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REVIEW ARTICLE
Year : 2021  |  Volume : 22  |  Issue : 3  |  Page : 195-214

Topical therapy for atopic dermatitis: A review


Department of Pediatrics, Division of Dermatology, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, Washington, USA

Date of Submission05-Jul-2020
Date of Decision11-Oct-2020
Date of Acceptance12-Dec-2020
Date of Web Publication30-Jun-2021

Correspondence Address:
Robert Sidbury
Department of Pediatrics, Division of Dermatology, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, Washington
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpd.ijpd_148_20

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  Abstract 


Background: Pediatric atopic dermatitis(AD) is very common, but its management is frustrating for the dermatologist, child and parents alike as this chronic inflammatory skin disease is marked with numerous difficult to control flares. Although country specific guidelines for AD exist, there is paucity of data with respect to dedicated topical care regimens for AD management in pediatric population. Purpose: This is a broad based review exploring various topical practices and management options to manage pediatric AD during flares and in remissions. Scope: The PubMed database was searched (to 1 June 2020) for English-language articles containing the keywords atopic dermatitis, atopic eczema, topical calcineurin inhibitor(TCI), topical corticosteroid(TCS), topical phosphodiesterase inhibitors, crisaborole, topical therapy. Articles focusing on topical managment for children with AD were chosen for further review. A limitation is that this is not a systematic review of the literature. We have relied heavily on The Indian Dermatology Expert Board Members 2019 Management Guidelines on AD and the 2014 American Academy of Dermatology (AAD) guidelines, soon to be updated. In our review, we focus on Skin directed therapies to repair and maintain healthy skin barrier, suppress inflammatory response, control flares, control itch and manage infectious triggers. Topicals can be used as first line therapy in mild AD, adjuvant for moderate-severe AD or as maintenance to keep the disease in remission. Topical therapy in AD is not limited to TCS, TCI, Crisaborole or newer molecules but also involves moisturization, emollient care and bathing practices; which have been discussed. Conclusion: Multiple topical therapies and practices have been successfully used to treat children with AD. An understanding of the available treatment options will help dermatologists striving to achieve best practice in the management of pediatric AD.

Keywords: Topical management, Pediatric atopic dermatitis, Moisturizers, Topical Corticosteroids, Topical Calcineurin inhibitors, Crisaborole, Bathing practices


How to cite this article:
Minni K, Sidbury R. Topical therapy for atopic dermatitis: A review. Indian J Paediatr Dermatol 2021;22:195-214

How to cite this URL:
Minni K, Sidbury R. Topical therapy for atopic dermatitis: A review. Indian J Paediatr Dermatol [serial online] 2021 [cited 2021 Sep 26];22:195-214. Available from: https://www.ijpd.in/text.asp?2021/22/3/195/319942




  Introduction Top


Atopic dermatitis (AD), a chronic, recurrent inflammatory skin disease with common infantile onset and characterized by pruritic eczematous lesions with flexural predilection,[1] has increased prevalence in industrialized and low-income countries.[2] Its management is frustrating because of its recurrent nature, despite excellent management plans.[3]

While Hebra (1872) first proposed topical remedies such as soaps, oils, lotions, ointments, and tar,[4] AD treatment has evolved from emollients (1930s), Topical Corticosteroids (TCSs) (1960s), topical calcineurin inhibitors (TCIs) (2000s), topical phosphodiesterase inhibitors (2017), to current Janus kinase inhibitors and aryl hydrolase promoters. Although targeted biologicals have revolutionized moderate–severe AD (msAD) care, topical therapy (TT) remains fundamental.

