Dupilumab Treatment in Pediatric Patients Aged 6-11 Years with Severe Atopic Dermatitis Whose Disease Is Not Adequately Controlled: A Review.

Atopic dermatitis (AD) is the most common inflammatory skin disease in children. Children with severe AD have a multidimensional disease burden characterized by skin lesions, itching, frequent infections, sleep deprivation, and a high rate of comorbidities. These impact the mental health and overall quality of life of not only the children but also of their parents and caregivers. There are few effective available treatment options for young children with severe AD that are suitable for long-term use. Due to their adverse effects, practice guidelines consider systemic agents inappropriate for this age group, although they are still used off-label in extreme cases. The biologic dupilumab has recently been approved for children aged 6-11 years with severe (EU) and moderate-to-severe (USA) AD, offering hope to this population of patients with a high unmet clinical need. The purpose of this review is to describe the unmet needs of AD patients aged 6-11 years prior to dupilumab approval and to summarize existing clinical data supporting dupilumab's safety and efficacy in these children.

Maintenance of an Acidic Skin Surface with a Novel Zinc Lactobionate Emollient Preparation Improves Skin Barrier Function in Patients with Atopic Dermatitis.

INTRODUCTION: The skin of patients with atopic dermatitis (AD) is characterised by elevated pH. As a central homeostatic regulator, an increased pH accelerates desquamation and suppresses lipid processing, resulting in diminished skin barrier function. The aim of this study was to determine whether a novel zinc lactobionate emollient cream can strengthen the skin barrier by lowering skin surface pH. METHODS: A double-blind, forearm-controlled cohort study was undertaken in patients with AD. Participants applied the test cream to one forearm and a vehicle cream to the other (randomised allocation) twice daily for 56 days. Skin surface pH and barrier function (primary outcomes) were assessed at baseline and after 28 days and 56 days of treatment, amongst other tests. RESULTS: A total of 23 adults with AD completed the study. During and after treatment, a sustained difference in skin surface pH was observed between areas treated with the test cream and vehicle (4.50 ± 0.38 versus 5.25 ± 0.54, respectively, p < 0.0001). This was associated with significantly reduced transepidermal water loss (TEWL) on the test cream treated areas compared with control (9.71 ± 2.47 versus 11.20 ± 3.62 g/m2/h, p = 0.0005). Improvements in skin barrier integrity, skin sensitivity to sodium lauryl sulphate, skin hydration, and chymotrypsin-like protease activity were all observed at sites treated with the test cream compared with the control. CONCLUSION: Maintenance of an acidic skin surface pH and delivery of physiologic lipids are beneficial for skin health and may help improve AD control by reducing sensitivity to irritants and allergens.

Association between skin barrier development and early-onset atopic dermatitis: A longitudinal birth cohort study.

BACKGROUND: A diagnosis of atopic dermatitis (AD) is common during infancy; however, it is unclear whether differential skin barrier development defines this period and signals disease onset in predisposed individuals. OBJECTIVE: We sought to study (NCT03143504) and assess the feasibility of remote skin testing from birth to monitor skin barrier maturation and model association with an AD diagnosis by age 12 months. METHODS: Biophysical testing and infrared spectroscopy were conducted at the maternity ward and family home. Tape stripping collected samples for desquamatory protease and natural moisturizing factor analysis. The 4 common European filaggrin risk alleles were screened. RESULTS: A total of 128 infants completed the study, with 20% developing mild disease. Significant changes in permeability barrier function, desquamatory protease activity, and molecular composition assessed spectroscopically were observed longitudinally, but only subtle evidence of differential skin barrier development was noted between infant subgroups. Common filaggrin risk alleles were strongly associated with early-onset disease and conferred a significant reduction in natural moisturizing factor and water content by age 4 weeks. Accounting for a family history of atopy, these parameters alongside a greater lipid/protein ratio and reduced chymotrypsin-like activity at birth were associated with AD. Measured in ambient conditions, transepidermal water loss did not signal disease risk at any stage. CONCLUSIONS: Skin barrier dysfunction lacked an acquired modality but was considered proportional to cohort severity and suggests that a portfolio of tests used in a community setting has the potential to improve current AD risk evaluations from birth.

