atopic%20dermatitis
ATOPIC DERMATITIS
Atopic dermatitis or atopic eczema is a chronic, relapsing, familial, symmetric and pruritic inflammatory skin disease that commonly presents during early infancy and childhood, but can persist or start in adulthood.
It is commonly associated with elevated serum immunoglobulin E levels and a personal or family history of allergies, allergic rhinitis and asthma.
It is one of the most common skin diseases afflicting both children and adults.

Pharmacotherapy

Topical Corticosteroids

  • Used as 1st-line treatment for mild to severe atopic dermatitis and when non-pharmacological interventions have been unsuccessful 
  • Rapid symptomatic relief for acute flare-ups; also used for prevention of relapses
  • Choice of product will depend on severity of flare-up, distribution and site of lesions, patient’s age and preference, and other factors eg humidity
  • Anti-inflammatory and antipruritic activity through several mechanisms
    • Alteration in leukocyte number and activity
    • Suppression of mediator release (histamine, prostaglandins)
    • Enhanced response to agents that increase cyclic adenosine monophosphate (prostaglandin E2 and histamine via the histamine-2 receptor)
  • Follow the recommended restrictions regarding intensity and duration of use especially in children on delicate skin areas (eg face, neck and skin folds)
    • Intermittent use in combination with moisturizers is historically the standard therapy for atopic dermatitis
    • Continuous use can lead to adverse effect
  • Available in different potencies from mildly potent to very potent
    • Potency is also affected by the vehicle the product is formulated in (eg ointment, cream, lotion in decreasing order of efficacy)
    • Potency of topical corticosteroid does not relate to percentage stated (eg Hydrocortisone 2.5% versus Betamethasone dipropionate 0.05%)
    • Least potent but effective product should be used, especially if for long-term use
    • May use mid- and high-potency preparations (except when lesions are on face, groin or axillae) to control acute flares and then follow with lower potency preparations after clinical improvement is seen
    • Rebound flaring can occur if higher potency preparations are discontinued abruptly
    • A gradual decrease in potency should follow use of higher potency preparations
    • Therapy-resistant lesions may require potent topical corticosteroid used under occlusion

Solutions

  • Useful for the scalp or other hirsute areas
  • Alcohol content may be irritating when used on inflamed lesions

Lotions

  • Useful for minimal application to a large area or on hirsute areas
  • May also be used on exudative lesions and in hairy areas
Creams
  • Usually preferred for moist/weeping lesions
  • May be preferred during periods of excessive heat or humidity
  • Easier to apply but may be less effective

Ointments

  • Generally used for dry, scaly or lichenified lesions or if a more occlusive effect is needed (most occlusive vehicle)
  • Usually less additives are used
  • Evaporative losses are decreased

Systemic Corticosteroids

  • Short-term treatment (up to 1 week) should only be considered in treatment-resistant atopic dermatitis, acute severe exacerbations and as a bridge therapy to other steroid-sparing systemic treatments
  • Recommended dose: 0.5 mg/kg body weight 
  • Improve lesions but rebound flare-up usually occurs upon discontinuation
  • Use short-term and decrease chance of rebound effect by tapering oral form slowly while increasing topical corticosteroid treatment and continuously hydrating the skin
  • Various oral corticosteroids are available. Please see prescribing information for specific formulations in the latest MIMS.

Calcineurin Inhibitors - Topical Immunomodulators

  • Steroid-sparing agents for acute and maintenance therapy, topical calcineurin inhibitors inhibit inflammatory cytokine transcription in activated T cells and other inflammatory cells through inhibition of calcineurin
  • May be used on all body locations for extended periods of time, especially the face, hands and feet
  • All preparations are of a standard potency
  • There is no evidence of causal link between the use of calcineurin inhibitors and cancer
  • Preferred over topical corticosteroids when atopic dermatitis is unresponsive to steroid therapy, with presence of atrophy or telangiectasia secondary to steroid use, when affected areas are either the face, anogenital area, and/or skin folds, and for long-term treatments
  • Also used in patients with inadequate response to other topical therapeutic agents or when such treatments are not advised

