Topical Therapies





Key points





  • Optimal bathing practices can improve atopic dermatitis (AD) symptoms and limit disease flares. Best practices include daily bathing for less than 10 minutes in lukewarm water, utilizing neutral to mildly acidic nonsoap cleansers, and the immediate application of postbath emollients.



  • Topical corticosteroids represent the standard of care for acute AD flares. However, their prolonged use should be avoided, and their strength, vehicle, and frequency of application should be customized to each patient.



  • Topical calcineurin inhibitors represent a second-line therapy for AD in those patients who have either failed topical cortical steroid treatment, require long-term antiinflammatory treatment, or require treatment to sensitive areas such as the eyelids, face, and genitalia. Phosphodiesterase-4 inhibitors are a newer class of topical antiinflammatory medication, which represents an alternative to topical steroids and topical calcineurin inhibitors.



  • Topical antimicrobials are not recommended for the routine management of AD; we also discuss the role of dilute bleach as a bath additive and other such practices.



Introduction


Topical management for atopic dermatitis (AD) includes specific guidance on bathing, topical antiinflammatory medications, and antimicrobial approaches. This chapter summarizes the evidence behind and provides recommendations for optimal bathing practices, including frequency, duration, use of cleansers, and additives, and discusses the role of dilute bleach baths. The role of topical antiinflammatory medications is also reviewed, including topical corticosteroid utilization, and gives guidance on how to optimize acute flare management. Second-line therapies, including topical calcineurin inhibitors and phosphodiesterase-4 inhibitors, are similarly discussed, and recommendations are made for the role of these medications in AD. Lastly, the history behind the use of topical antimicrobial treatments and the importance of limiting their utilization is discussed. In sum, this chapter aims to provide an overview of the topical approach to AD, providing recommendations to optimize maintenance and flare-free intervals as well as guidance on the management of acute flares and refractory situations.


Bathing


Bathing represents a crucial component in the management of AD for epithelial hydration. It is also a salient factor of skin hygiene and can remove allergens, irritants, scale, and crust ( ). However, due to accompanying evaporation, overbathing or improper bathing can also lead to epithelial dryness and decreased epithelial barrier function driven by transepidermal water loss and the drying of the stratum corneum ( ). In practice, patients are often subject to conflicting recommendations from providers. Here, the aim is to present evidence supporting frequency and duration of bathing, the use of specific cleansers and/or soaps, dilute bleach baths, bath additives, and other less-studied bathing practices that may be observed in clinical practice.


Frequency of bathing


It is essential to note that all bathing recommendations discussed here are accompanied by the additional directive for application of a moisturizer or emollient ideally within 3 minutes of bathing. The time window is ideal at sealing in hydration and preventing the negative aspects of evaporation. Baths should be taken in lukewarm to warm water that is comfortable to the patient’s skin; excessively hot or cold water temperatures should be avoided. Further, no literature to date directly compares baths versus showers in AD patients, and as such, all recommendations in this chapter should be applied to both bathing methods.


The American management of AD guidelines recommends daily bathing, whereas the European guidelines do not explicitly comment on frequency ( ). Regardless, patients often receive conflicting recommendations. Historically, primary care physicians tend to recommend infrequent bathing; conversely, allergists, immunologists, and dermatologists have recommended frequent bathing ( ). These conflicting messages have been driven by the fact that some physicians have viewed bathing as drying to the skin, and specialists have viewed it as hydrating. Multiple survey studies have confirmed this trend ( ). Up to 75% of patients/families have reported confusion in how frequently to bathe, and 45.6% have reported receiving conflicting advice ( ). The primary benefit of bathing most likely stems from its hydrating qualities rather than its cleansing properties ( ).