Herein, we review TT of AD and highlight guidance provided by many country-specific guidelines[5],[6],[7],[8] published in the last 5 years.[1],[2],[3],[4],[5],[6],[7],[8],[9],[10] We rely heavily on The Indian Dermatology Expert Board Members 2019-Management Guidelines on AD and the 2014-American Academy of Dermatology (AAD) guidelines, soon to be updated.[11]

The goal of AD management is to reduce symptoms, prevent exacerbations and superinfection, and minimize treatment complications.[1] Patient and family education is most critical for treatment success. Skin-directed therapies constitute the first approach to management and aim at:

  1. General skin care maintenance - repairs and maintains healthy skin barrier (SB)
  2. Topical anti-inflammatory medications – suppresses inflammatory response and controls flares
  3. Itch control
  4. Managing infectious triggers.



  General Skin Care Maintenance Top


  • Wash immediately after contact to minimize exposure to environmental triggers (chlorine, sand, and grass)
  • Avoid overheating
  • Wear loose cotton clothing.



  Bathing (Showering/Cleansing and Washing) Top


Bathing, considered therapeutic in uncontrolled AD, serves physiological, psychological, and cultural functions by a salubrious balance of cutaneous flora. It is important to educate parents and patients on optimal bathing protocols, depending on individual patient, season, and symptoms.[5],[12]

Hebra recommended bathing three to four times daily. “Scholtz regimen” advocated avoiding bathing and applying lipid-free lotion instead at least once a day as per patient preferences.[13] Hanifin long advocated a daily 20-min soaking bath followed by the use of an emollient within 3 min of bathing.[14]

Chiang and Eichenfield concluded that the use of emollient alone yielded a significantly greater (P < 0.05) mean hydration over 90 min (206.2% baseline hydration) than bathing with immediate emollient (141.6%), bathing and delayed emollient (141%), and bathing alone (91.4%).[13] While simply applying moisturizer in a temperate zone gave maximum benefits, the same cannot be advocated for tropical zones with high humidity. Frequent bathing demonstrated clinically significant reduction in symptom severity when compared to infrequent bathing.[15] Soak and smear (or soak-and-seal) (SS) was shown to be effective acutely in msAD.[15]

Both American Academy of Allergy, Asthma and Immunology and AAD recommend once daily bathing (bath/shower) for 5–20 min.[16] While many pediatric dermatologists favor daily tub bathing over showering,[17] three-quarters of patients with/without eczema preferred showering. The specific frequency of bathing should be titrated to the individual patient, but moisturizing immediately after all baths or showers is immutable.[3]


  Temperature Top


The SB function recovers at 36°C–40°C.[5] Ideal bathing water temperature should be lukewarm (38°C–40°C) because itching is triggered at a skin temperature of ≥42°C. If a child is willing to happily bathe at a temperature slightly higher or lower than optimal, the greater good may be served by concession.


  Soaps/Detergents Top


Xerosis and irritation can be avoided by minimal use of soap in msAD during dry seasons.[5] There were still significant proportions of AD patients who preferred soap (40% of first-visit vs. 27% of review cases) and did not apply emollients after a bath/shower (25% of first-visit vs. 23% of review cases). Use of nonsoap cleansers (syndet) that are neutral to low pH, hypoallergenic, nonirritant, paraben, and fragrance-free are recommended.[1] Liquid syndets containing arginine, pyrrolidone, and carboxylic acid,[18] with a good skin and ocular tolerance, are preferred.[19]

In contrast, more liberal use of soap and detergents is desirous in patients with seborrheic skin, in sites where daily ointment is applied or exhibit recurrent skin infections.[5] Although soaps have no major role for AD management, many parents worry about it, so providing guidance on appropriate cleansing methods is appreciated.[5]

A randomized controlled trial (RCT) on Chinese children with mild-to-moderate AD (mmAD) found three cleansing systems (mild synthetic bar, an ultra-mild body wash with lipids, and an ultra-mild body wash with lipids and zinc pyrithione) equally safe and efficacious.[20] The AAD guidelines recommend against the use of bath additives and acidic spring water, with the exception of bleach.[21]

In addition, fragrance-free, dye-free detergents, humidification for indoor-heated homes, and cooling the home in hot summer months may enhance care.[22]


