Role of Actives in Emollients in Atopic Dermatitis

B. S. Chandrashekar1, Thomas Luger2, S. C. Rajendran3, Anchala Parathasaradhi4, Jayakar Thomas5, Anil Ganjoo6, Divya Sharma7, Rajetha Damishetty8, Nazima Ruby9, Vijayalakshmi Sujay10, Snehal Sriram11, Satish Udare12, Dhara Shah13, Jayesh Rajgopal*14

1Chief Dermatologist / Medical Director: Cutis, Academy of Cutaneous Sciences, Bengaluru

2Department of Dermatology, University of Muenster, Muenster, Germany

3Director and Senior Consultant Dermatologist at Cosmetic Skin Care Clinic, Koramangala, Bengaluru

4Senior Consultant Dermatologist at Anchala’s Skin Institute, Hyderabad

5Professor & Head, Chettinad Hospital and Research Institute, Chennai

6Director, Skinnovation Clinics, New Delhi

7Chief Consultant at Dr Divya’s Skin and Hair Solutions, Bangalore

8Additional Medical director, Oliva chain of 23 Hair and Skin Clinics

9Consultant Dermatologist, Radiant Skin Clinic, Bengaluru

10Consultant Dermatologist and Cosmetologist, Shree Skin and Cosmetic Clinic, Bengaluru

11Consultant and Head of Cosmetic Dermatology Department at Nahar Medical Center, Mumbai

12Medical Director of ‘Sparkle’ Skin and Aesthetic Centre, Vashi and ‘Disha Skin and Laser Institute’ Thane, Mumbai

13Head Medical Affairs, Mylan Pharmaceuticals Private Limited - A Viatris Company

14Senior Medical Manager, Mylan Pharmaceuticals Private Limited - A Viatris Company

The prevalence of atopic dermatitis (AD) in India is 2.7% (age 6–7 years) and 3.6% (age 13–14 years). Emollients remain mainstay treatment for atopic dermatitis. The present review article focuses on the role of active ingredients in emollients towards the management of AD. Article were selected by searching in database like Google Scholar and PubMed and were reviewed by the authors. Daily use of emollients from birth may significantly reduce the incidence of AD in a high-risk population. Emollients with a variety of active ingredients to target AD pathophysiology have been developed which contain active ingredients like liquorice extract (anti-inflammatory and anti-pruritic), niacinamide (restoration of barrier function), sterols (restoration of barrier function), laureth-9-polydocanol (anti-pruritic), xylitol (microbiome maintenance) and galacto-oligosaccharide (GOS) (microbiome maintenance). Emollient plus may be a useful adjunct to pharmacological therapy in AD and as maintenance therapy, providing rapid and significant improvements in skin moisture, epidermal barrier function, and signs and symptoms of AD.


Atopic dermatitis (AD) also known as atopic eczema (AE), is a chronic inflammatory, relapsing, and pruritic skin disease that affects patients of all age groups and ethnicities.1 It is characterized by recurrent eczematous lesions 1, and intense itch 1 and is often associated with elevated serum immunoglobulin E (IgE) levels.2 It affects up to approximately 2.4% of the population worldwide 3 and can also appear in adults.1 Onset of AD usually presents by the age of five years, but timely diagnosis and treatment will avoid future complications and improve patients’ quality of life.4 As per the International Study of Asthma and Allergies in Childhood (ISAAC), the prevalence of atopic dermatitis in India is 2.7% (age 6–7 years) and 3.6% (age 13–14 years).5 AD can have a profound, negative effect on the quality of life (QoL), including on social life, education, and work.6

Emollients remain the mainstay treatment for atopic dermatitis as they improve the epidermal barrier function, maintain skin integrity and appearance, reduce trans epidermal water loss, and restore the lipid barrier's ability to attract, hold, and redistribute water.2 The Indian guidelines also recommend the use of Moisturizers & Emollients as a first-line treatment for AD.2 Emollients contain a humectant or moisturizer (promoting stratum corneum hydration) and an occludent (reducing evaporation such as lipids or petrolatum). Emollients containing moisturizers are better compared to those without, for reducing investigator-reported severity and leading to fewer flares and reduced usage of topical corticosteroids (TCS).7 Daily use of emollients from birth may significantly reduce the incidence of AD in a high-risk population 8 although this was not confirmed in a clinical trial done in 1394 infants.9

