Atopic dermatitis.pdf for allergy learning

Important questions for learning asthma

1. Atopic Dermatitis
Vinay Mehta, M.D.
Allergy & Asthma Associates of
Southern California

2. Definition
•Chronic, pruritic, eczematous skin disease often
associated with elevated serum IgE levels and a
personal or family history of atopy
1. Eichenfield LF, et al. J Am Acad Dermatol. 2014;70(2):338-351
2. Whiteley J, et al. Curr Med Res Opin. 2016

3. Epidemiology
•Occurs most frequently in children, but also affects
adults
–Up to 25% of children
–Up to 7% of adults
•Onset commonly between ages of 3-6 months
–60% by age 1 yr
–85% by age 5 yrs
–Later age of onset and greater severity more
persistent AD
1. Eichenfield LF, et al. J Am Acad Dermatol. 2014;70(2):338-351
2. Guttman-Yassky E, et al. J Allergy Clin Immunol. 2011;127(5):1110-1118
3. Whiteley J, et al. Curr Med Res Opin. 2016

4. Epidemiology
•Study of infants (age 3-18 mos) with recent onset
AD (≤3 mos) showed that many will develop an
allergic condition within next 3 years:
–Asthma (10.7%)
–Allergic rhinitis (22.4%)
–Food allergy (15.9%)
–Allergic conjunctivitis (14.1%)
–≥1 atopic condition (37.0%)
Schneider L, et al. Pediatr Dermatol. 2016;33(4):388-398

5. Pathophysiology

6. Outside-in

7. Inside-out

8. Pathogenesis

9. •Acute lesions
–intensely pruritic
–erythematous papules and vesicles
–background of erythema
–Histology: CD4+ T cells
•Subacutelesions
–grouped or scattered erythematous, excoriated papules
•Chronic lesions
–thickened skin, increased
skin markings (lichenification)
–excoriated papules
–fibrotic papules and nodules
(prurigonodularis)
–Histology: eosinophilsand mononuclear cells
Lesions

10. Risk Factors
Strong association
•Family history of atopy
Odds of developing AD 3-5x
higher if both parents are
atopic
•Loss of function mutations
in the FLGgene (10% or
less)
–Earlier onset
–More severe, persistent
disease
–Eczema herpeticum
Moderate association
•African-American race
•Higher parental education
Unclear association
•Pet exposure
•Urban living
•Daycare
Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-351
Kelleher et al. JACI 2015;135:930-935

11. Diagnostic Features
Essential Features
•Pruritus
•Eczematous dermatitis (acute, subacute, chronic)
–Typical morphology and age-specific patterns
Facial, neck, and extensor involvement in infants and children
Current or previous flexural lesions at any age
Sparing of the groin and axillary regions
–Chronic or relapsing history
Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-351

12. Diagnostic Features
Important Features
•Early age of onset
•Atopy
–Personal and/or family history
–IgEreactivity
•Xerosis
Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-351

13. Diagnostic Features
Distribution
Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-351
Age Typical Distribution
0-2 years Erythematous papules and vesicleson cheeks, forehead, scalp
3-5 years More extensor involvement and transition towards chronic disease
Older children,
adults
Flexuralfolds, face/neck, upper arms/back, hands, feet, fingers, toes

14. Differential Diagnosis
•Other eczematous
disorders
–Contact dermatitis
–Seborrheic dermatitis
–Dyshidrotic eczema
–Hand eczema
–Nummular dermatitis
•Psoriasis
•Scabies
•Unusual disorders
–Ichthyoses
–Immune deficiency
diseases
–Photosensitivity
dermatoses
–Erythroderma of other
causes
–Cutaneous T-cell
lymphoma
Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-351

15. Laboratory Testing
•Laboratory testing not needed for most patients
1
•IgE level not elevated in 5-37%
2,3
•Numerous biomarkers, but none are reliable to
distinguish atopic dermatitis from other
inflammatory diseases
4,5
•Allergen skin testing helpful in those with
–Respiratory allergies (allergic rhinitis or asthma)
–Food allergies (do not routinely screen!)
1. EichenfieldLF, et al. J Am AcadDermatol. 2014;70:338-351.
2. Ott H, et al. Acta DermVenereol. 2009;89(3):257-261.
3. Folster-Holst, et al. Allergy. 2006;61(5):629-632.
4. Thijs J, et al. CurrOpinAllergy Clin Immunol. 2015;15(5):453-460.
5. Mansouri Y, et al. J Clin Med. 2015;4:858-87.

