Maskne: The Epidemic within the Pandemic: From Diagnosis to Therapy

Maskne, a newly coined term deriving from the contraction of mask-related acne, is a form of mechanical acne resulting from continuous textile–skin adherence and friction. Prolonged mask use heats up the face environment, thus modifying skin microbiota and sebum production. Although effective prevalence is unknown, since the pandemic began and the prolonged use of masks was extended to the general population, maskne has been a frequent topic of consultation among dermatologists. This term has been successfully introduced into common language, with more than 200,000 hashtags on social media, where it is also possible to find “home remedies” that can worsen this dermatosis. The aim of this paper is to discuss the pathogenesis, address clinicians on the correct differential diagnoses among facial dermatoses, and move towards the correct therapy.


Introduction
In last two years of the SARS-CoV-2 outbreak, people have had to modify their daily routine, introducing new habits and devices to reduce the risk of infection. Among all personal protective equipment (PPE), facial masks are the most employed and effective instrument to maintain a state of health [1]. Their use, first only among healthcare workers and then among general population, has led to an increase of facial dermatoses, i.e., acne, rosacea, seborrheic dermatitis, and contact dermatitis. This phenomenon was so prevalent that a new description term, maskne, has been coined. Maskne is a contraction of maskrelated acne and describes a form of acne in the O-area secondary to the prolonged use of facial masks [2]. Although effective prevalence is unknown, there is currently an increasing request for consultations due to acne onset or its worsening [3].
In a Turkish survey, conducted from December 2020 to February 2021, 101 healthcare workers (HCW) were screened for facial dermatoses and it emerged that acne prevalence was present in 55.4% of participants [4]. Similar findings resulted from another survey among HCW from Pakistan [5]. Acneiform eruptions have been documented in two larger cohorts of 454 [6] and 400 [7] subjects, where prevalence was respectively assessed to 39.9% and 43% of all adverse skin reactions due to prolonged face mask use.
Additional studies confirmed that rosacea, irritant contact dermatitis, and acne [8,9] worsened after mask use, even among children [10]. It is also acknowledged that acne could contribute to mask-induced itch [11].
Moreover, some risk factors, such as greater stress, the sleep deprivation HCW undergo during their shifts in COVID wards, and the consequent increasing in cortisol secretion may contribute to the development of acne [12].
Nevertheless, mask-related acne was also reported in a Chinese survey conducted in 2006 during in 2006 during the SARS epidemic, showing prevalence of acne in 59.6% of 109 workers with facial dermatoses [13].

Methods
This review was conducted by searching the terms "maskne", "mask related acne", and "facial dermatosis and mask" on PubMed and Embase. Articles containing "maskne" and/or "mask related acne" in their titles and articles with "facial dermatosis and mask" in their titles dealing with acne were included and analyzed. Clinical trials, reviews, case series, and case reports were included. Facial dermatosis related to oxygen masks was not considered. The search was limited to article written in English.

Definition and Pathogenesis
Maskne is a form of mechanical acne [6,14]. resulting from continuous textile-skin adherence and friction [15]. Furthermore, prolonged mask use determines a hot-humid microclimate on the skin surface, thus modifying sebum production and consequently microbiota [16]. The term maskne refers both to new diagnoses and to aggravation of pre-existing acneiform eruption [17].