Emollient Plus is a category of emollients that include extra skin-protecting ingredients. Emollients Plus contains active, non-medicated substances which can improve AD lesions through several synergistic modes of action, including preserving barrier lipid10. Use of Emollient Plus significantly improves clinical signs and symptoms, increases skin hydration, and improves the quality of life of subjects with mild AD as soon as 28 days. In addition, Emollients Plus has corticosteroid-sparing effect in subjects with mild to moderate AD11. This review primarily focuses on the role of active ingredients in emollients towards the management of AD.


The relevant articles were searched on databases like Google Scholar and PubMed using keywords “Atopic Dermatitis”, “Emollient Plus”, “Actives in Emollients”, “Atopic dermatitis management”. Articles which were primarily based on only emollients (without any active ingredients) were excluded from the review. The selected articles were reviewed by the authors and then included in the present article.

New Pathogenic Concepts of AD

The pathogenesis of AD is complex and multifactorial, driven by genetic, immune, and environmental factors.12 A healthy epidermal barrier has a complex composition comprising of structural proteins and epidermal lipids that provide a physical protective barrier against immunological, neuro-sensory, and microbial barrier, and ultraviolet (UV) light injury.13,14 Dysfunction of this epidermal barrier is a characteristic feature of the pathophysiology of AD, attributed to abnormalities in the formation of structural proteins (e.g., filaggrin) and lipid metabolism.15 This disruption allows the entry of external antigens that induce impaired innate immune responses leading to persistent skin inflammation and in turn, further damaging the skin barrier.16,17

Two hypotheses have been proposed for inflammatory lesions in atopic dermatitis which are (i) an imbalance of adaptive immune system; and (ii) defective epidermal barrier.18 An imbalance in T regulatory cells and T-helper cells type 1, 2, 17 and 22 causes an imbalance in the adaptive immune system. The Th2 differentiation of naive CD+4 (Cluster of differentiation) T-cells predominates causing increased production of interleukins (IL) IL-4, IL-5 and IL-13 leading to enhanced IgE level and Th1 differentiation is correspondingly inhibited.18 A defective epidermal barrier occurs due to reduced production of filaggrin and trans epidermal loss of water causing eczema (Fig. 1). Dry skin leads to increased penetration causing allergic sensitization, asthma, and hay fever.18


Figure 1: Mechanism of atopic dermatitis

Claudin-1 is a tight junction protein homogenously expressed in the stratum granulosum, 19 which is reduced in patients with AD. Restoring claudin-1 expression is important for preserving tight junction integrity.20 Involucrin is a cornified envelope-associated protein; reduced expression disturbs barrier function, so increasing involucrin may be beneficial in the skin of patients with AD.21 Caspase-14 is a late epidermal differentiation protein that is reduced in patients with AD. It catalyzes the degradation of pro-filaggrin; thus, is key to the formation of the SC.22 Keratin-16 is a type 1 intermediate cytoskeletal protein expressed in keratinocytes in response to epidermal barrier challenges. Keratin-16 is induced in AD and reducing its expression may help modulate the epidermal innate immune response.23

Preventive Strategies and General Measures

According to European guidelines (EuroGuiDerm) on atopic eczema, therapy with TCS (class II) or topical calcineurin inhibitors (TCI, e.g., Pimecrolimus), antiseptics, silver-coated textiles, topical crisaborole is recommended for mild (SCORAD <25) or transient eczema. Proactive therapy with TCI (Tacrolimus, Pimecrolimus) or TCS (class II or III), wet wraps, UV therapy (UVB 311 nm), psychosomatic counselling and climate therapy is recommended for moderate (SCORAD 25-30) or recurrent eczemas. Hospitalization, biologics such as dupilumab, tralokinumab, Janus kinase inhibitors such as abrocitinib, barictininib, upadacitinib, cyclosporin A, methotrexate, azathioprine, mycophenolate mofetil is recommended for patients with severe (SCORAD >50) or persistent eczema 7. The Indian guidelines also recommend the use of emollients and TCS as first-line therapy for AD.2

