II. Epidemiology
- Inherited sensitive skin (Atopic Patient)
-
Incidence
- Affects 11-12% of children in U.S. and 5-7% of adults
- Affects 17.8 Million people in U.S.
- Most cases go undiagnosed
- Onset
- Typically presents with first 2 years of life (most often within first 6 months)
- Diagnosed in first 5 years in 90% of patients
- Many cases remit by age 3-5 years
III. Pathophysiology
- Disrupted Epidermis due to underlying filaggrin Protein defect
- Filaggrin Gene (FLG) Defect
- Allows for Dermis immune cell exposure to environmental Antigens
- IgE Antibody response
- Increased T-helper 2 subtype activity (stimulate by Interleukin 4 and 13)
- Antigen-specific T-Cells secrete IgE binding factors
- Leads to inflammatory response
- Intense itching ensues due to a low itch threshold to provocative factors
- Scratching leads to further inflammation, resulting in a spiraling itch-scratch cycle
IV. Types
- Acute Atopic Dermatitis
- Weeping, crusting lesions with overlying Vesicles
- Subacute Atopic Dermatitis
- Dry, Scaling, erythematous Papules and Plaques or
- Pityriasis Alba
- Chronic Atopic Dermatitis
- Lichenification (e.g. Lichen Simplex Chronicus)
V. Associated Conditions: Atopic Triad (Family History)
- Eczematous Dermatitis (Atopic Dermatitis)
- Allergic Rhinitis
-
Asthma
- Lifetime asthma Prevalence in patients with Atopic Dermatitis: 30%
VI. Provocative Factors
- Sweating
- Bacterial colonization
- Rough clothing
- Chemical irritants
- Emotional Stress
- Foods
- Cow's milk
- Wheat
- Eggs
- Soy
- Peanut and tree nuts
- Fish
- Environment
- Dust or mold
- Cat dander
- Temperature changes
- Low humidity
VII. Symptoms: Pruritus
- Described as "The itch that rashes" (when scratched)
VIII. Signs: Infants and young children
IX. Signs: Older children and adults
- Dermatitis characteristics
- Similar Eczematous skin changes as with infants
- "Hot and sweaty fossa and folds"
- Excoriated lesions (pruritic)
- Dermatitis Location
- Flexor wrists and ankles
- Antecubital fossa
- Popliteal fossa
- Hands
- Upper Eyelid Inflammation (erythema, fine scale and lichenification)
- Anogenital area
X. Diagnosis: American Academy of Dermatology Criteria
- Major Criteria (all required)
- Chronic or relapsing history
- Eczema
- Pruritus
- Age-specific patterns
- Infants: Face, neck and extensor surfaces
- Children: Flexor surface involvement
- Axillary region and groin spared
- Common Additional Findings (optional, but often observed in atopic)
- Atopy History (or Family History)
- Onset at early age
- IgE Reactivity
- Xerosis
- Non-specific Other Findings
- Ocular or periorbital changes
- Vascular findings
- Facial pallor
- Dermatographism
- Dry Skin findings
- Keratosis Pilaris
- Pityriasis Alba
- Ichthyosis
- Hyperlinear palms
- Sequelae of scratching
- Lichenification (e.g. Lichen Simplex Chronicus)
- Prurigo Nodularis
- Perifollicular accentuation
- References
XI. Diagnosis: Diagnostic Tool
- Pruritus (Required) and
- Additional Criteria (3 or more of the following)
- Asthma or Allergic Rhinitis history
- Flexor fold involvement
- Flexor fold dermatitis visible on exam
- Generalized Dry Skin
- Onset of rash before age 2 years
- Efficacy
- Test Sensitivity: 95%
- Test Specificity: 97%
- References
XII. Differential Diagnosis: Varied Atopic Dermatitis presentations present a broad differential
- See Eczematous Skin Lesion
- See Pruritus
- Any age
- Children
- Older Adults
- Cutaneous T-Cell Lymphoma (older adults)
- Dermatitis Herpetiformis
- Nummular Eczema
- Psoriasis
- References
XIII. Complications (associated with intense scratching)
- Secondary infection
- Impetigo
- Cellulitis
- Eczema herpeticum (Kaposi varicelliform eruption)
- Painful papulovesicular rash spread over localized skin region
- Skin infected by Herpes Simplex Virus infection
- Direct scratching complications
- Infections (more common in atopy)
XIV. Management: Dermatology referral indications
- Diagnosis uncertain
- Pruritus and other symptoms refractory to treatment (especially if impacting sleep, school or work attendance)