Type of bathing and duration


Similar to the frequency of bathing, recommendations for duration historically lack consensus. The American Academy of Dermatology (US) guidelines recommend 5- to 10-minute baths, followed by the immediate application of emollients ( ). European guidelines recommend shorter (5-minute) baths, with the addition of bath oils in the final 2 minutes, followed by patting dry, and the immediate application of emollients ( ). Retrospective cohort studies have not shown a statistical significance between short bathing (<5 minutes) versus medium length bathing (5–10 minutes); extended baths (10–30 minutes) are associated with more severe AD ( ). This association of severity with longer duration of bathing may be confounding as those with more severe AD may bathe longer ( ). Those with severe AD and those with frequent infections are often recommended to take “soak and smear” baths, which consist of bathing for approximately 10 minutes, followed by the immediate application of antiinflammatory medications ( ). The US guidelines explicitly recommend such baths for patients with frequent exacerbations ( ).


Cleansers, soaps, and bathing practices


An essential component of bathing is the appropriate use of cleansers and soaps. The epidermis has a mildly acidic pH ranging between 4 and 5.5 ( ). This acid mantle is crucial for skin’s innate antimicrobial action and maintenance of the skin barrier ( ). Most soaps are alkaline due to the process of saponification. Exposure of the skin to this alkalinity can disrupt the epithelium’s acid mantle and be directly damaging to the stratum corneum leading to increased water loss and causing rigidity of the lipid components ( ). Soaps also remove physiologically normal oils and contain detergents and surfactants that can damage the epithelium leading to irritation and dry skin ( ).


Patients are presented with an abundance of options when choosing bathing products, including soaps, cleansers, and synthetic detergents (syndets). Soaps are made of long-chain fatty acid alkali salts created from the process of saponification; cleansers are mixtures of water and some form of active compound, including soaps, emulsifiers, surfactants, and detergents ( ). Syndets are nonsoap synthetic surfactants. One study examined the pH of all commercially available soaps and cleansers and found that all bars of soap had a pH between 9.9 and 10.7 except for syndet bars, which had a pH of 7 ( ). In the same study, most liquid cleansers were found to be less alkaline, but many still had a pH between 7.5 and 9.6; again, liquid syndets had a pH of 7 ( ). Based on the harmful effects of soaps and alkalinity, patients with AD are usually advised to use nonsoap hypoallergenic cleansers containing a neutral or mildly acidic pH ( ). Guidelines from Korea, Italy, and the United States directly recommend the use of syndets ( ). Notably, one study found that for patients with AD, the daily use of mildly acidic syndets significantly reduced clinical severity and symptomology in patients compliant with the regimen compared to those who were not ( ). Further, some data have shown that there may be no significant difference in eczematous symptoms when the use of soap is compared with bathing with water alone ( ). Thus daily cleanser use is not needed in AD patients, especially prepubertal children, as their potentially sensitive skin may be at high risk of experiencing irritating effects, and the sebum content of their skin is relatively lower (compared to adolescents and/or adults). In sum, the usage of neutral to mildly acidic cleansers should be recommended to patients, and they should also be counseled on the harmful effects of alkalinity.


Patients should also be directed to avoid damaging the epithelial barrier when using cleansers and take active steps to minimize friction when applying or removing soaps. They should be counseled to gently apply cleansers with the hands or soft microfiber cloths only, and to avoid the use of rougher texture wash cloths, loofahs, firm sponges, and/or scrubbing, as there is a risk of direct physical irritation. Cleansers should be quickly and gently rinsed off.


One unique aspect of bathing to be stressed with patients is the appropriate application of emollients. In 2009, a crossover study compared bathing without any application of emollients, bathing with immediate application, bathing with delayed 30-minute application, and emollient application without bathing effects on epithelial hydration ( ). This study found that patients who did not apply an emollient postbathing had decreased epithelial hydration in comparison to the emollient treatment arms ( ). Thus patients should be counseled that bathing without any application of an emollient may have directly negative impacts on epithelial hydration and be instructed to always use a postbath emollient.


Dilute bleach baths


In the past decade, dilute bleach baths have been increasingly recommended as an adjunct therapy for AD, especially for those patients who experience frequent infections as a trigger for flares. Bleach bath use was initially prompted by subjective parental reports of children’s symptoms lessening in summer months when they were often swimming in chlorinated pools ( ). The active component of bleach is sodium hypochlorite, which reacts with water to form hypochlorous acid. Hypochlorous acid then further dissociates, forming hypochlorite and superoxide radicals. These superoxide radicals are cytotoxic to bacteria and other microbes, including Staphylococcal aureus ( ). It was initially thought that dilute bleach baths provided an antimicrobial method free of concerns for resistance, which could both prevent infection and address S. aureus colonization ( ).