Characterisation of skin barrier defects in atopic dermatitis patients using Infrared Spectroscopy.

INTRODUCTION: Atopic dermatitis (AD) is characterised by skin barrier defects often measured by biophysical tools that observe stratum corneum (SC) functional properties. OBJECTIVE: To employ in vivo infrared spectroscopy alongside biophysical measurements to analyse changes in chemical composition of the SC in relation to AD severity. METHODS: We conducted an observational cross-sectional cohort study where attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectroscopy measurements were collected on the forearm alongside surface pH, capacitance, erythema and transepidermal water loss (TEWL) combined with tape stripping (STS) in a cohort of 75 participants; 55 AD patients stratified by phenotypic severity, compared to 20 healthy controls. Common filaggrin (FLG) variant alleles were genotyped. RESULTS: Reduced hydration, elevated TEWL and redness all associated with greater AD severity. Spectral analysis showed a reduction in 1465cm-1 (full width half maximum) and 1340 cm-1 peak areas indicative of less orthorhombic lipid ordering and reduced carboxylate functional groups that correlated with clinical severity (lipid structure r=-0.59, carboxylate peak area r=-0.50). CONCLUSION: ATR-FTIR spectroscopy is a suitable tool for the characterisation of structural skin barrier defects in AD and has potential as a clinical tool for directing individual treatments based on chemical structural deficiencies.

Potential application of PS-OCT in the safety assessment of non-steroidal topical creams for atopic dermatitis treatment.

Crisaborole 2% ointment is a non-steroidal treatment for mild-moderate atopic dermatitis (AD) and may produce fewer adverse effects than topical corticosteroids (TCS). We used PS-OCT to quantify dermal collagen at baseline and after 29 days of treatment with crisaborole and betamethasone valerate (BMV), in 32 subjects. PS-OCT detected a mean increase 1 × 10-6, 95% CI (6.3, 1.37) × 10-6 in dermal birefringence following TCS use (p < 0.0001, ad-hoc, not powered), whereas a change of -4 × 10-6, 95% CI (-32, 24) × 10-6 was detected for crisaborole (p = 0.77, ad-hoc, not powered). These results could suggest a differential effect on dermal collagen between the two compounds. PS-OCT may thus find an important role in safety assessment of novel AD treatment' and larger trials are warranted.

Targeting Skin Barrier Function in Atopic Dermatitis.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in the general population. Skin barrier dysfunction is the central abnormality leading to AD. The cause of skin barrier dysfunction is complex and rooted in genetic mutations, interactions between the immune pathway activation and epithelial cells, altered host defense mechanisms, as well as environmental influences that cause epithelial cell activation and release of alarmins (such as thymic stromal lymphopoietin) that can activate the type 2 immune pathway, including generation of interleukins 4 and 13, which induces defects in the skin barrier and increased allergic inflammation. These inflammatory pathways are further influenced by environmental factors including the microbiome (especially Staphylococcus aureus), air pollution, stress, and other factors. As such, AD is a syndrome involving multiple phenotypes, all of which have in common skin barrier dysfunction as a key contributing factor. Understanding mechanisms leading to skin barrier dysfunction in AD is pointing to the development of new topical and systemic treatments in AD that helps keep skin borders secure and effectively treat the disease.

c-Src activation as a potential marker of chemical-induced skin irritation using tissue-engineered skin equivalents.