- Facial Eczematous Dermatitis refractory to treatment
- Severe Atopic Dermatitis
- Frequent exacerbations of Eczematous Dermatitis
- Severe or recurrent Skin Infections
- Systemic medications (Immunosuppressive Agents) required for maintenance or frequent exacerbations
- Allergic Contact Dermatitis (consider on face, Eyelids and hands)
- Allergen specific Immunotherapy considered (IgE >150 IU/ml)
XV. Management: General Measures
- Chronic disease management
- Key primary measures
- See Pruritus Management
- See Dry Skin Management
- Includes Frequent skin Emollient use is paramount
- Allergan avoidance (limit to products free of perfume and clear of dye)
- Eliminate Environmental Allergens
- Atopic Dermatitis action plan (similar to Asthma Action Plan)
- Everyday Management (green zone)
- See Dry Skin Management
- Skin Lubricants (clear and free Emollients such as eucerin, vanicream, lubriderm) applied daily
- Bathing
- Take a daily, 5-10 min bath or shower with lukewarm water, soap-free cleanser (e.g. cetaphil)
- Pat dry after bathing and apply Skin Lubricant within 3 minutes
- Flare-Up Management (yellow zone)
- Continue green zone management
- Apply Topical Corticosteroid to affected areas twice daily
- Apply topical Calcineurin Inhibitor (e.g. Tacrolimus) to affected areas twice daily
- Severe Flare-Up, Infection or other complication (red zone)
- Continue green zone and yellow zone management
- Contact medical provider
- Everyday Management (green zone)
- Infection Control
- Keep Fingernails short and clean
- Staphylococcus aureus colonization in 90% of Eczema
- Treat superinfection (Impetigo) as needed
- Consider intranasal Bactroban to reduce seeding
- Consider twice weekly dilute bleach bath
- Use 1/2 cup regular bleach (6%) in 40 gallons of water (half full standard bathtub)
- Feeding Changes (Very controversial and NOT recommended)
- Food allergan testing is associated with high False Positive Rates and unnecessary restrictive diets
- Common Antigens related to Eczema
- Milk, Soy, Egg, Peanut, Wheat
- Uncertain whether diet changes improve Eczema
- Consider eliminating for 1 month above Antigens
- Consider starting with cow's milk elimination
- Consider Soy-based formula if persists
- Consider formal Allergy Testing
XVI. Management: Topical Corticosteroids for Exacerbation
- Consider instead of or in combination with alternative agents (e.g. Tacrolimus Ointment)
-
General
- Limited use only for exacerbations
- Avoid Under-treatment
- Consider applying only at night (but typically applied twice daily)
- Start early for exacerbations
- Treat all palpable areas
- Medium potency Corticosteroids appear as effective as low potency Corticosteroids with fewer adverse effects
- However, medium and high potency steroids are more effective than low potency steroids
- Lax (2022) Cochrane Database Syst Rev (3): CD013356 [PubMed]
- Ointments are preferred
- Better tolerated (less burning)
- Allergic Reaction to ointment base less common
- Helps moisten very Dry Skin
- Mild Exacerbation
- Use for 3-4 days only
- Low potency Topical Steroid (e.g. Hydrocortisone 2.5% or Desonide 0.05%)
- Moderate Exacerbation
- Taper over 2 weeks
- Use twice daily for 7 days, then
- Use once daily for 7 days
- For Face and Groin
- Limit to Level 5 Topical Corticosteroid or less
- Hydrocortisone (0.5%, 1%, 2.5%)
- For Eyelid
- Tridesilon 0.05% or Aclovate 0.05% ointment or cream applied twice daily for 5-10 days
- Consider Tacrolimus 0.1% ointment or Pimecrolimus 1% cream for refractory cases
- Risk of malignancy with longterm use (see below)
- For body (medium potency)
- Hydrocortisone valerate 0.2% (Westcort)
- Triamcinolone Acetonide 0.1% (Kenalog)
- Taper over 2 weeks
- Severe Exacerbation
- High Potency Topical Steroids
- Fluocinonide 0.05% (Lidex)
- Amcinonide 0.1% (Cyclocort)
- Try to avoid Systemic Corticosteroids
- Consider maintenance Topical Steroid
- Low potency Topical Steroid daily or
- Medium to High potency steroid twice weekly (e.g. weekend only)
- High Potency Topical Steroids
