BACKGROUND: Eczema (atopic dermatitis) is the most burdensome skin condition worldwide and cannot currently be prevented or cured. Topical anti-inflammatory treatments are used to control eczema symptoms, but there is uncertainty about the relative effectiveness and safety of different topical anti-inflammatory treatments.
OBJECTIVE: To compare and rank the efficacy and safety of topical anti-inflammatory treatments for people with eczema using a network meta-analysis.
METHODS: We searched the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and trial registries on 29 June 2023, and checked the reference lists of included studies.
METHODS: We included within-participant or between-participant randomised controlled trials (RCTs) in people of any age with eczema of any severity, but excluded trials in clinically infected eczema, seborrhoeic eczema, contact eczema, or hand eczema. We included topical anti-inflammatory treatments used for at least one week, compared with another anti-inflammatory treatment, no treatment, or vehicle/placebo. Vehicle is a \'carrier system\' for an active pharmaceutical substance, which may also be used on its own as an emollient for dry skin. We excluded trials of topical antibiotics used alone, complementary therapies, emollients used alone, phototherapy, wet wraps, and systemic treatments.
METHODS: We used standard Cochrane methods. Primary outcomes were patient-reported eczema symptoms, clinician-reported eczema signs and investigator global assessment. Secondary outcomes were health-related quality of life, long-term control of eczema, withdrawal from treatment/study, and local adverse effects (application-site reactions, pigmentation changes and skin thinning/atrophy were identified as important concerns through patient and public involvement). We used CINeMA to quantify our confidence in the evidence for each outcome.
RESULTS: We included 291 studies involving 45,846 participants with the full spectrum of eczema severity, mainly conducted in high-income countries in secondary care settings. Most studies included adults, with only 31 studies limited to children aged < 12 years. Studies usually included male and female participants, multiple ethnic groups but predominantly white populations. Most studies were industry-funded (68%) or did not report their funding sources/details. Treatment duration and trial participation were a median of 21 and 28 days (ranging from 7 days to 5 years), respectively. Interventions used were topical corticosteroids (TCS) (172), topical calcineurin inhibitors (TCI) (134), phosphodiesterase-4 (PDE-4) inhibitors (55), janus kinase (JAK) inhibitors (30), aryl hydrocarbon receptor activators (10), or other topical agents (21). Comparators included vehicle (170) or other anti-inflammatory treatments. The risk of bias was high in 242 of the 272 (89.0%) trials contributing to data analyses, most commonly due to concerns about selective reporting. Network meta-analysis (NMA) was only possible for short-term outcomes. Patient-reported symptoms NMA of 40 trials (6482 participants) reporting patient-reported symptoms as a binary outcome ranked tacrolimus 0.1% (OR 6.27, 95% CI 1.19 to 32.98), potent TCS (OR 5.99, 95% CI 2.83 to 12.69), and ruxolitinib 1.5% (OR 5.64, 95% CI 1.26 to 25.25) as the most effective, all with low confidence. Mild TCS, roflumilast 0.15%, and crisaborole 2% were the least effective. Class-level sensitivity analysis found potent/very potent TCS had similar effectiveness to potent TCI and was more effective than mild TCI and PDE-4 inhibitors. NMA of 29 trials (3839 participants) reporting patient-reported symptoms as a continuous outcome ranked very potent TCS (SMD -1.99, 95% CI -3.25 to -0.73; low confidence) and tacrolimus 0.03% (SMD -1.57, 95% CI -2.42 to -0.72; moderate confidence) the highest. Direct information for tacrolimus 0.03% was based on one trial of 60 participants at high risk of bias. Roflumilast 0.15%, delgocitinib 0.25% or 0.5%, and tapinarof 1% were the least effective. Class-level sensitivity analysis found potent/very potent TCS had similar effectiveness to potent TCI and JAK inhibitors and mild/moderate TCS was less effective than mild TCI. A further 50 trials (9636 participants) reported patient-reported symptoms