Atopic dermatitis -Management

How do we treat AD?

Multipronged approach that involves

Elimination of exacerbating factors

Restoration of the skin barrier function and hydration of the skin,

Patient education, and

Pharmacologic treatment of skin inflammation.

CLICK HERE FOR CLINICAL FEATURES AND DIAGNOSIS OF AD

How can we assess severity of AD?

As per NICE guidelines (National Institute for Health and Care Excellence)

Mild – Areas of dry skin, infrequent itching (with or without small areas of redness); little impact on everyday activities, sleep, and psychosocial well-being

Moderate – Areas of dry skin, frequent itching, redness (with or without excoriation and localized skin thickening); moderate impact on everyday activities and psychosocial well-being, frequently disturbed sleep

Severe – Widespread areas of dry skin, incessant itching, redness (with or without excoriation, extensive skin thickening, bleeding, oozing, cracking, and alteration of pigmentation); severe limitation of everyday activities and psychosocial functioning, nightly loss of sleep.

There are various disease severity scores like:

Scoring of Atopic Dermatitis [SCORAD] index,

Eczema Area and Severity Index [EASI], and the Patient-Oriented Eczema Measure [POEM]) and patient quality-of-life measurement scales have been tested and validated for use in clinical trials, but they are not commonly used in clinical practice.

What is the general approach for AD patients?

Patient education and counselling have been shown to improve the clinical symptoms.

It is essential to identify and eliminate triggering factors for AD, both during the period of acute symptoms and on a long-term basis to prevent recurrences.

Patients with AD should use soaps with minimal defatting properties and a neutral pH.

New clothing should be laundered before wearing to decrease levels of formaldehyde and other chemicals.

Residual laundry detergent in clothing may trigger the itch-scratch cycle; using a liquid rather than powder detergent and adding a 2nd rinse cycle facilitates removal of the detergent.

Use of SPF sunscreens should be used.

Avoidance of aeroallergen and food allergen.

What is the use of moisturizers?

Skin hydration is a key component of the overall management of patients with atopic dermatitis.

To maintain skin hydration, emollients should be applied at least two times per day and immediately after bathing or hand washing.

Thick creams, which have a low water content, or ointments (eg, petroleum jelly), which have zero water content, better protect against xerosis, but some patients may complain that they are greasy.

Since atopic skin is deficient in stratum corneum lipids (especially ceramide) and "natural moisturizing factor" (a mixture of hygroscopic amino acids resulting from filaggrin breakdown), moisturizers that contain those ingredients may be beneficial. There are a number of topical moisturizers available in the market by prescription. There are few data demonstrating their efficacy, but one randomized trial suggests that they are no more effective than over-the-counter emollients.

What is the data regarding bathing?

Warm soaking baths or showers using mild or soap-free cleansers should be part of the routine skin care for patients with atopic dermatitis. Some controversy exists concerning the frequency of bathing and whether showering or bathing is preferable in patients with atopic dermatitis.

Most experts recommend a hydrating bath followed by immediate emollient application, but others recommend a shower of short duration.

Till now there are no studies that has clearly supported the above claims by the experts.

Can we use bath additives for AD?

In absence of high-quality studies providing evidence of benefit, bath emollient additives (e.g., liquid paraffin, oils with or without emulsifiers, colloidal oatmeal) are widely used to improve skin hydration in children and adults with atopic dermatitis, especially in Europe, where their use is supported by national and international guidelines.

How do we treat pruritis?

Non-pharmacological therapy

Pharmacological therapy

What is the non-pharmacological therapy?

Proper skin hydration and moisturization

Tepid baths to hydrate and cool the skin followed by application of emollients

Wet wraps can be used.

Occlusive ointments are sometimes not well tolerated because of interference with the function of the eccrine sweat ducts and may induce the development of folliculitis. In these patients, less occlusive agents should be used.

Hydration by baths or wet dressings promotes transepidermal penetration of topical glucocorticoids.

Dressings may also serve as effective barriers against persistent scratching, in turn promoting healing of excoriated lesions.

Wet dressings are recommended for use on severely affected or chronically involved areas of dermatitis refractory to skin care. It is critical that wet dressing therapy be followed by topical emollient application to avoid potential drying and fissuring from the therapy.

