Atopic Dermatitis

See Also

Epidemiology

Inherited sensitive skin (Atopic Patient)
Incidence
1. Affects 11-12% of children in U.S. and 5-7% of adults
2. Affects 17.8 Million people in U.S.
3. Most cases go undiagnosed
Onset
1. Typically presents with first 2 years of life (most often within first 6 months)
2. Diagnosed in first 5 years in 90% of patients
3. Many cases remit by age 3-5 years

Pathophysiology

Disrupted Epidermis due to underlying filaggrin Protein defect
1. Filaggrin Gene (FLG) Defect
Allows for Dermis immune cell exposure to environmental Antigens
1. IgE Antibody response
2. Increased T-helper 2 subtype activity (stimulate by Interleukin 4 and 13)
3. Antigen-specific T-Cells secrete IgE binding factors
Leads to inflammatory response
1. Intense itching ensues due to a low itch threshold to provocative factors
2. Scratching leads to further inflammation, resulting in a spiraling itch-scratch cycle

Types

Acute Atopic Dermatitis
1. Weeping, crusting lesions with overlying Vesicles
Subacute Atopic Dermatitis
1. Dry, Scaling, erythematous Papules and Plaques or
2. Pityriasis Alba
Chronic Atopic Dermatitis
1. Lichenification (e.g. Lichen Simplex Chronicus)

Associated Conditions
Atopic Triad (Family History)

Eczematous Dermatitis (Atopic Dermatitis)
Allergic Rhinitis
Asthma
1. Lifetime asthma Prevalence in patients with Atopic Dermatitis: 30%

Provocative Factors

Sweating
Bacterial colonization
Rough clothing
Chemical irritants
Emotional Stress
Foods
1. Cow's milk
2. Wheat
3. Eggs
4. Soy
5. Peanut and tree nuts
6. Fish
Environment
1. Dust or mold
2. Cat dander
3. Temperature changes
4. Low humidity

Symptoms
Pruritus

Described as "The itch that rashes" (when scratched)

Signs
Infants and young children

Dermatitis characteristics
1. Erythema and Edema
2. Exudate
3. Crusting
4. Scaling
Dermatitis Location
1. Face (especially cheeks, hairline and behind ears)
2. Scalp
3. Trunk
4. Extensor surface of arms and legs

Signs
Older children and adults

Dermatitis characteristics
1. Similar Eczematous skin changes as with infants
2. "Hot and sweaty fossa and folds"
3. Excoriated lesions (pruritic)
Dermatitis Location
1. Flexor wrists and ankles
2. Antecubital fossa
3. Popliteal fossa
4. Hands
5. Upper Eyelid Inflammation (erythema, fine scale and lichenification)
6. Anogenital area

Diagnosis
American Academy of Dermatology Criteria

Major Criteria (all required)
1. Chronic or relapsing history
2. Eczema
3. Pruritus
4. Age-specific patterns
  1. Infants: Face, neck and extensor surfaces
  2. Children: Flexor surface involvement
  3. Axillary region and groin spared
Common Additional Findings (optional, but often observed in atopic)
1. Atopy History (or Family History)
2. Onset at early age
3. IgE Reactivity
4. Xerosis
Non-specific Other Findings
1. Ocular or periorbital changes
2. Vascular findings
  1. Facial pallor
  2. Dermatographism
3. Dry Skin findings
  1. Keratosis Pilaris
  2. Pityriasis Alba
  3. Ichthyosis
  4. Hyperlinear palms
4. Sequelae of scratching
  1. Lichenification (e.g. Lichen Simplex Chronicus)
  2. Prurigo Nodularis
  3. Perifollicular accentuation
References
1. Eichenfield (2014) J Am Acad Dermatol 70(2): 338-51 [PubMed]

Diagnosis
Diagnostic Tool

Pruritus (Required) and
Additional Criteria (3 or more of the following)
1. Asthma or Allergic Rhinitis history
2. Flexor fold involvement
3. Flexor fold dermatitis visible on exam
4. Generalized Dry Skin
5. Onset of rash before age 2 years
Efficacy
1. Test Sensitivity: 95%
2. Test Specificity: 97%
References
1. Brenninkmeijer (2008) Br J Dermatol 158(4): 754-65 [PubMed]

Differential Diagnosis
Varied Atopic Dermatitis presentations present a broad differential

See Eczematous Skin Lesion
See Pruritus
Any age
Children
Older Adults
1. Cutaneous T-Cell Lymphoma (older adults)
2. Dermatitis Herpetiformis
3. Nummular Eczema
4. Psoriasis
References
1. Leung (2003) Lancet 361(9352): 151-60 [PubMed]

