Key points
- •
Current first-line conventional treatments for atopic dermatitis include topical corticosteroids, emollients, and topical and/or systemic immunomodulators (e.g., dupilumab).
- •
However, a majority of patients with atopic dermatitis are interested in or have tried complementary and alternative medicine (CAM) approaches.
- •
CAM approaches with clinical evidence in atopic dermatitis include topical and oral oils, topical and oral micronutrients, bathing additives, fabric selection, and topical endocannabinoids.
- •
Treatment of atopic dermatitis can be augmented with CAM and can be strategically integrated with conventional therapies in appropriate cases.
Introduction
The goals of atopic dermatitis (AD) treatment are to (1) dampen skin inflammation, (2) decrease itch and pain, (3) repair the skin barrier, and (4) restore the microbiome. Conventional treatment of AD is therefore multitiered and includes a combination of emollients, topical antiinflammatory medications, and in more severe cases systemic immunosuppressants and immunomodulators. Conventionally, such immunosuppressants were not target specific and could be poorly tolerated due to their side effect profiles, thus limiting their value in long-term usage. There has not been a safe and efficacious immunosuppressive medication for moderate to severe AD until the recent introduction of dupilumab in 2017. Dupilumab is a monoclonal antibody targeting interleukin-4 (IL4) production approved for use in teens ages 12 to 17 and adults ( ).
While research has made great strides in AD treatment over the last 5 years, a recent survey found that more than half of patients with AD use complementary and alternative medicine (CAM) in addition to their conventional treatments (Darmstadt, 2004). Factors contributing to this staggering number may include treatment resistance or partial response to conventional therapy, safety concerns in infants and children, and the undesirable side effects of long-term topical steroids and systemic agents.
The National Center for Complementary and Alternative Medicine (NCCAM) of the National Insitutes of Health defines CAM as “a group of diverse medical and health care systems, practices, and products that are not presently considered to be part of conventional medicine” ( ). Complementary therapies typically refer to modalities used in tandem with conventional therapies, while alternative therapies are modalities used in place of conventional therapies. We believe that evidence-based CAM modalities may be integrated into conventional treatment plans to improve overall treatment outcomes and/or to limit side effects. For example, certain topical CAM products may reduce topical corticosteroid use and limit skin atrophy and hypopigmentation side effects.
This chapter discusses the existing scientific evidence for CAM in AD, including topical and oral oils, micronutrients, bathing additives, topical endocannabinoids, fabric selection, and cryotherapy. We specifically examine the role of these modalities in augmenting conventional AD treatment. Additional CAM modalities, including acupuncture, acupressure, cupping, herbal supplements, sleep hygiene, and mind-body techniques, will be discussed in Chapter 27 .
Topical natural oils
Natural oils are an attractive treatment modality due to their high free fatty acid (FFA) and triglyceride (TG) content. Long-chain fatty acids, particularly linoleic acid, are components of a healthy skin barrier that are deficient in AD patients ( ). Replacement of these FFAs with topical oils is a potential treatment strategy.
One thing to note is that each topical oil has a unique ratio of FFAs and TGs, which in turn dictates efficacy in AD ( ). For example, oils composed mainly of monounsaturated oleic acid increase skin permeability more than oils containing an even mix of both mono- and polyunsaturated fatty acids. Topical oils also come in various forms and concentrations. When recommending a natural oil to patients, we recommend that patients look for a cold-pressed and/or, virgin natural oil product. Essential oils, which are highly concentrated, and fragranced oils are known triggers of irritant and allergic contact dermatitis and should be avoided in AD patients ( ). A list of topical and oral oils used for AD is summarized in Table 26.1 .
