Atopic Dermatitis (AD) Flashcards by J H

Factors Associated With an Increased Risk of Developing AD

Heredity
~70% of patients with AD have a positive
family history of atopic disease1 (asthma, eczema, allergic rhinitis, allergic conjunctivitis)
 Decreased ceramide levels in the
epidermis, which impair water-holding
capacity and barrier function (Incr in
Transepidermal Water Loss)
 Additional alterations in epidermal barrier
genes (e.g. those encoding loricrin,
involucrin) have been observed2

Race
 Higher prevalence of eczema in African-
American children (17.3%) compared with
Caucasian children (10.4%, OR 1.6)5,6
 The role of race and ethnicity in adult
eczema and AD is less clear6
genes that change epidermis (ceramides)

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Environmental Factors Are Also Associated With an Increased Risk
of Developing AD

The global prevalence of AD varies
significantly, suggesting that
environmental factors may confer
increased risk of AD1
 Environmental factors play a crucial role
in the sensitization to allergens and the
induction of chronic skin inflammation2

Outdoor climate
Low temperature ▲ risk
High UV light exposure Protective (more skin cancer)
Urban setting (vs rural) ▲ risk
Pollution/tobacco smoke ▲ risk
Microbial exposure
Antibiotic exposure ▲ risk
Day care attendance in first
2 years of life Protective
Dog exposure early in life Protective

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Clinical Presentation of AD Ranges in Severity*

Mild Form (BSA < 3%) 
Moderate Form (BSA 3 – 10%) 
Severe Form (BSA ?10%)
also take qual of life into account

darker skin tone
Less erythema, violaceous-greyish hue [and] hypo- or
hyperpigmentation may actually be the main indicators (image A)
• Location in darker skin typical on extensors vs. flexor (image B)
• Hypo- or Hyper-pigmentation with chronic sequela (image B)
• Follicular accentuation may be present (image C)
- Looks like a rash resembling goosebumps. Inflammation of the hair follicles. (look like folliculits)

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Scratching in Response to Pruritus (Itch) Perpetuates

Skin Signs and Symptoms

itch impacts cycle of life
Scratching

Disturbed skin barrier function

Penetration of irritants and allergens

Irritation and persistent Inflammation

Itching

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Patients with AD Experience Debilitating Effects that Impact
Day-to-Day Functioning

Sexual difficulties
Affectedcrelationships
Sports participation
Shopping, home, garden activities
Work/studying
Social/leisure activities
Influenced clothes worn

AD Symptoms (e.g. Pruritus) Frequent and intense itch1

Disease Exacerbations (e.g. Flares)
Persistent signs and symptoms

Mental Health Disorders
Anxiety and depression1

Sleep Disturbances
Difficulty falling asleep and
frequent awakenings1

Work Productivity
Absenteeism and presenteeism (at school but not able to focus or perform)

Impaired QoL
Daily activities, social functioning, and life-course

Comorbidities, Including
Skin Infections
Other atopic diseases1
Bacterial, viral, fungal infections3

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Guidelines on Comorbidities Associated with Atopic Dermatitis

Immune system
and skin barrier1,2
Environmental Genetic1,3 4,5

Multifactorial
etiology of AD

There is strong evidence that AD in adults is associated with select allergic, atopic, immune-
mediated, mental health and bone health comorbidities and skin infections.
There is some evidence supporting an association between AD in adults and substance
use, ADHD, and elements of metabolic syndrome.
Evidence suggests a small association with various cardiovascular conditions. (higher baseline inflamm)
The association between AD in adults and autism spectrum disorders, myocardial infarction,
stroke, and metabolic syndrome as a whole is uncertain.
Clinicians should be aware of comorbidities associated with AD. Further research is needed
to determine whether screening or management of comorbidities is beneficial for adults with
AD.

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In Chronic Skin Lesions, Type 2 (Including Th2) Signaling Persists
With an Increase in Th1 Activation1-3

see slide 16

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Overview of Treatment Options for AD

emollient+moisturier +
coritcosteorids
+ systemic

for many pts

topical corticosteroids
calcineurin inhib (tacrolimus,pimecrolimus,
PDE4inhib (crisaborole)

systemic: phottx: UVA/UVB
systemic immunosuppressive drugs: corticosteroids, cyclosporine, azathio, methotrexate, dupil, alitretinoin, JAK inhib

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Emollients and Moisturizers: Overview and Recommendations

 Hydration of skin as part of a basic skin
regimen for all patients with AD, regardless
of severity1–3
 Suggest the use of products with
ceramides to help restore barrier function
 Moisturizers with hydrophilic base (e.g.
glycol and glyceryl stearate, soy sterols)1,2
 Emollient creams/ointments or emollient
bath oils and soap substitutes1,2

 Use liberally and frequently as part of
normal daily care routine1,2
• EADV recommends at least a twice-daily
application1
• Japan recommends combining with TCS, as
well as continuous application even in the
absence of symptoms3

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Emollients and Moisturizers:Considerations and Select Safety Risks