Complications (associated with intense scratching)

Secondary infection
1. Impetigo
2. Cellulitis
3. Eczema herpeticum (Kaposi varicelliform eruption)
  1. Painful papulovesicular rash spread over localized skin region
  2. Skin infected by Herpes Simplex Virus infection
Direct scratching complications
1. Lichen Simplex Chronicus
2. Prurigo Nodularis
Infections (more common in atopy)

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)

Management
General Measures

Chronic disease management
Key primary measures
1. See Pruritus Management
2. See Dry Skin Management
  1. Includes Frequent skin Emollient use is paramount
3. Allergan avoidance (limit to products free of perfume and clear of dye)
4. Eliminate Environmental Allergens
Atopic Dermatitis action plan (similar to Asthma Action Plan)
1. Everyday Management (green zone)
  1. See Dry Skin Management
  2. Skin Lubricants (clear and free Emollients such as eucerin, vanicream, lubriderm) applied daily
  3. Bathing
    1. Take a daily, 5-10 min bath or shower with lukewarm water, soap-free cleanser (e.g. cetaphil)
    2. Pat dry after bathing and apply Skin Lubricant within 3 minutes
2. Flare-Up Management (yellow zone)
  1. Continue green zone management
  2. Apply Topical Corticosteroid to affected areas twice daily
  3. Apply topical Calcineurin Inhibitor (e.g. Tacrolimus) to affected areas twice daily
3. Severe Flare-Up, Infection or other complication (red zone)
  1. Continue green zone and yellow zone management
  2. Contact medical provider
Infection Control
1. Keep Fingernails short and clean
2. Staphylococcus aureus colonization in 90% of Eczema
3. Treat superinfection (Impetigo) as needed
4. Consider intranasal Bactroban to reduce seeding
5. Consider twice weekly dilute bleach bath
  1. Indicated in moderate to severe Eczema (NNT 10 to improve symptoms within 4 weeks)
  2. Not effective in mild Eczema
  3. Use 1/2 cup regular bleach (6%) in 40 gallons of water (half full standard bathtub)
Feeding Changes (Very controversial and NOT recommended)
1. Food allergan testing is associated with high False Positive Rates and unnecessary restrictive diets
2. Common Antigens related to Eczema
  1. Milk, Soy, Egg, Peanut, Wheat
3. Uncertain whether diet changes improve Eczema
4. Consider eliminating for 1 month above Antigens
  1. Consider starting with cow's milk elimination
  2. Consider Soy-based formula if persists
  3. Consider formal Allergy Testing

Management
Topical Corticosteroids for Exacerbation

Consider instead of or in combination with alternative agents (e.g. Tacrolimus Ointment)
General
1. Limited use only for exacerbations
2. Avoid Under-treatment
3. Consider applying only at night (but typically applied twice daily)
4. Start early for exacerbations
5. Treat all palpable areas
6. Medium potency Corticosteroids appear as effective as low potency Corticosteroids with fewer adverse effects
  1. However, medium and high potency steroids are more effective than low potency steroids
  2. Lax (2022) Cochrane Database Syst Rev (3): CD013356 [PubMed]
7. Ointments are preferred
  1. Better tolerated (less burning)
  2. Allergic Reaction to ointment base less common
  3. Helps moisten very Dry Skin
Mild Exacerbation
1. Use for 3-4 days only
2. Low potency Topical Steroid (e.g. Hydrocortisone 2.5% or Desonide 0.05%)
Moderate Exacerbation
1. Taper over 2 weeks
  1. Use twice daily for 7 days, then
  2. Use once daily for 7 days
2. For Face and Groin
  1. Limit to Level 5 Topical Corticosteroid or less
  2. Hydrocortisone (0.5%, 1%, 2.5%)
3. For Eyelid
  1. Tridesilon 0.05% or Aclovate 0.05% ointment or cream applied twice daily for 5-10 days
  2. Consider Tacrolimus 0.1% ointment or Pimecrolimus 1% cream for refractory cases
    1. Risk of malignancy with longterm use (see below)
4. For body (medium potency)
  1. Hydrocortisone valerate 0.2% (Westcort)
  2. Triamcinolone Acetonide 0.1% (Kenalog)
Severe Exacerbation
1. High Potency Topical Steroids for no more than 4 weeks (and not on face, groin, skin folds)
  1. Fluocinonide 0.05% (Lidex)
  2. Amcinonide 0.1% (Cyclocort)
2. Try to avoid Systemic Corticosteroids
3. Consider maintenance Topical Steroid
  1. Low potency Topical Steroid daily or
  2. Medium to High potency steroid twice weekly (e.g. weekend only)
    1. Berth-Jones (2003) BMJ 326:1367-70 [PubMed]

