¹Faculty of Medicine, University of Toronto, Toronto, ON, Canada
²Windsor Clinical Research, Windsor, ON, Canada
³Western University, Schulich School of Medicine, Windsor, ON, Canada

Conflict of interest:
Cindy Kang and Monica Shah have no conflicts of interest to disclose. Jerry Tan has been a consultant, investigator and/or speaker for Almirall, Bausch, Boots/Walgreens, Cipher, Galderma, L’Oréal, Promius, Sun and Vichy. Disclaimers: This manuscript is an original submission. Views expressed in the submitted article are our own and not official positions of our institutions.

Abstract:
The diagnosis and classification of rosacea has been modified to reflect presenting features. On exclusion of differentials, the diagnosis of rosacea is based on the presence of either (1) phymatous changes, or (2) centrofacial persistent erythema. In their absence, diagnosis can be established by presence of any two of: flushing/transient erythema, papules and pustules, telangiectases, or ocular manifestations. Management of rosacea depends on presenting feature(s), their severity, and impact. General management includes gentle skin care, sun protection, and trigger avoidance. Evidence-based treatment recommendations include topical brimonidine and oxymetazoline for persistent erythema; topical azelaic acid, ivermectin, metronidazole, minocycline and oral doxycycline, tetracycline and isotretinoin for papules and pustules; vascular lasers and light devices for telangiectases; and omega-3 fatty acids and cyclosporine ophthalmic emulsion for ocular rosacea. While surgical or laser therapy can be considered for clinically noninflamed phyma, there are no trials on their utility. Combination therapies include topical brimonidine with topical ivermectin, or topical metronidazole with oral doxycycline. Topical metronidazole, topical ivermectin, and topical azelaic acid are appropriate for maintenance therapy. In conclusion, the updated phenotype approach, based on presenting clinical features, is the foundation for current diagnosis, classification, and treatment of rosacea.

Key Words:
alpha-adrenergic agonist, anti-parasitic, antibiotic, diagnosis, dicarboxylic acid, erythema, laser therapy, management, phenotype approach, phyma, retinoids, rosacea, telangiectasia

Table of Content:

1. Introduction
2. Quality of Evidence
3. Diagnosis
4. Evaluation and Differential Diagnosis
5. Associated Comorbidities
6. Management
7. Conclusion

Introduction

Rosacea is a chronic inflammatory dermatosis affecting the centrofacial region (cheeks, chin, nose, and central forehead), with a prevalence of 5.5% of the adult population.¹ While rosacea has been considered to primarily affect fair-skinned individuals, this may be due to difficulty in detecting facial redness in darker skin types. Nevertheless, rosacea patients of Asian, Hispanic, or African ancestry have been described in literature.² Women are more likely to develop rosacea, however, when present in men, the disease tends to be more severe.³ The typical age of onset is after 30 years old;^4,5 however, ocular rosacea can occur as early as 22 months of age.⁶ Pediatric rosacea is rare and is usually associated with a family history of the condition.^6,7 Ocular manifestations of rosacea occur in more than 50% of rosacea patients.⁸

There are several flare triggers in patients with rosacea including temperature changes, heat, cold, exercise, ultraviolet radiation, spicy food, and alcoholic beverages.⁹ Microbes have also been implicated in the pathophysiology of rosacea, including Demodex species, Bacillus oleronius, Staphylococcus epidermidis, Helicobacter pylori, and Bartonella quintana.¹⁰ The immune system, neurogenic inflammation, and vascular hyperreactivity are central to the pathophysiology of rosacea. Specifically, innate immune system activation via toll-like receptor 2 (TLR2), transient receptor potential (TRP) ion channels, and proinflammatory cytokines contribute to clinical manifestations of rosacea.¹¹

Rosacea has a significant impact on the emotional, social, and occupational wellbeing of affected individuals. Due to the altered facial features characterising this disease, patients with rosacea frequently experience stigmatization. Consequently, they can suffer from depression and anxiety and tend to avoid social situations.¹²

The phenotype approach establishes diagnosis and management based on the presenting features of the individual.¹³ While previously classified according to subtypes, each potentially comprising multiple signs and symptoms, this nomenclature should be abandoned as it limits the ability to study, evaluate, and treat individual features.¹³ The phenotype approach more accurately addresses patient features and can facilitate focused treatment on those of greatest severity and impact.¹³ Thus, this review provides an overview of the updated phenotype approach in the diagnosis and management of rosacea.