as a continuous outcome but could not be included in NMA. Clinician-reported signs NMA of 32 trials (4121 participants) reported clinician signs as a binary outcome and ranked potent TCS (OR 8.15, 95% CI 4.99, 13.57), tacrolimus 0.1% (OR 8.06, 95% CI 3.30, 19.67), ruxolitinib 1.5% (OR 7.72, 95% CI 4.92, 12.10), and delgocitinib 0.5% (OR 7.61, 95% CI 3.72, 15.58) as most effective, all with moderate confidence. Mild TCS, roflumilast 0.15%, crisaborole 2%, and tapinarof 1% were the least effective. Class-level sensitivity analysis found potent/very potent TCS more effective than potent TCI, mild TCI, JAK inhibitors, PDE-4 inhibitors; and mild TCS and PDE-4 inhibitors had similar effectiveness. NMA of 49 trials (5261 participants) reported clinician signs as a continuous outcome and ranked tacrolimus 0.03% (SMD -2.69, 95% CI -3.36, -2.02) and very potent TCS (SMD -1.87, 95% CI -2.69, -1.05) as most effective, both with moderate confidence; roflumilast 0.15%, difamilast 0.3% and tapinarof 1% were ranked as least effective. Direct information for tacrolimus 0.03% was based on one trial in 60 participants with a high risk of bias. For some sensitivity analyses, potent TCS, tacrolimus 0.1%, ruxolitinib 1.5%, delgocitinib 0.5% and delgocitinib 0.25% became some of the most effective treatments. Class-level analysis found potent/very potent TCS had similar effectiveness to potent TCI and JAK inhibitors, and moderate/mild TCS was more effective than mild TCI. A further 100 trials (22,814 participants) reported clinician signs as a continuous outcome but could not be included in NMA. Investigator Global Assessment NMA of 140 trials (23,383 participants) reported IGA as a binary outcome and ranked ruxolitinib 1.5% (OR 9.34, 95% CI 4.8, 18.18), delgocitinib 0.5% (OR 10.08, 95% CI 2.65, 38.37), delgocitinib 0.25% (OR 6.87, 95% CI 1.79, 26.33), very potent TCS (OR 8.34, 95% CI 4.73, 14.67), potent TCS (OR 5.00, 95% CI 3.80, 6.58), and tacrolimus 0.1% (OR 5.06, 95% CI 3.59, 7.13) as most effective, all with moderate confidence. Mild TCS, crisaborole 2%, pimecrolimus 1%, roflumilast 0.15%, difamilast 0.3% and 1%, and tacrolimus 0.03% were the least effective. In a sensitivity analysis of low risk of bias information (12 trials, 1639 participants), potent TCS, delgocitinib 0.5% and delgocitinib 0.25% were most effective, and pimecrolimus 1%, roflumilast 0.15%, difamilast 1% and difamilast 0.3% least effective. Class-level sensitivity analysis found potent/very potent TCS had similar effectiveness to potent TCI and JAK inhibitors and were more effective than PDE-4 inhibitors; mild/moderate TCS were less effective than potent TCI and had similar effectiveness to mild TCI. Longer-term outcomes over 6 to 12 months showed a possible increase in effectiveness for pimecrolimus 1% versus vehicle (4 trials, 2218 participants) in a pairwise meta-analysis, and greater treatment success with mild/moderate TCS than pimecrolimus 1% (based on 1 trial of 2045 participants). Local adverse effects NMA of 83 trials (18,992 participants, 2424 events) reporting application-site reactions ranked tacrolimus 0.1% (OR 2.2, 95% CI 1.53, 3.17; moderate confidence), crisaborole 2% (OR 2.12, 95% CI 1.18, 3.81; high confidence), tacrolimus 0.03% (OR 1.51, 95%CI 1.10, 2.09; low confidence), and pimecrolimus 1% (OR 1.44, 95% CI 1.01, 2.04; low confidence) as most likely to cause site reactions. Very potent, potent, moderate, and mild TCS were least likely to cause site reactions. NMA of eight trials (1786 participants, 3 events) reporting pigmentation changes found no evidence for increased pigmentation changes with TCS and crisaborole 2%, with low confidence for mild, moderate or potent TCS and moderate confidence for crisaborole 2%. NMA of 25 trials (3691 participants, 36 events) reporting skin thinning found no evidence for increased skin thinning with short-term (median 3 weeks, range 1-16 weeks) use of mild TCS (OR 0.72, 95% CI 0.12, 4.31), moderate TCS (OR 0.91, 95% CI 0.16, 5.33), potent TCS (OR 0.96, 95% CI 0.21, 4.43) or very potent TCS (OR 0.88, 95% CI 0.31, 2.49), all with low confidence. Longer-term outcomes over 6 to 60 months showed increased skin thinning with mild to potent TCS versus TCI (3 trials, 4069 participants, 6 events with TCS).
