Lecture 38 - Atopic Dermatitis

what is atopic dermatitis

An inflammatory disorder of the skin with an onset usually in early childhood

Some children will truly outgrow AD but a proportion of patients will have persistent disease into adulthood

is atopic dermatitis hereditary

yes

Atopic Disease: ~70% of patients with AD have a positive family history of atopic disease (asthma, allergic rhinoconjunctivitis and food allergies)

what are examples of environmental factors that can trigger atopic dermatitis

low temperature

urban setting (vs rural)

pollution/tobacco smoke

antibiotic exosure

what are examples of environmental factors that are protective against atopic dermatitis

high UV light exposure

daycare attendance in first 2 years of life

dog exposure early in life

what is the clinical presentation of atopic dermatitis

Ill-defined patches of erythema/inflammation, scale and excoriations

In skin of colour less erythema, violaceous-greyish hue [and] hypo- or hyperpigmentation may actually be the main indicators

• Hypo- or hyperpigmentation with chronic sequela

Thickened skin with increased skin markings often in response to chronic rubbing (Lichenification)

pruritus (itch) and generalized dry skin

Follicular accentuation may be present (Looks like a rash resembling goosebumps. Inflammation of the hair follicles)

how can BSA be used to classify atopic dermatitis as mild, moderate, or severe

mild = BSA <3%

moderate = BSA 3-10%

severe = BSA >10%

what is the itch-scratch cycle

itching → scratching → disturbed skin barrier → penetration of irritants and allergens → irritation and persistent inflammation → itch (cycle repeats)

what is the impact of atopic dermatitis on day to day functioning

AD symptoms (itch)

sleep disturbances

disease exacerbations (flares)

comorbidities, including skin infections

impaired QoL

mental health disorders

work productivity

what is the distribution of AD on the body

Facial and extensor dermatitis in infants

Flexural and fold dermatitis in older children

Prominence of facial and hand dermatitis in adults

In skin of colour, more extensor involvement has been noted

what are tools to score the disease severity of AD

Eczema Area and Severity Index (EASI)

SCORing Atopic Dermatitis (SCORAD) - Used in Research Trials

what is the Eczema Area and Severity Index (EASI)

Measures the extent (area) and severity of atopic dermatitis

The minimum EASI score is 0 and the maximum EASI score is 72

Score of 16 qualifies patient for biologic

what is the SCORing Atopic Dermatitis (SCORAD) tool

Based on area, intensity, subjective symptoms (itch)

Max score 20 = bad

what are some criticisms of validated tools

Score assigned for redness which may not be apparent in skin of colour (SOC), leads to under diagnosis and under treatment.

what are some of the qualities that AD scoring tools assess

Body region affected and how much (BSA)

Signs of inflammation (redness, violaceous hues, warmth, swelling, pain)

Thickness of plaques

Intensity of itch (Look for scratch marks)

Intensity of lichenification

Dryness of skin

Oozing, crusting

Ask about impact on quality of life (recall Dermatology Life Quality Index questionnaire)

what is a general treatment algorithm for AD

1. non-pharm → moisturizers/emollients

2. topical intervention (TCS, TCI, JAKi, PDE4)

3. reactive management (phototherapy, oral/injectable corticosteroids)

what are approved systemic therapies for refractory disease

Dupilumab

Tralokinumab/Lebrikizumab

Upadacitinib/Abrocitinib

what are unapproved systemic therapies for refractory disease

Cyclosporine

Azathioprine

Methotrexate

Mycophenolate mofetil

what are examples of topical calcineurin inhibitors

tacrolimus

pimecrolimus

what are examples of topical JAKi

Ruxolitinib

Delgocitinib

what ar eexamples of topical PDE4 inhibitors

Crisaborole

Roflumilast

what are some non-biologic systemic therapy

phototherapy (UVA/UVB)

systemic immunosuppressive drugs → corticosteroids (prednisone), JAKi (Upadacitinib/ Abrocitinib), cyclosporine, azathioprine, methotrexate, Mycophenolate mofetil

what are examples of biologic systemic therapt

Tralokinumab/ Lebrikizumab

Dupilumab

what is the MOA of topical Calcineurin Inhibitors (Tacrolimus, Pimecrolimus)

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

what are adverse effects of topical calcineurin inhibitors

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

what are indications for topical calcineurin inhibitors

Indicated for patients who have failed to respond adequately to other topical treatments, or when those treatments are not advisable.