  Bleach Baths Top


Bleach (sodium hypochlorite solution) has been used as a disinfectant for nearly a century. Huang et al. showed that twice weekly dilute bleach bath (BB), in conjunction with periodic intranasal mupirocin, reduced bacterial superinfection and improved eczema severity below the neck [Table 1].[23] However, BB do not kill Staphylococcus aureus (SA)[24] instead reduce nuclear factor-kappa B-mediated epidermal, pathology to have more anti-inflammatory than antibacterial action.[17]
Table 1: Preparation of bleach bath

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A 2018 meta-analysis found no BB benefit over plain water baths and raised the potential issue of asthma exacerbations, although large, well-designed studies are lacking. It also indicated that hydration followed by emollient application was responsible for the improvement seen in those who benefit from BB, rather than bleach itself. However, these results have been called into question for varied reasons including heterogeneity of data, and most pediatric dermatologists continue to favor adjunctive use of BB.[25]

Triclosan-containing antiseptics, a BB alternative, may cause irritation if not diluted properly. Diluted potassium permanganate soaks are rather commonly used to remove crusts by reducing epidermal colonization and for SB restoration.[26]


  Moisturizers Top


Xerosis, most universal feature of AD,[27] is due to excessive transepidermal water loss (TEWL) from both lesional and nonlesional skin, which manifests clinically when stratum corneum (SC) water content drops <10%, and enzymatic processes become impaired, leading to abnormal skin desquamation and corneocyte accumulation.[15] Hydration is critical, even during remission. Many products are available, and the selected formulation should be cosmetically acceptable and reasonably priced, to encourage accessibility and good compliance.[28]

Moisturizers improve SC water content and suppress itching by recovering and maintaining SB functions.[29] Fragrance-free, dye-free, and preservative-free[3],[30] moisturizers immediately after birth and thereafter also decrease the risk of AD onset (strength of recommendation A, level of evidence I).[5],[10] It should be applied at least once daily to the entire body, regardless of whether dermatitis is present.[13] After patient education and counseling in a British study, the quantity of moisturizer used increased 800% (average use of 426 g per week per patient) while AD severity decreased with the percentage of patients using moderate/potent TCS decreased.[3],[31] A Cochrane review on moisturizers containing humectants, lipids, and/or ceramides reported reduced rate of AD flares and enhanced TCS efficacy.[21] In the worst scenario, applying wrong moisturizer could increase dermatitis and asthma risk [Table 2].[32]
Table 2: Types and uses of moisturizers in atopic dermatitis

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Currently, there is insufficient evidence supporting the use of one type of moisturizer over another. However, patients and caregivers should be cautioned that skin care products are not subject to approval by the Food and Drug Administration (FDA) and that claims of efficacy or purity are often unsubstantiated while the so-called “natural” and “organic” skin care products with natural oils (e.g., mustard oil) may be sensitizing in some individuals with AD [Table 3].[31]
Table 3: Vehicular types and preparation: Uses, advantages, and comments

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  Emollients Top


Emollients should be applied on xerotic/lichenified skin not covered by clothes twice daily, and at least once daily to the entire surface of the skin, more when undressing children for other reasons. They are available as leave-on creams, ointments, oils, soap replacement, or bath additives[4] and provide exogenous lipids to reduce signs of inflammation [Table 4].[26],[33]

Daily application of full-body emollients in high-risk AD neonates[7] within 3 weeks of birth reduced the cumulative incidence in 32% of Japanese and 50% of British and American neonates[3],[32] and preterm infants.[10] Early emollient use repaired SB function and prevented penetration of antigens and TEWL. These studies offer a safe, inexpensive, practical intervention for primary prevention of AD [Table 5].[5],[17]
Table 4: Types of emollients as vehicles

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Table 5: Studies on emollient use among pediatric atopic dermatitis patients

