Lecture-3: Dermatitis. Toxicoderma. Eczema. Psoriasis. Lichenplanus. Bullous Dermatosis

LECTURE-3
DERMATITIS. TOXICODERMA. ECZEMA. PSORIASIS.

LICHENPLANUS. BULLOUS DERMATOSIS
Program Overview
Video 1. Epidemiology
Video 2. Pathophysiology
Video 3. Clinical Assessment
Video 4. Medical Management: Overview
Video 5. Medical Management 1
Video 6. Medical Management 2
Video 7. Prevention of Flares
Video 8. Emerging Therapies
Learning Objectives
After participating in this program, the participant
will be able to:
1) Examine the epidemiology and pathogenesis of AD
and the relevance to the management of patients
with AD .
2) Integrate a proactive approach to long-term disease
management in AD, with a focus on prevention of
flares, assessment of disease activity, and patient
education.
3) Discuss the mechanisms, efficacy, and safety data for
emerging biologic therapies and which patients are
likely to benefit.
Video 1
EPIDEMIOLOGY
Atopic Dermatitis: Definition
• Chronic, pruritic, eczematous skin disease1,2
– Often associated with elevated serum IgE levels and
a personal or family history of type I allergies,
allergic rhinitis, and asthma
• Atopic dermatitis = atopic eczema1
• Atopic dermatitis ≠ eczema
• ICD codes for atopic dermatitis and eczema are
different
1. Eichenfield LF, et al. J Am Acad Dermatol. 2014;70(2):338-351.
2. Whiteley J, et al. Curr Med Res Opin. 2016;doi:10.1080/03007995.2016.1195733.
Case Scenario: Emily
• HPI: Emily is being seen for her 6-month well-
child visit
– Red cheeks with edema and exudation
– Emily has dry skin with generalized itching,
sometimes making it difficult for her to fall asleep
• Medications: none
• Allergies: dairy products aggravate skin itching
and rash
• FH: father and mother with seasonal allergic
rhinitis
• PE: skin – facial eczema, xerosis of face, as well
extensor surfaces of joints
Atopic Dermatitis: Epidemiology
• Occurs most frequently in children, but
also affects adults1,2
– Up to 25% of children
– Up to 7% of adults
• Prevalence higher in women than men2,3
• Onset commonly between ages of 3 and 6
months1,2
– 60% by age 1 year
– 85% to 90% by age 5 years
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;doi:10.1080/03007995.2016.1195733.
Atopic Dermatitis: Epidemiology (cont)
• Severity1
– In children
• Mild (two-thirds), moderate (one-quarter); severe
(<10%)
– Percentage of people with severe AD increases with age
• Pooled analysis of 45 studies (N=110,651) showed2
– Children who developed AD by age 2 y had less persistent
disease
– 80% of children with AD had disease resolution by 8 years
after diagnosis, >95% by 20 years after diagnosis
– Later age of onset and greater severity  more persistent
AD
1. Chernyshov PV, et al. Clin Cosmet Investig Dermatol. 2016;9:159-166.
2. Kim JP, et al. J Am Acad Dermatol. 2016;75(4):681-687.
• Study of infants (age 3-18 mos) with recent
onset AD (≤3 mos) showed many developed
an allergic condition over 3 years
– Asthma (10.7%)
– Allergic rhinitis (22.4%)
– Food allergy (15.9%)
– Allergic conjunctivitis (14.1%)
– ≥1 atopic comorbidity (37.0%)
Schneider L, et al. Pediatr Dermatol. 2016;33(4):388-398.

• Impact on children varies over time
– 0-3 years: parental exhaustion, emotional distress 
impaired mother-child attachment
– 3-10 years: teasing, bullying, avoid social
interactions and sports
– 10 years to adulthood: low self-esteem
Chernyshov PV, et al. Clin Cosmet Investig Dermatol. 2016;9:159-166.