Although the efficacy of TCS has been demonstrated, they are associated with impairment of the epidermal barrier function and skin atrophy 24, limiting their use in sensitive skin areas, and preventing long-term use. In addition, patient’s fears of side effects from corticosteroids (i.e., corticophobia) are common.8,25 Emollients remain the mainstay treatment for atopic dermatitis.2 Emollients should be recommended in sufficient quantities, and they should be used liberally and frequently, with a minimum of 250g per week for children. It is also advisable to utilize soap alternatives and emollient bath oils. In the winter, emollients with a higher lipid content are ideal. Regular use of emollient has a short- and long-term steroid-sparing effect in mild-to-moderate AD.

An induction of remission with TCS or TCI is required first.8 Most emollients showed some beneficial effects, producing better results when used with active treatment, prolonging the time to flare, and reducing the number of flares and amount of TCS needed to achieve similar reductions in eczema severity.26 Several non-medicated products containing putative active ingredients are used for topical treatment of AE, referred to as “emollients plus” per European guidelines. Emollients plus contain flavonoids, bacterial lysates, or synthetic derivatives of menthol.7

Rationale for Selected Active Ingredients in a Novel Emollient Plus

Despite an increasing range of topical medications, emollients remain a fundamental part of AD management.27 Emollients with a variety of active ingredients to target AD pathophysiology have been developed.28 A novel generation of Emollient Plus has been developed which could not only act as maintenance therapy for AD but would also have synergistic anti-inflammatory effect.10 Some of the active ingredients present in a novel emollient plus are liquorice extract (anti-inflammatory and anti-pruritic), niacinamide (restoration of barrier function), sterols (restoration of barrier function), laureth-9-polydocanol (anti-pruritic), xylitol (microbiome maintenance) and galacto-oligosaccharide (GOS) (microbiome maintenance) (Fig. 2).


Figure 2: Components of Emollient plus

Inhibition against tumor necrosis factor-α production and nuclear factor-kB activation was seen in peritoneal mouse macrophages pre-treated with glycyrrhetinic acid (one of the main bioactive ingredients in liquorice) for 30 minutes, followed by lipopolysaccharide 100 ng/mL for 24 hours indicating its anti-inflammatory response.29 In a randomized, double-blind, placebo-controlled trial in patients with mild-to-moderate AD (n=90), a 73% reduction in pruritus scores was reported in those treated with liquorice extract 2% versus baseline after 2 weeks.30

 Topical application of niacinamide 0.5% and soy phytosterol 0.5% recovered approximately 95% of epidermal barrier integrity 8 days after tape stripping in six healthy volunteers.31 In a double-blind study involving 41 females with sun-damaged skin, niacinamide 2% twice daily significantly reduced TEWL (by up to 20%) versus control over a 24-day treatment period.32

In cell suspensions from a patient with AD, xylitol 5%/farnesol 0.2% cream inhibited the production of glycocalyx and dissolved fibrin fibers, synergistically inhibiting biofilm formation by S. aureus.33 In a randomized, double-blind, placebo-controlled trial in 17 patients with AD, the ratio of total S. aureus bacteria significantly decreased with xylitol and farnesol after 7 days compared with baseline (p=0.016) and with placebo (p=0.08).34 Polydocanol 3% and urea 5% substantially reduced itching in patients with skin disorders.35

Mode of Action of the Components of Emollient Plus

Liquorice extract

Liquorice contains over 400 compounds, including triterpene saponins and flavonoids 36. The anti-inflammatory effects of liquorice extract are attributed to its flavonoids and other active compounds 36,37. Liquorice flavonoids, such as isoliquiritigenin, mitigate inflammation by inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway via suppression of ERK1/2 and p38 phosphorylation 36. Liquorice flavonoids exhibit antioxidant activity, which can help reduce inflammation by neutralizing reactive oxygen species (ROS), potent inflammatory mediators38. Compounds in liquorice, such as glycyrrhizic acid (GA), liquiritin (LQ), and liquiritigenin (LG), inhibit the elevation of pro-inflammatory mediators like inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and interleukin (IL)-6 in cells37. Liquorice treatment can up-regulate the expression of Claudin in tight junction proteins, improving intestinal mucosal damage and exerting a therapeutic effect39.


