Atopic%20dermatitis%20(pediatric) Treatment

Goals of Therapy

• Reduce symptoms
• Prevent exacerbations
• Minimize treatment risks

Management Approach

• Identification and eradication of exacerbating factors
• Restoration of skin barrier function
• Skin hydration
• Patient education
• Pharmacological therapy
  • Topical therapy is the 1st-line treatment for children with atopic dermatitis
  • Choice of therapy is based on patient preference, presence of comorbidities, disease extent, severity and impact on quality of life, presence of secondary infection, and treatment availability, mode of administration, cost and adverse effects

Corticosteroids (Topical)

• Used as 1st-line treatment for mild-severe atopic dermatitis
• Moderately potent and potent corticosteroids should be used for the treatment of clinical exacerbation over short periods of time
• Mildly potent corticosteroids are recommended for maintenance therapy
• Use of super-potent topical corticosteroids is not recommended in children because of increased risk of adverse events
• 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)
• Rapid symptomatic relief of acute flare-ups
• Continuous use can lead to adverse effects, thus recommended restrictions regarding intensity and duration of use on delicate skin areas (eg face, neck and skin folds) should be followed
  • Intermittent use (1-2 times/week) in combination with moisturizers is historically the standard therapy for atopic dermatitis
• May occasionally cause hypersensitivity reactions in non-resolving or worsening atopic dermatitis despite good compliance with application 
• Topical corticosteroids are available in different potencies from mild to very potent
  • Potency is also affected by the vehicle the product is formulated in (eg cream, ointment)
• Choice of product will depend on severity of flare-up, distribution of lesions and other factors (eg humidity)
• Least potent but effective product should be used
• 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 for a short period of time and under close supervision

Calcineurin Inhibitors (Topical)

• Inhibit inflammatory cytokine transcription in activated T cells and other inflammatory cells through inhibition of calcineurin
• 2nd-line therapy for patients with chronic atopic dermatitis unresponsive to, intolerant of, or with contraindications to other topical therapies
  • Helps reduce subsequent flare-ups or relapses with intermittent use
• Equated to medium potency strength of topical corticosteroids 
• Topical calcineurin inhibitor and topical corticosteroid use in a concomitant or sequential manner may be recommended
• 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
• Common side effects: Transient burning, erythema and pruritus
• Avoid the use of these agents in children younger than 2 years of age
• Use only for short periods of time using minimum amount necessary to control symptoms
• Avoid continuous use and avoid use in patients with compromised immune systems

Pimecrolimus

• Safety and efficacy has been shown in children >2 years of age with mild-moderate atopic dermatitis
  • Pruritus relief has been seen as early as day 3 of use
  • 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

• Indicated for moderate-severe atopic dermatitis
  • May be used for up to 1 year without loss of effectiveness, increase in infection risk or other non-application-site adverse effects
  • Well-tolerated with transient skin burning/irritation
• Studies have confirmed the efficacy of Tacrolimus 0.03% compared to low potency topical corticosteroids in children

Crisaborole (Topical)

• A selective phosphodiesterase-4 inhibitor which prevents pro-inflammatory cytokine production
• Approved by the US FDA for the treatment of mild-moderate atopic dermatitis in patients ≥3 months

Biological Agents
Dupilumab

• The first human monoclonal antibody approved for 1st-line treatment of moderate-severe atopic dermatitis for children ≥6 years old unresponsive to topical treatments and cannot tolerate systemic treatments
• Recommended for children ≥12 years with refractory atopic dermatitis and for whom phototherapy is not feasible 
• Significant improvements in disease activity, symptoms, and quality of life were seen in patients given Dupilumab involved in several clinical studies

Tralokinumab

• Recommended for children ≥12 years with moderate to severe atopic dermatitis uncontrolled by topical therapies and are candidates for systemic therapy
• A human, high-affinity IgG4 monoclonal antibody which acts by neutralizing IL-13
• Combination treatment with topical corticosteroids, topical calcineurin inhibitors, and UV light is possible

Other Biological Agents

• Other biologicals undergoing clinical trials or are currently being used as off-label therapy for atopic dermatitis include Baricitinib, Fezakinumab, Lebrikizumab, Mepolizumab, Nemolizumab, Omalizumab, Rituximab, Tezepelumab, Tofacitinib, and Ustekinumab

Skin Infections¹

• Clinical infections at treatment sites should be cleared before starting anti-inflammatory agents
• May need to treat reservoirs of the infection to prevent recurrence (eg nose, groin)