Video 2
PATHOPHYSIOLOGY
Pathogenic Mechanisms in Acute Atopic Dermatitis
• Immune triggers
stimulate the
release of
inflammatory
mediators
Peng W, et al. Clin Exper Allergy. 2015;45:566-574.

Pathophysiology
Complex interplay Barrier Dysfunction Environmental Factors

of 3 factors Ceramide reduction Climate Smoking
• Barrier Increased proteases Skin pH
dysfunction Filaggrin deficiency Microbiome
• Immunological
• Environmental Pruritus
Th2 cells Th17 cells Tregs
ILC2 Eosinophils Mast cells
Immunological Factors
Egawa G, et al. Cogent Biol. 2015;1;1103459.

Disease Biomarkers Are Needed
• Biomarkers are being identified to1,2:
– Facilitate diagnosis
– Assess disease severity
– Identify AD disease phenotypes  targeted therapy
– Predict individual responses to medications
1. Mansouri Y, et al. J Clin Med. 2015;4:858-87.

2. Thijs JL, et al. J Clin Med. 2015:4:479-487.
Video 3
CLINICAL ASSESSMENT
Case Scenario: Jack
• Jack is a 13-year-old male, accompanied by his mother.

• During the visit, he is noted to frequently scratch the flexural areas
of his arms.
• History: Jack has complained of dry, itchy skin on his arms for
many years that worsened over the past 2 years. Symptoms are
worse in the winter.
– Mother had asthma and father has seasonal allergies
– Jack has asthma since 4 years of age
• PE:
– Dry skin
– Erythema, dryness, lichenification noted in
flexural areas of both arms
- Hyperlinear palms and increased scaling on legs
- Mom also shows hyperlinear palms/dry legs
Image courtesy of DermNetNZ.org under the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 (
http://creativecommons.org/licenses/by-nc-nd/3.0/nz/) with no changes.
Patient Assessment in Routine Clinical
Practice
Recommended as part of PE Not recommended in

• General questions practice
– Itch • Disease severity
– Impact on daily activity, sleep
– Disease persistence measurement scales*
• Associated conditions • Quality of life measurement
– Rhinitis/Rhinoconjunctivitis scales
– Asthma
– Food allergy
– Sleep disturbance
– Depression
*Not recommended outside of a clinical trial. US Food and Drug Administration requires Investigator Global Assessment that is
used for product labeling.
Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-351.
Risk Factors
Strong association Moderate association

• Family history of atopy • African-American race
– Odds of developing atopic dermatitis • Higher parental education
• Both parents are atopic: 3 to 5- Unclear association

fold higher risk • Pet exposure
• Urban living
• Loss of function mutations in the • Daycare
FLG gene (minority – 10% or less)
– Earlier onset
– More severe, persistent disease
– Eczema herpeticum

Kelleher et al. JACI 2015;135:930-935.
Transepidermal Water Loss at 2 Days of Life as a
Predictor of Atopic Dermatitis
Odds Ratio (OR) of Developing Atopic
8
Dermatitis*
Odds Ratio of Developing Atopic Dermatitis
7 Interpretation:
6 Infants in top quartile
5 at 2 days are 7.1
4
times more likely to
3
be diagnosed with
2
1
AD at 1 year.
0
N=1903 infants† 2 Days
*Patients
Kelleher M, et al.were
J Allergy grouped by percentiles based on history of parental atopy and transepidermal water loss test reading score at 2
Clin Immunol. 2015;135(4):930-935.
days. TEWL threshold scores were 5.0 gwater/m2/h (25th percentile), 7.0 gwater/m2/h (50th percentile), and 9.0 gwater/m2/h (75th
percentile).
†
1597 infants screened. At 6 months, 18.7% were diagnosed with AD. At 12 months, 15.5% were diagnosed with AD
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

Diagnostic Features (cont)
Important Features (seen in most)
• Early age of onset
• Atopy
– Personal and/or family history
– IgE reactivity
• Xerosis