Quality of Evidence

The PubMed database was searched for systematic reviews, meta-analyses, and guidelines on the diagnosis, classification, and management of rosacea, with a focus on phenotypes. Key words included “rosacea” and “diagnosis” or “classification” or “management” or “guidelines” or “treatment”. There were no limits on age, sex, or nationality or year of publication. Only studies published in English on human subjects were included.

Diagnosis

The diagnosis of rosacea is clinical and based on specific features according to the ROSacea COnsensus expert panel (ROSCO)¹³ and the National Rosacea Society (NRS).¹⁴ On clinical exclusion of other conditions with similar presenting features, the diagnosis of rosacea is established with either: (1) phymatous changes, or (2) centrofacial persistent erythema (Table 1).^13,15 In their absence, diagnosis can be established by the presence of any two of the following major features: flushing/transient erythema, papules and pustules, telangiectases (Table 1), or ocular rosacea (Table 2).^13,15 Minor features, such as burning, stinging, dry sensation of the skin, or edema are not diagnostic of rosacea (Table 1).¹⁵ The diagnosis of rosacea in darker skin types (Fitzpatrick phototypes V and VI) is difficult as erythema and telangiectasia may not be readily visible, and a high level of suspicion based on minor features is required. A less common variant of rosacea is granulomatous rosacea, with multiple brown, yellow, or red cutaneous papules of uniform size. Occasionally, skin biopsy may be useful for diagnostic support.¹³

Table 1: Descriptions of cutaneous rosacea features by consensus

Consensus of an expert panel of 19 dermatologists from Argentina (n = 1), Brazil (n = 1), Canada (n = 1), France (n = 1), Germany (n = 2), India (n = 1), Italy (n = 1), the Netherlands (n = 1), Qatar (n = 1), Singapore (n = 1), South Africa (n = 1), the U.K. (n = 1) and the U.S.A. (n = 6); and two ophthalmologists from Germany (n = 1) and the U.S.A (n = 1). Some panellists abstained when their clinical expertise did not extend to a particular subject.
Reprinted from Schaller M. et al., 2019, Br J Dermatol, 176, p. 1273.¹⁵

Table 2: Descriptions of ocular rosacea features

Note that these are recommendations rather than consensus due to n = 2. Both ophthalmologists voted ‘Agree’ or ‘Strongly agree’ to the descriptions.
Consensus of an expert panel of 19 dermatologists from Argentina (n = 1), Brazil (n = 1), Canada (n = 1), France (n = 1), Germany (n = 2), India (n = 1), Italy (n = 1), the Netherlands (n = 1), Qatar (n = 1), Singapore (n = 1), South Africa (n = 1), the U.K. (n = 1) and the U.S.A. (n = 6); and two ophthalmologists from Germany (n = 1) and the U.S.A (n = 1). Some panellists abstained when their clinical expertise did not extend to a particular subject.
Reprinted from Schaller M. et al., 2019, Br J Dermatol, 176, p. 1274.¹⁵

Evaluation and Differential Diagnosis

Differential diagnoses of rosacea depend on the clinical feature(s) present (Table 3). Examples include contact dermatitis, photodermatitis, seborrheic dermatitis, and systemic lupus erythromatous for facial erythema; perimenopausal flushing, emotional flushing, carcinoid syndrome, and mastocytosis for flushing; and acne vulgaris and folliculitis for papules and pustules.¹⁶ Exclusion of mimics can be established by taking an adequate history, performing a directed physical evaluation for distinguishing features, and further testing as required.