Pimecrolimus

  • Safety and efficacy have been shown in children >2 years of age and adults with mild-moderate atopic dermatitis
    • Pruritus relief has been seen as early as day 3 of use; does not cause atrophy
    • Prevents flare-ups and results in significant steroid-sparing effect when used for up to 12 months
  • When used in early stages of disease, it has shown to be therapeutically advantageous over typical moisturizers plus topical corticosteroids in long-term use

Tacrolimus

  • Rapidly decreases the signs and symptoms of atopic dermatitis in adults and children >2 years of age
    • Improvement is seen within 3-7 days of therapy and sustained for at least 12 months
    • Well-tolerated with transient skin burning/irritation; less incidence of atrophy compared to steroids
  • Studies have confirmed the efficacy of Tacrolimus 0.03% compared to low-potency topical corticosteroids in children and the efficacy of Tacrolimus 0.1% compared to mid-potency topical corticosteroids in adults

Biologic Therapy

Dupilumab

  • A human immunoglobulin G4 monoclonal antibody approved for use in adult patients with moderate to severe atopic dermatitis uncontrolled by 1st-line treatments and who are candidates for systemic therapy
  • Binds to the interleukin-4Ra subunit thereby inhibiting interleukin-4 and interleukin-13 cytokine-induced responses which includes proinflammatory cytokine, chemokines and IgE release
  • Combination with emollients and as-needed topical anti-inflammatory agents is recommended

Other Biologicals

  • Further studies are needed to prove the efficacy of Nemolizumab, Rituximab, Mepolizumab, Omalizumab, and Ustekinumab for atopic dermatitis
    • Trial treatment with Mepolizumab may be considered in select patients unresponsive to standard therapies
    • The following biologic agents are being studied for atopic dermatitis: Lebrikizumab, Nemolizumab, Upadacitinib, Tralokinumab, Tezepelumab

Immunosuppressants

Azathioprine

  • Used for severe/refractory disease unresponsive or with contraindications to Ciclosporin therapy
  • Thiopurine methyltransferase (TMPT) levels should be monitored while patient is on Azathioprine to test for myelosuppression
  • Most children respond to low doses
  • There is increasing evidence supporting its efficacy in severe refractory atopic dermatitis
  • May cause nausea, fatigue, myalgia, liver dysfunction and bone marrow depression in patients deficient in thiopurine methyltransferase

Ciclosporin (Cyclosporin A)

  • First-line option for short-term use in chronic, severe refractory disease in adults who require systemic immunosuppressive treatment
    • Condition tends to return after discontinuation of therapy but not always at the original severity level
  • May be used in children and adolescents with refractory or severe disease
  • Long-term use is not justified because of risks of hypertension and renal and liver dysfunction
  • Various oral immunosuppressants are available. Please see prescribing information for specific formulations in the latest MIMS

Methotrexate

  • May be considered for severe/refractory disease unresponsive or with contraindications to Ciclosporin therapy
  • Studies showed that efficacy of Methotrexate for atopic dermatitis is comparable to that of Azathioprine and Ciclosporin

Mycophenolate mofetil

  • May be considered for severe/refractory disease unresponsive or with contraindications to Ciclosporin therapy
Phosphodiesterase type-4 (PDE-4) Inhibitor
Apremilast
  • May be considered in patients with moderate to severe atopic dermatitis unresponsive to standard treatments but further studies are needed to establish its efficacy and safety
Crisaborole
  • Approved in the US for mild to moderate atopic dermatitis in patients 2 years old and older
    • Studies showed improvement in symptoms (ie erythema, induration, oozing) with Crisaborole use
Antihistamines
  • Oral sedating antihistamines are typically used for soporific effect to facilitate sleep and to prevent increase of itch intensity at night
  • Studies of oral non-sedating antihistamines have shown variable results in controlling pruritus; however, they may be useful in a small group of patients with associated urticaria
  • Topical antihistamines are usually not helpful in relieving pruritus and may cause allergic contact dermatitis
  • Various oral antihistamines are available. Please see prescribing information for specific formulations in the latest MIMS
Alitretinoin
  • A derivative of Isotretinoin with anti-inflammatory effects used for severe chronic hand atopic dermatitis unresponsive to 1st-line treatments
Allergen-specific Immunotherapy
  • May be considered for select patients with severe disease with house dust mite, birch or grass pollen sensitization, and concomitant history of clinical exacerbation after exposure or positive atopy patch test
Skin Infections
  • Clinical infections at treatment sites should be cleared before starting anti-inflammatory agents
  • May need to treat reservoirs of the disease to prevent recurrence (eg nose, groin)
  • Various antibiotics, antivirals and antifungals are available. Please see prescribing information for specific formulations in the latest MIMS