To perform a dilute bleach bath, 0.25 cup of household bleach (typically 6% sodium hypochlorite) is added to a regular-sized bathtub half-full of warm water in which the patient bathes for 5 to 10 minutes. With these instructions, the bleach concentration ends up being approximately 0.005% ( ). Some recommend a capful to a smaller bath for infants/toddlers and more (0.5 cup to full tub) for older children, teens, and adults. It is recommended to include the term dilute so that patients are not fearful of exposure to full concentration and its potentially harmful effects.


Further studies now demonstrate the benefit of bleach baths to be antiinflammatory and antipruritic most likely due to microbiome modulation ( ). Hypochlorite’s antiinflammatory properties are multifactorial and include the inhibition of nuclear factor kappa B (NFκB), decreased mitogen-activated protein kinase (MAPK) activation, reduction of immunoglobulin E (IgE), reduction of proinflammatory cytokines, and decreased levels of interleukin-12 (IL12), which drives the conversion from a T helper 2 (Th2) to a T helper 1 (Th1) inflammatory response ( ). Hypochlorite’s antipruritic properties are currently hypothesized to be due to reduced peripheral nerve stimulation ( ). Interestingly, in vitro studies have found that bleach is cytotoxic and can eradicate biofilms but not at doses below 0.01% ( ). Importantly, the use of dilute bleach baths has not been found to be harmful to the epithelial barrier function, nor does it seem to affect epithelial hydration any differently than water, although the data are based on a one-time only exposure ( ).


The initial study that investigated the use of dilute bleach baths was conducted in 2009. Patients with moderate to severe AD were treated with 2 weeks of oral cephalexin and then randomized to receive either intranasal mupirocin and dilute bleach baths or a placebo for 3 months ( ). This study found significant improvement in AD severity and affected area for the treatment group ( ). In the past decade, multiple studies, including three randomized controlled trials (RCTs), have failed to replicate these findings ( ; ; ). Multiple systemic reviews, via pooled data analysis, have also failed to show any statistically significant benefit of dilute bleach baths over regular baths ( ). Yet, each of these reviews has shown that both methods of bathing decrease the severity of AD ( ). The lack of replicable benefit of dilute bleach baths versus regular water baths could indicate that its primary benefit may be via epithelial hydration or that it could be a product of small poorly designed studies. Interestingly, dilute bleach baths side effect profile is not significantly different from regular baths, thus they are frequently recommended as a safe and effective adjunctive strategy ( ).


The Canadian, Italian, and Taiwanese guidelines recommend dilute bleach baths for patients with frequent infections ( ). Considering the cumulative evidence, dilute bleach baths provide a low-cost adjunctive treatment that may provide relief to patients with severe, frequently exacerbated AD and should be recommended for those patients. A few limited studies have investigated the potential use of bleach wipes or body wash containing bleach for those of whom submergent bathing is not feasible ( ). Although early results are promising, they are not readily available as part of clinical practice. In the meantime, these patients may choose to make their own dilute bleach solution and use a soaked gauze to apply to active skin lesions. A 0.005% sodium hypochlorite solution can be made by adding 4.15 mL (~1 tsp) of 6% household bleach to 500 mL of water, and this may be used as a spray-on body wash. Other patients may choose to swim in chlorinated pools; it should be suggested to limit the amount of times going into and out of the pool to curb transepithelial water loss and drying effect. Lastly, patients should be counseled that following sodium hypochlorite exposure, they may briefly rinse the skin with tap water to prevent residual bleach from potentially causing epithelial irritation.


Bath additives


Bath additives most commonly include oils or emollients. Conventional oils are balmandol, paraffin, soybean, mineral, and olive oil surfactant ( ). The primary theory behind their use is that oils leave a film on the skin that can promote hydration as well as functioning as a humectant (retaining moisture) ( ). However, investigational studies have not shown any significant benefit to their use ( ). It is also essential to note that although commonly suggested, olive oil has been shown to negatively impact the epithelial barrier in AD patients ( ). While bath additives are mentioned in a few international guidelines, they cannot be explicitly recommended as a component of care. Patients should be counseled that they can make bath surfaces slippery and can pose a safety hazard in this way.