Table 3: Differential diagnoses of rosacea

Information from Asai et al., 2016,¹⁶ Ogé et al., 2015,¹⁹ Scheinfeld et al., 2010,⁵⁵ and Izikson et al., 2006.⁵⁶

Associated Comorbidities

Associations between rosacea and metabolic, cardiovascular, gastrointestinal (GI), neurologic, and psychiatric diseases have been established (Table 4).¹⁷ Some of these share common innate inflammatory elements with rosacea, such as macrophage and macrophage-derived mediators, reactive oxygen species, matrix metalloproteinases, interleukin-1b (IL-1b), and tumor-necrosis-factor (TNF).¹⁸

Table 4: Rosacea and associated comorbidities

CI = confidence interval, N/A = not available, OR = odds ratio, P = probability

Management

The goals of rosacea treatment are to reduce the severity of features and the frequency and intensity of flares.¹³ General management includes routine skin care: gentle cleansers, moisturizers, sun protection, and avoidance of triggers.^16,19 Specific treatments should be targeted at clinical features (Table 5 on pages 7-8). If multiple features are present, combination treatment should be considered.¹⁶ The phenotype approach allows for such feature-based treatment according to the severity and impact of the presentation.²⁰ An updated systematic review of rosacea treatment based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework, is outlined below (Table 5).²¹

Table 5: Treatment recommendations and certainty of evidence

CI = confidence interval, Er:YAG = erbium-doped yttrium aluminium garnet, I2 = heterogeneity, IPL = intense pulsed light, MD = mean difference, MR = modified release, N/A = not available, Nd:YAG = neodymium-doped yttrium aluminum garnet, NNTB = number needed to benefit, NNTH = number needed to harm, PDL = pulsed dye laser, P = probability, RCT = randomized controlled trial, RR = relative risk
Information from van Zuuren et al., 2019.²¹

Flushing/Transient Erythema

No randomized controlled trials available.

Persistent Erythema

Evidence to support the efficacy and safety in transient reduction of persistent erythema was derived from two randomized vehicle-controlled trials for topical brimonidine 0.33% gel²² and topical oxymetazoline 1% cream.^23,24 Quality of evidence for efficacy was reported as high-certainty for brimonidine 0.33% gel and moderate-certainty for oxymetazoline 1% cream.²¹ Adverse event frequency was similar to vehicle for both brimonidine²² (moderate-certainty evidence)²¹ and for oxymetazoline^23,24 (moderate-certainty evidence).²¹ In both, there is ongoing concern about the potential risk of worsening erythema with repeated use.^25,26

Papules and Pustules

Dicarboxylic Acids

Topical azelaic acid 15% foam twice daily is a safe and effective treatment for papules and pustules^27,28 (high-certainty evidence)²¹ with an adverse event frequency similar to vehicle^27,28 (moderate-certainty evidence)²¹ according to two randomized vehicle-controlled trials.^27,28

Another randomized controlled trial showed that azelaic acid 15% gel may be more effective in reducing mean nominal lesion count than metronidazole 0.75% gel²⁹ (moderate-certainty evidence).²¹ These differences, however, were not reproducible and were considered to be unimportant.^30,31

Antiparasitics

Topical ivermectin 1% cream once daily is more effective in the treatment of papules and pustules compared to vehicle³² (high-certainty evidence),²¹ and compared to metronidazole 0.75% cream twice daily³³ (moderate-certainty evidence).²¹ Adverse event rates for topical ivermectin were similar compared to vehicle³² (moderate-certainty evidence)²¹ and topical metronidazole.³³

Retinoids

In two randomized controlled trials, low-dose oral isotretinoin 0.25 mg/kg and low-dose oral isotretinoin 0.30 mg/kg were more effective than placebo³⁴ (high-certainty evidence)²¹ and oral doxycycline (100 mg for 14 days, then tapered to 50 mg)³⁵ (moderate-certainty evidence),²¹ respectively. The frequency of adverse events was higher for isotretinoin compared to placebo³⁴ (moderate-certainty evidence),²¹ but similar to oral doxycycline³⁵ (moderate-certainty evidence).²¹