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Interestingly, a multicenter RCT-barrier enhancement for eczema prevention study concluded that daily emollient during the 1st year of life did not delay, suppress, or prevent eczema at the age 2 years and found some evidence to suggest an increased risk of skin infections with use.[3] While in another primary prevention RCT, the development of AD by 12 months of age was prevented neither by regular use of bath oil additives and face emollient cream on at least 4 days per week from 2 weeks of age nor by early complementary feeding introduced from age 12 weeks [Table 6].[4]
Table 6: Emollient preference according to atopic dermatitis severity

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Oils

Conventionally, Indians use natural oils to massage, thereby treat and prevent AD. Oil massage helps improve SB and increases growth by kinesthetic and tactile stimulation.[26]

Safflower oil, sunflower seed oil, and sea buckthorn seed oil are natural oils with the highest linoleic acid to oleic acid ratios. Sunflower oil repaired and maintained SB in preterm infants with 41% decreased risk for developing nosocomial infections compared to controls.[34] However, olive oil, having relatively low linoleic acid to oleic acid ratio, significantly deteriorated SB by disrupting SC lipid structure and homeostasis and promoted pityrosporum overgrowth [Table 7].[34]
Table 7: Emollients and their use in atopic dermatitis

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Oils or antiseptic products cannot be recommended for standard practice due to mixed evidence. Oily cleansers containing mineral oils are preferred to minimize allergenicity.[10]

Starch left after cooking rice, baking soda, and oatmeal baths are also popular in India, but no trials are available for the same. In a study, colloidal oatmeal, avenanthramides, shea butter, and oat oil containing daily cleansing and an emollient cream were found to be safe, well tolerated, and effective as an adjuvant treatment in children with xerosis and AD.[35]

Vehicle

Humidity, occlusive dressings, and impaired SB can increase percutaneous absorption of a topical medication.[36] Other chemicals frequently used as vehicles in skin care products such as lanolin, propylene glycol, ethylene diamine, and formaldehyde can cause hypersensitivities [Table 8].[31]
Table 8: Vehicular emollients

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Volume

Age, affected body surface area (BSA), frequency of application, and duration of therapy should be considered in determining realistically the amount of dispensed medication. A volume (~0.5 g) measuring 5 mm in diameter that is pushed out from a tube to an area between the tip and first joint of the second finger is appropriate for two palms (2% BSA) in adults (fingertip unit) [Table 9].[5] The recommended emollient use is 150–200 g/week for children and up to 500 g/week for adults.[10]
Table 9: Fingertip units for pediatric population

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Controlled studies comparing the effectiveness of medicated cosmetics and devices, proposed as therapeutic aids (prescription emollient devices), are limited and have not demonstrated greater efficacy over traditional agents [Table 6].[10],[31]


  Topical Corticosteroids (TCSs) Top


Hydrocortisone, developed first by Sulzberger and Witten, has been used topically for AD for more than 60 years,[3],[27] with its efficacy and safety demonstrated in >100 RCTs.[5],[17],[28] TCSs act on immune cells, inhibit phospholipase A2, and interfere with antigen processing and release of inflammatory mediators, resulting in reduced inflammation, mitotic activity, and protein synthesis [Table 10].[37] TCSs are not indicated for the treatment of xerosis and/or lichenification.[10]
Table 10: Topical corticosteroid use

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Indications

  1. mmAD: First line
  2. Severe AD: Adjuvant to systemic therapy.


Use

The preferred TCS depends upon potency, vehicle, application site, BSA, severity, and lesion. Cosmetically acceptable formulations encourage good compliance. Infants and children require careful monitoring.[5]

Application

TCSs should be applied as a thin layer until absorbed once or twice daily (morning and evening: after bathing) to affected areas until these areas are smooth to touch and no longer red or itchy.[5],[13] When inflammation is reduced, the frequency of applications should be decreased to once a day or intermittently to induce remission. Normally, just 1% of the TCS applied supplies all of its therapeutic action; the remaining 99% is removed from the skin surface by rubbing, washing, and exfoliation.[10]

The soak and smear (SS) method is recommended for poorly responsive lesions because it produces a higher absorption of TCS.[10] Occlusive dressings involve placing TCS on the skin and covering with either a wet or dry dressing. This technique has been used for more than 20 years in AD treatment, despite little definitive evidence for its efficacy.