 Symptomatic relief; do not treat underlying inflammation1
 Nonprescription/nonreimbursable in most countries1
 Large quantities of ointments or creams are required; messy application1,2
 Use without sufficient topical anti-inflammatory therapy increases existing risk of
disseminated bacterial and viral infection in patients with AD1

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Mechanism of Action - topical corticosteroids

 Act on a variety of immune cells (i.e. T
cells, dendritic cells, macrophages),
suppress the release of inflammatory
cytokines, and interfere with antigen
processing1

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Description of Use- topical corticosteroids

 Treat active lesions and help prevent
relapses1
 Anti-inflammatory glucocorticosteroids1
• Low-, medium-, or high-potency creams or
ointments1–3
 Apply on hydrated lesional skin; wet
wraps may increase efficacy with more
severe disease1,2,*
 Follow fingertip1–3
• 1 FTU = amount squeezed from a tube to
the first crease of an adult finger
• 1 FTU covers 2 adult handprints worth of
skin.

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Adverse Effects & Safety Considerations - topical corticosteroids

 Cutaneous: skin atrophy, purpura, telangiectasia, striae, focal hypertrichosis, and
acneiform or rosacea-like eruptions
 Systemic (high potency): risk of hypothalamic-pituitary-adrenal axis suppression with
continuous use
 Work through “steroid-phobia”!
• Results in misinformation, under treatment and low adherence

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Treatment Guideline Recommendations1–3

 No recommendation for selection of potency
 Gradual dose tapering
 Proactive therapy (e.g. twice-weekly application) in the long-term follow-up
may help reduce relapses

Topical Corticosteroids: Recommendations
 No recommendation for selection of potency or gradual tapering
 Proactive therapy (e.g. twice-weekly application) on areas that commonly
flare to help reduce relapses or increase time to first flare

 Select potency based on severity of lesion*
 Gradual dose tapering and discontinuation after reductions in inflammatory symptoms
 Proactive therapy (e.g. twice-weekly application) may help maintain remission

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Topical Calcineurin Inhibitors
(Tacrolimus (Protopic®) & Pimecrolimus (Elidel®

MOA

 Inhibit calcineurin-dependent T cell activation,
block secretion of inflammatory cytokines;
effects on dendritic and mast cell activation.

Transient burning sensations, skin tingling,
pruritus at site of application; tolerance usually
develops within a few days

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Topical Calcineurin Inhibitors

description of use

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 Indicated for patients who have failed to
respond adequately to other topical
treatments, or when those treatments are not
advisable
 These products work more slowly than
corticosteroids
 Used BID
 Tacrolimus ointment (0.03%, 0.1%)
• Use: 0.03% >2 years of age
0.1% > 16 years of age
 Pimecrolimus cream (1%)
• Use: > 3 mos

Topical Calcineurin Inhibitors: Recommendations

read

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 Especially indicated in problem areas (e.g. face, intertriginous sites, anogenital area)
 Proactive therapy (e.g. twice-weekly application of tacrolimus) may reduce relapses

Topical Calcineurin Inhibitors: Recommendations

 Particular use at sensitive skin sites (e.g. face and skin folds) and on actively affected areas as a
steroid-sparing agent
 Proactive therapy (e.g. 2–3 times per week) on areas that commonly flare to help prevent relapses

 Only tacrolimus is recommended
 Recognized as a drug to be used on the face and neck
 Proactive therapy (e.g. twice-weekly application) to maintain remission

Topical PD4 inhibitor (Crisaborole (Eucrisa®))
MOA
Adverse Effects & Safety Considerations1,2

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 Inhibit PDE4
 New pathway implicated in pathogenesis of
inflammatory skin disorders such as atopic
dermatitis and psoriasis

Approximately 4.5% might have local skin
irritation from treatment

Topical PD4 inhibitor (Crisaborole (Eucrisa®))

description of use

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 Indicated for patients with mild to moderate
atopic dermatitis over the age of 2 years
 At Day 29 approximately 50% of patients were
clear or almost clear
 Dispensed as a 60g ointment
 Applied BID
 Do not use on mucous membranes
 Use: > 2 years

Phototherapy

MOA
Adverse Effects & Safety Considerations1,2

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 Apoptosis of inflammatory cells, inhibition
of Langerhans cells, and alteration of
cytokine production

 Potential long-term risk of developing skin
cancer and premature aging of the skin
 Short-term undesirable effects (e.g.
pruritus, actinic damage, local erythema,
and tenderness, burning, and stinging)

Description of Use

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 Treat patients with AD lesions who do not
respond to topical treatments1,2
 Specialized equipment emits selective
spectra of UV radiation:1–3
• Narrowband UVB (311–313 nm)
• Broadband UVB (280–320 nm)
• UVA + UVB (280–400 nm)
• UVA1 (340–400 nm)*
 TCS and emollients should be considered at
the beginning of phototherapy to reduce
chance of a possible flare
 Use of TCI, cyclosporine, and azathioprine
should be avoided
 Beneficial effects vary from person to person
 Limited by availability and requires frequent
travel to a provider