Bacterial Infections

• S aureus is commonly cultured from eczematous skin and is often the cause of localized infections
• Topical therapy
  • May be used to treat mild and localized secondary infection
  • Fusidic acid, Mupirocin, and Retapamulin are treatment options
  • Neomycin may cause allergic contact dermatitis
  • Retapamulin is recommended for children ≥9 months
  • Prolonged use should be avoided to decrease risk of bacterial resistance
• 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 (Kaposi’s varicelliform eruption) and may require systemic Acyclovir treatment in a hospital setting
• Prophylactic oral antiviral agents may be used to suppress recurrent cutaneous herpetic infections

Fungal Infections

• Role of fungi in atopic dermatitis is questionable
• Superficial dermatophytosis and Pityrosporum ovale may be treated with systemic or topical antifungals

Antihistamines¹

• Oral sedating antihistamines may be useful if the patient has comorbidities (allergic rhinitis, urticaria or dermatographism) and sleep disturbance
  • They are best used at bedtime since pruritus is typically worse 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

Systemic Corticosteroids¹

• Should only be considered in treatment-resistant atopic dermatitis
• Most commonly used formulations are Prednisone and Prednisolone for oral and IV administration with dosing based on body weight and tapering course to decrease risk of adrenal suppression
• Routine use in children and adolescents is discouraged but may be used for severe atopic dermatitis with the following conditions:
  • Lack of or with contraindications to other treatment options
  • As a bridge to phototherapy or other systemic therapies
  • For the provision of immediate relief during acute flares
  • When a major life event is anticipated 
• Improves 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
• Decreased linear growth may be observed with long-term administration of systemic corticosteroids in children and adolescents

Systemic Immunosuppressants¹ 

• Minimal effective dose should be applied once response is attained and sustained
• Continued adjunctive therapy allows the use of the lowest dose and duration of systemic agent

Abrocitinib

• Oral Janus kinase (JAK) 1 inhibitor used for the treatment of refractory moderate to severe atopic dermatitis which is inadequately controlled with other systemic drugs (including biologics) or when use of those therapies is not advisable
• May be used with or without topical corticosteroids
• Not recommended to be used in combination with other JAK inhibitors, biologic immunomodulators or with other immunosuppressants
• A large, randomized, safety clinical trial showed an increased risk of malignancy (lymphoma and lung cancer), all-cause mortality (including sudden cardiovascular death), major adverse cardiovascular events (MACE; defined as cardiovascular death, myocardial infarction, and stroke), and thrombosis (including pulmonary embolism and venous and arterial thrombosis) with another JAK inhibitor compared to tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis

Azathioprine

• Used for severe/refractory disease
• Thiopurine methyltransferase (TMPT) levels should be taken pretreatment and while on treatment to determine dose and test for myelosuppression to decrease risk of myelotoxicity
• Monitor hematologic and liver function parameters
• Safer than Ciclosporin and has been used long-term
  • Most patients respond to low doses
• Adverse reactions: Nausea, fatigue, myalgia, liver dysfunction and bone marrow depression in patients deficient in thiopurine methyltransferase

Ciclosporin

• Alternative treatment option for children and adolescents with refractory atopic dermatitis when Dupilumab or phototherapy are not desirable, accessible or effective 
• Effective for short-term use in severe refractory disease
  • Condition tends to return after discontinuation of therapy but not always at the original severity level
•  Long-term use is not justified because of risks of hypertension and renal dysfunction

Methotrexate

• Alternative treatment option for children with severe atopic dermatitis and intolerant or with contraindications to Ciclosporin
• Folate supplementation is recommended during treatment with Methotrexate

Mycophenolate mofetil

• Alternative treatment option for children with severe refractory atopic dermatitis and intolerant or with contraindications to Ciclosporin

Ruxolitinib

• A topical Janus kinase (JAK) inhibitor
• Approved by the US FDA for short-term treatment of mild-moderate atopic dermatitis in immunocompetent patients >12 years of age and unresponsive to other topical therapies

Upadacitinib

• An oral selective and reversible inhibitor of JAK enzymes (preferentially JAK1 or JAK1/3), which are intracellular enzymes involved in the stimulation of hematopoiesis and immune cell function through a signaling pathway
• Used in patients ≥12 years old with refractory moderate to severe atopic dermatitis which is inadequately controlled with other systemic drugs (including biologics) or when use of those therapies is not advisable
• Not recommended to be used in combination with other JAK inhibitors, biologic immunomodulators or with other immunosuppressants

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
  • Vitamin D supplementation and use of prebiotics/probiotics may reduce symptoms but are not routinely recommended

¹Various antibiotics, antifungals and antivirals are available. Please see prescribing information for specific formulations in the latest MIMS.