16. Laboratory Testing
•~50% of children with AD will have positive skin
tests or specific-IgEtests to one or more foods
–Cow’s milk, egg, wheat, and peanut
•…BUT sensitization is clinically irrelevant in most
cases
•Dietary elimination has notshown to be beneficial
in most cases
•Food restriction in toddlers can result in lower
weight, height, head circumference, and BMI

17. Management of Atopic Dermatitis

18. Goals of Therapy
•Reduce the number and severity of flares
•Reduce pruritus and improve quality of life
•Maintain normal activities of daily living
•Maximize disease-free periods
•Prevent infectious complications
•Avoid/minimize side effects of therapy
Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299
Lyons JJ, et al. Immunol Allergy Clin North Am. 2015;35(1):161-183

19. Overview of AD Management
M. Boguniewicz et al. Ann Allergy Asthma Immunol 120 (2018) 10–22

20. Skin Hydration
•Bathing followed by immediate application of an
occlusive emollient (soak & seal)
•Frequent bathing is associated with a greater
improvement in extent and severity of eczema
compared to infrequent bathing
•Emollient
–Use generously -no danger from “excess use”
–Ointments better than lotions (high water and low
oil content tend to evaporate easily)
Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.
Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132.

21. Skin Hydration
•General recommendations:
–Warm (not hot) water
–Baths better than shower
–Fragrance-free non-soap cleansers preferred
–No evidence that bath additives (i.e. oatmeal,
oils) superior to emollients alone
Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.
Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132.

22. Trigger avoidance
•Irritants (soaps, detergents)
•Skin infections (Staphylococcus aureus, herpes
simplex)
•Contact allergens (i.e. nickel, fragrances,
preservatives, neomycin)
•Heat
•Low humidity
•Occlusive fabrics
•Stress & anxiety
No evidence that dietary interventions are helpful
in reducing the AD severity or preventing flares

23. Mild AD
M. Boguniewicz et al. Ann Allergy Asthma Immunol 120 (2018) 10–22

24. Antiseptic Measures
•Dilute bleach baths may reduce Staph colonization
over bathing alone
•Add 1/2 cup of bleach (6% sodium hypochlorite) to a
40-gallon (151-liter) bathtub filled with warm water
•Soak from the neck down or just the affected areas
of skin for about 10 minutes
•Rinse and gently pat dry with a towel
•Apply moisturizer generously
Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.
Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132.

25. Topical Corticosteroids
•Recommended if symptoms are not controlled by
moisturizers alone
•Low-potency (group 5 and 6)
–Twice daily for 2-4 weeks
•Medium to high potency (group 3 and 4)
–May use for up to 2 wks, then replace with
lower-potency preparations
•Ultra-high-potency (group 1 and 2)
–No more than 1-2 weeks
–Non-facial, non-skinfold areas
Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299
Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132

26. Topical Corticosteroids
•Potent corticosteroids should not be used on
mucous membranes, face, eyelids, genitalia, and
intertriginous areas
•Twice-daily application needed for most until signs
and symptoms improve
•For frequent, repeated outbreaks at the same site,
maintenance “proactive” therapy with intermediate-
potency TCS 2-3x/wkmay be beneficial
Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299
Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132

27. Topical Corticosteroids
•Adverse effects of TCS
–Local-striae, skin atrophy, periorbital dermatitis,
rosacea, allergic contact dermatitis
–Systemic
Dependent on skin surface area involved,
skin thickness, use of occlusive dressing,
duration of use, potency
Risk of adrenal suppression greatest in
infants and small children
Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299
Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132

28. Topical Corticosteroids
•Low potency for face, groin, axilla
Hydrocortisone 1%-2.5%
Desonide0.05%
•Medium potency for trunk and extremities
Triamcinolone acetonide 0.1%
Fluocinolone 0.025%
•High potency (never use on face, groin, or axilla)
Clobetasolpropionate 0.05%
Betamethasone dipropionate0.05%

29. How Much to Apply?
a)Measurements & quantities are relative to adult hand/finger sizes, regardless of age group
b)Quantity for creams should be increased by 10% over ointment

30. Moderate AD
M. Boguniewicz et al. Ann Allergy Asthma Immunol 120 (2018) 10–22

31. Topical Calcineurin Inhibitors (TCI)
•Pimecrolimus cream 1%; tacrolimus 0.03% and
0.1% ointment
•Block production of proinflammatory cytokines and
other inflammatory mediators
1,2
•Advantages vs. TCS
2
–For face, anogenital, skin folds, and other
sensitive areas
–Does not cause skin atophy
–Steroid-sparing: reduces overall TCS use
1. Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299
2. Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132

32. Topical Calcineurin Inhibitors (TCI)
•2-3x/wk “proactive” application effective in
preventing recurrence
1,2
•Local adverse effects such as stinging and burning
are most common
1,2
and primarily occur when
applied to acutely inflamed lesions
•Increased risk of malignancy not observed
3
, but
black box warning for theoretical risk persists and
requires reassurance when prescribed
1. Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.
2. Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132.
3. Siegfried EC, et al. BMC Pediatr. 2016;16:75.