what are clinical pearls for topical calcineurin inhibitors

These products work more slowly than corticosteroids

Used BID

use of higher dose formulations is based on age

what is the MOA of topical PDE4 inhibitor (Crisaborole (Eucrisa®))

Phosphodiesterase-4 (PDE4) inhibitor

Pathway implicated in pathogenesis of inflammatory skin disorders such as atopic dermatitis and psoriasis

what are adverse effects of Crisaborole (Eucrisa®)

Approximately 4.5% might have local skin irritation from treatment (patients complain about stinging)

what are indications for Crisaborole (Eucrisa®)

Indicated for patients with mild to moderate atopic dermatitis ≥3 months of age

what are clinical pearls for Crisaborole (Eucrisa®)

At Day 29 approximately 50% of patients were clear or almost clear

Applied BID

Do not use on mucous membranes

Use: > 2 years

what is the MOA of Topical PD4 inhibitor (Roflumilast (Zoryve®))

Phosphodiesterase-4 (PDE4) inhibitor

Pathway implicated in pathogenesis of inflammatory skin disorders such as atopic dermatitis and psoriasis

what are adverse effects of Roflumilast (Zoryve®)

Mild application site reaction ▪

Mild weight loss was noted in 4% of patients in the pivotal trials.

Diarrhea is an infrequent event with topical roflumilast (loose stools during start of treatment). Not really seen with topical.

Headache

There have been no studies to date examining drug-drug interactions with topical roflumilast

what are indications for Roflumilast (Zoryve®)

Approved in Canada for mild-moderate AD (0.15% cream) for ≥6 years

Indicated in plaque psoriasis in patients ≥12 years of age and seborrheic dermatitis in patients ≥9 years of age

what are clinical pearls for Roflumilast (Zoryve®)

Available in 0.3% cream and 0.3% foam formulations, 0.15% cream strength for AD

Applied once daily

what is the MOA of topical JAKi (Ruxolitinib (Opzelura®))

Topical Janus kinase (JAK) inhibitor

JAK inhibitors block the signalling pathway of several cytokines in the inflammatory

what are adverse effects of topical JAKi (Ruxolitinib (Opzelura®))

Risk of application site reaction, urticaria, diarrhea and nasopharyngitis

There is a boxed warning regarding the risk of developing serious infections, malignancies, thrombosis or MACE.

• Assess risk based on topical formulation!

what are indications for topical JAKi (Ruxolitinib (Opzelura®))

Approved for mild-moderate AD in patients ≥2 years

what are clinical pearls for topical JAKi (Ruxolitinib (Opzelura®))

Available in 1.5% cream applied twice daily

Topical JAK inhibitors do not require bloodwork monitoring

what is the MOA of topical JAKi (Delgocitinib (Anzupgo®))

Topical Janus kinase (JAK) inhibitor

JAK inhibitors block the signalling pathway of several cytokines in the inflammatory

what are adverse effects of topical JAKi (Delgocitinib (Anzupgo®))

Risk of application site reaction, urticaria, diarrhea and nasopharyngitis

There is a boxed warning regarding the risk of developing serious infections, malignancies, thrombosis or MACE.

• Assess risk based on topical formulation!

what are indications for topical JAKi (Delgocitinib (Anzupgo®))

Approved for moderate–severe chronic hand AD in patients ≥18 years

what are clinical pearls for topical JAKi (Delgocitinib (Anzupgo®))

Available in 2% cream applied twice daily

Avoid in patients at risk of thrombosis, current infection (including TB) or with history of skin cancers.

Topical JAK inhibitors do not require bloodwork monitoring

what is the MOA of phototherapy

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

what are adverse effects and safety considerations of phototherapy

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)

what are indications for phototherapy

Treat patients with AD lesions who do not respond to topical treatments

what are clinical pearls for phototherapy

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

what is the MOA of oral/injectable cortocosteroids

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

what are indications for oral/injectable corticosteroids

Short-term treatment of acute flare in patients with severe AD

Use only in short courses as a bridge to steroid-sparing immunosuppressants

what are adverse effects and safety considerations for oral/injectable corticosteroids