Bacterial Infections

  • Staphylococcus aureus is commonly cultured from eczematous skin and is often the cause of localized infections
  • Short-term topical therapy
    • May be used to treat localized areas
    • Fusidic acid, Mupirocin, Neomycin and Retapamulin are treatment options
    • Neomycin may cause allergic contact dermatitis
    • Retapamulin is recommended for children >9 months
  • Oral therapy
    • Usually necessary to treat widespread infected lesions
    • Anti-staphylococcal penicillins, macrolides, 1st- and 2nd-generation cephalosporins, and Clindamycin are treatment options

Viral Infections

  • Patients may develop secondary herpes infections inclusive of eczema herpeticum and Kaposi’s varicelliform eruption and may require systemic Acyclovir or Valaciclovir treatment in a hospital setting
  • Topical agents such as KOH, Cantharidin, Tretinoin, or Cidofovir and physical treatments such as cryotherapy and curettage, may be used for eczema molluscatum

Fungal Infections

  • May be considered as a possible complication of atopic dermatitis
  • Antifungal therapy (eg topical Ketoconazole or Ciclopirox olamine, systemic Itraconazole or Fluconazole) may be considered in patients with head and/or neck involvement or with IgE-sensitization to Malassezia spp
  • Superficial dermatophytosis and Pityrosporum ovale may be treated with systemic or topical antifungals

Other Pharmacotherapeutic Options:

  • Further studies are needed to prove the efficacy of probiotics, topical sodium cromoglycate, vitamin D, Tofacitinib, mast cell stabilizers and leukotriene antagonists (eg Montelukast) in atopic dermatitis

Non-Pharmacological Therapy

Avoidance of Trigger Factors

  • Avoid foods identified as allergens in controlled food challenges
  • Avoidance of aeroallergens (eg house dust mites, may result in improved symptoms)
    • Use dust mite-proof encasings on pillows, mattresses and box springs
    • Wash bedding weekly in hot water (>58°C)
    • Remove bedroom carpeting and curtains
    • Decrease indoor humidity to levels below 60%
    • Evidence suggests that allergen-specific immunotherapy may be an option in treating select patients with sensitivity to aeroallergens
  • In most cases, trigger factors cannot be specifically identified
    • Apply holistic approach to avoidance since trigger factors are usually multiple

Common Trigger Factors

  • Wool clothing, pollen, extreme temperature, sweat, products with perfumes or preservatives, foods, cigarette smoke and animal dander

Psychological Factors

  • Emotional factors (eg anxiety, stress and anger) cause disease exacerbation, induce immune activation and increase pruritus and scratching
  • Psychological evaluation and counseling should be considered in patients who have difficulty with emotional triggers or who have psychological problems

Skin Care

  • Hydration of skin with emollients is essential to treatment of atopic dermatitis

Bathing

  • Soap substitutes with minimal defatting activity, moisturizer-containing, fragrance-free, hypoallergenic, and a neutral to low pH are preferred
  • If possible, limit soap use to hands, feet, genitalia, axillae
  • Limit bathing to once daily for 5-10 minutes using warm water
  • Pat dry after bath and apply moisturizer or bath oils within 2 minutes of bath
  • Studies have shown a decrease in bacterial infection (eg staphylococcal, methicillin-resistant Staphylococcus aureus), disease severity, and flare-ups in patients taking regular bleach baths (1:1200 dilution of 6% hypochlorite bleach; 10-minute soak, 3x/week)
    • Bleach baths with intranasal Mupirocin are highly recommended for patients with moderate-severe disease with recurrent secondary bacterial infection
    • Topical antiseptic agents (eg Sodium hypochlorite 0.005% bath) may be considered in patients with chronic, treatment-resistant disease
  •  Salt baths may also be used to help shed dead keratin materials from the skin
  • Oatmeal products added to bath may be soothing but do not increase water absorption by the skin
  • Thermal spring water balneotherapy may be considered in patients with mild to moderate disease
  • Topical medications are best applied after bathing because of greater penetration of hydrated skin
  • Various products are available. Please see prescribing information for specific formulations in the latest MIMS