Distribution
Age Typical Distribution

0-2 years Erythematous papules and vesicles on cheeks, forehead, scalp
3-5 years More extensor involvement and transition towards chronic disease
Older children, adults Flexural folds, face/neck, upper arms/back, hands, feet, fingers, toes
Atopic Dermatitis: Differential Diagnosis
• Other eczematous • Unusual disorders
disorders – Ichthyoses
– Contact dermatitis – Immune deficiency
– Seborrheic dermatitis diseases
– Dyshidrotic eczema – Photosensitivity
– Hand eczema dermatoses
– Nummular dermatitis – Erythroderma of other
causes
• Psoriasis
– Cutaneous T-cell
• Scabies lymphoma

Role of the Laboratory
• Laboratory testing not needed for most patients1
• IgE level not elevated in 5% to 37%2,3
• Numerous biomarkers, but none are reliable to
distinguish atopic dermatitis from other inflammatory
diseases4,5
• Allergen skin testing helpful in those with
– Respiratory allergies (allergic rhinitis or asthma)
– Food allergies: screening – will only suggest food sensitization
1. Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-351.

2. Ott H, et al. Acta Derm Venereol. 2009;89(3):257-261.
3. Folster-Holst, et al. Allergy. 2006;61(5):629-632.
4. Thijs J, et al. Curr Opin Allergy Clin Immunol. 2015;15(5):453-460.
5. Mansouri Y, et al. J Clin Med. 2015;4:858-87.
Video 4
MEDICAL MANAGEMENT: OVERVIEW
Case Scenario: Wynonna
• Wynonna is a 7-year-old female diagnosed at age 9 months with
AD primarily involving her forearms and lower legs
• Current meds: emollients 1-2 x/day + low-potency TCS
• Upon questioning, Wynonna reports that her pruritus has not
improved, and is sometimes unbearable when she plays soccer.
She also says it is sometimes difficult to fall asleep
• PE: moderate erythema with numerous excoriations noted on
trunk, arms and legs but no sign of infection
Goals of Therapy
1. Reduce the number and severity of flares

2. Reduce pruritus and improve quality of life
3. Maintain normal activities of daily living
4. Maximize disease-free periods
5. Prevent infectious complications
6. 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.
Overview of Atopic Dermatitis Management
Mild Disease
Basic Management
 Skin Care
-Moisturizers
-Warm bath/shower
 Trigger Avoidance
Acute Treatment
Low-potency TCS 2x/d
applied to inflamed skin
Modified from Eichenfield LF, et al. Pediatrics. 2015;136(3):554-565.
TCI, topical calcineurin inhibitor; TCS, topical corticosteroid

Overview of Atopic Dermatitis Management
(cont)
Mild Disease Moderate-to-Severe Disease
Basic Management Acute Treatment Flare not
 Skin Care  Medium-potency TCS applied to resolved Consider
within 7 days
-Moisturizers inflamed skin  Nonadherence
-Warm bath/shower  Consider 2° infection; treat with  Misdiagnosis
 Trigger Avoidance antibiotic if present  Referral
-Introduce dilute bleach baths
2-7x/wk as maintenance
Maintenance TCI Maintenance TCS

Acute Treatment
Low-potency TCS 2x/d
applied to inflamed skin For relapsing course (frequent/persistent flares despite treatment)
TCS applied at first signs/symptoms or to flare-prone areas
Modified from Eichenfield LF, et al. Pediatrics. 2015;136(3):554-565.