| Oil | Treatment regimen | Studied effect |
|---|---|---|
| Topical oils | ||
| Sunflower seed oil |
|
|
| Sunflower oleodistillate | 2% cream every other day in combo with/topical corticosteroid | Improved lichenification, excoriation, and quality of life ( ) |
| Virgin coconut oil | 2×/day for 8 week | Reduced SCORAD and TEWL ( ) |
| Manuka honey | Daily overnight application for 1 week | Improved atopic dermatitis (AD) lesions ( ) |
| Menthol | 3% cream daily for 1 month | Reduced itch ( ) |
| Tea-tree oil (in acne) | 5% tea-tree oil gel for 3 months |
|
| Olive oil | 6 drops 2×/day for 5 weeks | Reduction in the integrity of stratum corneum and induced mild erythema in participants with and without AD ( ) |
| Combination oils | 100,000 IU of superoxide dismutase and 4% of a combination of plant extracts (blackcurrant seed oil, sunflower oil concentrate, balloon vine extract) | Reduced SCORAD and pruritus as well as improved quality of life ( ) |
| Oral oils | ||
| Hempseed oil | 2 tbsp for 8 weeks | Improved plasma fatty acid levels and reduced dryness and pruritus at 2 weeks ( ) |
Sunflower seed oil
Sunflower seed oil (SSO) contains linoleic acid, an omega-6 FFA, which is a major fatty acid component of the skin barrier. Linoleic acid exerts positive effects through potent activation of peroxisome proliferator-activated receptor-α (PPAR-α)—a nuclear receptor found in skin cells that plays a role in regulating keratinocyte proliferation, maintaining skin barrier homeostasis, and dampening inflammation ( ). PPAR-α has significantly reduced gene expression in both the skin of lesional and nonlesional AD patients, and its loss likely contributes to the dysregulated inflammatory cascade in AD ( ).
Daily SSO application for 4 weeks has been shown to improve skin erythema and transepidermal water loss (TEWL) in AD patients. Long-term usage is likely needed to maintain its beneficial benefits ( ). Studies in children also suggest that SSO may reduce rates of cutaneous infections. A randomized controlled trial (RCT) of preterm infants in Egypt found that topical application of SSO three times daily significantly reduced rates of invasive nosocomial infections compared with infants who did not receive SSO ( ). Another trial found that topical application of SSO significantly reduced mortality rates in preterm hospitalized infants, likely due to enhanced skin barrier integrity ( ). Given its low cost and efficacy, SSO application has a role in skin barrier repair and can potentially be a lifesaving topical treatment for preterm infants in developing countries.
Sunflower oleodistillate
Sunflower oleodistillate (SOD), a derivative of SSO, is produced through a mineral distillation process resulting in a lipid-rich oil composed largely of oleic and linoleic acids. Compared with naturally occurring SSO, the physical processing of SOD results in a product with a 10-fold higher concentration of phytosterols and vitamins ( ). This phytosterol content confers additional antiinflammatory and barrier-promoting promoting properties ( ). A RCT of 86 pediatric patients with moderate AD found that the addition of 2% SOD to conventional topical corticosteroid therapy led to statistically significant improvements in lichenification, excoriation, and quality of life when compared to once- or twice-daily application of steroids alone ( ). SOD appears to decrease steroid requirements and thus may be a safe alternative in patients who cannot tolerate topical corticosteroids ( ).
Virgin coconut oil
Virgin coconut oil (VCO) is produced by a wet-milling and cold-press process that does not involve heat or chemical processing ( ). VCO contains monolaurin, a medium-chain fatty acid that demonstrates broad-spectrum antibacterial activity against Staphylococcus aureus ( ). Patients with AD are frequently and disproportionately colonized by S. aureus when compared to healthy counterparts. A meta-analysis of 95 observational studies in AD patients reported a pooled prevalence of S. aureus colonization of 70% in lesional skin, 39% in nonlesional skin, and 62% in the nares ( ). A double-blind, controlled trial of 52 patients with AD found that VCO significantly reduced the objective-SCORAD severity index (O-SSI) through its antibacterial activity against S. aureus (based on its culture results) and overall antimicrobial activity as compared to virgin olive oil ( ).