Avoidance of Trigger Factors

All Irritants

• Lipid solvents (soaps, detergents)
  • New clothes should be laundered before wearing to decrease levels of formaldehyde and other chemicals added
  • When washing, use liquid instead of powder detergent, and do another rinse cycle to remove detergent completely from clothes
• Disinfectants (swimming pool chlorine)
• Occupational irritants
• Household fluids (meats, juices from fresh fruits)

Contact and Aeroallergens

• Furry animals (cats, dogs)
• Molds
• Human dander (dandruff) resulting in overgrowth of yeast
• Dust mites
  • Avoidance include use of dust mite-proof encasings on pillows and mattresses, washing bedding in hot water weekly remove bedroom carpeting and curtains, decrease indoor humidity level by air conditioning, avoid upholstered sofa

Others

• Foods
  • Flaring/occurrence of atopic dermatitis with a specific food may warrant elimination diet in patients with moderate-severe atopic dermatitis
  • Skin prick tests (SPT) and measurement of specific immunoglobulin E (IgE) are used to determine sensitization to a particular food
  • Limited food allergy testing may be considered in children <5 years with moderate-severe atopic dermatitis and disease unresponsive to previous therapies and/or with history or allergic reaction to a specific food
  • Negative results are useful for ruling out suspected allergens
• Climate
  •  Consider temperature and humidity control to avoid increased pruritus due to heat and perspiration
  •  Prolonged sun exposure may increase evaporative losses due to sweating
•  Hormones (menstrual cycle)
•  Psychological factors
  •  Emotional factors (eg anxiety 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 and restoration of skin barrier function are essential in atopic dermatitis treatment
• Regular skin cleansing with the use of soaps, synthetic detergent (syndet) bars, and topical antiseptics and antibiotics helps reduce abnormal microbial colonization to restore the skin microbiome

Bathing¹

• Soap substitutes with minimal defatting activity and a neutral pH are preferred
• Soaking bath or shower daily for 10-15 minutes using warm water and “soak-and-seal” approach not to exceed 2 baths in 1 day
  • “Soak-and-seal” is the immediate application of prescribed topicals and emollients after bathing
  • May also consider using bath oils within the last 2 minutes of bathing
• Topical medications are best applied after bathing because of greater penetration of hydrated skin
• Bleach baths with intranasal Mupirocin may be used for moderate-severe disease with frequent bacterial infections
• Salt baths may be used in patients with heavily impetiginized or ichthyotic skin
• Oatmeal products added to bath may be soothing but do not increase water absorption by the skin

Moisturizers¹

• Effects: 
  • Emollients (eg Glycerol stearate, lanolin, soy sterols) provide lubrication, improve the epidermal barrier, and help soften skin surface
    • Newly developed emollients contain ingredients that positively influence the skin microbiome of atopic dermatitis patients
  • Occlusive agents (eg Dimeticone, Mineral oil, petrolatum) provide a physical barrier against water evaporation
  • Humectants (eg Urea, Glycerol, Lactic acid, pyrrolidone carboxylic acid [PCA]) help retain moisture in the stratum corneum
    • Urea, lactate, PCA and amino acids (eg Arginine) are components of NMF which maintains adequate hydration of the skin thus optimizing the barrier function of the stratum corneum
• 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)
  • 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
  • Glycyrrhetinic acid and Allantoin have anti-inflammatory properties that help reduce pruritus
  • 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
  • Niacinamide and sunflower seed oil improve skin barrier function by reducing transepidermal water loss
  • Olive oil application is not recommended as it may aggravate xerosis and atopic dermatitis
• Emollients should be applied for at least 3 times daily (in the morning and afternoon immediately after bath and at night before bedtime) or in flare-up condition every 3-4 hours
• Avoid products with preservatives or fragrances
• If product stings, it should not be used

Wet Dressings

• May be used on weeping lesions or severely affected areas
  • Discomfort, folliculitis and impetigo reported as common adverse effects
  • 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
  •  Temporary increased systemic absorption of corticosteroids reported

Phototherapy

• Broad-band ultraviolet B (UVB) and ultraviolet A (UVA), narrow-band UVB and UVA-1 or combined UVA and UVB can be useful in atopic dermatitis
• Narrowband UVB is the initial phototherapy of choice due to its safety profile and availability
• Effects include acceleration of wound healing, cell migration and barrier repair, suppression of pro-inflammatory cytokines, and promote antimicrobial peptide production 
• Phototherapy should be avoided in infants and young children
• Photochemotherapy with Psoralens and UVA should be restricted to patients with widespread severe atopic dermatitis
• UV therapy should be reserved for pediatric patients older than 6 years of age who present with severe refractory atopic dermatitis
• A yearly skin exam is recommended if with continued phototherapy
• Relapse following cessation of therapy frequently occurs
• Adverse reactions:
  • Short-term: Erythema, skin pain, pigmentation, itching
  • Long-term: Premature skin aging and potential cutaneous malignant diseases