Niacinamide plays a pivotal role in NAD+ synthesis, contributing to redox reactions and energy production in cutaneous cells40. This helps restore cellular energy levels and promotes healthy skin function. Niacinamide has been shown to attenuate oxidative stress and inflammatory responses in the skin40. This can help reduce inflammation and promote healing, thereby restoring the skin’s barrier function40. Niacinamide is known to improve skin barrier function and reduce trans epidermal water loss by increasing ceramide and free fatty acid levels41. It also increases production of epidermal proteins, including keratin, involucrin, and filaggrin41.

Galacto-oligosaccharides (GOS)

Galacto-oligosaccharides (GOS) are oligosaccharides formed by β-galactosidase transgalactosylation42. They are indigestible food components that can pass through the upper gastrointestinal tract relatively intact and ferment in the colon to produce short-chain fatty acids (SCFAs) that further regulate the body’s intestinal flora42. GOS ferments in the colon to produce SCFAs42. SCFAs have been shown to enhance the growth of beneficial microorganisms, which can help in alleviating symptoms of atopic dermatitis43. GOS performs well compared to other oligosaccharides in regulating gut microbiota42. This is important because a balanced gut microbiota is associated with improved immune response and reduced inflammation, both of which are crucial in managing atopic dermatitis43. GOS has been found to minimize the production of interleukin-10 and suppress the production of cytokines, such as interleukin 1744. These cytokines are involved in the inflammatory response, so their regulation can help in managing atopic dermatitis44.


Xylitol is known to hydrate the skin and improve its barrier function. In addition to the skin-hydrating properties, xylitol exerts anti-irritant and anti-inflammatory effects in a dose-dependent manner10. This can help reduce the inflammation and irritation commonly seen in AD. Xylitol induces gene expression changes in the keratinocytes which are the primary type of cell found in the epidermis. Xylitol has been found to decrease TEWL in patients with AD after 7 days of use. Xylitol has selective antibacterial and prebiotic activity, which can help maintain the skin microbiome45. A balanced skin microbiome is crucial for maintaining skin health and preventing flare-ups in conditions like AD46.