In a RCT of 117 pediatric patients with AD, twice-daily application of VCO for 8 weeks led to significant improvements in SCORAD and TEWL as compared to mineral oil ( ). In preterm very low-birthweight neonates who have an immature stratum corneum, VCO has been used to reduce TEWL eventuating in improved barrier function ( ). The efficacy of VCO is theorized to be due to its superior ability to penetrate the skin and reduce inflammation ( ). Due to its safety and efficacy in both adults and children, VCO is a great alternative daily moisturizer for AD patients or an adjunct to current therapy.
Borage seed oil
Patients with AD are thought to have a reduced rate of conversion from linoleic acid to γ-linolenic acid (GLA), dihomo-γ-linolenic acid, or arachidonic acid as compared with healthy subjects ( ). Thus AD patients are deficient in the barrier-forming FFA GLA. Borage seed oil (BSO), which contains 23% GLA, one of the highest concentrations found in a plant, may be helpful in replenishing barrier GLA ( ). To date, topical BSO has not been studied in AD patients. Sparse investigations of oral BSO supplementation and BSO-containing clothing have had mixed results in improving AD symptomatology and severity ( ). Additional studies are needed to elucidate the role of BSO in AD.
Menthol
Cooling baths have been shown to be beneficial in AD patients ( ), and cooling may be one strategy for combating itching sensations. Menthol is a naturally occurring cyclic terpene alcohol that has a cooling and antipruritic effect when applied to the skin. Menthol’s antipruritic properties are due to its activity on the TRMP8 receptor in C fibers (unmyelinated pain fibers) ( ), direct stimulation of A-delta fibers (myelinated pain fibers) ( ), and selective activation of κ-opioid fibers ( ).
An itch-relieving moisturizing cream containing 3% menthol and ceramides significantly reduced itch in healthy individuals and AD patients; however, 1/60 participants reported stinging sensations ( ). Menthol has also been shown to cause allergic contact dermatitis ( ), and high concentration (40%) products may cause erythema and burning ( ). Moreover, menthol promotes TEWL at a level higher than regular rubbing alcohol, so it should be used with caution in xerotic skin, and should not substitute a proper emollient ( ). Larger RCTs are needed to investigate the positive and negative effects of menthol in AD patients. A 3% menthol is the appropriate concentration to recommend to patients with AD who are interested in menthol products.
Tea-tree oil
Tea-tree oil (TTO) is an essential oil derived from the leaves of the Australian plant Melaleuca alternifolia ( ). TTO contains terpinen-4-ol, a potent antibacterial agent against methicillin-resistant S. aureus (MRSA) and was shown to be as effective as topical mupirocin against S. aureus in vivo ( ). TTO has been studied in acne vulgaris, and topical application was shown to have a statistically significant effect on mean total acne lesions ( ). However, to date, no RCTs have been conducted in AD patients. We suggest avoiding all essential oils, including TTO, in AD patients due to their potential for triggering contact dermatitis ( ).
Olive oil
Despite the perceived safety and benefit of most natural oils in AD, olive oil promotes and exacerbates AD. The negative effects of olive oil are due to its high ratio of short-chain oleic to linoleic acid (7:1), which increases TEWL ( ). Oleic acid also disrupts cutaneous homeostasis through its activation of NMDA cell surface receptors, resulting in delayed barrier repair and epidermal hyperplasia ( ). In a RCT, six drops of oil twice daily for 5 weeks led to a significant reduction in the integrity of stratum corneum and induced mild erythema in participants with and without AD, when compared to SSO. These negative effects of olive oil were more prominent in AD patients when compared to healthy counterparts ( ). A clinical trial of 115 healthy neonates found that olive oil is especially damaging to the immature stratum corneum of infants because it disrupts crucial neonatal lipid organization in the skin ( ). Olive oil and related products should be discouraged in AD patients.
Combination topicals
Superoxide dismutase is an antioxidant enzyme that reduces oxidative stress and inflammation and has antipruritic properties in AD. Superoxide dismutase reduces production of nitrogen oxide and inflammatory cytokines such as tumor necrosis factor-α (TNF-α), IL1, and IL6, thereby decreasing itch ( ). A RCT of 20 AD patients (from 8 months to 72 years old) trialed a novel topical agent containing 100,000 IU of superoxide dismutase and 4% of a combination of plant extracts (blackcurrant seed oil, sunflower oil concentrate, balloon vine extract) and found that the topical preparation significantly reduced SCORAD and pruritus as well as improved quality of life ( ). No adverse events were reported. Larger, single-ingredient, placebo-controlled trials of superoxide dismutase are needed before it can be recommended in AD.