Skin irritancy to topically applied chemicals is a significant problem that affects millions of people worldwide. New or modified chemical entities must be tested for potential skin irritancy by industry as part of the safety and toxicity profiling process. Many of these tests have now moved to a non-animal-based format to reduce experiments on animals. However, these tests for irritancy potential often rely on monolayer cultures of keratinocytes that are not representative of the skin architecture or tissue-engineered human skin equivalents (HSE) using complex multi-gene expression panels that are often cumbersome and not amenable for high throughput. Here, we show that human skin equivalents increase abundance of several phosphorylated kinases (c-Src, c-Jun, p53, GSK3α/ß) in response to irritant chemical stimulation by phosphokinase array analysis. Specific phosphorylation of c-SrcY419 was confirmed by immunoblotting and was plasma membrane-associated in basal/spinous cells by phospho-specific immunohistochemistry. Moreover, c-SrcY419 phosphorylation in response to the irritants lactic acid and capsaicin was inhibited by the c-Src inhibitors KB-SRC and betaine trimethylglycine. These data provide the first evidence for c-Src specific activation in response to chemical irritants and point to the development of new modes of rapid testing by immunodetection for first-pass screening of potential irritants.

Moisturizer therapy in prevention of atopic dermatitis and food allergy: To use or disuse?

OBJECTIVE: To critically appraise the evidence for the role of regular moisturizer application in early life to prevent atopic dermatitis (AD) and food allergy (FA). DATA SOURCES: Primary peer-reviewed literature. STUDY SELECTIONS: Original research articles based on systematic reviews, interventional studies, retrospective studies, case-control studies, and cohort studies related to the subject matter. RESULTS: There is good evidence to show that epicutaneous sensitization through a defective skin barrier is important in the development of AD and FA. This supports moisturizer use in prevention because some of them have been proven to restore skin barrier with clear benefits in AD, whereas there is some limited evidence that these products may reduce allergic sensitization. However, moisturizers have varied effects depending on ingredients and formulation, some of which are paradoxical, such as increasing transepidermal water loss and enhancing penetration of substances in the skin. These effects may be responsible for some of the conflicting outcomes of prevention studies, some of which suggest that moisturizers are not useful in prevention of AD and FA, whereas others show a positive trend. Interestingly, there is some suggestion that moisturizers may increase the risk for allergy development perhaps through these paradoxical effects. CONCLUSION: Although moisturizer use is beneficial in the management of AD, current evidence suggests that it may be ineffective in prevention of AD and FA. Further studies are needed to determine the effects of moisturization on allergic sensitization and inflammation and to investigate whether moisturizer type, frequency, duration, and age of application substantially affect the prevention and development of these allergies.

Different types of emollient cream exhibit diverse physiological effects on the skin barrier in adults with atopic dermatitis.