Antibiotics

Several randomized vehicle- or placebo-controlled trials demonstrated the efficacy of topical metronidazole 1% cream,^36-38 topical minocycline 1.5% and 3% foam,³⁹ oral doxycycline 40 mg modified-release (MR),⁴⁰ and oral tetracycline 250 mg twice daily^41,42 in the treatment of papules and pustules. The quality of evidence for efficacy was moderate-certainty for the first three treatments, but low-certainty for oral tetracycline.²¹ Adverse event frequency was similar to vehicle/placebo for topical metronidazole^36-38 (moderate-certainty evidence),²¹ oral doxycycline,⁴⁰ and oral tetracycline,^41,42 but higher than vehicle for topical minocycline39 (moderate-certainty evidence).²¹ Topical clindamycin 1% cream or gel was found to be no more effective than vehicle for any outcome⁴³ (low-to-moderate certainty evidence).²¹ Compared to oral doxycycline 40 mg MR, oral minocycline 100 mg is similarly effective⁴⁴ (moderate-certainty evidence)²¹ with no differences in the rate of adverse events⁴⁴ (low-certainty evidence).²¹ Compared to oral doxycycline 100 mg, oral azithromycin 500 mg three times a week then tapered is similarly effective in reducing lesion counts⁴⁵ (very low-certainty evidence).²¹ Finally, 40 mg MR doxycycline is as effective as 100 mg with fewer side effects.⁴⁶

Telangiectases

There is low-to-moderate certainty evidence that long pulsed dye laser (PDL), neodymium-doped yttrium aluminum garnet (Nd:YAG) laser, and intense pulsed light (IPL) therapy reduce telangiectasia.²¹

Clinically Non-inflamed Phyma

Physical modalities, such as ablative laser surgery using carbon dioxide or erbium-doped yttrium aluminium garnet (Er:YAG) modalities, electrosurgery, or cryosurgery, may improve clinically noninflamed phyma.¹⁶ However, it is difficult to determine their effectiveness due to the lack of evaluation by randomized controlled trials.^16,21

Clinically Inflamed Phyma

While there are no randomized controlled trials evaluating the efficacy of treatments for clinically inflamed phyma, oral doxycycline or oral isotretinoin are still recommended.^16,21

Ocular Rosacea

One randomized placebo-controlled trial supported omega-3 fatty acids (180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid) one capsule twice daily⁴⁷ (moderate-certainty evidence)²¹ in the treatment of ocular rosacea. Another randomized controlled trial supported cyclosporine ophthalmic emulsion 0.05% twice daily versus artificial tears⁴⁸ (low-certainty evidence)²¹ and versus oral doxycycline 100 mg twice daily for the first month followed by 2 months once daily⁴⁹ (low-certainty evidence).²¹ For the cyclosporine ophthalmic emulsion, there were no differences in the rate of adverse events compared to artificial tears (low-certainty evidence).²¹ For severe ocular rosacea or when there is diagnostic uncertainty, referral to an ophthalmologist should be arranged.²¹

Combination Therapies

Treatment combinations may address several different clinical features of rosacea. For example, compared to vehicle, topical brimonidine 0.33% gel with topical ivermectin 1% cream can effectively reduce both erythema and papules and pustules.⁵⁰ Compared to metronidazole 1% gel alone, metronidazole 1% gel with oral doxycycline 40 mg MR can reduce lesion counts to a greater extent.⁵¹

Finally, randomized controlled trials reported no difference in efficacy between oral minocycline 45 mg with or without topical azelaic acid 15% gel⁵² (moderate-certainty evidence)²¹ or between topical clindamycin phosphate 1.2% with tretinoin 0.025% gel compared to placebo⁵³ (moderate-certainty evidence).²¹ However, in the latter, there was a higher rate of adverse events in the topical clindamycin/tretinoin group compared to placebo (moderate-certainty evidence).²¹

Maintenance Therapies

Topical metronidazole 0.75% gel, ivermectin 1% cream, and azelaic acid 15% gel are reported as effective and safe for maintenance therapy of papules and pustules.^21,54

Conclusion

The diagnosis and classification of rosacea has evolved to a phenotype approach to accurately address the clinical features presenting in an individual and to advance epidemiological and clinical trials research.¹³ This review details the rosacea phenotype approach to diagnosis and classification, and summarizes current evidence-based treatment recommendations for individual features. There is no singularly effective treatment for all features of rosacea. There is an unmet need for high quality investigations for treatment of inflamed phyma, flushing/transient erythema, and ocular rosacea.