Oral oils
Oral hempseed oil
Omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) such as GLA and stearidonic acid (SDA) account for 80% of the composition of hempseed oil. PUFAs are skin barrier building blocks that play a role in regulating permeability and decreasing TEWL ( ). In a RCT of 20 patients with chronic AD, oral hempseed oil significantly improved plasma fatty acid levels and reduced dryness and pruritus at 2 weeks when compared to oral olive oil. While PUFAs are abundant in hempseed oil, olive oil has low levels of PUFAs, which may contribute to its lack of efficacy in AD ( ). The trial reported no adverse events with the use of hempseed oil supplements. Larger, longitudinal (>2 weeks), placebo-controlled studies are needed before oral hempseed oil can be recommended to patients.
Borage seed oil and evening primrose
Two additional oral oils that contain large amounts of PUFAs are evening primrose oil (EPO) and BSO. EPO contains 8% to 10% GLA; BSO contains at least 23% GLA ( ). A 2013 Cochrane review of 27 studies with a total of 1596 patients found that neither oral BSO nor EPO are efficacious in improving global AD symptoms or quality of life. Adverse effects included mild gastrointestinal upset ( ). One case report found an increased risk of inflammation, thrombosis, and immunosuppression with prolonged use of EPO; another study found an increased risk of bleeding with patients on concomitant warfarin therapy ( ). To date, there does not appear to be convincing evidence for either oral EPO and BSO in the treatment of AD. One alarming case report in 2011 found that 1 week of BSO use was associated with development of status epilepticus in a 41-year-old woman ( ).
Topical micronutrients
Vitamin B 12
Vitamin B 12 is a water-soluble vitamin found in several cobalt-bound forms collectively known as the cobalamins. The most common commercial forms of B 12 are cyanocobalamin and methylcobalamin. Vitamin B 12 is crucial for red blood cell production (lack of B 12 leads to megaloblastic anemias), DNA synthesis, and neurologic function. Animal meat from animals that ingest dirt through feeding (e.g., chickens, cattle) are common sources of dietary B 12 . One major action of vitamin B 12 is its inhibition of nitric oxide synthase, attenuating nitric oxide synthesis. Nitric oxide is a small molecule that induces microvascular vasodilation, which manifests as erythema in the skin. Additionally, nitric oxide activates components of the inflammatory response such as T-cell proliferation ( ). In a RCT of 49 adults with AD, topical 0.07% vitamin B 12 applied twice daily resulted in significant improvement of AD symptoms as compared to placebo after 8 weeks. A similarly designed RCT of 21 children with AD found the same results by week 2 of treatment with topical B 12 ( ). Due to its low side effect profile, vitamin B 12 may be recommended following treatment with high-potency glucocorticoids to prevent relapse and is considered safe to use in children ( ). Vitamin B 12 topical cream can be made by a compounding pharmacy using the following ingredients: 0.07 g cyanocobalamin (vitamin B 12 ), 46 g persea gratissima oil (avocado oil), 45.42 g water, 8 g TEGO Care PS or methyl glucose stearate (an emulsifier), 0.26 g potassium sorbate (a preservative), and 0.25 g citric acid. The cream is pink in color due to its B 12 content and has even been referred to as “Pink Magic.”