BACKGROUND: Eczema (atopic dermatitis; AD) is a very common itchy skin condition affecting 1 in 5 children and up to 1 in 10 adults worldwide. The skin of eczema sufferers is prone to redness, irritation and dryness because it does not form an effective barrier, i.e. the ability of the skin to stop irritants, allergens and microorganisms getting into the body. Skin barrier dysfunction is a hallmark of AD. The regular and liberal (600 g/week for an adult) use of emollients is recommended for all patients with eczema), even between episodes of itching and redness, to soften and soothe the skin. In England alone, almost 9 million prescriptions for emollient creams were issued in 2018, at a cost of over £50 million. Despite this widespread use, relatively little is known about how commonly prescribed emollient creams affect the skin's barrier, and thus the role of moisturizers in AD development and progression remains unclear. We set out to compare three different types of emollient cream and a no-treatment control. AIM: To compare the barrier-strengthening properties of a new moisturizer containing urea and glycerol (urea-glycerol cream; UGC), with those of a glycerol-containing moisturizer (glycerol cream; GC), a simple paraffin cream (PC) with no humectant, and a no-treatment control (NTC). METHODS: This was an observer-blinded prospective Phase 2 within-subject multilateral single-centre randomized controlled trial in adults with AD (Clinical Trials #NCT03901144). The intervention involved 4 weeks of treatment, twice daily, with the three products applied to one of four areas on the forearms the (the fourth area was the untreated control, randomized allocation). Skin properties [dryness, transepidermal water loss (TEWL), hydration and natural moisturizing factor (NMF) levels] were assessed before, during and after treatment to see what happened to the skin's barrier. The primary outcome was skin sensitivity to the irritant sodium lauryl sulfate (SLS) after treatment. We performed tests on the skin before and after treatment to see what happened to the skin's barrier. RESULTS: In total, 49 patients were randomized, completed treatment and included in the analysis. UGC significantly reduced the response to SLS as indicated by a reduction in TEWL compared with NTC (-9.0 g/m2 /h; 95% CI -12.56 to -5.49), with PC (-9.0 g/m2 /h; 95% CI -12.60 to -5.44) and with GC -4.2 g/m2 /h; 95% CI 7.76 to -0.63). Skin moisturization improved at sites treated with UGC compared with NTC and PC, and this was accompanied by concordant changes in dryness and NMF levels. Subgroup analysis suggested FLG-dependent enhancement of treatment effects. CONCLUSION: The study showed that not all emollient creams for eczema are equal. The simple paraffin-based emollient, which represents the most widely prescribed type of emollient cream in England, had no effect on the skin's barrier and reduced the skin's NMF. UGC markedly improved the skin's barrier and protected against irritation. GC performed better than PC, but not as well as UGC. UGC strengthened the skin barrier through a mechanism involving increased NMF levels in the skin, and imparted protection from SLS-induced irritation. By helping correct a major pathophysiological process, UGC has the potential to improve the long-term control of AD. The results show that different emollient creams have different effects on our skin, and only certain types have the ability to improve the skin's barrier and protect against irritants that trigger eczema.

Effect of seasonal change on the biomechanical and physical properties of the human skin.

In this study, the effect of one cycle of winter to summer seasonal transition on the mechanical and physical properties of skin was investigated in vivo. Fourteen healthy skin volunteers aged between 22 and 42 years were studied at the volar lower and upper arms. The findings indicate a 22.15% and 34.29% decrease in trans-epidermal water loss (TEWL) and the average epidermal roughness (AER), respectively. Also, improved skin properties were observed such as a 25.48% rise in average epidermal hydration (AEH), 22.59% in skin thickness, 38.64% and 21.92% in melanin and redness, respectively, as well as an 8.25% rise in its firmness and 23.14% in elasticity when strained with uniaxial deformations. An inverse correlation was established between TEWL and AEH with a linear relationship between stratum corneum roughness versus TEWL as well as thickness and hydration. Also, the skin firmness exhibited a direct proportionality with TEWL and an inverse correlation with skin hydration where these relationships were stronger in summer than in winter. Furthermore, time-dependent results demonstrated three-staged elastic, viscoelastic and creep deformations with high, moderate and low strain rates respectively at both anatomical locations. The winter season displayed lower skin firmness and elasticity of 0.37 mm and 0.04 mm compared to 0.40 mm and 0.06 mm in summer accordingly. Anatomically, the two arm regions displayed different results with the upper arm having more consistent results than the lower arm. These results will find relevance in sensor skins and exoskeletons in Medicare, robotic and military technologies as well as innovations in cosmetics and dermatology.

Vehicles for atopic dermatitis therapies: more than just a placebo.

A topical vehicle is a 'carrier system' for an active pharmaceutical (or cosmetic) substance, referred to hereafter as the drug, but a vehicle may also be used on its own as an emollient to ameliorate dry skin. It is well established that the vehicle plays an important role in determining the bioavailability of a given drug at its ultimate target within the skin. Yet in the treatment of atopic eczema/dermatitis (AD), wherein the structure and function of the skin's outer barrier play a pivotal role in the development and course of the condition, the interaction of the vehicle with this barrier carries a particular importance. It is now clear that the often-considered inert excipients of a vehicle bring about changes within the skin at the molecular level that promote barrier restoration and enhance innate immune defenses with therapeutic value to AD patients. Moreover, the vehicle control in randomized controlled trials (RCTs) increasingly displays significant efficacy. In light of this, we consider the implications of vehicle design in relation to AD pathophysiology and the role vehicles play as controls in RCTs of new drug treatments for this condition.