Wet dressing therapy can be complicated by maceration and secondary infection and should be closely monitored by a physician.

What are the pharmacological therapies for itching?

Topical steroids and calcineurin inhibitors

Systemic immunosuppressants

Dupilumab

Oral antihistamines

What is the role of oral antihistamines?

Systemic antihistamines act primarily by blocking the histamine H1 receptors in the dermis, thereby reducing histamine-induced pruritus.

Histamine is only one of many mediators that induce pruritus of the skin, so patients may derive minimal benefit from antihistaminic therapy.

Because pruritus is usually worse at night, sedating antihistamines (hydroxyzine, diphenhydramine) may offer an advantage with their soporific side effects when used at bedtime.

Doxepin hydrochloride has both tricyclic antidepressant and H1 - and H2 -receptor blocking effects.

Short-term use of a sedative to allow adequate rest may be appropriate in cases of severe nocturnal pruritus.

Studies of newer, non-sedating antihistamines have shown variable effectiveness in controlling pruritus in AD,

although they may be useful in the small subset of patients with AD and

concomitant urticaria

What are the pharmacological therapies for AD?

Topical steroids

Topical calcineurin inhibitors

Phosphodiesterase inhibitors

Tar preparations

Antihistamines

Systemic steroids

Cyclosporine

Monoclonal antibody therapy

MMF, Methotrexate

Azathioprine

Topical steroids are the cornerstone of therapy of AD.

What are the types of topical steroids?

There are 7 groups based on potency.

How do we prescribe topical steroids?

Mild cases less potent steroids like desonide, hydrocortisone are used

Applied 1-2 per day for 2-4 weeks

 

For moderate AD

Medium to high potency steroid (group 3 and 4) are used. e.g. triamcinolone, betamethasone dipropionate.

n patients with acute flares, super high- or high-potency topical corticosteroids (groups 1 to 3 can be used for up to two weeks and then replaced with lower-potency preparations until the lesions resolve.

The face and skin folds are areas that are at high risk for atrophy with corticosteroids. Initial therapy in these areas should start with a low-potency steroid, such as desonide 0.05% ointment.

High-potency topical corticosteroids are generally avoided in skin folds and on the face. However, limited, brief use (five to seven days) of potent corticosteroids may produce a rapid response, after which patients can be switched to lower-potency preparations.

Use of Topical calcineurin inhibitors:

Non-steroidal immunomodulating agent which do not cause skin atrophy and other steroid related side effects.

They can be used as an alternative to topical corticosteroids for the treatment of mild to moderate atopic dermatitis involving the face, including the eyelids, neck, and skin folds.

Tacrolimus ointment and pimecrolimus cream are applied twice a day.

Tacrolimus comes in two strengths. The 0.1% formulation is appropriate initial therapy for adults (and those >15 years old), and the 0.03% formulation is appropriate for children and for adults who do not tolerate the higher dose.

In patients who do not tolerate tacrolimus because of burning or stinging, pimecrolimus may be better tolerated.

US FDA has approved use of tacrolimus and pimecrolimus for use in children above 2 years of age.

What is the mechanism of action of tacrolimus?

Inhibits cytokine production and alters APCs function in skin.

What are the side effects of tacrolimus?

Pruritis, erythema and transient burning sensation. They are as efficacious as a medium potency steroid.

When are tacrolimus prescribed?

Topical calcineurin inhibitors may be better than topical corticosteroids in the treatment of patients whose AD is poorly responsive to topical steroids, patients with steroid phobia, and those with face and neck dermatitis, in whom ineffective, low-potency topical corticosteroids are typically used because of fears of steroid-induced skin atrophy.

What is the use of Phosphodiesterase inhibitors?

Crisaborole is a topical phosphodiesterase 4 (PDE4) inhibitor approved by the FDA for the treatment of mild to moderate atopic dermatitis in adults and children three months of age and older.

After initial therapy how to prescribe maintenance therapy?

After induction of remission, intermittent therapy with moderate- to high-potency topical corticosteroids (groups 3 to 5) should be started.

The steroid should be applied once daily to previously affected skin areas for two consecutive days per week (eg, weekends) and may be continued for up to 16 weeks.