CONCLUSIONS: Potent TCS, JAK inhibitors and tacrolimus 0.1% were consistently ranked as amongst the most effective topical anti-inflammatory treatments for eczema and PDE-4 inhibitors as amongst the least effective. Mild TCS and tapinarof 1% were ranked amongst the least effective treatments in three of five efficacy networks. TCI and crisaborole 2% were ranked most likely to cause local application-site reactions and TCS least likely. We found no evidence for increased skin thinning with short-term TCS but an increase with longer-term TCS.

Itching is a prominent clinical manifestation of sensitive skin; it reduces cutaneous barrier function, mainly caused by dryness. Scratching to relieve itching destroys the skin barrier, thus forming the itch-scratch cycle that results in additional disruption of skin barrier and chronic itching. Treatment involves alleviation from itching for sensitive skin. Recently, substance P (11-amino acid neuropeptide of the tachykinin family) and neurokinin 1 receptor (NK1R) have been considered to provide a key pathway to treat chronic itching. A single-center, open-label study was conducted comprising subjects with dry, itchy, and sensitive skin to evaluate the efficacy of two types of itch-relief moisturizers, mist and lotion, containing maltotetraose (MTO). In all, 35 subjects used mist containing MTO, resulting in significant improvement in itch score from 1 minute to 2 hours following single application. On the other hand, 34 subjects applied lotion containing MTO for 1 week, resulting in significant improvement in itch score, skin hydration, and clinical scores of erythema/redness and dryness; however, in both cases, improve-ment was not observed in the measurement of transepidermal water loss (TEWL). It was concluded that two types of itch-relief moisturizers containing MTO were effective for dry, itchy, and sensitive skin.

Psoriasis is characterized by an aberrant immune response due to myeloid dendritic cells and T helper cells intertwining with keratinocyte hyperproliferation. Skin integrity alterations may predispose patients to physiological imbalances, such as xerosis, reduced elasticity, and increased friability. This study aims to assess the epidermal barrier dysfunction in chronic plaque psoriasis and gain a comprehensive view of the dynamic changes in the epidermal barrier during various topical therapies. Adult patients with chronic plaque psoriasis were enrolled in this observational study. For each patient, skin barrier parameters, stratum corneum hydration (SCH), transepidermal water loss (TEWL), elasticity, erythema, and melanin levels were measured in lesional and non-lesional skin. Two extensions of the initial study design, with subsequent epidermal barrier determinations, were made as follows: one in which patients with moderate psoriasis were treated with clobetasol propionate 0.5% and the second one in which mild psoriasis was treated with either clobetasol propionate 0.5% or clobetasol propionate 0.5% with 10% urea. TEWL and erythema were found to be higher in the sites affected by psoriatic lesions than the unaffected sites, while SCH and elasticity were decreased. Severe psoriasis presented with higher TEWL (p = 0.032), erythema (p = 0.002), and lower SCH (p < 0.001) compared with the mild and moderate forms. SCH significantly improved during clobetasol propionate 0.5% treatment (p = 0.015). Clobetasol propionate 0.5% with 10% urea was found to be superior to clobetasol propionate 0.5% in improving TEWL and SCH in psoriasis.

UNASSIGNED: Atopic eczema is a common childhood skin problem linked with asthma, food allergy and allergic rhinitis that impairs quality of life.