XVII. Management: Refractory to Corticosteroids
- Anti-infective agents
- See Dilute bleach baths as above
- Indication: Impetigo type superinfection
- Staphylococcus aureus coverage
- Herpes Simplex Virus (HSV) coverage if suspected (see Eczema herpeticum under complications)
-
Systemic Corticosteroids
- Indicated
- Severe Eczema exacerbations
- Refractory to high potency Topical Steroid
- Precautions
- Limit use to 1-2 weeks
- Works too well (Derails Topical Steroid treatment)
- Indicated
- Miscellaneous agents
- Ultraviolet Phototherapy
- Narrow Band UV B Phototherapy
- PUVA has also been used
- Indicated in widespread refractory Atopic Dermatitis
- Accolate 20 mg orally twice daily
- Ultraviolet Phototherapy
- Monoclonal Antibodies
- General
- Antiinflammatory, injectable monoclonal antibodies self-administered every other week
- Unlike other Biologic Agents, does not increase serious infection risk or require lab monitoring
- Risk of Corneal Inflammation or Conjunctivitis (return for Eye Pain or Vision change)
- Dupilumab (Dupixent)
- Injectable Monoclonal Antibody for age >6 years in refractory Eczema (also Asthma, Nasal Polyps)
- Approved in 2022 for age >6 months with severe Eczema
- Effective, but very expensive ($3000/month)
- Longest track record for Monoclonal Antibody use in Eczema
- Ariens (2018) Ther Adv Chronic Dis 9(9): 159-70 [PubMed]
- Injectable Monoclonal Antibody for age >6 years in refractory Eczema (also Asthma, Nasal Polyps)
- Tralokinumab (Adbry)
- Antiinflammatory, injectable Monoclonal Antibody similar to Dupilumab (Dupixent)
- Only approved for use in adults
- Costs $3300/month in 2022
- References
- (2022) Presc Lett 29(3): 18
- General
-
Calcineurin Inhibitors (topical)
- Highly effective agents
- Risk of Skin Malignancy or Lymphoma with prolonged use (FDA black box warning)
- Tacrolimus Ointment (Protopic)
- Tacrolimus 1% is approved for adults only, and is as effective as potent Topical Corticosteroids
- Tacrolimus 0.03% is approved for age 2 years old and older
- Pimecrolimus Cream (Elidel)
- Weaker, but may be better tolerated than the Tacrolimus Ointment
- Pimecrolimus 1% cream is approved for age 2 years and older
-
Janus Kinase Inhibitor (JAK Inhibitor)
- General
- JAK Inhibitors suppress Cytokines and reduce inflammation and Pruritus
- Requires laboratory monitoring including Serum Creatinine
- Associated with serious adverse effects (cancer risk, venous thrombosis)
- Drug Interactions
- Ruxolitinib (Opzelura)
- Topical JAK Inhibitor
- FDA approved for mild to moderate Eczema
- Limit to third-line therapy when refractory to other measures
- Preparations: 1.5% cream ($2000 per 60 grams in 2021)
- Risk of Shingles, serious infections and Nonmelanoma Skin Cancer
- Systemic JAK Inhibitors also risk cancer and thrombosis (10% of Opzelura is absorbed)
- Abrocitinib (Cibingo)
- Oral JAK Inhibitor indicated for adults with Eczema
- Cost $4900/month in U.S. 2022
- Upadacitinib (Rinvoq)
- Oral JAK Inhibitor indicated for age >12 years with Eczema
- Cost $5700/month in U.S. 2022
- General
- Phosphodiesterase 4 Inhibitor
- Crisaborole Ointment (Eucrisa)
- Phosphodiesterase 4 Inhibitor
- Adjunct to moderate Eczema refractory to Corticosteroids for age >2 years old
- Apply in thin layer twice daily
- Expensive ($700/month)
- Paller (2016) J Am Acad Dermatol 75(3):494-503 +PMID: 27417017 [PubMed]
- Crisaborole Ointment (Eucrisa)
- Other Immunosuppressants and Antiinflammatory Agents (Topical and systemic agents)
- Cyclosporine (Sandimmune)
- Azathioprine (Imuran)
- Methotrexate
- Hydroxyquinolone
- Tar Preparations
XVIII. References
- (2022) Presc Lett 29(3): 18
- Claudius and Behar in Herbert (2020) EM:Rap 20(8): 5-7
- Kaplan (2001) CMEA Medicine Lecture, San Diego
- Berke (2012) Am Fam Physician 86(1): 35-42 [PubMed]
- Burks (1998) J Pediatr 132(1): 132-6 [PubMed]
- Drake (1995) Arch Dermatol 131:1403-8 [PubMed]
- Frazier (2020) Am Fam Physician 101(10): 590-8 [PubMed]
- Krakowski (2008) Pediatrics 122(4): 812-24 [PubMed]
- Reitamo (2000) Arch Dermatol 136:999-1006 [PubMed]