Novel Emollient Plus in the Management of AD

Several studies, both pre-clinical and clinical, have demonstrated the efficacy and safety of emollient plus in patients with AD (Table 1). In an in vitro study, skin organ cultures were subject to tape stripping (100 repeated applications and subsequent removals of adhesive tapes to the skin surface) as a model for skin barrier damage.10 Emollient plus significantly increased epidermal thickness in organ cultures treated with 100% emollient plus solution versus those treated with diluent solution (p<0.01). The use of emollient plus significantly (p<0.01) increased epidermal thickness, increased claudin-1, caspase-4 and involucrin expression and decreased kerartin-16 expression in organ cultures.47 Emollient plus significantly reduced pruritus in patients compared to baseline (Day 1: 42.6% reduction; Day 21: 40.7% reduction) and untreated areas. Following treatment, pruritus reduced from a mean rating of 5.4 (on a 0–10 VAS) at baseline to 3.1–4.4 across all evaluation time points (3.2 at Day 21). Emollient plus also significantly improved skin moisture levels at each evaluation time point versus baseline in these patients, increasing up to 111.5% at Day 21 versus baseline (mean [SEM]: 27.7 [2.5] vs 13.1 [1.0]; p<0.001).48 In another study, the use of emollient plus significantly reduced pruritis and improved skin hydration in patients with AD.49 Pimecrolimus followed by emollient plus is a useful treatment approach in the management of mild to moderate AD. Emollient plus after Pimecrolimus cream was able to maintain regression of flare-up to at least 4 months in almost all patients. Improvement was seen in all other clinical efficacy outcomes: IGA, erythema, xerosis, oedema, bleeding, excoriations and lichenification, VAS for dryness, itching and sleep loss and the SCORAD score, and was associated with optimal tolerability.49 To date, no adverse events have been reported with emollient plus in patients with AD, and most patients have confirmed that it is cosmetically acceptable. Some clinical researchers were concerned that the use of GA and glycyrrhizin may lead to increased systemic glucocorticoid and mineralocorticoid toxic effects. However, there is no such evidence available till date.50 Prebiotics like galacto-oligosaccharide can reduce AD up to 32% in children 51 although few studies have reported that use of probiotics may cause increased rate of recurrent episodes of wheezing bronchitis in AD patients.52 An open, single center, randomized controlled trial in Slovakia was conducted with 119 patients with mild to moderate AD11. The primary efficacy criterion of the study was the amount of corticosteroid used. The results showed that between baseline and day 28, the mean amount of corticosteroid used was significantly lower in the emollient 'plus' group compared to the control group. The emollient 'plus' group also had fewer days of corticosteroid application and fewer applications per day11. The study demonstrated that the daily use of the emollient 'plus' balm resulted in significant corticosteroid-sparing effects in patients with mild to moderate AD. The emollient 'plus' balm reduced the amount of corticosteroid used, the number of days of application, and the frequency of applications per day. The treatment was well-tolerated and showed similar improvements in AD severity and quality of life compared to the control group11.

Table 1: Studies with novel emollient plus

Study design






Study 1. Gasparri. 2019

Observational pilot study (n=10 AD patients); comparisons were made between treated versus

non-treated areas on each patient

Investigate the efficacy of Emollient plus on skin

moisture, epidermal barrier function, and AD signs and symptoms

Ten otherwise healthy Caucasian adults with clinical signs of AD

Emollient plus applied twice daily to areas of AD on one side of the body, with treated and untreated areas for comparison.

Performed at baseline, 1, and 2 days after the first application of

Emollient plus, and after 7 and 21 days of twice-daily treatment

Significant reduction in pruritus was seen versus baseline (Day 1: 42.6% reduction; Day 21: 40.7% reduction) and versus untreated areas. 80% of patients were ‘satisfied’ or ‘very satisfied’ with Emollient plus

Study 2. Quadri, et al. 2021 – Pre-clinical analysis


An in-vitro study, using a tape-stripping mediated skin barrier disruption model

Investigate the effect of Emollient plus on skin barrier recovery


After tape stripping, epidermal cells were treated with either Emollient plus or diluent (control) and cultured

Samples were analyzed at 18 hours (skin barrier integrity analysis) or up to

120 hours (lipid restoration analysis)


Emollient plus significantly increased epidermal thickness in organ cultures.

Study 3: Quadri, et al. 2021 – Clinical analysis


Double-blind, randomized, placebo-controlled study in patients with mild-to- moderate AD in clinical remission

Evaluate the role of Emollient plus in hydration and vascularization of

the skin

Male (n=10) or female (n=10) between the

ages of 24 and 60 with mild- to-moderate AD in clinical remission phase

Assigned to one of two treatment groups: Group 1: n=10 (5 male), Emollient plus once daily Group 2: n=10 (5 male), placebo once daily

Performed at baseline, and after 1 and 2 months of once-daily treatment with Emollient plus or placebo

After 2 months of treatment with Emollient plus, a significant reduction in epidermal thickness was seen versus placebo

Study 4: Sparavigna, et al. 2019


Single center, randomized, double-blind study in patients with mild AD

Primary objective: efficacy of Emollient plus versus vehicle on pruritus

Patients were male or female aged 24–50 years (mean age: 40 years) with mild AD (SCORAD <25)