The Role of Microbiota
Mask use is responsible of the disruption of skin microbiota balance causing bacterial dysbiosis. It has been demonstrated that cutaneous microbiota develops with the age [18]: infant skin is more sensitive to inflammatory diseases such as atopic dermatitis and diaper dermatitis and to infections such as S. Aureus and candidiasis. Maturation of microbiota from childhood to adulthood has been demonstrated to have a pivotal role in preventing inflammatory skin diseases. During the transition through puberty, sebum overproduction has been linked to colonization by Cutibacterium acnes, while its decrease seems to be related with the lower sebum secretion observed in aging skin.
The main actor in acne is Cutibacterium acnes, which, as the most prevalent species, accounts for 90% of microbiota of the pilo-sebaceous unit. Its density varies with age, increasing from adolescence to middle adult age and then decreasing from 40-50 years old. C. acnes is involved in a double mechanism: on one hand, colonies of C. acnes use sebum lipids as a metabolic intermediate to promote their growth, on the other, they favor sebum production by increasing the activity of diacylglycerol acyltransferase. Moreover, the porphyrins released by C. acnes are catalytic factors for the oxidation of squalene, a main component of sebum [19]. Dysbiosis seems to select pathogen species of C. acnes and activates innate immunity causing cutaneous inflammation [20]. A recent study [21] suggests that the severity of inflammation in acne may be explained by the loss of diversity of C. acnes phylotypes with the selection of phylotype IA1, which enhances the innate immune system, thereby promoting the release of inflammatory cytokines.
In any case, if correctly balanced, C. acnes is considered a fundamental commensal for skin health because of its role in maintaining low pH, thus preventing Staphylococcus aureus and Streptococcus spp. proliferation.
The significance of Malassezia in acne is not totally clear, though it is known for its pathogenetic role in seborrheic dermatitis and in Pityrosporum folliculitis, a clinical mimic of acne. Malassezia hydrolyzes free fatty acids in sebum, which may affect the abnormal keratinization of hair follicles and promote the secretion of pro-inflammatory cytokines from keratinocytes and monocytes [19].
Dysbiosis is also responsible of other skin diseases; in particular, flare-ups of eczema are significantly related to S. Aureus colonization, Gram-negative folliculitis may aggravate acne, Fusobacteria are involved in perioral dermatitis, and Demodex follicolorum seems to be linked to rosacea [19].

The Microenvironment: Temperature and pH
Different studies have reported the aggravation of acne during the summer season in relation to higher temperature. In particular, the most severe cases have been observed in tropical and subtropical climates, likely due to humidity [15,18].
The close correlation between high temperature and acne flare can be explained by the effect of higher temperature on the sebum excretion rate. Sebum excretion increases by 10% for each 1 • C rise. Furthermore, squalene could become significantly greater in surface lipids when temperature increases [19]. Moreover, the increase of humidity plays a role through the poral occlusive effect, irritation, and swelling of the skin. Both sweat and increased humidity may cause acute obstruction and aggravate acne [20].
The same alterations are reproduced by the facial mask use because: -It makes the air temperature between skin and mask higher due to the restricted area and its closes adherence to the skin, particularly at the boundaries; -It increases sweat retention, especially in people affected by hyperhidrosis; -It reduces air recirculation, favoring the deposition of exhaled damp hair and toxins.
Therefore, masks may produce a microclimate similar to a greenhouse, thus favoring microbiota that contribute to the development of acne.
A study conducted on 20 participants aimed to compare facial skin temperature and heat flow using medical-surgical equipment [22]. A statistically significant difference in humidity, heat, breathing difficulty, and discomfort was present. Infrared thermography images demonstrated temperature changes at the perioral region and superior lip immediately after removal of the mask, compared with baseline conditions in both types of PPE, while no temperature augmentations were observed on the forehead, cheeks, and nose/mouth.
As far as the pH of skin, there is no consensus if lower pH contributes the development of acne [23]; However, changes in pH contribute to dysbiosis and thus promote the development of this disease.
Finally, mask-wearing might create a new intertriginous area where different type of microorganisms can grow [13,20]

Characteristics of Masks
FFP2/KN95 masks are greater risk factors for the development of acne than surgical masks because of their higher humidity, occlusion, and temperature [4].
In the study of Techasatian et al. [6], it emerged that four types of masks are frequently used by the general population: surgical masks, cloth masks, surgical masks covered by a piece of cloth, and N95/FFP2 mask. This paper [6] showed that different factors are responsible for skin side effects. The first one is the mask type: surgical masks and surgical masks covered by a piece of cloth are related to major risks; immediately followed by the duration of mask wearing (especially over 4-6 h/day) and reutilization of the same mask. In addition, the use of sanitizers for masks seemed to have a dual effect: direct skin irritation and predisposition to the occlusion mechanism.
This discrepancy between the causative role of surgical masks and KN95/FFP2 might be explained by the fact that KN95 are more utilized by healthcare workers and less among the general population.
Cloth masks were more involved than surgical and FFP2/KN95 masks in the development of acne in an Indian study [24]. The explanation given by the authors is that people used cloth masks for many days without adequate washing and hygiene practices, with a consequent accumulation of sweat and environment dirt.
It has been also demonstrated that textile dyes, rubber, rubber antioxidants, chemical adhesives, and formaldehyde may influence the development of allergic (ACD) and irritant contact dermatitis (ICD) over areas in contact with face masks [25,26].