Dry occlusive dressings up to 7–14 days are usually reserved for small patches of eczematous skin resistant to conventional application of TCSs [Table 11].[14]
Table 11: Preferred formulation of topical steroids in atopic dermatitis

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Side effects

The TCS absorption rate by skin region is 13.0, 6.0, 1.0 and 42 on the cheek, neck, forearm, and scrotum, respectively.[5] Children have greater risk of TCS absorption owing to greater BSA [Table 12].[38]
Table 12: Side effects and management outcomes of topical corticosteroids

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TCS causes skin to go through three phases – pre-atrophy, atrophy, and tachyphylaxis. Atrophy causes a burning sensation, and further steroid use causes vasoconstriction and soothing of the burning. On withdrawal, compensatory dilatation beyond initial diameter may occur known as the “trampoline-like effect.” Release of endothelial nitric oxide stores results in “hyperdilation” of vessels.[38] Local and systemic side effects (SEs) are negligible except for slight thinning of the skin and hair growth when TCSs are used appropriately. Incidental striae may occur in (pre) pubertal children.[3] There are also other potential local effects when used around the eyes (intraocular hypertension, cataracts) or mouth (periorificial dermatitis). Local irritation, mood change, gynecomastia, genital hypertrichosis, and staphylococcal infection are commonly encountered with TCS use in children.[39] Systemic SEs including hypothalamic–pituitary–adrenal axis (HPA) suppression are rare, and no specific monitoring is recommended for children,[17] as also demonstrated by an observational study of Australian children.[14]

As a general rule, it is better to take a holiday of TCS for 2 weeks after a continuous period of 2-week application to prevent TCS-related SE and tachyphylaxis.[9] The maximum monthly amount of medium- or high-potency TCS to be used is equal to 15 g in infants, 30 g in children, and 60–90 g in adults.[10]

Discontinuation

The rapid remission induced by potent TCS may lead to misuse by patients and parents, leading to its application at either during a flare with prompt stoppage on relief leading to another flare or an addiction for continuous use beyond 4 weeks to prevent flare leading to SE. When inflammation and itch attenuate, TCS should not be discontinued abruptly, rather gradually tapered or administered intermittently while maintaining remission to avoid withdrawal rebound.[5],[10] Tapering strategies consist of using a less potent TCS on a daily base or keeping a more potent one while reducing the frequency of application (intermittent regimen).[10]

Steroid phobia

TCS phobia can be an occult cause of therapeutic misadventure.[34] Failure to respond to a treatment plan including TCS can be interpreted by providers as an indication for a stronger TCS; if in fact the lack of efficacy is due to TCS phobia, this is precisely the wrong next step. The key to avoid this vicious cycle is education on the front end and awareness of the possibility of TCS phobia throughout the treatment course. Providers should do more than simply caution against skin thinning; rather they should describe what steroid-induced atrophy might look like and how it can be avoided.

Steroid-induced atrophy is entirely reversible in its earliest telangiectatic stages; taking the time to review these features is empowering to families and will lead to better adherence and outcomes. Patients generally should be treated with the least potent TCS that is effective.[40]


  Topical Calcineurin Inhibitors Top


TCIs, used as steroid-sparing agents,[17],[36] were approved in 2000–2001 as second line for AD treatment in adults and children >2 years of age [Table 13].[10],[38] Tacrolimus, produced by bacterium Streptomyces tsukubaensis, and pimecrolimus, a chemical derivative of ascomycin, produced by Streptomyces, act on eosinophils, basophils, and mast cells by blocking production of inflammatory cytokines and decreasing T-lymphocyte activation by Langerhans cells.[10] Although there is a theoretical risk of immunosuppression,[14] TCIs have shown to have greater specificity and no impact on connective tissue.[38]
Table 13: Topical calcineurin inhibitors