Emollients can be liberally used multiple times per day.

How do we treat flare?

Flares of atopic dermatitis that occur during intermittent treatment may be treated by resuming continuous use of topical corticosteroids or calcineurin inhibitors that have been effective for the patient in the past.

Those children who have frequent flares can be treated with low potency steroids intermittently for 2 consecutive days in a week.

How do we treat acute exacerbations of chronic AD?

In adolescents and adults, an acute exacerbation of chronic atopic dermatitis can sometimes be aborted by a short course of systemic glucocorticoids (eg, prednisone 40 to 60 mg/day for three to four days, then 20 to 30 mg/day for three to four days). This strategy is not recommended for infants and young children.

How do we treat cases refractory to topical steroid and calcineurin inhibitors?

Phototherapy or

Systemic Immunomodulatory therapy

Role of phototherapy

Narrow Band UV-B phototherapy as first-line therapy for adult patients with moderate to severe atopic dermatitis that is not controlled with topical therapy.

Phototherapy is usually administered two to three times per week. Topical corticosteroids can be continued as needed during phototherapy. Additional emollients may be necessary since phototherapy may increase skin dryness.

Phototherapy is not suitable for infants and young children.

Systemic therapies:

Dupilumab is a fully human monoclonal antibody that binds to the alpha subunit of the interleukin (IL) 4 receptor and inhibits downstream signaling of IL-4 and IL-13.

It is useful for patients with moderate to severe AD not responding to topical therapy and in whom phototherapy is not feasible or acceptable.

Dupilumab is also an option for patients who are not candidates for or failed previous treatment with conventional immunosuppressive agents, such as cyclosporine, methotrexate, mycophenolate mofetil, or azathioprine.

Compared with conventional immunosuppressive agents, dupilumab has a favorable safety profile and may be used for long-term treatment of atopic dermatitis.

However, cost may be a major consideration with dupilumab.

Exacerbation or new onset of head and neck dermatitis ("dupilumab facial redness") has been reported in approximately 4 to 10 percent of adult patients treated with dupilumab after a median time of 65 days after initiating dupilumab.

Cyclosporine:

Cyclosporine (5mg/kg/day) for short-term and long-term (1 yr) use has been beneficial for children with severe, refractory AD.

Oral cyclosporine is not recommended in infants and young children with atopic dermatitis. In older children and adolescents, the use of cyclosporine should be reserved for the most severe cases that failed to respond to optimal topical treatment and where there is a significant, negative impact on quality of life.

Cyclosporin forms a complex with an intracellular protein, cyclophilin, and this complex in turn inhibits calcineurin, a phosphatase required for activation of NFAT (nuclear factor of activated T cells), a transcription factor necessary for cytokine gene transcription.

Methotrexate, MMF and Azathioprine can be used in severe cases.

What are the other unproven therapies?

Probiotics containing Lactobacillus rhamnosus strain GG

Human recombinant IFN-γ

Allergen immunotherapy

Chinese herbal medicine

Vitamin D

Melatonin

How do we treat infections in AD?

Bacterial infection by Staph aureus is common in AD

Treat with oral macrolides in case of MSSA and oral cephalosporin in cases of MRSA.

Dilute bleach baths (cup of bleach in 40 gallons of water) twice weekly may be also considered to reduce S. aureus colonization.

In one randomized trial, the group who received the bleach baths plus intranasal mupirocin (5 days/mo) had significantly decreased severity of AD at 1 and 3 mo compared with placebo.

Patients rinse off after the soaking. Bleach baths may not only reduce S. aureus abundance on the skin but also have anti-inflammatory effects.

For HSV infection in AD

Topical corticosteroids should be temporarily discontinued if HSV infection is suspected. Reports of life-threatening dissemination of HSV infections in patients with AD who have widespread disease mandate antiviral treatment.

Treat with oral acyclovir.

Persons with AD are also susceptible to eczema vaccinatum , which is similar in appearance to eczema herpeticum and historically follows smallpox(vaccinia virus) vaccination.

Antifungal agents for dermatophytal infection.

What are the complications?

Skin infections

Exfoliative dermatitis

Atopic keratoconjuctivitis

Keratoconus