Clinical Features of Maskne
Acne related to masks occurred more frequently on the chin than the cheeks and it appeared as mild papular eruptions, accompanied by comedones and seborrhea [1,4].

Diagnostic Criteria
We propose five diagnostic criteria for maskne: I. Appearance of acne after six weeks of mask-use or aggravation of pre-existing acne in the mask area [15,16]; II. Elementary lesions as papules, pustules, and comedones; III. Localization in the area of mask or O-area; IV. Temporal relationship with mask use: aggravation/development of acne with prolonged usage (>4-6 h/day [6]) and improvement when not worn for a long period; V. Exclusion of other dermatoses such as perioral dermatitis, rosacea, seborrheic dermatitis, ICD, and ACD [15] Given the similarities between acne related to mask and acne vulgaris, maskne classification may reflect the one adopted for acne according to European Guidelines [27].

Other Mask Related Facial Dermatosis: Differential Diagnosis
Maskne is only one of the multiple PPE-related facial dermatoses that have been reported since the SARS-CoV-2 outbreak began [16]. Before starting treatment, it is of high importance to consider all possible differential diagnosis. Below, we have listed the most common causes of dermatological eruption triggered or exacerbated by using facial masks.

Irritant Contact Dermatitis
Irritant contact dermatitis (ICD) is an eczematous eruption resulting from direct contact with chemicals or physical irritants. Clinically, lesions begin with erythema, oedema, and vesicles limited to the contact area, then scaling, lichenification, erosions, and ulcerations can appear. The patient may complain of burning and itching sensations. Risk factors include a personal or familial history of atopic dermatitis; severity varies depending on the type of irritant and time of exposure. Specifically, mask-related ICD involves pressure areas (forehead, cheeks, nasal bridge, and ears) in prolonged PPE users (mainly more than 6 h/day). Eruption tends to ameliorate with regular mask breaks and application of moisturizers [16]. To reduce pressure in the convex areas of the face, some authors have suggested the possibility of dressing mask margins with silicon [28].

Allergic Contact Dermatitis
Allergic contact dermatitis (ACD) is an exogenous eczema induced by a delayed IV hypersensitivity reaction to an external allergen. Since clinical manifestations can mimic ICD, patch test positivity is often an essential instrument to diagnosis. Like mask ICD, the severity of facial ACD is proportional to PPE time of exposure and resolution can be achieved only after complete avoidance of causative allergens [16]. Exposure of the following substances may be responsible for ACD [29]: -Metal wires (nickel and cobalt) are present to adapt masks to the facial convex area. Metals ions can reach the skin when masks are consumed or repetitively used; -Formaldehyde is present in raw materials as a contaminant released from product packaging and a by-product of polypropylene degradation; -Adhesive chemicals such as methyldibromo glutaronitrile are present in masks; -Rubber accelerators are involved in the production of mask elastic bands and include substances such as thiurams, carbamates, dialkyl thioureas, and N-isopropyl-Nphenyl-p-phenylendiamine.

Rosacea
Rosacea is a common chronic inflammatory skin disease with different clinical subtypes. Since the presence of papules and pustules can mimic acne, evidence of multiple telangiectasias and absence of comedones are key signs to differentiate the two entities. Rosacea usually involves the "T zone" of the face, including convex areas such as forehead, nose, cheeks, and chin, beyond the area covered by masks. Since the outbreak began, rosacea-like eruptions limited to mask area and flares of chronic cases of rosacea have both been reported [16,30]. Similar to acne, in both cases etiopathogenetic mechanisms involve plural factors such as increased humidity, temperature changes, alteration of innate immunity, and microbiome dysbiosis [30].