UNASSIGNED: To determine whether advising parents to apply daily emollients in the first year can prevent eczema and/or other atopic diseases in high-risk children.
UNASSIGNED: A United Kingdom, multicentre, pragmatic, two-arm, parallel-group randomised controlled prevention trial with follow-up to 5 years.
UNASSIGNED: Twelve secondary and four primary care centres.
UNASSIGNED: Healthy infants (at least 37 weeks\' gestation) at high risk of developing eczema, screened and consented during the third trimester or post delivery.
UNASSIGNED: Infants were randomised (1 : 1) within 21 days of birth to apply emollient (Doublebase Gel®; Dermal Laboratories Ltd, Hitchin, UK or Diprobase Cream®) daily to the whole body (excluding scalp) for the first year, plus standard skin-care advice (emollient group) or standard skin-care advice only (control group). Families were not blinded to allocation.
UNASSIGNED: Primary outcome was eczema diagnosis in the last year at age 2 years, as defined by the UK Working Party refinement of the Hanifin and Rajka diagnostic criteria, assessed by research nurses blinded to allocation. Secondary outcomes up to age 2 years included other eczema definitions, time to onset and severity of eczema, allergic rhinitis, wheezing, allergic sensitisation, food allergy, safety (skin infections and slippages) and cost-effectiveness.
UNASSIGNED: One thousand three hundred and ninety-four newborns were randomised between November 2014 and November 2016; 693 emollient and 701 control. Adherence in the emollient group was 88% (466/532), 82% (427/519) and 74% (375/506) at 3, 6 and 12 months. At 2 years, eczema was present in 139/598 (23%) in the emollient group and 150/612 (25%) in controls (adjusted relative risk 0.95, 95% confidence interval 0.78 to 1.16; p = 0.61 and adjusted risk difference -1.2%, 95% confidence interval -5.9% to 3.6%). Other eczema definitions supported the primary analysis. Food allergy (milk, egg, peanut) was present in 41/547 (7.5%) in the emollient group versus 29/568 (5.1%) in controls (adjusted relative risk 1.47, 95% confidence interval 0.93 to 2.33). Mean number of skin infections per child in the first year was 0.23 (standard deviation 0.68) in the emollient group versus 0.15 (standard deviation 0.46) in controls; adjusted incidence rate ratio 1.55, 95% confidence interval 1.15 to 2.09. The adjusted incremental cost per percentage decrease in risk of eczema at 2 years was £5337 (£7281 unadjusted). No difference between the groups in eczema or other atopic diseases was observed during follow-up to age 5 years via parental questionnaires.
UNASSIGNED: Two emollient types were used which could have had different effects. The median time for starting emollients was 11 days after birth. Some contamination occurred in the control group (< 20%). Participating families were unblinded and reported on some outcomes.
UNASSIGNED: We found no evidence that daily emollient during the first year of life prevents eczema in high-risk children. Emollient use was associated with a higher risk of skin infections and a possible increase in food allergy. Emollient use is unlikely to be considered cost-effective in this context.
UNASSIGNED: To pool similar studies in an individual patient data meta-analysis.
UNASSIGNED: This trial is registered as ISRCTN21528841.
UNASSIGNED: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/67/12) and is published in full in Health Technology Assessment; Vol. 28, No. 29. See the NIHR Funding and Awards website for further award information.
Eczema is a troublesome itchy skin condition affecting 1 in 5 children and 1 in 10 UK adults. There is no cure and affected children are more likely to develop food allergies. We wanted to see if we could prevent eczema by protecting the skin of babies at higher risk of developing eczema (with an immediate relative with eczema, asthma or hay fever) with moisturisers used to treat dry skin. Previous research suggested that protecting the skin barrier might also prevent food allergy. One thousand three hundred and ninety-four families took part in a study; half of them were asked to apply moisturiser every day to their newborn baby for the first year and half to look after their baby’s skin in the normal way. At the age of 2 years, we did not see any difference in how common eczema was between the two groups: 23% had eczema in the moisturiser group and 25% in the normal care group. It did not matter how we defined eczema – whether examined by a researcher or parent report. We did not find any differences in related conditions like asthma or hay fever either. We found that children using moisturisers had seen their doctor slightly more often for mild skin infections. There was a hint that food allergy might have been increased in the moisturiser group, but there was not enough data to be sure. We followed up the children to age 5 years, but we still did not find any benefits from using moisturisers in early life. Since this study, other similar research has been done using newer types of moisturisers, but their results are the same. This study shows that using daily moisturisers on healthy babies with a high risk of eczema does not prevent eczema. It is one less thing for busy families to worry about.

