreased) levels of B-glucoscerebrosidase/ acid sphingomyelinase?
decreased, which are involved in the acid mantle formation/ epidermal barrier in lipid processing
Lesional skin in AD contains (elevated/ decreased) levels of Kallikrein 5/7, due to an imbalance caused by which gene mutation?
Bonus: a Bi-allelic loss of this / mutation of this gene is implicated in which syndrome?
Elevated levels - these are proteases, aka increased protein degradation
this is due to a genetic mutation SPINK5, which increases levels of endogenous serine proteases
Bonus: Netherton syndrome
Acute AD lesions demonstrate increased levels of which T helper?
Th2
Chronic AD lesions demonstrate increased activity of which T helper cells (two)
Bonus: which T helper has variable levels in both chronic/ acute lesions?
Th1 and 22
Bonus: Th17
Interleukin(s) ___ have a key role in Th2 differentiation, IgE production and eosinophil recruitment?
Bonus, which monoclonal antibody targets these?
IL4 and IL13
Dupilumab
Th17 have a strong roll in innate immunity (neutrophilic recruitment), their presence in new onset pediatric AD lesions is seen by increased levels of which interleukins
IL17 and IL19
Increased colonization by which bacterial species is seen during acute flares of AD, this is due to what?
Staphlylococcus species, decreased acid mantle/ decreased antimicrobial peptides and altered cytokine profiles and in some cases, filaggrin deficiency (for those with the genetic predisposition)
Describe
On the right upper back, right extensor arm, right flank there are diffusely distributed papules and plaques with excoriations, crusting and some lichenification on right elbow as well as fine scale on right buttocks
Describe
A- lichenification, scale and punctate excoriations in the antecubital fossa
B- coalescing papules and lichenification on the ankle d/t chronic scratching/ rubbing
C- Thick eczematous plaques with excoriation on the dorsal hand and wrist
describe
Prurigo like dome shaped/ nodular papules and nodules with central hemorrhagic crust (likely chronic eczema)
describe
nummular, erythematous plaques with oozing and crusting on both extensor legs
What is this called?
cheilitis sicca (eczema of the lips)
An eczema variant affecting Acral sites is aka
Juvenile plantar dermatosis
glazed erythema, scale and fissuring on the balls of the feet/ plantar aspect of toes in children with AD
In AD, impaired epidermal barrier function due to decreased water content in the ____ _____ leads to easier entry of irritants
stratum corneum. This promotes pruritus and initiates inflammation
Describe
The keratosis pilaris rubra (KPR) variant features numerous tiny, “grain-like” follicular papules superimposed on prominent confluent erythema (see Fig. 12.16B); often widespread on face & ears > trunk & proximal extremities, and tends to persist after puberty; presence of erythema rather than hyperpigmentation differentiates KPR from erythromelanosis follicularis faciei et colli, and a lack of atrophy in KPR differentiates it from keratosis pilaris atrophicans (see Ch. 38)
What is this known as
Pityriasis Alba
multiple, ill-defined hypopigmented macules/ patches, usually .5 - 2cm with fine scaling on face, cheeks, shoulders and arms
usually seen in darker skinned adolescents with AD, thought to result from low grade eczematous dermatitis that disrupts the transfer of melanosomes from melanocytes to keratinocytes
DDx includes post inflammatory hyper/ hypopigmentation from a severe eczematous lesion
Major triggers for Atopic Derm
FADS
Fragrances, fabrics, food allergies
Allergens
Dry environments, detergents
Stress, smoking, sweating, soaps, showering (too long/ hot)
Why do psoriatic patients not get infections in their skin wounds vs. Atopic derm patients?
Psoriatic patients have increased antimicrobial peptides vs. Atopic derm patients having less
*AD patients get staph aureus
What are some other features of atopic dermatitis in children that can help your diagnosis?
Eyes: Dennie-Morgan lines & allergic shiners
Face & Neck: Pityriasis alba & hyperlinear neck folds
Extremities: hyperlinear palms, keratosis pilaris
Histology of AD features → acute vs subacute vs chronic lesions
Acute → spongiosis, perivascular lymphocytes and histiocytes, occasional eosinophils
Subacute → less spongiosis, increased acanthosis
Chronic → much less spongiosis, much more increased acanthosis, dermal fibrosis, hyperkeratosis
Treatment ladder for AD
- Avoid triggers (FADS)
- Moisturize (daily, after exiting shower, bland emollients/ petroleum)
- Low/ mid potency topical steroids, calcineurin inhibitor
- non-sedating antihistamines and sedating at night
- consider narrow band UVB, prednisone, cyclosporine, AZA, myophenolate, MTX, dupilumab
Acute AD has which T cell predominate versus chronic AD?
In acute AD, which cytokines predominate?
Th2 cells predominate in Acute AD → increased eosinophilia leading to increased IgE mediated inflammation
IL4, 5, 12 and 13 associated with Acute AD
Chronic AD → Th1 predominates with increased IFN-gamma