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¹Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
²Division of Dermatology, Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
³Lynde Institute for Dermatology, Markham, ON, Canada

Conflict of interest:
Funding sources: None. Conflicts of interest: Sara Mirali has no conflicts of interest to declare. Patrick Fleming has received honorarium and/or consulting and/or advisory boards and/or speaking fees for AbbVie, Altius, Amgen, Aralez, Bausch Health, Cipher, Galderma, Eli Lilly, L’Oréal, UCB, Janssen, Novartis, Pfizer, and Sanofi-Genzyme. Charles Lynde has acted as a principal investigator, speaker and/or consultant and/or advisory board member for AbbVie, Amgen, AnaptysBio, Avillon, Arcutis, Bristol-Myers Squibb, Celgene, Cipher, Genentech, GlenMark, Incyte, Janssen, Leo Pharma, L’Oréal, Kyowa, Pfizer, Merck, Novartis, and Sanofi.

Abstract:
During the COVID-19 pandemic, prolonged usage of personal protective equipment (PPE) and frequent handwashing has exacerbated or caused skin diseases, particularly amongst frontline workers. Skin conditions, such as atopic dermatitis, irritant contact dermatitis, and hand eczema, affect patients’ quality of life and their ability to work. These conditions can be managed by frequent moisturization and washing with gentle cleansers. In this review, we discuss the properties of effective moisturizers and cleansers for patients with skin diseases related to enhanced infection control procedures.

Key Words:
COVID-19, personal protective equipment, PPE, skin pH, eczema, atopic dermatitis, irritant contact dermatitis, acne, hand eczema

Table of Content:

1. Introduction
2. PPE-related Dermatitis
3. Moisturizers
4. Hand Eczema
5. Cleansers
6. Conclusion

Introduction

During the COVID-19 pandemic caused by the novel coronavirus SARS-CoV2, health authorities advised frontline workers and the public to take infection control precautions. Current evidence suggests that COVID-19 is transmitted through respiratory droplets and contact with contaminated surfaces.¹ To prevent transmission, frequent handwashing and prolonged usage of personal protective equipment (PPE), such as goggles, masks, face shields, and gloves, are recommended. These enhanced precautions can cause or exacerbate inflammatory skin conditions, which impact patients’ quality of life and, in some cases, their ability to work.² Moreover, associated symptoms, such as pruritis affecting the face, increase the risk of transmission.

Recent studies have shown that 75-97% of healthcare workers (HCWs) treating COVID-19 patients suffered from adverse skin reactions, including contact and pressure urticaria, rosacea, perioral dermatitis, contact dermatitis, or aggravation of preexisting skin disorders. The most commonly affected areas were the hands, cheeks, and nasal bridge.^2,3 These adverse effects are not restricted to HCWs4 and are mainly caused by the hyperhydration effects of PPE, friction, epidermal barrier breakdown, and contact reactions. All of these can aggravate preexisting skin diseases or cause new skin diseases, many of which can be controlled with proper moisturization. In this review, we discuss the role of moisturizers and cleansers in the management of skin conditions caused by frequent handwashing and PPE.

PPE-related Dermatitis

Atopic dermatitis (AD) and irritant contact dermatitis (ICD) are common types of eczema that are characterized by pruritus, eczematous lesions, xerosis, and lichenification. AD is a chronic relapsing inflammatory skin condition that often develops at a young age, while ICD is caused by direct contact of the skin with environmental, chemical, or physical agents that disrupt the epidermal barrier.^5,6 AD and ICD can be exacerbated or caused by wearing PPE for long periods of time.^2,3

Prolonged usage of PPE can also exacerbate or cause acne vulgaris.^7,8 The tight seal and humid environment created by masks, particularly N95s, aggravates acne (also known colloquially as maskne). This is likely because pressure on the skin can rupture comedones and block pilosebaceous ducts. Moreover, the humid microclimate within the mask is ideal for bacterial growth and prevents filaggrin (FLG) breakdown, which contributes to skin barrier disruption.^8,9 In addition to AD and acne, masks can exacerbate other inflammatory skin disorders, such as rosacea and perioral dermatitis.^7,8

