Atopic Dermatitis (AD) Flashcards
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)
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
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)
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
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
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.
In Chronic Skin Lesions, Type 2 (Including Th2) Signaling Persists
With an Increase in Th1 Activation1-3
see slide 16
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
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
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
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
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.
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
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
Topical Calcineurin Inhibitors
(Tacrolimus (Protopic®) & Pimecrolimus (Elidel®
MOA
AE
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
Topical Calcineurin Inhibitors
description of use
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
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
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
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
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
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
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
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\
AE
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
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
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