Oral micronutrients
Vitamin D
Vitamin D or calciferol is a fat-soluble vitamin that exerts its effects on cutaneous homeostasis via regulation of calcium, magnesium, and phosphate levels. The two major forms of vitamin D are D 2 and D 3 (ergo- and cholecalciferol) and are found in dietary supplements and fortified foods. D 2 (ergocalciferol) is human made and added to foods, whereas D 3 (cholecalciferol) is synthesized within the skin from 7-dehydrocholesterol. Vitamin D deficiency has been associated with AD severity. Serum levels of 25-hydroxycholecalciferol of 40 to 60 ng/mL are recommended for proper immune function ( ). A 2019 systematic review concluded that vitamin D oral supplements decrease eczema severity in adults and children with AD ( ). In two similarly designed RCTs, daily vitamin D 3 supplementation at 1000 IU improved global investigator scores (IGA) and eczema severity (EASI) after just 1 month ( ). Another RCT found that daily supplementation for 60 days with 1600 IU vitamin D 3 led to significant improvements in SCORAD and Three-Item Severity Score (TIS) when compared to healthy controls ( ). Although largely positive effects have been reported, mixed efficacy of vitamin D in AD patients was reported in two small RCTs ( ). Given the positive results in AD patients, safety, and low cost, vitamin D should be considered as an adjunct in both adult and pediatric patients.
Vitamin E
Vitamin E, also known as tocopherol, is an antioxidant that has been shown to decrease levels of serum immunoglobulin E (IgE) in AD patients ( ). A RCT of 70 adults with AD found that supplementation with oral vitamin E (400 IU/day for 4 months) significantly improved AD symptoms as compared to placebo, and these effects were sustained for 3 months after treatment ( ). A similar single-blinded RCT of 96 patients with AD showed that oral vitamin E (400 IU/day for 8 months) led to significant improvements in AD symptoms and a decrease in serum IgE in 50% of patients. A RCT of 44 patients examined the effects of combination vitamin E with additional emollients and antioxidants into a nonsteroidal cream (MD 2011001) and found significant reductions in AD symptoms ( ).
In a randomized, double-blind, placebo-controlled trial of 45 patients, an association between vitamin E plasma levels and SCORAD was noted after supplementation, but no correlation was found between vitamin D plasma levels and SCORAD. However, the greatest SCORAD reduction was observed in a third, combination treatment arm receiving both vitamins D and E, which suggests a potential synergistic relationship ( ). A RCT of 58 adults and children with AD supplemented with either vitamin D 3 at 5000 IU/day or placebo for 3 months found that serum levels of vitamin D 3 greater than 20 ng/mL in conjunction with standard therapy reduced SCORAD ( ). Regardless of treatment group, a lower SCORAD correlated with serum levels of 25(OH)D 20 ng/mL and above, and no significant differences were noted between patients with serum levels of 20 ng/mL and above versus 30 ng/mL and above ( ).
Low-dose vitamin E supplementation may be an effective adjunctive therapy for AD patients ( ). Research has not found any adverse events with consumption of vitamin E in food products; however, vitamin E supplementation has a known potential to disrupt the clotting cascade and platelet activation. It should be used with caution and/or avoided in patients on anticoagulants (e.g., warfarin, novel oral anticoagulants [NOACs]) or those with hemophilia.
L-histidine
L-histidine is an amino acid that supports the skin barrier formation. Filaggrin, an important protein that contributes to barrier function, relies on histidine for enhanced processing ( ). Both filaggrin mutations and L-histidine deficiency in the skin have been linked with the development of AD in adults and infants ( ). In a double-blind, randomized pilot study of 24 adult AD patients, 4 g of oral L-histidine supplements significantly reduced AD severity after 4 weeks of treatment as compared to placebo with no reported adverse effects. The clinical effects of L-histidine were similar to that of midpotency topical corticosteroids, suggesting that L-histidine may be a safe, nonsteroidal approach to AD ( ). However, larger RCTs are needed to confirm these findings before further recommendations can be made.
Bathing additives
Bathing additives and oils are substances added to bath water for their antiinflammatory, skin barrier repair, antimicrobial, and antioxidative properties. They are most useful as an adjunct treatment for inflammatory dermatoses affecting a large body surface area. Patients using bathing oils should be reminded of the potential for falls due to oily skin after product use. Clinicians should recommend that patients gently towel off excess oil from the skin after bathing before stepping out of the tub or shower. A list of bathing additives used for AD is depicted in Table 26.2 .