Enhancement of stratum corneum lipid structure improves skin barrier function and protects against irritation in adults with dry, eczema-prone skin.

BACKGROUND: The skin of patients with atopic dermatitis is characterized by abnormal stratum corneum lipid levels. Consequently, the lamellar matrices are disrupted and skin barrier function is diminished, increasing skin sensitivity to irritants and allergens. OBJECTIVES: To determine whether a cream containing ceramides, triglycerides and cholesterol in a multivesicular emulsion can reinforce the skin barrier and protect against skin irritation. METHODS: A randomized observer-blind intrapatient-controlled study in 34 adults with dry, eczema-prone skin was conducted. Each participant underwent 4 weeks of treatment with the test cream on one forearm and lower leg and a reference emollient cream on the other. Skin properties were determined before and after treatment. Lipid structure was assessed by Fourier-transform infrared spectroscopy using a novel interface. RESULTS: Skin barrier integrity was greater at sites treated with the test cream [effect size for area under the transepidermal water loss curve -162, 95% confidence interval (CI) -206 to -118]. Skin sensitivity to sodium lauryl sulfate was reduced (-0·5 points visual redness, 97·57% CI -1·00 to -0·25), as was transepidermal water loss (-15·3 g m-2 h-1 , 95% CI -20·3 to -10·4) compared with the reference. Sites treated with the test cream displayed enhanced lipid chain ordering, which was significantly associated with skin barrier integrity (r = 0·61). Compared with the reference, treatment with the test cream increased hydration (8·61 capacitance units, 95% CI 6·61-10·6) and decreased signs of dryness. CONCLUSIONS: The test cream facilitates skin barrier restoration and protects the skin from dryness and irritation. Compared with a commonly prescribed emollient in the UK, the test cream is highly suited to the management of dry, sensitive skin.

Determination of Chemical Irritation Potential Using a Defined Gene Signature Set on Tissue-Engineered Human Skin Equivalents.

There are no physical or visual manifestations that define skin sensitivity or irritation; a subjective diagnosis is made on the basis of the evaluation of clinical presentations, including burning, prickling, erythema, and itching. Adverse skin reaction in response to topically applied products is common and can limit the use of dermatological or cosmetic products. The purpose of this study was to evaluate the use of human skin equivalents based on immortalized skin keratinocytes and evaluate the potential of a 22-gene panel in combination with multivariate analysis to discriminate between chemicals known to act as irritants and those that do not. Test compounds were applied topically to full-thickness human skin equivalent or human ex vivo skin and gene signatures determined for known irritants and nonirritants. Principle component analysis showed the discriminatory potential of the 22-gene panel. Linear discrimination analysis, performed to further refine the gene set for a more high-throughput analysis, identified a putative seven-gene panel (IL-6, PTGS2, ATF3, TRPV3, MAP3K8, HMGB2, and matrix metalloproteinase gene MMP-3) that could distinguish potential irritants from nonirritants. These data offer promise as an in vitro prediction tool, although analysis of a large chemical test set is required to further evaluate the system.

Imaging striae distensae: a comparison between PS-OCT and digital dermoscopy.

Stretch marks or striae distensae (SD) cause emotional distress and negatively affect the psychological well-being of patients. We investigate and compare two methods for quantifying the severity of SD: visual scoring of images captured using a clinical visible-light dermatological camera (C-Cube, Pixience Inc) and measuring the local birefringence of skin using polarization-sensitive optical coherence tomography (PS-OCT). Data on skin visually affected by SD and visually normal skin were collected from 19 human volunteers. Our results show a weak correlation between visual scores of the C-Cube images and the birefringence values obtained from the PS-OCT system. SD datasets have a significantly larger birefringence values compared to visually normal datasets.

The effect of water hardness on atopic eczema, skin barrier function: A systematic review, meta-analysis.