Other bathing practices


Additional practices worth mentioning include the use of acetic acid (vinegar) baths, the influence of water hardness, home therapies such as addition of oatmeal or rice bran, and balneotherapy. Acetic acid has anti– S. aureus properties, and it has historically been used in the inpatient setting, similar to dilute bleach baths, for patients with AD flares ( ). Although it has decades of historical use, it has not been formally investigated and therefore cannot receive a specific recommendation.


Water hardness also has been thought to be associated with triggering AD. It has been hypothesized that the high concentrations of calcium and magnesium in water could irritate the skin, that hard water contains individual irritants, and that hard water leads to more aggressive soap use that in turn could damage the epithelium ( ). Large-scale epidemiologic studies have failed to identify an association with water hardness and AD ( ). The addition of water softeners also has not been proven to be beneficial ( ).


Oatmeal and rice bran are commonly used home remedies that may be encountered in clinical practice. As oatmeal contains hydrophilic carbohydrates, it is thought to help with epithelial hydration ( ). It also contains vitamin E and saponin, which can be cleansing and antioxidative ( ). Rice bran contains inositol and γ-oryzanol, which can be antiinflammatory by inhibiting NFκB and other acids that are thought to benefit epithelial health ( ). However, robust clinical evidence is lacking for these modalities, and their use cannot be directly recommended.


Balneotherapy involves bathing in mineral springs. This practice is centuries old, and the three most studied geographic areas are the Dead Sea, La Roche-Posay Thermal Center in France, and the Blue Lagoon in Iceland. Each location has different mineral properties, but for AD, they all claim to decrease inflammation and improve skin hydration ( ). Although a few small trials have shown clinical benefit of balneotherapy in AD, there are no robust controlled trials to date. Therefore balneotherapy is likely unfeasible for the majority of patients. Lastly, similar to balneotherapy, families may express interest in the utilization of magnesium (Epsom) salts (MgSO 4 ) and potassium permanganate as Epsom salts are theoretically hydrating and potassium permanganate is an antiseptic. No robust clinical evidence supports their use in AD and therefore they cannot be specifically recommended.


Recommendations


In conclusion, taking into consideration the entirety of the existing evidence around bathing, our recommendations are in concordance with the American Academy of Dermatology and European guidelines as follows:




  • Daily bathing is recommended.



  • Baths/showers with lukewarm water should be less than 10 minutes, followed by the immediate application of emollients.



  • Appropriate cleansers are nonsoap based and neutral to mildly acidic.



  • Cleansers should be applied gently with hands, rinsed off with water, and patted dry.



  • Aggressive physical manipulation and scrubbing, including the use of sponges, wash cloths, and loofahs, should be avoided.



  • Dilute bleach baths can be considered for patients with frequent AD exacerbations or infections as triggers.



  • Bath additives or home remedies should not be explicitly recommended but do not need to be discouraged.



Topical management with antiinflammatories


Topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), and/or phosphodiesterase-4 (PDE4) inhibitors should be considered in patients who fail to respond to gentle skin care and emollient therapy regimens alone. Topical antimicrobials should also be considered as adjunct treatment in appropriate patients. Topical medications contain both active ingredients and vehicles. Table 20.1 depicts the various vehicle contents and their appropriate application conditions.