Video 5
MEDICAL MANAGEMENT I
Skin Hydration
• Bathing followed by immediate application of emollient

• Emollient
– Use generously - no danger from “excess use”
– Lotions vs creams vs oils vs ointments

Eichenfield LF, et al. J Am Acad Dermatol. 2014;71(1):116-132.
Skin Hydration (cont)

• Emollient
• General recommendations are:
– Warm (not hot) water
– Bath better than shower
– 5-10 minutes
– Neutral/low pH, hypoallergenic, fragrance-free non-soap cleansers preferred

Skin Hydration (cont)

• Emollient
• General recommendations are:
– Warm (not hot) water
– Bath better than shower
– 5-10 minutes
– Neutral/low pH, hypoallergenic, fragrance-free non-soap
cleansers preferred
• Bleach baths now standard of maintenance care for
pediatric moderate-to-severe AD
Topical Corticosteroids (TCS)
• Recommended if symptoms are not controlled by moisturizers
alone
• Low-potency
– Maintenance therapy to prevent exacerbations
• Intermediate- and high-potency (halogenated)
– Exacerbations for short period or proactive therapy

Topical Corticosteroids (TCS) (cont)
• Recommended if symptoms are not controlled by moisturizers
alone
• Low-potency
– Maintenance therapy to prevent exacerbations
• Intermediate- and high-potency (halogenated)
– Exacerbations for short period or proactive therapy
• Ultra-high-potency
– No more than 1-2 weeks
– Non-facial, non-skinfold areas
• Potent, fluorinated corticosteroids should not be used on mucous
membranes, face, eyelids, genitalia, and intertriginous areas or in
young infants beyond a few days

• 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/wk may
be beneficial

• 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/wk may
be beneficial
• 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

Topical Calcineurin Inhibitors (TCI)
• Pimecrolimus cream 1%; tacrolimus 0.03% and 0.1% ointment

• Block production of proinflammatory cytokines and other
inflammatory mediators1,2
• Advantages vs. TCS2
– For face, anogenital, skin folds, or other sensitive areas
– No atrophogenic properties; can reverse steroid-induced atrophy
– Steroid-sparing: reduce overall TCS when used for maintenance
1. Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.

Topical Calcineurin Inhibitors (TCI) (cont)
• 2-3x/wk “proactive” application effective in preventing

recurrence1,2
• Local adverse effects such as stinging and burning are most
common1,2 and primarily occur when applied to acutely inflamed
lesions
• Increased risk of malignancy not observed3, but black box warning
for theoretical risk persists and requires reassurance when
prescribed

3. Siegfried EC, et al. BMC Pediatr. 2016;16:75.
Other Topical Options
• Crisaborole: Topical phosphodiesterase-4 (PDE4) inhibitor

approved in December 2016 for mild-to-moderate AD in children
age ≥2 y
Other Topical Options (cont)

age ≥2 y
• Tar preparations1,2
– No randomized trials have demonstrated efficacy
– Should not be used on acutely inflamed skin
– Tar shampoo may be beneficial


age ≥2 y
• Topical antihistamines1,2
– Not recommended because of lack of evidence supporting efficacy,
risk of absorption and of contact dermatitis
– Even oral anthistamines are only used in AD for their soporific effects or for
associated allergic disorders (nonsedating antihistamines)


age ≥2 y
• Topical antihistamines1,2
– Not recommended because of lack of evidence supporting efficacy,
risk of absorption and of contact dermatitis
– Even oral anthistamines are only used in AD for their soporific effects or for
associated allergic disorders (nonsedating antihistamines)
• Topical antimicrobials2
– Not recommended because of lack of efficacy, risk of contact dermatitis
– Exception: antiseptic dilute bleach baths3-5
3. Hon KL, et al. J Dermatolog Treat. 2016;27(2):156-162.
4. Wong SM, et al. J Dermatol. 2013;40(11):874-880.
5. Huang JT, et al. Pediatrics. 2009;123:e808-e814.
Additional Considerations
• Identify and eliminate triggering factors
– Avoidance of common irritants – soaps/detergents/wool/occlusive
fabrics
– Potential contact allergens, such as fragrance, preservatives, botanicals
– Recommend control of temperature and humidity
– Consider possible allergy triggers (other than foods) with skin tests,
although skin tests (and allergy patch tests) are poorly predictive of
triggering factors
– Allergen immunotherapy
• Selected patients with aeroallergen sensitivity – may worsen AD

