Complementary and Alternative Medicines for the Treatment of Atopic Dermatitis

The pathogenesis of atopic dermatitis (AD) is multifactorial, involving a complex interplay between genetic susceptibility, skin barrier abnormalities, immune deregulation, and environmental triggers.^1,2 As such, current therapies for AD embrace a multifactorial approach, with topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI) to target inflammation, emollients to restore the skin barrier, antipruritic agents to help reduce self-inflicted skin damage, and avoidance of exacerbating factors. Due to the complex pathogenesis of AD and adverse effects associated with TCS and TCI, a growing movement has formed among patients, parents, and practitioners seeking alternatives to standard of care (SOC) therapies.³ 

Complementary and alternative medicine (CAM) is a growing field of therapy utilized by more than 30% of AD patients searching for innovative approaches to treatment.⁴ The high prevalence of CAM use in patients with AD may suggest that the treatment expectations of some patients may not be fully met by conventional therapies. According to definitions by the National Institutes of Health, complementary therapies utilize nonmainstream practices in conjunction with SOC or conventional therapies; when these practices are used in place of SOC or conventional therapies, they are considered alternative therapies.⁵ The prevalent and ambiguous advertising often associated with these products may confuse patients and cast doubts on the validity of these treatments to physicians. Additionally, CAM therapies frequently fall outside of SOC because too little evidence exists to determine whether they accomplish their intended purposes. Therapies within CAM for AD can be divided into three categories: natural treatments, diet and supplementation, and mind-body approaches. This article aims to inform readers about the various CAM therapies for AD and their respective efficacies. 

Natural Treatments
Natural herbal therapies have been utilized for a wide range of diseases, including AD. Sunflower seed oil (SSO) can be considered an emollient; 60% of SSO composition is linoleic acid, a necessary fatty acid in the maintenance of epidermal barrier function.^3,6 SSO has a high vitamin E content and can convert linoleic acid to arachidonic acid, a precursor to both prostaglandin E2 and 15-hydroxyeicosatetraenoic acid (15-HETE).^3,6,7 15-HETE inhibits the leukotriene B4-induced chemotaxis of neutrophils, which may decrease cutaneous inflammation in patients with AD.⁷ When applied twice daily to AD lesions, SSO shows a beneficial effect on skin barrier function via improved dermatoscopic features and improved scores in three indexes of severity: Children’s Dermatology Life Quality Index (CDLQI), Eczema Area and Severity Index (EASI), and Investigator Global Assessment (IGA).^3,6

Another natural oil, virgin coconut oil (VCO), is a popular ingredient in hair, skin, and nail products. VCO contains high levels of lauric acid, a fatty acid with antimicrobial and anti-inflammatory properties that may improve the degree of Staphylococcus aureus skin colonization.^1,3,6 In patients with AD, VCO was shown to be superior to virgin olive oil in the clearance of S aureus colonies and more efficacious, lowering the objective component of SCORing of Atopic Dermatitis (SCORAD) indexes after therapy (P=.004).^1,3,6 VCO was also superior to mineral oil as an emollient, improving transepidermal water loss (TEWL) and both objective and subjective components of SCORAD post therapy (P=.0069 and P=.0021, respectively), while simultaneously alleviating symptoms of xerosis including dryness and rash.^1,3

Traditional Chinese herbal therapy (TCHT) treats the perceived underlying imbalances of the body believed by some to cause AD, rather than treating AD itself. TCHT decreases the release of proinflammatory cytokines and chemokines by suppressing the recruitment and activation of eosinophils, increasing treatment efficacy, and decreasing the minimum effective dose of TCS when used complementary to SOC.^1,3,8 Although initially promising, conclusive evidence supporting reduction in AD severity with oral or topical TCHT is lacking.⁹ Additionally, cases of hepatotoxicity and death have been reported with the use of TCHT for the treatment of AD.³ While TCHT may have some therapeutic benefit in AD, long-term safety profiles and the exact combinations of herbal therapies necessary for efficacious treatment are not well defined.³

Borage oil (BO) and evening primrose oil (EPO) were used historically as treatments for AD due to their high content of gamma-linolenic acid, which has been hypothesized to be deficient in patients with AD.¹⁰ Neither oil improves global AD symptoms, thus further studies of BO or EPO are difficult to justify.^10,11