Moisturizers

  • Water-in-oil emollients are preferred; occlusive agents and humectants also used
    • Useful for the treatment of active disease and both prevention and maintenance therapy
    • Helps reestablish and preserve the stratum corneum
  • Effects:
    • Emollients (eg Glycerol stearate, Lanolin, Soy sterols) provide lubrication and helps soften skin surface
    • Occlusive agents (eg Dimethicone, Mineral oil, Petrolatum) provide a physical barrier against water evaporation
    • Humectants (eg Urea, Glycerol, Lactic acid) help retain moisture in
  • A comparative review of different clinical studies on moisturizers revealed that proper use reduces pruritus, reduces topical corticosteroid use, and prevents flares and recurrences
    • Clinically significant reduction in disease severity with moisturizer use compared to no moisturizers was seen
    • Moisturizer combined with Fluticasone propionate applied 2x/week was more effective in preventing flares compared to moisturizers alone
    • Better efficacy was noted in patients who used topical active treatment combined with moisturizers compared to using topical active treatment alone 
  • Patient preference and treatment area will determine formula used in moisturizers [eg Ceramides, Hydroxypalmitoyl sphinganine, Palmitoylethanolamide (PEA), Liquid paraffin, Mineral oils, Glycerin, Hyaluronic acid, Shea (Butyrospermum parkii) butter, Telmesteine, Glycyrrhetinic acid, Lactic acid]
    • Glycyrrhetinic acid has anti-inflammatory properties that helps reduce pruritus
    • Urea-containing moisturizers reduce rate of flares but may cause transient burning and stinging after application
    • Oat- and Glycerol-containing moisturizers also reduce rate of flares but with lesser side effects and lessens the use of topical corticosteroids
    • The anti-inflammatory and antibacterial properties of Licochalcone contained in some moisturizers are comparable to the efficacy of combination therapy of moisturizers and 1% Hydrocortisone acetate cream
  • Should be applied all over at least twice daily regardless of the presence of active dermatitis
  • Avoid products with preservatives or fragrances; if product stings, seek expert advice
  • Reports of studies suggest that the use of emollients in infants might prevent atopic dermatitis development in high-risk patients
  • Various products are available. Please see prescribing information for specific formulations in the latest MIMS.

Wet Wrap Therapy

  • May be used for chronic and refractory lesions or for moderate-severe weeping lesions
    • Cools inflamed skin, maintains hydration, and decreases scratching
    • Can help reduce water loss and disease severity in patients with moderate-severe atopic dermatitis
  • Combined with topical corticosteroids can be effective in treating refractory cases

Phototherapy

  • Considered in patients with recalcitrant disease or when 1st-line therapy with topical agents has been unsuccessful
  • Broad-band UVB and UVA, narrow-band UVB and UVA-1 or combined UVA and UVB can be useful
    • Treats chronic lichenified forms of moderate-severe disease; high doses of UVA-1 may be given for acute flares
    • Effectively reduces colonization of S aureus and Malassezia sp and mediate cytokine production
  • Photochemotherapy with Psoralens and UVA should be restricted to patients with widespread severe atopic dermatitis
  • May be combined with corticosteroids and emollients in phases of acute flares and to prevent future flare-ups
  • Relapse after therapy cessation frequently occurs
  • Adverse reactions:
    • Short-term: Erythema, skin pain, pigmentation, itching
    • Long-term: Premature skin aging and potential cutaneous malignant diseases

Immunoadsorption

  • Treatment option for patients with severe, treatment-refractory disease with high serum IgE levels
  • An extracorporeal technique that utilizes immunoadsorption columns to deplete the IgE serum level that may lead to the reduction of disease activity
  • Studies showed significant decrease in SCORAD and disease activity improvement
Editor's Recommendations
Most Read Articles
20 Sep 2019
Both adalimumab and phototherapy increase overall and skin-related quality of life (QoL) in psoriasis patients, although phototherapy appears to be better, a recent study has shown.
Roshini Claire Anthony, 24 Sep 2019

Once-daily oral omadacycline demonstrated noninferiority to twice-daily linezolid in treating acute bacterial skin and skin structure infections (ABSSSI), the phase III OASIS-2* study showed.