BACKGROUND: Hard domestic water has been reported to worsen atopic eczema (AE) and may contribute to its development in early life. OBJECTIVE: To review the literature on the relationship between the effect of water hardness (high calcium carbonate; CaCO3 ) on (a) the risk of developing AE, (b) the treatment of existing AE and (c) skin barrier function in human and animal studies. DESIGN , DATA SOURCES AND ELIGIBILITY CRITERIA: We systematically searched databases (MEDLINE, Embase, Cochrane CENTRAL, GREAT and Web of Science) from inception until 30/6/2020. Human and animal observational and experimental studies were included. The primary outcomes were risk of AE and skin barrier function. Studies were meta-analysed using a random effects model. Evidence certainty was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. RESULTS: Sixteen studies were included. Pooled observational data from seven studies on 385,901 participants identified increased odds of AE in children exposed to harder versus softer water (odds ratio 1.28, 95% CI 1.09, 1.50; GRADE certainty: very low). Two mechanistic studies in humans reported higher deposition of the detergent sodium lauryl sulphate in those exposed to harder versus softer water. Two randomized controlled trials comparing water softeners with standard care did not show a significant difference in objective AE severity with softened water (standardized mean difference 0.06 standard deviations higher, 95% CI 0.16 lower to 0.27 higher; GRADE certainty: moderate). CONCLUSIONS & CLINICAL RELEVANCE: There was a positive association between living in a hard water (range: 76 to > 350 mg/L CaCO3 ) area and AE in children. There is no evidence that domestic water softeners improve objective disease severity in established AE. There may be a role of water hardness in the initiation of skin inflammation in early life, but there is a need for further longitudinal and interventional studies.

An Investigation of the Skin Barrier Restoring Effects of a Cream and Lotion Containing Ceramides in a Multi-vesicular Emulsion in People with Dry, Eczema-Prone, Skin: The RESTORE Study Phase 1.

INTRODUCTION: The replenishment of skin lipids depleted in the dry skin state is a desirable therapeutic target to restore skin moisturization; however, there is limited evidence demonstrating the success of this approach through the use of topical emollients. The purpose of this study was to provide evidence of the benefits of a cream and equivalent lotion containing skin lipids in a multi-vesicular emulsion for the management of dry skin. The hypothesis was that the test cream and test lotion could sustain skin moisturization for longer than traditional emollients by sustainably delivering skin lipids. METHODS: A double-blind intra-subject vehicle-controlled single open-application test on the lower legs in people with dry, atopic dermatitis (atopic eczema)-prone, skin was conducted. There were six treatment sites, three per lower leg in each participant, which were treated with the test cream, the test lotion, three reference creams commonly prescribed in the UK and no treatment as a control. After baseline measurements of skin hydration, 100 µl of the test/reference creams was applied to each of the relevant treatment sites (random site allocation). Following treatment, measurements of skin hydration and scoring of visual dryness was conducted at timed intervals (3, 6, 12 and 24 h post-product application). RESULTS: The test cream and lotion both significantly increased skin hydration and reduced skin dryness for at least 24 h following a single application compared to a no treatment control site. Compared to three reference emollient creams the test cream and test lotion were the only products capable of sustaining clinically meaningful improvements in skin moisturization for 24 h. CONCLUSION: The sustained moisturization imparted by the test products reduces the need for frequent emollient application, often requiring 3-4 applications per day for traditional emollients, and should reduce the high burden of managing dry skin conditions like atopic dermatitis.

Hygiene and emollient interventions for maintaining skin integrity in older people in hospital and residential care settings.