Skin penetration of an active pharmaceutical ingredient is key to developing topical drugs. This penetration can be adjusted for greater efficacy and/or safety through the selection of dosage form. Two emerging dosage forms, cream-gel and gel-in-oil emulsion, were tested for their ability to deliver diclofenac into the skin, with the target of maximising skin retention while limiting systemic exposure. Prototypes with varying amounts of solvents and emollients were formulated and evaluated by in vitro penetration testing on human skin. Cream-gel formulas showed better skin penetration than the emulgel benchmark drug even without added solvent, while gel-in-oil emulsions resulted in reduced diffusion of the active into the receptor fluid. Adding propylene glycol and diethylene glycol monoethyl ether as penetration enhancers resulted in different diclofenac penetration profiles depending on the dosage form and whether they were added to the disperse or continuous phase. Rheological characterisation of the prototypes revealed similar profiles of cream-gel and emulgel benchmark, whereas gel-in-oil emulsion demonstrated flow characteristics suitable for massaging product into the skin. This study underlined the potential of cream-gel and gel-in-oil emulsions for adjusting active penetration into the skin, broadening the range of choices available to topical formulation scientists.

BACKGROUND: Preterm infants are highly susceptible to infections, which significantly contribute to morbidity and mortality. This systematic review and meta-analysis investigated the effectiveness of topical emollient oil application in preventing infections among preterm infants.
METHODS: A comprehensive search was conducted across multiple electronic databases (PubMed, Cochrane, Scopus, Clinical trials, Epistemonikos, HINARI and Global Index Medicus) and other sources. A total of 2185 articles were identified and screened for eligibility. The quality of included studies was assessed using the Cochrane Risk of Bias Tool for randomised controlled trials. Data analysis was performed using StataCrop MP V.17 software. Heterogeneity among the studies was evaluated using the I2 and Cochrane Q test statistics. Sensitivity and subgroup analyses were conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist guided the presentation of the results.
RESULTS: Of 2185 retrieved articles from initial searches, 11 met eligibility criteria and were included in the final analysis. A random effects meta-analysis revealed that infants who received massages with emollient oils had a 21% reduced risk of infection (risk ratio=0.79, 95% CI 0.64 to 0.97, I2=0.00%). Subgroup analyses indicated that preterm babies who received topical emollient oil massages with coconut oil, administered twice a day for more than 2 weeks, had a lower likelihood of acquiring an infection compared with their non-massaged counterparts.
CONCLUSIONS: It is quite evident from this analysis that topical emollient oil application in preterm neonates is most likely effective in preventing infection. However, further studies, particularly from the African continent, are warranted to support universal recommendations.

BACKGROUND: The baseline therapy of atopic dermatitis (AD) includes emollient therapy, prevention of triggering factors and proper patients\' education. Appropriate level of education about AD among patients is crucial for successful treatment of the disease.
OBJECTIVE: To compare and evaluate the level of knowledge about baseline therapy in atopic dermatitis (AD) between the adults with AD and the parents of children with AD.
METHODS: Adult patients with AD (n=180) and parents of children with AD (n=106) completed an original questionnaire covering issues of emollient therapy and bathing. For statistical comparison a chi - square test was used with significance level of 0,05.
RESULTS: With significance level of 0,05, the chi - square test showed a statistically significant difference comparing both groups. 52,38% adults and 68,73% parents proved to know the principles of basic therapy (p<0,05). 55,00% adults and 50,00% parents have not been informed how to apply emollients appropriately (p>=0,05). 75,56% and 74,53%, respectively, seek additional education about it (p>=0,05). 63,89% adults and 49,06% parents have not been informed about the principles of bathing (p<0,05). 70,00% and 74,54%, respectively, expect more comprehensive explanation of bathing rules (p>=0,05).