Additional Considerations (cont)
• Identify and eliminate triggering factors
– Avoidance of common irritants – soaps/detergents/wool/occlusive
fabrics
– Potential contact allergens, such as fragrance, preservatives, botanicals
– Recommend control of temperature and humidity
– Consider possible allergy triggers (other than foods) with skin tests,
although skin tests (and allergy patch tests) are poorly predictive of
triggering factors
– Allergen immunotherapy
• Selected patients with aeroallergen sensitivity – may worsen AD
• Limited data regarding the benefits of leukotriene inhibitors
(shown to be ineffective for AD)

• Patient and family education
– Chronic nature of disease, exacerbating factors, efficacy and safety of
treatments
– Demonstrate skin care techniques
– Provide written treatment plan
– Refer to other healthcare providers as needed
– Advise of patient support organizations

• Patient and family education
– Chronic nature of disease, exacerbating factors, efficacy and safety of
treatments
– Demonstrate skin care techniques
– Provide written treatment plan
– Refer to other healthcare providers as needed
– Advise of patient support organizations
• Patient and family quality of life often impaired

– Additional treatment may be needed for itching, behavioral disorders,
and sleep disturbances

Video 6
MEDICAL MANAGEMENT II
Difficult-to-Treat Patients with Atopic
Dermatitis
• Phototherapy
– Narrowband UVB most commonly used due to low risk profile,
relative efficacy, availability, clinician experience
– Incidence of adverse events considered to be low
• Most common are actinic damage, local erythema/tenderness,
pruritus, burning, stinging
– Rarely used because of poor accessibility and often poorly tolerated,
especially for acute AD
– Home phototherapy a consideration for patients with poor adherence
Sidbury R, et al. J Am Acad Dermatol. 2014;71(2):327-349.

Dermatitis (cont)
• Systemic agents
– Lack of comparative trial data makes it difficult to determine the relative
efficacy and safety of available options
– Most commonly used in US are

• Cyclosporine, methotrexate, mycophenolate mofetil
– Corticosteroids
• Should be avoided if possible due to side effects, risk for abuse
• Reserved for acute, severe exacerbations as a short-term bridge to
other systemic, non-steroid therapy in adults; no role in children
Sidbury R, et al. J Am Acad Dermatol. 2014;71(2):327-349.

Dermatitis (cont)
• Systemic agents (cont)
– Antimicrobials1
• Recommended only in patients with clinical evidence of bacterial evidence
– Antihistamines1
• Sedating ones may be beneficial in the setting of sleep loss secondary to
pruritus
1. Sidbury R, et al. J Am Acad Dermatol. 2014;71(2):327-349.

Dermatitis (cont)
• Systemic agents (cont)
– Antimicrobials1
• Recommended only in patients with clinical evidence of bacterial evidence
– Antihistamines1
• Sedating ones may be beneficial in the setting of sleep loss secondary to
pruritus
• Other interventions that have not been proven to work and are
not supported in treatment guidelines
– Primrose oil, omega-3, vitamin D, aromatherapy
– Probiotics/Synbiotics2,3
• Limited data suggest benefit of synbiotics (combination of prebiotics
and probiotics) but not probiotics
• Highly dependent on strains, doses
2. Rather IA, et al. Front Microbiol. 2016;7:507.
3. Chang YS, et al. JAMA Pediatr. 2016;170(3):236-242.
Video 7
PREVENTION OF FLARES
Case Scenario: Juan
• Juan is a child seen for continuing care of atopic dermatitis

• History
– Diagnosed 3 years ago with atopic dermatitis at age 11 months
– Achieves good symptom relief with basic measures (bathing,
moisturizers, control of triggers)
– However, experiences frequent flares which cause him to scratch
intensely  developed secondary skin infection
Prevention of Flares
• Preventing or at least increasing the time interval between flares

is a critical goal of management
• Important to act quickly in treating a flare1

1. Wollenberg A, et al. JEADV. 2016;30:729-747.
Prevention of Flares (cont)

• Two approaches (with continued basic management)2,3, 4
Reactive Proactive
TCI or TCS applied at first TCS 2-3 times/week or
signs/symptoms of flare TCI 2-3 times/week