33. Treatments that are not Recommended
Systemic corticosteroids
•Potential for short-term and long-term health risks
•Frequently lead to rebound AD flares
Topical antihistamines
•Not recommended because of lack of evidence
supporting efficacy and risk of contact dermatitis
Non-sedating antihistamines
•Not recommended unless if being used to treat
other atopic disorders

34. Treatments that are not Recommended
Sedating antihistamines
•May be only on a short-term intermittent basis to
help with sleep
Systemic antibiotics
•Not recommended unless if signs of a bacterial
infection
Topical antimicrobials
•Not recommended because of lack of efficacy, risk
of contact dermatitis
–Exception: antiseptic dilute bleach baths

35. Severe AD
M. Boguniewicz et al. Ann Allergy Asthma Immunol 120 (2018) 10–22

36. Wet Wrap Therapy
•Useful for acute lesions
•Apply a wet layer of clothing
or dressing on wet skin and
leave on for several hours
•Apply a dry layer on top
•Hands/feet: use wet tube
socks; cover with dry tube
socks or gloves

37. Phototherapy
•UV-A and UV-B therapy are useful
adjuncts for chronic AD because of its
anti-inflammatory, antibacterial, and
immunomodulatory effects
•Not recommended in children <12yrs
•Short-term adverse effects:
–erythema, burns, pruritus,
pigmentation
•Long-term adverse effects:
–premature skin aging, cutaneous
malignancies

38. Dupilumab
•Humanized monoclonal IL-4Rαantibody that inhibits
downstream signaling of IL-4 and IL-13

39. Dupilumab

40. AD Pathogenesis

41. Dupilumab
Indications
•Treatment of moderate-to-severe AD in ≥6 months
of age whose disease is not adequately controlled
with topical prescription therapies
Dosing:

42. Severity measures in atopic dermatitis
Investigator Global Assessment scale

43. Severity measures in atopic dermatitis
Eczema Area and Severity Index

44. Severity measures in atopic dermatitis
Phan NQ, et al. Acta Derm Venereol. 2012 Sep;92(5):502-7

45. Skin clearance (IGA 0 or 1)

46. Skin clearance (EASI-75) in adults
Simpson EL, et al. N Engl J Med. 2016.
P<.001 for all comparisons between
dupilumab and placebo

47. Skin clearance (EASI-75) in
adolescents
P<.001 for all comparisons between
dupilumab and placebo

48. Skin clearance (EASI-75) in children
P<.001 for all comparisons between
dupilumab and placebo

49. Skin clearance (EASI-75) in infants and
preschoolers
P<.001 for all comparisons between
dupilumab and placebo

50. Itch reduction (≥4 points) in adults
P<.001 for all comparisons between
dupilumab and placebo

51. Itch reduction (≥4 points) in
adolescents
P<.001 for all comparisons between
dupilumab and placebo

52. Itch reduction (≥4 points) in children
P<.001 for all comparisons between
dupilumab and placebo

53. Itch reduction (≥ 4 points) in infants to
preschoolers
P<.001 for all comparisons between
dupilumab and placebo

54. Safety profile
P<.001 for all comparisons between
dupilumab and placebo
•The safety profile of dupilimabin adolescents, children, and infants to
preschoolers was similar to that of adults

55. Systemic immunosuppressant therapy
•Cyclosporine is a drug of choice for acute relief
•Recommended dose: 3-5 mg/kg per day for 6
weeks, then taper
•Not recommended in children
•Potential side effects: nephrotoxicity, hypertension,
hypertrichosis, gum hyperplasia, increased
susceptibility to infections
•Monitoring of patients: check blood pressure and
serum creatinine every two weeks for three months,
followed by monthly monitoring
•corticosteroids are effective in the short-term,

56. Systemic immunosuppressant therapy
•Systemic corticosteroids are effective in the short-
term, but rebound flares and long-term side effects
are limiting
•Allergen immunotherapy has shown some benefit in
dust mite sensitized patients but it may take 9-12
months for seeing positive results

57. Take Home Message
•Atopic dermatitis is a chronic, relapsing, pruritic,
eczematous skin disease often associated with an
impaired quality of life
•Its pathology involves a complex interaction among
host susceptibility genes, altered skin barrier
function, T2 immune response, and the environment
•AD is the first disease in the atopic march
•The imbalance in immune function is primarily
caused by IL-4 and IL-13
•The recent approval of dupilumab in India can be a
potential “game changer”