CONCLUSIONS: Adults with AD have lesser knowledge about baseline therapy than parents of children with AD. Both groups express a very strong need for education about baseline therapy in AD.

Atopic dermatitis (AD) is a chronic, recurring, inflammatory skin condition. Xerosis, pruritus, and rash make the clinical diagnosis. Adequate skin care and regular emollient use are key in management. Topical corticosteroids are the first-line treatment for AD flare-ups. Wet wrap therapy can improve AD severity and extent. Topical calcineurin inhibitors are second-line treatments. Emollient use, topical corticosteroids and calcineurin inhibitors, and bleach baths can help prevent flare-ups. Patients with refractory AD that might require immunomodulatory treatments, such as dupilumab (Dupixent), Janus kinase inhibitors, or phototherapy, should be referred to a dermatologist. Seborrheic dermatitis (SD) is a common, chronic, relapsing, inflammatory condition that involves sebaceous skin areas. Infection with Malassezia species and the inflammatory response to it are the probable etiologies. The clinical diagnosis is made by the presence of hallmark greasy, yellow scales on the scalp or face. Infantile SD most commonly involves the scalp and forehead and typically is self-limited. In infants, application of emollients followed by hair brushing and shampooing may be effective. In infants and children, if the condition does not improve with this treatment, topical ketoconazole shampoo, gel, or lotion is safe and effective. Refractory cases of SD can be managed with topical corticosteroids and calcineurin inhibitors.

Pityriasis rubra pilaris (PRP) is a rare skin condition. The etiology of PRP is unknown; however, it has been associated with infections, autoimmune diseases, and neoplasms. Here we describe the cases of 2 pediatric patients with PRP triggered by a respiratory syncytial virus infection concurrently with obstructive bronchial syndrome. PRP resolved after treatment with topical emollients, topical corticosteroids, and calcineurin inhibitors.
La pitiriasis rubra pilaris (PRP) es una enfermedad dermatológica poco frecuente. Se desconoce su etiología, sin embargo, se ha asociado a infecciones, enfermedades autoinmunes y neoplasias. Se describen los casos de dos pacientes pediátricos que presentaron PRP gatillada por una infección por virus sincicial respiratorio mientras cursaban un síndrome bronquial obstructivo. Los cuadros de PRP remitieron luego del tratamiento tópico con emolientes, corticoesteroides tópicos e inhibidores de la calcineurina.

Xerosis is experienced by almost everyone at some time in their lives and the foundation of management of dry skin (both consumer- and healthcare professional--directed) rests on the use of moisturizers. Given the wide range of available moisturizers, counseling patients about selecting the optimum moisturizer for their individual situation relies on knowledge of ingredients and formulations. Traditionally, the main focus for many moisturizers centered on the core functional and structural role of ceramides within the epidermal barrier.  However, while a key aspect of transepidermal water loss and other skin barrier functions, components other than ceramides are equally essential in increasing moisturization. The skin\'s natural moisturizing factors (NMFs) are a complex mixture of water-attracting compounds such as amino acids, urea, lactate, pyrrolidone carboxylic acid (PCA), and electrolytes which play a fundamental role in preserving physiologic function by regulating the water content of the stratum corneum. By facilitating water retention, NMFs contribute significantly to the suppleness, elasticity, normal desquamation, and overall integrity of the skin barrier. Incorporation of NMFs into moisturizers addresses critical deficiencies in the skin\'s moisture balance that exist in xerotic and atopic skin, and in many skin disorders, mitigating signs and symptoms associated with xerosis and promoting optimal skin health. The biochemical composition of NMFs and the intricate interplay with epidermal homeostasis translate to a central role in moisturizers used for prophylactic and therapeutic management of various dry skin conditions, beyond ceramides alone. J Drugs Dermatol. 2024;23(6):466-471.     doi:10.36849/JDD.8358.