3. Eichenfield LF, et al. Pediatrics. 2015;136(3):554-565.
4. Schmitt J, et al. Br J Dermatol. 2011;164(2):415-428.

• Two approaches (with continued basic management)2,3, 4
Reactive Proactive
TCI or TCS applied at first TCS 2-3 times/week or
signs/symptoms of flare TCI 2-3 times/week
• Antiseptic/Antibiotic therapy
– Topical- dilute bleach bath (minimally twice-weekly; severe may require
daily)
– Systemic- S. aureus most common pathogen; MSSA >> MRSA
• Oral cephalosporin; amoxicillin/clavulanate
3. Eichenfield LF, et al. Pediatrics. 2015;136(3):554-565.
4. Schmitt J, et al. Br J Dermatol. 2011;164(2):415-428.
• Patient/Family education1,2
– Promote adherence to maintenance therapy
– Written action plan
– Multidisciplinary teaching3
– Dermatological, nutritional, psychological components
• Psychological support is particularly important in those with emotional triggers
or experiencing significant distress
• Nutritional education particularly important in children with food allergies

3. Spielman SC, et al. J Clin Med. 2015;4:1156-1170.
• Control trigger factors: more important for associated allergic
disorders1,2
– Hard to demonstrate that allergic triggers play a role in AD
– Young children- food allergies (probably <10% and especially in severely
affected children with AD)
– Older children and adults- environmental aeroallergens

Video 8
EMERGING THERAPIES
Crisaborole: New Topical for Mild-to-
Moderate AD
• Overview
– Phosphodiesterase-4 inhibitor  ↑ cAMP  ↓ release of pro-
inflammatory cytokines
– Approved by FDA December 2016
• Phase 3 trials
– 2 randomized, double-blind, vehicle-controlled trials
– Patients
• Age ≥2 years with diagnosed atopic dermatitis, ≥5% treatable body surface area, IGSA
score of 2 or 3
• Excluded: biologic therapy or systemic corticosteroids within 28 days, TCS/TCI within 14
days
– Treatment
• Ointment applied twice daily to each lesion (except scalp) for 28 days
IGSA, Investigator’s Static Global Assessment score; TCI, topical calcineurin inhibitor; TCS, topical corticosteroid
Paller AS, et al. J Am Acad Dermatol. 2016;75(3):494-503.
Crisaborole: Results of 2 Phase 3 Trials
% of Patients with ISGA of Clear (0) or Almost Clear (1) at Day 29

100%
Crisaborole
80% P=.005
P<.001
60%
51.7%
48.5%
40.6%
40%
29.7%
20%
0%
AD-301 AD-302
Trial AD-301: Crisaborole (n=503), vehicle (n=256); Trial AD-302: crisaborole (n=513), vehicle (n=250)
Crisaborole: Results of 2 Phase 3 Trials (cont)
% of Patients with Improvement in AD Signs at Day 29
100%
Crisaborole
P<.001 P<.001
80% P=.008 P<.001
59% P<.001 60%

60% 55%
52%
48% 48%
40% 40% 41%
40%
30%
20%
0%
Erythema Exudation Excoriation Induration/ Lichenification
Papulation
Trial AD-301: Crisaborole (n=503), vehicle (n=256); Trial AD-302: crisaborole (n=513), vehicle (n=250)
Case Scenario: Tamika
• Tamika is a 32-year-old female diagnosed with severe AD at age 23

years
• She has been treated with intensive topical therapy as well as
systemic medications, and has either developed adverse effects or
not responded (cyclosporine; mycophenolate mofetil;
methotrexate)
• Preventive therapy with twice-weekly topical corticosteroid
therapy has yielded limited benefit
• She continues to experience impaired quality of life, including
poor sleep, which has made it difficult for her as a school teacher
Dupilumab
• Fully human
monoclonal
antibody that
blocks IL-4-
receptor- 
blocks actions of
the Th-2 cytokines
IL-4 and IL-13
• Subcutaneous
Peng W, et al. Clin Exper Allergy. 2015;45:566-574.
injection
Dupilumab: Phase 2b Trial
• Patients: Adults with moderate-to-severe AD with inadequate

response to topical treatment
• Randomized (1:1:1:1:1:1) to 16 weeks of treatment with:

– Dupilumab 300 mg every week
– Dupilumab 300 mg every 2 weeks
– Dupilumab 100 mg every 4 weeks or
– Placebo every week
Thaci D, et al. Lancet. 2016;387(10013):40-52.

Dupilumab: Phase 2b Trial Results
Change in EASI Score from Baseline to 8 Weeks

Dupilumab
Placeb... 100 mg... 300 mg... 200 mg... 300 mg... 300 m...
0%
-18%
-45%
-64% -65% -68%

-74%

N=379
P<0.0001 dupilumab (all doses) vs placebo
Dupilumab: Phase 2b Trial Results (cont)
• Results:
– Improvements in EASI score were significantly greater at all doses of
dupilumab vs placebo
– Treatment-emergent adverse event in 81% (dupilumab) and 80%
(placebo)
• Nasopharyngitis: 28% (dupilumab) vs 26% (placebo)

Dupilumab: Phase 3 Trials (SOLO 1 and SOLO
2)
• 2 Separate phase 3, double-blind, parallel-group clinical trials
– SOLO 1 and SOLO 2
• Adults with chronic moderate-to-severe AD inadequately
controlled by topical treatment or for whom topical treatment
was inadvisable
– Investigator Global Assessment score 3 or 4
• IGA determines severity of AD and clinical response to treatment [range 0 (clear) to 4
(severe)]
Simpson EL, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1610020.

Dupilumab: Phase 3 Trials (cont)
• Randomized to:
– Dupilumab 300 mg every week
– Dupilumab 300 mg every other week or
– Placebo
• Moisturizers bid for ≥7 d before randomization, then throughout
trial
• Topical or systemic rescue treatment allowed
– If systemic rescue treatment  patient discontinued (categorized as no
response)

Dupilumab: Phase 3 Trials Results
Primary Endpoint*
% of Patients with Qualifying IGA Score
100% Placebo QW Dupilumab QOW Dupilumab QW
80%
60%
40% 38% 37% 36% 36%
20%
at Week 16
10% 8%
0%
SOLO 1 SOLO 2
P<.001 for all comparisons between

dupilumab and placebo
*Reduction from baseline of ≥2 points on the IGA at week 16.

Dupilumab: Phase 3 Trials Results (cont)
Secondary Endpoint*
% of Patients with EASI75 at Week 16
100%
80%
60% 52%
51% 48%
44%
40%
20% 15% 12%
0%
SOLO 1 SOLO 2
P<.001 for all comparisons between

dupilumab and placebo
*Improvement from baseline of at least 75% on the Eczema Area and Severity Index (EASI) at week 16.

• Significantly greater improvement with dupilumab vs placebo
regarding
– Pruritus
– Sleep
– Symptoms of anxiety or depression
– Quality of life
• Fewer patients treated with dupilumab used rescue medication

(19% vs 52%)

Adverse Event, % SOLO1 SOLO 2
Placebo Dupilumab QOW Dupilumab QW Placebo Dupilumab QOW Dupilumab QW

(n=222) (n=229) (n=218) (n=234) (n=236) (n=237)
≥1 AE 65 73 69 72 65 66
≥1 Serious AE 5 3 1 6 2 3
Injection site reaction 6 8 19 6 14 13
AD exacerbation 30 13 10 35 14 16
Headache 6 9 5 5 8 9
Allergic conjunctivitis 1 5 3 1 1 1
Conjunctivitis 1 5 3 <1 4 4
Nasopharyngitis 8 10 11 9 8 8
Non-skin infection 22 30 31 24 25 26