Seborrheic Dermatitis
Seborrheic dermatitis (SD) is a very common skin disorder that affect all ages; predominantly, it has a bimodal distribution with a peak during infancy and adulthood and higher incidence among immunocompromised patients. It is characterized by greasy yellow scales overlying well defined erythematous patches. A key element to diagnosis is the typical facial distribution on nasolabial folds, eyebrows, ears, retroarticular folds, and scalp; extra-facial involvement includes the chest, axilla, and groin [31]. In the last two years, with the increasing use of facial mask, multiple studies have pointed out clinical worsening of patients with chronic SD. The increase of temperature created by the mask induces an increased sebum excretion rate, more on less equal to 10% for each 1 • C. These factors together may be responsible for higher permeability of the skin barrier, increasing sweating and abnormalities in Malassezia spp. proliferation [32].

Perioral Dermatitis
Perioral dermatitis (PD) is a benign eruption consisting of small inflammatory papules and pustules around the mouth [33]. Since the perioral region is the most common area of distribution, differentiate PD from maskne can be a diagnostic challenge. History of direct or indirect topical steroid and cosmetic usage and sparing of the vermillion border are characteristic of PD. However, long duration mask use can predispose or aggravated PD with similar mechanism to ACD, ICD, and SD [16].

Urticaria
Among various PPE complications, pressure and contact urticaria need to be mentioned [34]. In the first case, the immediate or delayed appearance of wheals is possible on sites of pressure. In the second case, urticaria can be elicited from mask allergens (e.g., formaldehyde); it typically appears immediately after contact and resolves within 24 h after avoidance of the trigger. While pressure urticaria involves specific area such as the nasal bridge, forehead, and cheeks, contact urticaria can appear all over the face [35].

Folliculitis
Facial folliculitis significantly resembles acne vulgaris, steroid acne, or maskne. Regardless of different aetiologies, it clinically appears with monomorphic papules and pustules, and rarely with nodules. Typically, it involves facial hair and is found mainly in men. Cutaneous swabs are recommended to exclude bacterial and fungal infection [16].

Advice and Therapies
Counseling about educational therapy, treatment expectations, and skin care is important for maximizing patients' adherence to treatment.
The first approach consists in educational therapy. Suggested behaviors are as follows: I. Do not re-use the same mask for many days, according to the producer's instructions [24]; II. Avoid the use of sanitizers for mask [4]; III. Wash hands before putting on the mask and after removing it [4]; IV. Apply non-comedogenic moisturizers before and after mask use [15]; V. Replace FFP2/N95 and surgical masks after 3 days and 4 h, respectively [4,16]; VI. Take breaks of 15 min every 2 h from mask-use if feasible, always according to regulations and laws in force [4].
Generally, we do not recommend a specific type of mask, since masks must be chosen in relation to the personal risk of exposure. However, white color equipment reduces the possible risk of irritating/allergic contact dermatitis.
Since approved guidelines for treatment of maskne do not exist, instructions are taken from acne vulgaris therapies [15], as we do in our experience. The choice depends on the morphology of acne lesions (papules, pustules, comedones) and acne severity (mild, moderate, severe). As general rules, mild acne should be treated with topical products; a combination of topical agents or an association between topical and systemic therapies are suggested for moderate acne, while severe forms usually require both systemic and topical therapies [36]. In all cases, dermo-cosmetic products for daily skin care are highly recommended due to their synergistic effect with pharmacological agents and their role in maintenance therapy and management of side effects.
Herein, we propose a therapeutical scheme for maskne adapted from acne therapy guidelines compared with what is mentioned in literature about maskne and to our personal experience.