Glucose intolerance

Cushing’s syndrome

Glaucoma

Myopathy

Hypertension

Infections

Cataracts

Osteonecrosis

In some patients, skin lesions may worsen significantly following cessation of therapy

what should be monitored for patients using oral/injectable corticosteroids

Blood pressure

Ophthalmologic examination

Hypothalamic-pituitary-adrenal axis suppression testing

Bone density evaluation

what are adverse effects of systemic cyclosporine

Multiple toxicities associated with long-term or high-dose therapy, including nephrotoxicity, hepatotoxicity and carcinogenicity (lymphomas and other malignancies)

Hypertrichosis

Gingival hyperplasia

Hypertension

Avoid excess unprotected sun exposure

Monitor for infection development

what should be monitored for systemic cyclosporine

Baseline urinalysis

Tuberculosis

Renal and liver function

Lipids

Blood pressure

CBC, differential, platelets

Mg+, K+, uric acid

HCG if indicated

what are clinical pearls for systemic cyclosporine

Rapid onset of response compared to MTX

High relapse rates upon discontinuation (80% by 2 mos)

Use only as short-term rescue treatment

Use caution when administering with drugs that inhibit or induce CYP3A4 or P-glycoprotein

what are adverse effects of systemic methotrexate

Relatively well tolerated

Possible AEs associated with MTX treatment can be mitigated with proper dosage titration

what should be monitored with systemic methotrexate

Hepatitis B and C

HIV if indicated

Pulmonary function tests if indicated

Tuberculosis

Renal and liver function

CBC, differential, platelets

HCG if indicated

what are clinical pearls for systemic methotrexate

Use in patients with stable disease

Need to supplement with folic acid

what is the MOA of systemic Dupilumab (Dupixent®)

A biologic that works through inhibiting the pro-inflammatory cytokines of IL4 and IL13

what are adverse effects and safety considerations of Dupilumab (Dupixent®)

Injection site reactions, conjunctivitis, blepharitis, headaches, oral herpes, gastritis, arthralgia

Not to be used in pregnancy

what are clinical pearls for Dupilumab (Dupixent®)

Treat patients aged 6 months and older

Dose is different for patients weighing <60 kg (much lower!!)

Baseline labs? - There is no formal blood work or lab monitoring that needs to be completed on therapy

what is the MOA of systemic Tralokinumab (Adtralza®)

A biologic that works through inhibiting the pro-inflammatory cytokines IL13 only

what are adverse effects and safety considerations for Tralokinumab (Adtralza®)

Injection site reactions, conjunctivitis, blepharitis, headaches, increased URTIs

Not to be used in pregnancy

what are clinical pearls for

Use in > 12 years age

There is no formal pre-workup that needs to be completed

There is no formal blood work or lab monitoring that needs to be completed on therapy

what is the MOA of systemic Lebrikizumab (Ebglyss®)

A biologic that works through inhibiting the pro-inflammatory cytokines IL13 only

what are adverse effects and safety considerations for Lebrikizumab (Ebglyss®)

Injection site reactions, allergic conjunctivitis, dry eye, herpes zoster

Not to be used in pregnancy

what are clinical pearls for Lebrikizumab (Ebglyss®)

For use in adults and adolescents aged 12 years and older who have moderate to severe atopic dermatitis

There is no formal pre-workup that needs to be completed

There is no formal blood work or lab monitoring that needs to be completed on therapy

what is the MOA of systemic Upadacitinib (Rinvoq®), Abrocitinib (Cibinqo®)

An oral agent that works through inhibiting the pro-inflammatory Janus kinase pathway

what are adverse effects and safety considerations for Upadacitinib (Rinvoq®), Abrocitinib (Cibinqo®)

Headaches, URTI, nausea, acne

Theoretical increased risk of infections, thromboembolic events, major adverse cardiovascular events (MACE), lymphoma (JAK inhibitor class effect)

Infection risk (including TB, herpes zoster and pneumonia)

Contraindicated in pregnancy

what are clinical pearls for Upadacitinib (Rinvoq®), Abrocitinib (Cibinqo®)

administered once daily

Need formal workup prior to starting: TB test, CXR, HBV, HCV, HIV, CBCdiff, LFT, RFT, Lipids

Use in > 12 years age

At 12 week point, can repeat CBC diff, RFT, LFT and check lipids → Then routine monitoring as per practice guidelines

Increased risk of adverse reactions in Asian patients (i.e. herpes zoster (shingles))

what basic skincare measures should be used in AD

Gentle cleansers

Moisturizer

Sunscreen

should antihistamines be used for pruritus in AD

No

Pruritus in AD is not histamine-mediated and therefore does not respond well to histamine blockade