 From biblical references to Greek mythology, therapeutic bathing in mineral water baths or pools has been regarded as a healing solution to patients with chronic skin diseases. Consistent use of these baths is associated with decreased disease severity and improved quality of life measures in AD patients.¹² These minerals are postulated to be immunomodulatory and anti-inflammatory via inhibition of tumor necrosis factor alpha-induced adhesion molecules and modulation of IL-8.¹² However, the concomitant presence of warm weather and sun exposure during time spent in the bathing areas creates difficulty identifying which aspect of therapeutic bathing produces benefits.¹² Warm climates are associated with a lower prevalence of AD, and sun exposure beneficially impacts AD through a similar mechanism to phototherapy.¹² Replication of these mineral baths at home is possible by bathing in a 10% Dead Sea salt solution with narrowband UV-B light. This combination improves the SCORAD index of patients with AD when compared with narrowband UV-B phototherapy alone (P<.001).¹² A follow-up approach to therapeutic bathing in patients with AD involves wet wrap therapy to induce a rapid benefit for patients through occlusive skin moisturization with emollients. The process begins by applying topical medications and moisturizers to damp skin and then immediately covering it with a layer of damp cloth, typically pajamas soaked in warm water with gauze applied to exposed areas.¹² A subsequent layer of dry cloth is then added, and the wrapping is left in place for several hours or overnight.¹² This technique may improve medication efficacy by reducing the total amount of corticosteroid used during treatment periods, potentially decreasing the risk of side effects associated with TCS use.¹² Compared to pretreatment, wet wrap therapy improves the epidermal barrier by increasing the water content of the skin, decreasing TEWL, and acting as a physical barrier to reduce skin trauma associated with scratching.^12,13 

Diet and Supplementation
Diet has long been postulated to be behind the development of as well as a potential cure for AD due to the increased prevalence of food allergies in children with AD.² However, current data is inconclusive and does not support the use of any specific diet in the treatment of AD aside from avoiding proven food allergens. Although strict dietary practice is not recommended as a treatment for AD due to possible consequences of dietary restriction, the American Academy of Dermatology (AAD) does recommend testing for food allergies in children younger than 5 years with intractable AD or known food-induced reactions.¹⁴ 

Treatment of AD with supplementation of vitamins and biotics is a thriving area of research and debate. Microflora alteration through the use of probiotics, prebiotics, and synbiotics may convey allergy protective effects, reducing possible predisposition for AD.¹⁰ Supplementation with probiotics may provide health benefits in AD both by replenishing commensal bacteria essential for stimulating immune system development and by preventing the overgrowth of pathologic bacteria, as microflora diversity prevents the shift toward type 2 helper T cell-mediated immunity and the subsequent development of allergic disease.^10,15 Probiotics decrease the SCORAD index in children with AD as compared with a control group (P<.001), with the strongest evidence supporting Lactobacillus species administered for 12 weeks in children 1 year or older.^10,15,16 Supplementation with Bifidobacterium, another probiotic, may be beneficial in preventing development of AD; infants whose mothers supplemented their diets with Bifidobacterium for the last 4 weeks of pregnancy and who themselves were given powder containing Bifidobacterium with breast milk or formula for the first 6 months of life had a decreased risk of developing AD in the first 18 months of life compared with controls.¹⁷ Bifidobacterium can be found naturally in foods such as kimchi, kefir, yogurt, and sauerkraut.

Prebiotics are foods or supplements containing nondigestible ingredients to stimulate the growth and activity of nonpathologic microorganisms.¹⁰ Naturally occurring sources of prebiotics include artichokes, asparagus, bananas, onions, and garlic.¹⁸ Though not extensively studied, initial results suggest prebiotics alone have similar efficacy to synbiotics for lowering the SCORAD index in children with AD (P<.05).^10,15 Compared with placebo, synbiotics improved SCORAD scores (P=.03) when given to children 1 year or older (P=.048), but supplementation was not beneficial when given to infants younger than 1 year (P=.13).^10,15,19 Improvements in SCORAD were observed when the synbiotics utilized contained mixed strains of bacteria (P=.03) vs single strains of bacteria (P=.22).^10,15,19 While not currently recommended by the AAD, probiotics and prebiotics used in combination hold potential in the treatment of AD. Further understanding of the strains, dosing, and targeted populations would be beneficial.^10,14,15

Though a possible link between vitamin D deficiency and AD has been a research focus, it is uncertain whether low levels of vitamin D are a possible cause or result of chronic inflammation in AD.¹⁰ Vitamin D deficiency is present in some children with AD, but many studies show no correlation between degree of deficiency and disease severity.^10,20 However, other studies demonstrate levels of vitamin D are lower in patients with moderate to severe AD than with mild disease (P<.001).^10,20,21 Because of these conflicting results, there is no current recommendation from the AAD for vitamin D supplementation. In a 2019 meta-analysis, vitamin D₃ supplementation decreased SCORAD and EASI scores when compared with control groups (z = 6.76; P<.00001).²⁰ This supports the efficacy of daily supplementation, especially in patients with moderate to severe AD who may be vitamin D deficient.²⁰

Another vitamin utilized in the treatment of AD is topical vitamin B₁₂ (TB₁₂). TB₁₂ is a scavenger of nitric oxide and successfully lowers the Six Area Six Sign Atopic Dermatitis (SASSAD) scores when compared with placebo in patients with AD (P<.001).²² Two randomized controlled trials support the use of TB₁₂ in treating AD, with both demonstrating decreases in SCORAD scores when compared with placebo (z = 5.77; P<.00001).^15,20 Because evidence for TB₁₂ is limited, further understanding of its potential mechanism and efficacy is indicated to solidify it as a viable treatment option.^15,23