Topical Treatment of Maskne
Dermatologists may suggest a cleanser for acne-prone skin that removes sebum, dirt, cosmetics, and bacteria. In particular, gentle non-comedogenic antibacterial detergent with a pH between 5 and 7.3, close to normal skin, should be preferred [37]. Despite the common perception of an excess of seborrhea on the face, excessive face cleaning is not recommended, at most twice a day, in order to prevent inflammation and peeling and to avoid the rebound effect with consequent hypersecretion of sebum.
The application of dermo-cosmetic cream has the aim of sealing, moistening, and moisturizing the epidermis by reducing water loss, attracting water to the dermis. and makes the skin smooth and soft, respectively. It is also important to avoid scrubbing of affected areas and popping pimples to prevent irritation and increased inflammation [38]. The selection of dermo-cosmetic cream must be accurate. For example, natural moisturizing factors as sodium hyaluronate and polyglutamic acid are humectants that reduce transepidermal water loss without any irritation when worn under occlusion [20]. In contrast, some emollients (e.g., lanolin, glycerol stearate, glyceryl stearate, soy sterols, petrolatum, mineral oil, and dimethicone) may enhance their occlusive power under the mask. Softening creams containing niacinamide have sebostatic and anti-inflammatory effects [39]. Patients affected by hyperhidrosis could benefit from powder formulations that prevent occlusion and absorb excess moisture. Products based on zinc oxide formulations reduce humidity and are stable in powder compounds [20].
The most commonly used topical agents have been collected in Table 1. These molecules should be applied once a day for 4-12 weeks, preferably on evening [36,40].
According to Han et al. [24], patients suffering from maskne may benefit from the use of dermo-cosmetics for acne-prone skin. In maskne, antibiotics (AB) and fixed combinations of retinoids and AB, especially in hydrogel formulation, were more effective and safer [20] than agents such as benzoyl peroxide (PB), salicylic acid, and retinoids alone due to the risk ok irritation under the mechanical occlusion of masks. In contrast, Rudd et al. [16] have proposed retinoids alone. To minimize the risk of irritating dermatitis, Kaul et al. have suggested a short contact therapy, especially in those with pre-existing acne [41]. In this paper, it is also underlined that retinoids should be preferred to BP for their power in reducing acne flares. In our experience, the main results have been first obtained with daily skin care using appropriate products for acne. We feel also confident recommending zinc oxide formulations for reducing humidity, as did Teo et al. [20]. For moderate to severe forms, topical drugs have been necessary.
We have experienced a major a risk of irritation with products containing retinoids alone than with fixed combinations of retinoids and AB in hydrogel formulations. Excesses of erythema, dryness and desquamation have been observed with retinoids alone under the prolonged use of masks.

Systemic Treatment of Maskne
Systemic agents are summarized in Table 2 [31]. Oral antibiotics improve inflammatory lesions by inhibiting the growth of C. acnes within the pilosebaceous units. They are proposed for moderate to severe inflammatory acne and for all forms resistant to topical therapies. In order to avoid bacterial resistance, treatments are limited to continuous therapy for three to four months. Oral isotretinoin is the drug that combats the four pathogenetic aspects of acne: sebum production, follicular hyperkeratinization, inflammation, and C. acnes. It is well accepted as a treatment for severe, recalcitrant, and nodular acne. Oral contraceptives containing estrogen and progestin may reduce androgen action via a variety of mechanisms.
In the majority of articles aboutmaskne, systemic therapies are not described in detail, while traditional acne treatments are suggested to obtain benefits [24,41,42]. Only the use of tetracycline is reported in the literature [2].
There are no reports supporting the use of isotretinoin or hormonal therapy for maskne so far.
Oral zinc may be taken into consideration as systemic drug alone or in support to oral AB [43]. Although the exact mechanism of action remains poorly elucidated, it is believed to act directly on the microbial inflammatory equilibrium and to facilitate antibiotic absorption when used in combination. Moreover, it seems to suppress sebum production by its antiandrogenic activity [44].

Conclusions
Maskne and all skin conditions related to the prolonged use of masks are emerging dermatoses. In this review, we proposed diagnostic criteria for mask-related acne and address the differential diagnoses of dermatological conditions triggered by mask-use. As far as therapeutic strategies, maskne requires the correct use of skin care cosmetics for acne prone skin and the use of topical treatments, i.e., sebum-regulators and emollients.

Conflicts of Interest:
The authors declare no conflict of interest.