Moisturizers

Moisturizers are widely used to treat AD and ICD. Moisturizers treat damaged skin by repairing the stratum corneum, increasing hydration, and reducing transepidermal water loss (TEWL). In addition to restoring the skin barrier and relieving symptoms, frequent use of moisturizers can reduce the need for topical steroids.¹⁰ While steroids may reduce inflammation, they can also compromise the skin barrier and increase TEWL.¹¹

An effective moisturizer should contain an occlusive barrier, humectants, and emollients (Table 1). Occlusives block TEWL by forming a film on the surface of the skin, while humectants retain moisture by attracting water from the environment and from the dermis. Emollients soften the skin by repairing the stratum corneum’s lipid-rich matrix and filling the spaces between desquamating corneocytes.

Table 1: Basic properties of an effective moisturizer

PCA = pyrrolidine carboxylic acid; TEWL = transepidermal water loss

Treatment with moisturizers is largely based on patient compliance. Consumer preferences must be taken into account as compliance will likely be poor if patients are unsatisfied with the treatment.¹² An ideal moisturizer should be non-irritating, hydrating, cosmetically appealing, pH balanced, and contain ceramides.^10,13,14 Moreover, an ideal moisturizer should be inexpensive and widely available.

Non-irritating

Sensory reactions are a common adverse effect of moisturizers. Sensory reactions consist of burning or stinging sensations without evidence of inflammation.¹⁵ Although urea, lactic acid, and pyrrolidine carboxylic acid (PCA) are clinically effective humectants, they cause irritation in some patients, particularly in those with damaged skin.^12,16,17 In contrast, the humectant glycerin is well-tolerated.¹⁶ Preservatives, such as benzoic acid and sorbic acid, can also cause irritation (Table 2).^12,17

Table 2: Side effects of moisturizers and potential causes

Adapted from Lynde et al.²³
PCA = pyrrolidine carboxylic acid
MCI/MI = methylchloroisothiazolinone/methylisothiazolinone

Fragrances are the most common allergen found in moisturizers and are the most frequent cosmetic cause of allergic contact dermatitis.^18,19 Fragrances can also cause photo contact dermatitis and contact urticaria.²⁰ Moisturizers should be fragrance-free and fragrance-related allergens, such as benzyl alcohols, essential oils, and biologic additives should also be avoided.¹⁸ dermatitis and contact urticaria.²⁰ Moisturizers should be fragrance-free and fragrance-related allergens, such as benzyl alcohols, essential oils, and biologic additives should also be avoided.¹⁸

Moisturizers may contain or be used alongside treatments for acne vulgaris, such as retinoids and benzoyl peroxide. These compounds can disrupt the skin barrier and cause further irritation, particularly if patients recently integrated them into their skincare routine.²¹ To prevent maskne, skincare routines should be limited to a pH-balanced gentle non-soap cleanser and mild moisturizer free of irritants. Products with a physiological skin surface pH (4.0-6.0) should be used to reduce inflammation and improve skin barrier function.²² Changes in skincare routine (i.e., addition of a retinol) should be incorporated with caution because mask occlusion may worsen irritation from new products. Likewise, cosmetic products should not be used as mask occlusion will intensify product delivery to the skin, increasing irritation and maskne.

Hydrating Properties

Moisturizers derive their hydrating properties from humectants that attract water from the dermis and from the external environment. Within the stratum corneum, corneocytes contain natural moisturizing factors (NMF), a humectant mixture derived from amino acids and salts. NMF are made of amino acids produced by the breakdown of the protein FLG, which retains water within the corneocytes and maintains skin hydration.²⁴ Patients suffering from AD are deficient in FLG, resulting in increased TEWL and impaired skin barrier function.²⁵ Moisturizers containing FLG breakdown products have been shown to improve barrier function in AD patients.²⁶

Commonly used humectants include the FLG breakdown products lactic acid and PCA, as well as urea. Another frequently used humectant is hyaluronic acid, which has been shown to be efficacious in mild-to-moderate AD.²⁷ If patients are sensitive to these humectants, a moisturizer with glycerin should be considered. Glycerin is an effective humectant that is inexpensive and well-tolerated.¹⁶ Because humectants draw up water from the dermis, they must be used in combination with an occlusive agent to prevent TEWL.²⁸