Mind-Body Approaches
Psychological stress is often a component of AD and may exacerbate disease processes.¹⁵ The majority of mind-body approaches within CAM are utilized as complementary treatments in Western medicine to mitigate stress in patients with AD. Hypnosis, biofeedback, and meditation are often used as relaxation techniques to help reduce stress by encouraging mindfulness. One study assessing combined hypnosis and biofeedback in the treatment of AD demonstrated an improvement in subjective assessment of symptomatology when compared with placebo at 8 and 20 weeks of therapy.¹² These techniques have also been suggested as research-based, psychological approaches to control itching and scratching, thus breaking the cycle of AD and allowing skin to heal.²⁴

Progressive muscle relaxation (PMR) is another mental relaxation technique that may be utilized as adjunctive therapy for AD. Compared with a control group given only conventional therapy, the addition of PMR reduces state anxiety scores measured with the State-Trait Anxiety Inventory (STAI) in patients with AD after 1 month of twice-daily incorporation (P=.04).²⁵ The degree of pruritus and loss of sleep also decreased after 1 month in the PMR treatment group (P=.001 and P=.007, respectively).^12,25

Massage therapy (MT) is a physical technique involving the manual manipulation of soft tissue with intentions of promoting health and well-being.²⁶ Massage is well known to relieve stress and anxiety, but MT may also help reduce critical features of AD including pruritus, skin erythema, and xeroderma.²⁶ MT can be used complementary to emollient application, but it is important to test all oils and lotions prior to utilization to pre-identify and avoid possible triggers of AD. MT should be avoided if the skin is compromised thus vulnerable to infection.²⁶

Acupuncture is another technique practiced for centuries as a therapeutic approach to a broad array of pathologies, with recent studies exploring its role in the treatment of AD.²⁷ Qu Chi (LI11), the acupoint located on the lateral end of the transverse cubital crease in the elbow, is commonly targeted for pruritus management.^12,27 Acupuncture use to reduce itch perception, measured by Visual Analogue Scale (VAS), is as effective as cetirizine when comparing preventative interventions for pruritus (P<.05) and superior to cetirizine as an abortive intervention (P<.05).²⁷ Acupuncture also decreases basophil activation, measured by cluster of differentiation (CD) 63 surface expression, improving the IgE-mediated immunity of AD.^27,28 Similarly, acupressure is now being studied as a possible treatment for AD and is useful in patients who may shy away from the idea of needles. Acupressure accesses the same acupoints utilized in acupuncture but applies pressure through a tiny metal pellet instead of puncturing the skin with needles.²⁹ Self-administered acupressure applied at the Qu Chi point used in conjunction with SOC resulted in a decrease in pruritus and lichenification after 4 weeks of therapy (P=.03) compared with SOC alone.²⁹ It is uncertain whether these benefits are produced by local tissue modulation or the global effects of stress reduction and improved well-being seen in acupoint therapies. Despite the potential of these techniques as AD treatments, current evidence of acupuncture as treatment for AD is likely insufficient, revealing a need for further research to assess efficacy.³⁰ 

Conclusion
As more evidence-based research becomes available for many of the CAM therapies discussed above (eTable^{1,3,6-10,12,14-17,19,20,22-29}), it is important for physicians to stay informed about alternate therapeutic approaches in treating patients with AD. Providers who remain aware of the literature surrounding these therapies are equipped to have informative discussions with their patients about the appropriate use of CAM. Practitioners can best provide their expertise to patients by supporting further study of the safety and efficacy of CAM therapies while continuing to treat their patients’ AD with current SOC.⁶

Mr Samsel is a medical student and research fellow at the Center for Dermatology Research in the department of dermatology at Wake Forest School of Medicine in Winston-Salem, NC. Ms Heron is a medical student and research associate at the Center for Dermatology Research in the department of dermatology at Wake Forest School of Medicine. Dr Feldman is with the Center for Dermatology Research and the departments of dermatology, pathology, and social sciences & health policy at Wake Forest University School of Medicine and the department of dermatology at the University of Southern Denmark, Odense, Denmark. Dr Taylor is assistant professor of dermatology at the Center for Dermatology Research in the department of dermatology at Wake Forest School of Medicine.

Disclosure: Dr Feldman has received research, speaking, and/or consulting support from a variety of companies including Galderma, GSK/Stiefel, Almirall, Leo Pharma, Boehringer Ingelheim, Mylan, Celgene, Pfizer, Valeant, AbbVie, Samsung, Janssen, Lilly, Menlo, Merck, Novartis, Regeneron, Sanofi, Novan, Qurient, National Biological Corporation, Caremark, Advance Medical, Sun Pharma, Suncare Research, Informa, UpToDate, and National Psoriasis Foundation. He is founder and majority owner of www.DrScore.com and founder and part owner of Causa Research, a company dedicated to enhancing patients’ adherence to treatment. The remaining authors have no relevant financial relationships.

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