Pro-inflammatory Targets
• Interleukins • Janus kinase inhibitor

– IL-4 receptor-
• Thymic stromal lymphopoietin
– IL-5
• H4-receptor blocker
– IL-12/IL-23 p40
– IL-13 • Liver X receptor agonist
– IL-22
– IL-31
– IL-31 receptor

Lecture-3: Dermatitis. Toxicoderma. Eczema. Psoriasis. Lichenplanus. Bullous Dermatosis

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Lecture-3: Dermatitis. Toxicoderma. Eczema. Psoriasis. Lichenplanus. Bullous Dermatosis

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LECTURE-3

DERMATITIS. TOXICODERMA. ECZEMA. PSORIASIS.

Schneider L, et al. Pediatr Dermatol. 2016;33(4):388-398.

Chernyshov PV, et al. Clin Cosmet Investig Dermatol. 2016;9:159-166.

Peng W, et al. Clin Exper Allergy. 2015;45:566-574.

Complex interplay Barrier Dysfunction Environmental Factors

Th2 cells Th17 cells Tregs

ILC2 Eosinophils Mast cells

Egawa G, et al. Cogent Biol. 2015;1;1103459.

1. Mansouri Y, et al. J Clin Med. 2015;4:858-87.

• Jack is a 13-year-old male, accompanied by his mother.

Recommended as part of PE Not recommended in

Strong association Moderate association

• Both parents are atopic: 3 to 5- Unclear association

Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-351.

Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-351.

Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-351.

Age Typical Distribution

Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-351.

1. Eichenfield LF, et al. J Am Acad Dermatol. 2014;70:338-351.

1. Reduce the number and severity of flares

Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.

Modified from Eichenfield LF, et al. Pediatrics. 2015;136(3):554-565.

TCI, topical calcineurin inhibitor; TCS, topical corticosteroid

Maintenance TCI Maintenance TCS

Modified from Eichenfield LF, et al. Pediatrics. 2015;136(3):554-565.

TCI, topical calcineurin inhibitor; TCS, topical corticosteroid

• Bathing followed by immediate application of emollient

Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.

• Bathing followed by immediate application of emollient

Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.

• Bathing followed by immediate application of emollient

Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.

Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.

Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.

Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.

• Pimecrolimus cream 1%; tacrolimus 0.03% and 0.1% ointment

1. Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.

• 2-3x/wk “proactive” application effective in preventing

1. Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.

• Crisaborole: Topical phosphodiesterase-4 (PDE4) inhibitor

• Crisaborole: Topical phosphodiesterase-4 (PDE4) inhibitor

1. Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.

• Crisaborole: Topical phosphodiesterase-4 (PDE4) inhibitor

1. Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.

• Crisaborole: Topical phosphodiesterase-4 (PDE4) inhibitor

Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.

Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.

Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.

• Patient and family quality of life often impaired

Schneider L, et al. J Allergy Clin Immunol. 2013;131(2):295-299.

Sidbury R, et al. J Am Acad Dermatol. 2014;71(2):327-349.

– Most commonly used in US are

Sidbury R, et al. J Am Acad Dermatol. 2014;71(2):327-349.

1. Sidbury R, et al. J Am Acad Dermatol. 2014;71(2):327-349.

• Juan is a child seen for continuing care of atopic dermatitis

• Preventing or at least increasing the time interval between flares

TCI, topical calcineurin inhibitor; TCS, topical corticosteroid

• Preventing or at least increasing the time interval between flares

TCI, topical calcineurin inhibitor; TCS, topical corticosteroid

• Preventing or at least increasing the time interval between flares

1. Sidbury R, et al. J Am Acad Dermatol. 2014;71(2):327-349.

1. Sidbury R, et al. J Am Acad Dermatol. 2014;71(2):327-349.