Cosmetically Appealing

Moisturizers are formulated to be non-greasy, non-comedogenic, and smoothing. The consistency of a moisturizer depends on its emulsification. Creams are available as water-in-oil (W/O) or oil-in-water (O/W) emulsions. O/W emulsions are less viscous compared to W/O emulsions, which have an oil content between 15-30%. A higher oil content retains more moisture but increases the greasiness of the product.¹⁵

New emulsion technologies allow for better delivery of active ingredients. Multivesicular emulsions (MVE^®) are multi-lamellar emulsions with a series of concentric spheres containing oil and water. Ingredients are stored within the oil or water phases and layers are released slowly over time. While traditional emulsions release all of their ingredients at once, MVEs^® allows for sustained release, increasing the effective duration of the product.²⁹

pH Balanced

Normal physiological skin surface pH ranges from 4.0-6.0 but is elevated in AD, ICD, and acne.^30-32 Elevated skin pH can result in inflammation, disrupted stratum corneum cohesion, and impaired skin permeability. Moreover, for individuals with acne-prone skin, high pH moisturizers can interfere with the efficacy of topical acne treatments.^22,33 To improve skin barrier function, moisturizers at physiological skin surface pH (4.0-6.0) should be used, although there is limited clinical evidence directly linking low pH moisturizers and reduced irritation.

Ceramide Content

The stratum corneum’s lipid-rich matrix is composed of approximately 50% ceramides, 25% cholesterol, and 10-20% fatty acids.³⁴ Ceramides are synthesized in keratinocytes and play an important role in skin barrier maintenance, cell adhesion, and epidermal differentiation. Reductions in ceramide correlate with clinical irritation and barrier disruption.³⁵ Natural ceramides are expensive to synthesize but moisturizers containing synthetic ceramides have been shown to reduce symptoms and improve quality of life in patients with AD and ICD.^10,13,14,36

Hand Eczema

Hand eczema (HE) is the most common form of ICD.³⁷ Anionic surfactants, commonly found in hand soaps, disrupt the stratum corneum by damaging proteins and the processing of new lipids, allowing for greater penetration of irritants and TEWL.³⁸ Likewise, extended exposure to water disrupts the stratum corneum’s lipid structure and increases skin permeability.³⁹ Other irritants, such as organic solvents used in hand sanitizers, strip away lipids from the stratum corneum, although they are less damaging compared to harsh detergents.⁴⁰

Cleansers

Cleansers are mainly available as soaps, combars, and synthetic detergents (syndets) (Table 3 & Table 4). Soaps are typically very alkaline and range from pH 9.0-10.0. In contrast, syndets contain synthetic detergents and are acidic or neutral (pH 5.5- 7.0). Combars are a combination of soaps and syndets.⁴¹ While soaps are more effective at removing soluble proteins and lipids, their high pH disrupts the skin barrier and causes irritation.⁴² Fragrance-free, hypoallergenic, non-soap cleansers that are neutral to low pH are recommended.⁴³ Frequent handwashing with low pH cleansers is preferred as they have been shown to be less irritating.⁴⁴

Table 3: Cleanser categories

Table 4: Allergens in cleansers

Adapted from Rundle et al.⁴⁰

Conclusion

Prolonged PPE usage and frequent handwashing increases the risk of developing or aggravating skin diseases, such as AD, ICD, acne, and HE. Routine moisturization with non-irritating, pH-adjusted, ceramide-based products and gentle cleansing with a pH-adjusted cleanser can treat the unique dermatological challenges posed by COVID-19 (Table 5).

Table 5: Ideal characteristics of moisturizers/cleansers and summary of recommendations

AD = atopic dermatitis; FLG = filaggrin; PCA = pyrrolidine carboxylic acid; TEWL = transepidermal water loss

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Brincidofovir tablets and oral suspension

Plasminogen, humantvmh

Halobetasol propionate lotion 0.01% w/w

Nomacopan for SC use

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