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A recent meta-analysis demonstrated that tacrolimus is more effective than pimecrolimus in reducing both inflammation and pruritus in pediatric AD.[3],[5] It is important to take into account the age limit, potential adverse effects, and cost.[22],[28] There are now some published data on the safety of pimecrolimus (1%) cream, in particular, for children with AD for 5 years that support infantile use through early childhood [Table 14].[22]
Table 14: Topical calcineurin inhibitors - Indications and contraindications

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Application

A volume of 0.1 g (corresponding to a volume squeezed by 1 cm from a 5-g tube) is appropriate for a 10 cm.[2],[5] In accordance with physical status, the maximum volume of a 0.03% tacrolimus ointment per use was 1 g for children (2–5 years).[5] TCIs should be applied twice a day for 2–3 weeks and then once a day until resolution of the skin lesions and itch symptoms.[5] If there is no improvement after 2 weeks of treatment, alternative options must be considered.[10]

Efficacy

Efficacy depends on drug absorption, application site, and SB function.[5] With a molecular weight of approximately 800 Da, TCIs do not penetrate beyond the dermis.

Adverse effects

In 2005, the US FDA recommended a “black box” warning, citing a potential cancer risk with the medication.[3] However, several studies have shown that intermittent or continuous use of TCI did not cause systemic immunosuppression or increase bacterial or viral infections risk during 5 years follow-up.[10] Reassuringly, TCIs have been used in children for >15 years with no reports of malignancy, and there is little to no concern for systemic absorption or systemic immunosuppression.[3],[41]

TCI can cause application site stinging, especially if used on raw, eroded, or ulcerative lesions.[5] Application site reactions such as a transient burning and hot flushes occur in up to 10% patients; however, most symptoms resolve with improved SB. Adequate forewarning regarding this possibility could improve compliance.[5]

Application techniques

Wet wrap technique

In 1991, Goodyear described wet wraps as a form of occlusive treatment.[42] Different variations of this technique have been used (bandages soaked with emollients or diluted corticosteroids or bandages soaked with warm water/wet pajamas or re-wetting or not re-wetting the bandages every hour) for 2–14 days over exudative, infected, or lichenified lesions.[10] This leads to intense hydration and excellent penetration of medications while providing a physical barrier against scratching [Figure 1].[28]
Figure 1: Procedure for wet wrap technique

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The absorption of the TCS increases under occlusion, while hydration of the skin itself leads to a 4–5-fold increase in absorption. Although rapid improvement in AD occurs, the risk of HPA axis suppression limits its long-term use. The most suitable TCSs for wet wrap technique (WWT) are fluticasone propionate, methylprednisolone aceponate, mometasone furoate, hydrocortisone acetate, or prednicarbate mixed with a hydrophilic emollient to 10% dilution (1 part of steroid and 9 parts of emollient) for the body or a 5% dilution for face.[10],[42]

WWT can be performed at home by dressing the patient in moist pajamas (dampened by warm water) covered by a pair of dry pajamas overnight. This should follow application of TCS and/or emollient therapy. The temperature in the child's room should be warm to prevent chilling. Dabade et al. reported that 83% of patients treated with an intensive regimen of TCS and wet dressings showed >50% improvement of AD severity in a short time period (mean 3.6 days).[43] The Indian panel members suggested that its use might not be feasible in every region of India due to varied climatic conditions. However, wherever suitable, WWT can be used in severe or resistant patients >6 months of age.[10] Limited WWT, such as to a solitary refractory lesion on an extremity, may be more feasible.