Emollient plus (n=58 forearms) or vehicle (n=39 forearms) applied twice daily to the left or right forearm for 28 days

Performed at baseline, and after 14 and

28 days of treatment with Emollient plus or vehicle

Significant reduction of pruritus compared with baseline (T14 d: 53%, p<0.05; T28 d: 89%, p<0.05) and with vehicle (T14 d: 53% vs 23%, p<0.05; T28 d:

89% vs 60%, p<0.05, respectively)

Study 5: Gasparri, et al. 2021


Monocentric, open study in subjects predisposed to AD

Evaluate the changes in skin microbiome after 28 days of treatment versus baseline in Emollient plus - treated areas

Eleven patients considered predisposed to AD: very dry skin; ≥1 episode of dermatitis during life; skin

prone to irritation/erythema; and frequent itching

Emollient plus was applied twice daily between the neck and shoulders for

28 days

To assess alpha microbiome diversity, bacterial DNA

was extracted from treated areas at baseline and after 28 days of treatment

Microbial diversity improved in the majority of subjects following 28 days of treatment with Emollient plus.

Study 6: Sparavigna, et al. 2020


Open-label, single-arm, interventional, multicentre study in patients previously treated with pimecrolimus

Primary objective: Evaluate the time to flare, defined as the time to next disease exacerbation

One hundred and one patients, both genders aged >12 years with

mild-to-moderate AD (IGA=2 or 3), who had responded successfully to 1% pimecrolimus cream

Emollient plus was applied twice daily for 4 months

Performed at baseline, and after 14 days, then every month for 4 months

Emollient plus after 1% pimecrolimus, was able to maintain regression of flare-up to at least 4 months in 99% of the patients. Percentage of patients who had an IGA of 2 decreased over time from 17% at baseline to 2% at Month 4.

Limitations of the Studies

Patients with AD often have increased penetration of allergens, immune dysregulation due to defective skin barrier. 53 Frequent use of emollients and topical medication predisposes the patients towards developing allergic contact dermatitis. 53 Farnesol has been reported to be a contact allergen.54 Galacto-oligosaccharide was also reported to cause allergic reactions among atopic population in Singapore.55 Although most of the studies done with Emollient Plus have shown positive results, these studies have the limitations such as small sample size and single center designs. Most of the studies were done in patients >12 years of age. Patch testing should also be done to check for potential allergens. Clinicians need to be aware that these promising studies may not translate into real-life benefit.


Emollient application should be a key component of atopic dermatitis patients' therapy regimens because there is strong evidence that it can lessen the severity of the condition and the requirement for pharmaceutical intervention. In clinical trials, a novel emollient plus improved several cardinal symptoms and processes implicated in AD, including pruritus, skin hydration and epidermal barrier function. It has also shown to improve cutaneous microbial diversity. The complementary approach with pimecrolimus 1% cream and a new emollient plus is useful in the management of mild to moderate AD. Novel Emollient plus may be a useful adjunct to pharmacological therapy in AD and as maintenance therapy, providing rapid and significant improvements in skin moisture, epidermal barrier function, and signs and symptoms of AD. It can maintain the flare-free period for a long period of time. The choice of applying a cream, ointment or lotion depends on the environmental conditions.56


The authors acknowledge Arghya Bhattacharya, Ph. D for medical writing support (Viatris). The figures were created with

Conflict of Interest

Dr Jayesh Rajgopal and Dr Dhara Shah are employees of Viatris. All other authors have no competing interest.


The medical writing and funding were done by Viatris.

Data Availability Statement

No underlying data was collected or produced in this study.


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Article Info

Article Notes

  • Published on: May 30, 2024


  • Atopic dermatitis
  • Emollients
  • Anti-inflammatory
  • Atopic eczema
  • Emollient plus


Dr. Jayesh Rajgopal,
Mylan Pharmaceuticals Private Limited - A Viatris Company, Bengaluru, India; Orcid Id: 0009-0003-4251-1394; Tel: (+91) 99771 38848;

Copyright: ©2024 Rajgopal J. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License.