Table 20.1

Vehicles of topical medications and their appropriate application conditions




































Vehicle type Purpose Example/use
Powder Drying Aesthetically acceptable; hygiene, body folds
Gel, shake suspension Drying, cooling Lightweight, less comedogenic
Liquid (lotion, solution, foam) Drying to neutral Diffuse or hair-bearing surfaces
Oil Neutral to emollient Diffuse surfaces
Cream (water in oil or oil in water) Neutral to emollient Patient preference, elegance, may sting if applied to eroded surfaces
Ointment-paste Barrier/occlusion Protective; diaper, body folds, erosions
Ointment Emollient/occlusion Infants and young children, maximal absorption but greasy, less elegant


Topical corticosteroids


TCS were introduced in the 1950s and subsequently found to be effective for a number of skin diseases. Today there are several preparations and strengths with hundreds of RCTs supporting their efficacy and safety ( ). TCS are considered standard treatment for AD owing to their effective antiinflammatory properties. TCS downregulate T lymphocytes, monocytes, macrophages, and dendritic cells resulting in impaired antigen processing and suppression of proinflammatory cytokine production. As such, TCS are an effective way to treat and/or prevent the pruritus and inflammation associated with AD ( ).


TCS are divided into seven classes based on vasoconstriction properties ( Table 20.2 ). Class VII is the lowest potency; class I is the highest. Patient age, anatomic site of application, and the severity of dermatitis are all important considerations when deciding which class of TCS is appropriate. Additionally, insurance coverage may vary between options within the same class, affecting cost to the patient. Older children and adults may have preferences for TCS vehicle. Petroleum-based products (ointments) may not be realistic during a school day or sports activities as compared to cream formulations that readily absorb, while ointments are preferred for their potency and tolerability in infants who are not affected by the choice of vehicle. Vehicles that contain water or alcohol for consistent emulsification (lotions, foams, and some creams) may be more elegant to use but can also sting on contact, especially to open or eroded skin. Lotions, solutions, gels, and foams are less commonly used for patients with AD compared with other inflammatory skin conditions, but their use may be helpful to consider for scalp and other hair bearing areas. Involving the patient/family in choice of vehicle may improve compliance, as consistency with application when used is integral to therapeutic success. Ensuring families are provided with sufficient quantity of medication and adequate refills is important.



Table 20.2

Topical corticosteroid classification




































Class Potency Examples
VII Low Hydrocortisone acetate cream, ointment, gel, lotion, and solution 0.5%–2.5%
VI Low


  • Alclometasone dipropionate cream and ointment 0.05%



  • Betamethasone valerate lotion 0.05%



  • Desonide cream, gel, ointment, lotion, and foam 0.05%



  • Fluocinolone acetonide cream and solution 0.01%



  • Triamcinolone acetonide cream and lotion 0.025%

V Medium


  • Betamethasone valerate cream and lotion 0.1%



  • Clocortolone pivalate cream 0.1%



  • Fluocinolone acetonide cream 0.025% or oil and shampoo 0.01%



  • Fluticasone propionate cream and lotion 0.05%



  • Flurandrenolide cream and lotion 0.05%



  • Hydrocortisone butyrate cream, ointment, lotion, and solution 0.1%



  • Hydrocortisone valerate cream 0.2%



  • Triamcinolone acetonide ointment 0.025% or lotion 0.1%

IV Medium


  • Betamethasone valerate foam 0.12%



  • Desoximetasone cream 0.05%



  • Fluocinolone acetonide ointment 0.025%



  • Flurandrenolide ointment 0.05%



  • Mometasone furoate cream and lotion 0.1%



  • Triamcinolone acetonide cream and ointment 0.1%

III High


  • Betamethasone dipropionate cream and lotion 0.05%



  • Betamethasone valerate ointment 0.1% and foam 0.12%



  • Fluticasone propionate ointment 0.005%



  • Triamcinolone acetonide ointment 0.1% or cream 0.5%

II High


  • Betamethasone dipropionate cream and lotion 0.05%



  • Desoximetasone cream and ointment 0.25% or gel 0.05%



  • Fluocinonide cream, ointment, gel, and solution 0.05%



  • Mometasone furoate ointment 0.1%



  • Triamcinolone acetonide ointment 0.5%

I Ultrahigh


  • Betamethasone dipropionate ointment 0.05%



  • Clobetasol propionate gel, ointment, cream, lotion, foam, and solution 0.05%



  • Fluocinonide cream 0.1%



  • Flurandrenolide tape 4 mcg/cm 2



  • Halobetasol propionate ointment and cream 0.05%

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Jun 18, 2022 | Posted by in Dermatology | Comments Off on Topical Therapies
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