There is limited evidence to support the routine use of BBs, SS techniques, and WWT; larger scale RCTs are needed to better understand their efficacy.[33],[42]

TCS and TCI can be used as:[9]

  • Proactive therapy (PT)
  • Reactive therapy
  • Intermittent therapy
  • Weekend therapy
  • Intermittent hot spot therapy (hot spots imply the body areas known to relapse commonly, for example, antecubital fossa).


Proactive application of TCS ± TCI twice weekly to areas subject to recurrences effectively controls AD.[3],[5],[27] This strategy reduced the number of relapses and lengthened the symptom-free interval effectively than emollient use alone. PT aims to control subclinical disease using minimal amounts of TCS without causing steroid-induced skin atrophy.[1]

In contrast, reactive therapy is used to control inflammation with anti-inflammatory topical drugs on relapse.[5] According to the European guidelines,[43] response should be re-evaluated after 12 months to decide whether to continue PT. If relapse occurs, TCS/TCI can be restarted with two applications per day. Any lymphadenopathy should be noted before starting therapy and monitored throughout therapy.[1],[10] For maintenance therapy, it should be noted that PT with twice weekly mild-to-mid potency TCS and even the use of moisturizers alone can help in maintenance.[7]


  Antibiotics Top


In AD, SA colonization on skin and/or nose varies from 60% to 100%.[3],[10] Secondary infection, evident clinically by pustules, oozing, and honey-colored crusts, is often associated with AD flare.[3] Obtaining swabs from affected skin and nares may be helpful to identify infection and direct further management only when bacterial resistance is suspected; because given the rate of SA carriage, a positive culture may not add more than clinical judgment.

Current practices for SA colonization and/or infection management include antiseptics (particularly diluted BB twice weekly), topical antibiotics (including periodic intranasal mupirocin), and when necessary, systemic antibiotics.[14]

Topical antibiotics are appropriate for localized areas of infection,[1] but not for simple colonization, while systemic antibiotics are preferred for widespread/multiple impetiginized lesions.[7] Fusidic acid (FA), retapamulin, and mupirocin applied twice daily with bandage or thrice daily without bandage for 7–10 days are most appropriate for limited skin lesions.[3],[10],[28] Most topical antibiotics are available in two formulations: cream (exudative lesions) and ointment (dry lesions). Since mupirocin-resistant staphylococci strains have been isolated, treatment should not be prolonged >10 days. Mupirocin should be used cautiously in children <1 year because of a lack of studies in this age group.[1]

Since 2007, retapamulin has been US-FDA approved for impetigo in children >9 months with Staphylococcus pyogenes and methicillin-resistant SA. The recommended therapeutic regimen involves twice daily applications a day for 5 days in a month for 3–18 months. The effectiveness of 5 days of retapamulin ointment therapy is comparable to that of FA used longer; however, it should be reserved for strains resistant to conventional treatments.[10],[44]

Irritation, itching, and contact dermatitis to preservatives (lanolin, cetyl alcohol, and stearyl alcohol) are common with topical antibiotics. The existence of FA-resistant SA is probably due to its widespread and often inappropriate use in chronic dermatoses.[16] Intranasal mupirocin and BBs effectively prevent recurrent bacterial infections and may be utilized prophylactically.[3],[27]

Although TCS–antibiotic combinations are used for treating eczematous lesions near anterior nares, flexures, perianal areas, and finger or toe web spaces to reduce SA load, none have shown superior clinical efficacy in AD studies. In India, neomycin-containing topical antibacterials are commonly prescribed for cuts, minor burns, etc. Sharma reported contact allergy to neomycin, gentamicin, and chinoform in AD with cross-sensitivity between neomycin and gentamicin as high as 40%. Hence, most dermatologists do not prefer neomycin as a topical antibiotic. It is quite possible that gentamicin might induce sensitization in many AD patients. Those who cease to respond to TCS–gentamicin combination actually develop gentamicin sensitivity rather than steroid tachyphylaxis. The sensitization potential of mupirocin does not appear to be a major issue presently.[45] The DEBM recommends not only against the indiscriminate use of topical or oral antibiotics but also against the use of TCS–antibiotic.[7]