Management
Refractory to Corticosteroids

Anti-infective agents for Impetigo or other skin superinfection
1. See Dilute bleach baths as above
2. Indicated only in active Skin Infection
3. Staphylococcus aureus coverage
4. Herpes Simplex Virus (HSV) coverage if suspected (see Eczema herpeticum under complications)
Systemic Corticosteroids
1. Indicated
  1. Severe Eczema exacerbations
  2. Refractory to high potency Topical Steroid
2. Precautions
  1. Most guidelines recommend avoiding Systemic Corticosteroids if at all possible
  2. Limit use to 1-2 weeks
  3. Works too well (Derails Topical Steroid treatment)
Calcineurin Inhibitors (topical)
1. Highly effective agents applied daily
2. Risk of Skin Malignancy or Lymphoma with prolonged use (FDA black box warning)
3. Tacrolimus Ointment (Protopic)
  1. Tacrolimus 1% is approved for adults only, and is as effective as potent Topical Corticosteroids
  2. Tacrolimus 0.03% is approved for age 2 years old and older
4. Pimecrolimus Cream (Elidel)
  1. Weaker, but may be better tolerated than the Tacrolimus Ointment
  2. Pimecrolimus 1% cream is approved for age 2 years and older
Miscellaneous agents
1. Ultraviolet Phototherapy
  1. Narrow Band UV B Phototherapy
  2. PUVA has also been used
  3. Indicated in widespread refractory Atopic Dermatitis
2. Leukotriene Receptor Antagonist
  1. Zafirlukast (Accolate) 20 mg orally twice daily

Management
Biologic Agents and Other Specialty Prescribed Agents

Monoclonal Antibodies
1. General
  1. Antiinflammatory, injectable monoclonal antibodies self-administered every other week
  2. Unlike other Biologic Agents, does not increase serious infection risk or require lab monitoring
  3. Risk of Corneal Inflammation or Conjunctivitis (return for Eye Pain or Vision change)
2. Dupilumab (Dupixent)
  1. Injectable Monoclonal Antibody for age >6 years in refractory Eczema (also Asthma, Nasal Polyps)
    1. Approved in 2022 for age >6 months with severe Eczema
  2. Effective, but very expensive ($3000/month)
  3. Longest track record for Monoclonal Antibody use in Eczema
  4. Ariens (2018) Ther Adv Chronic Dis 9(9): 159-70 [PubMed]
3. Tralokinumab (Adbry)
  1. Antiinflammatory, injectable Monoclonal Antibody similar to Dupilumab (Dupixent)
  2. Only approved for use in adults
  3. Costs $3300/month in 2022
4. References
  1. (2022) Presc Lett 29(3): 18
Janus Kinase Inhibitor (JAK Inhibitor)
1. General
  1. JAK Inhibitors suppress Cytokines and reduce inflammation and Pruritus
  2. Requires laboratory monitoring including Serum Creatinine
  3. Associated with serious adverse effects (cancer risk, venous thrombosis) and carries FDA boxed warning
  4. Drug Interactions
2. Ruxolitinib (Opzelura)
  1. Topical JAK Inhibitor
  2. FDA approved for mild to moderate Eczema
    1. Limit to third-line therapy when refractory to other measures
  3. Preparations: 1.5% cream ($2000 per 60 grams in 2021)
  4. Risk of Shingles, serious infections and Nonmelanoma Skin Cancer
    1. Systemic JAK Inhibitors also risk cancer and thrombosis (10% of Opzelura is absorbed)
3. Abrocitinib (Cibingo)
  1. Oral JAK Inhibitor indicated for adults with Eczema
  2. Cost $4900/month in U.S. 2022
4. Upadacitinib (Rinvoq)
  1. Oral JAK Inhibitor indicated for age >12 years with Eczema
  2. Cost $5700/month in U.S. 2022
Topical Phosphodiesterase 4 Inhibitor
1. Crisaborole Ointment (Eucrisa)
  1. Phosphodiesterase 4 Inhibitor
  2. Adjunct to moderate Eczema refractory to Corticosteroids for age >2 years old
  3. Apply in thin layer twice daily
  4. Expensive ($700/month)
  5. Paller (2016) J Am Acad Dermatol 75(3):494-503 +PMID: 27417017 [PubMed]
Other Immunosuppressants and Antiinflammatory Agents (Topical and systemic agents)
1. Cyclosporine (Sandimmune)
2. Azathioprine (Imuran)
3. Methotrexate
4. Hydroxyquinolone
5. Tar Preparations

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]
Chu (2024) Ann Allergy Asthma Immunol 132(3): 274-312 [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]