Phototherapy: Recommendations

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 Treat chronic, pruritic, lichenified AD forms
 Not indicated in the acute stages (except UVA1)

 Treat nonresponders to topical treatments
 Can be used as maintenance therapy in patients with chronic disease

 Treat nonresponders to topical treatments

Oral/Injectable Corticosteroids

MOA
descrip of use

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 Suppress expression of inflammatory genes,
including:
• Cytokines, chemokines, adhesion molecules,
inflammatory enzymes, receptors and proteins

 Short-term treatment of acute flare in patients
with severe AD1–3
 Systemic glucocorticosteroids
(e.g. prednisone, prednisolone, and
triamcinolone acetonide)1,2

Oral/Injectable Corticosteroids\

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 Increased risk with duration of use; safety
risks include:
• Glucose intolerance
• Cushing’s syndrome
• Glaucoma
• Myopathy
• Hypertension
• Infections
• Cataracts
• Osteonecrosis
 In some patients, skin lesions may worsen
significantly following cessation of therapy

Oral/Injectable Corticosteroids\ | monitoring

```  Blood pressure  Ophthalmologic examination  Hypothalamic-pituitary-adrenal axis suppression testing  Bone density evaluation ```

Oral/Injectable Corticosteroids: Recommendations

 Short-term (up to 1 week) treatment to treat an acute flare • Long-term use is not recommended due a largely unfavorable risk–benefit ratio  Limited to adult patients with severe AD  Short-term (up to 1 week) treatment to treat an acute flare  Exclusively reserved for acute, severe exacerbations  Short-term bridge therapy to other systemic, steroid-sparing therapy  If necessary, short-term course may be administered for severe AD

Cyclosporine MAO (know general) desc of use

```  Broad-spectrum immunosuppression • Inhibits activation of T cells, NK cells, and APCs • Blocks interleukin-2 and GM-CSF production Mechanism ``` ```  Licensed in many European countries: indicated for patients with severe AD1  Off-label use in US: recommended for patients who do not respond to topical treatments2,3  Approved in Japan: indicated for patients with severe AD who do not respond to topical treatments4 ```

Cyclosporine: Safety Risks see more warnings nad precautions

``` Select Potential Toxicities1  *Nephrotoxicity  *Hypertension  Tremor  Hypertrichosis  Headache  Gingival hyperplasia ```  Maximum use of 1-2 years

Guideline Recommendations for Other | Systemic Immunosuppressive Drugs1–3,

slide 40

Dupilumab (Dupixent®) moa ae

 A biologic that works through inhibiting the pro-inflammatory cytokines of IL4 and IL13  Injection site reactions, allergic conjunctivitis, blepharitis, headaches, increased URTIs

Dupilumab (Dupixent®) Description of Use

 Usual dosing is 600mg sc at week 0, followed by 300mg sc q 2 weeks  There is no formal pre-workup that needs to be completed  There is no formal blood work or testing that needs to be completed on therapy

Tralokinumab (Adtralza®) Mechanism of Action Adverse Effects and Safety Considerations

 A biologic that works through inhibiting the pro-inflammatory cytokines IL13 only  Injection site reactions, allergic conjunctivitis, blepharitis, headaches, increased URTIs

Tralokinumab (Adtralza®) Description of Use

Upadacitinib (Rinvoq®) JAK inhibiotr Mechanism of Action Adverse Effects and Safety Considerations

 An oral agent that works through inhibiting the pro-inflammatory Janus kinase pathway ```  Headaches, URTI, nausea, acne  Theoretical increased risk of infections, thromboembolic events, major adverse cardiovascular events (MACE), lymphoma (JAK inhibitor class effect)  Contraindicated in pregnancy ```

Upadacitinib (Rinvoq®) | Description of Use

 Usual dosing is 15mg po daily  Can increase to 30mg po daily if no response  Need formal workup prior to starting: TB test, CXR, HBV, HCV, HIV, CBCdiff, LFT, RFT  At 12 week point, can repeat CBC diff, RFT, LFT and check lipids  Then routine monitoring as per practice guidelines

Scoring of Disease Severity and Assessment of Treatment Effect

problme is red colouris not always apparent on all skin of colour, leads to under diagnosis, under treatment

Serving our Diverse Communities

 The product is only as good as the patient’s willingness to use the product  Is the product cosmetically appealing? • Is it greasy and is this a problem for the patient? • Does it leave a white film on darker skin tones? • Is it affordable for the duration of therapy?  Limited data specifically looking at management, and the efficacy of management strategies for patient population. • Increased risk of post-inflammatory hyperpigmentation in darker-skinned patients with therapy that may cause irritation: • Clinicians need to be vigilant when implementing lasers and light-based therapies. • Patients with darker skin types have more labile melanocytes, which means aggressive treatment may cause more hyperpigmentation.  Patients with skin of colour underrepresented in clinical trials and limited data available

Atopic Dermatitis (AD) Flashcards

(37 cards)