Transplantation of skin microbiota including coagulase-negative staphylococci or other species of bacteria, which directly compete with SA, may potentially be used to treat or prevent AD development.[16] Possible benefits of using commensal strains of coagulase-negative Staphylococcus epidermidis and Staphylococcus hominis from healthy donors applied to AD skin or spraying the commensal Gram-negative Coccobacillus Roseomonas mucosa (NCT03018275) or targeted transplant lotion of coagulase-negative staphylococci (NCT03151148) applied to the arms of AD patients have shown clinical improvement.[46],[47] Emollients supplemented with Gram-negative Vitreoscilla filiformis lysates demonstrated significantly greater benefit than placebo. Strain-level differences in S. epidermidis might impact the relative burden of SA on the skin of AD patients.[46]


  Antivirals Top


About 3% of AD cases are prone to viral infections such as herpes simplex, varicella zoster viruses, molluscum contagiosum, human papilloma virus, hand foot mouth disease, eczema coxsackicum, and eczema herpeticum,[48] where oral antivirals are preferred.


  Antifungals Top


AD children are susceptible to superficial fungal infections; hence, age-appropriate antifungal creams are required for management. Older children and adolescents, in particular who present with worsening dermatitis of the head and neck area, may benefit from pityrosporum-directed therapy.

Apart from those mentioned above, there are numerous other topicals which have been used both over-the-counter and along prescriptions [Table 15].
Table 15: Other topical agents for management of atopic dermatitis

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  Recent Advances Top


As our understanding of the AD pathophysiology deepens, molecules targeting novel immunological and pro-inflammatory pathways, delivery systems, and formulations are being developed [Table 16].[11]
Table 16: Newer topicals in pipeline

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Complementary and alternative medicines

Since internet revolution, many AD patients have tried most complementary and alternative treatments, with little evidence sensing that current allopathic treatments do not target “root” cause. Oral unsaturated fatty acids (evening primrose oil, borage oil), polyunsaturated fatty acids, and animal and fish oils are not recommended for AD treatment. Chinese herbal medicine has mixed evidence precluding its recommendation on broader scale. Crude plant extracts are not recommended as may cause contact sensitization and dermatitis. Other alternative treatments with limited evidence include acupuncture/acupressure, hypnosis, massage, biofeedback, balneotherapy, sunflower seed oil, coconut oil, pale sulfonated shale oil, Vitamin B12, Vitamin E, East Indian sandalwood oil, melatonin, L-histidine, and Manuka honey and select herbal preparations. Olive oil should be avoided and may exacerbate xerosis and AD.[40]


  Conclusion Top


This review has outlined the essential components to good skin care: avoidance of triggers and irritants, proper cutaneous hydration, safe sustainable use of anti-inflammatories, and itch and infection control [Table 17] and [Figure 2]. A primary reason for relapse in patients well controlled by newer biologic medications is complacency with topical care. There are many exciting topical and systemic drugs in the AD pipeline; however, none will likely eliminate the need for a comprehensive topical regimen [Table 18].[56]
Table 17: Topical management of atopic dermatitis

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Figure 2: Use of topical applications in atopic dermatitis according to body site

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Table 18: Topical management of atopic dermatitis

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Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Rajagopalan M, De A, Godse K, Krupa Shankar DS, Zawar V, Sharma N, et al. Guidelines on management of atopic dermatitis in India: An evidence-based review and an expert consensus. Indian J Dermatol 2019;64:166-81.  Back to cited text no. 1
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Abstract
Introduction
General Skin Car...
Bathing (Showeri...
Temperature
Soaps/Detergents
Bleach Baths
Moisturizers
Emollients
Topical Corticos...
Topical Calcineu...
Antibiotics
Antivirals
Antifungals
Recent Advances
Conclusion
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