BACKGROUND: Ageing has a degenerative effect on the skin, leaving it more vulnerable to damage. Hygiene and emollient interventions may help maintain skin integrity in older people in hospital and residential care settings; however, at present, most care is based on "tried and tested" practice, rather than on evidence. OBJECTIVES: To assess the effects of hygiene and emollient interventions for maintaining skin integrity in older people in hospital and residential care settings. SEARCH METHODS: We searched the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL, up to January 2019. We also searched five trials registers. SELECTION CRITERIA: Randomised controlled trials comparing hygiene and emollient interventions versus placebo, no intervention, or standard practices for older people aged ≥ 60 years in hospital or residential care settings. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. Primary outcomes were frequency of skin damage, for example, complete loss of integrity (tears or ulceration) or partial loss of integrity (fissuring), and side effects. Secondary outcomes included transepidermal water loss (TEWL), stratum corneum hydration (SCH), erythema, and clinical scores of dryness or itch. We used GRADE to assess the quality of evidence. MAIN RESULTS: We included six trials involving 1598 residential care home residents; no included trial had a hospital setting. Most participants had a mean age of 80+ years; when specified, more women were recruited than men. Two studies included only people with diagnosed dry skin. Studies were conducted in Asia, Australasia, Europe, and North America. A range of hygiene and emollient interventions were assessed: a moisturising soap bar; combinations of water soak, oil soak, and lotion; regular application of a commercially available moisturiser; use of two different standardised skin care regimens comprising a body wash and leave-on body lotion; bed bath with "wash gloves" containing numerous ingredients; and application of a hot towel after usual care bed bath. In five studies, treatment duration ranged from five days to six months; only one study had post-treatment follow-up (one to eight days from end of treatment). Outcomes in the hot towel study were measured 15 minutes after the skin was wiped with a dry towel. Three studies each had high risk of attrition, detection, and performance bias. Only one trial (n = 984) assessed frequency of skin damage via average monthly incidence of skin tears during six months of treatment. The emollient group (usual care plus twice-daily application of moisturiser) had 5.76 tears per month per 1000 occupied bed-days compared with 10.57 tears in the usual care only group (ad hoc or no standardised skin-moisturising regimen) (P = 0.004), but this is based on very low-quality evidence, so we are uncertain of this result. Only one trial (n = 133) reported measuring side effects. At 56 ± 4 days from baseline, there were three undesirable effects (itch (mild), redness (mild/moderate), and irritation (severe)) in intervention group 1 (regimen consisting of a moisturising body wash and a moisturising leave-on lotion) and one event (mild skin dryness) in intervention group 2 (regimen consisting of body wash and a water-in-oil emulsion containing emollients and 4% urea). In both groups, the body wash was used daily and the emollient twice daily for eight weeks. There were zero adverse events in the usual care group. This result is based on very low-quality evidence. This same study also measured TEWL at 56 ± 4 days in the mid-volar forearm (n = 106) and the lower leg (n = 105). Compared to usual care, there may be no difference in TEWL between intervention groups, but evidence quality is low. One study, which compared application of a hot towel for 10 seconds after a usual care bed bath versus usual care bed bath only, also measured TEWL at 15 minutes after the skin was wiped with a dry towel for one second. The mean TEWL was 8.6 g/m²/h (standard deviation (SD) 3.2) in the hot towel group compared with 8.9 g/m²/h (SD 4.1) in the usual care group (low-quality evidence; n = 42), showing there may be little or no difference between groups. A lower score is more favourable. Three studies (266 participants) measured SCH, but all evidence is of very low quality; we did not combine these studies due to differences in treatments (different skin care regimens for eight weeks; wash gloves for 12 weeks; and single application of hot towel to the skin) and differences in outcome reporting. All three studies showed no clear difference in SCH at follow-up (ranging from 15 minutes after the intervention to 12 weeks from baseline), when compared with usual care. A clinical score of dryness was measured by three studies (including 245 participants); pooling was not appropriate. The treatment groups (different skin care regimens for eight weeks; a moisturising soap bar used for five days; and combinations of water soak, oil soak, and lotion for 12 days) may reduce dryness compared to standard care or no intervention (results measured at 5, 8, and 56 ± 4 days after treatment was initiated). However, the quality of evidence for this outcome is low. Outcomes of erythema and clinical score of itch were not assessed in any included studies. AUTHORS' CONCLUSIONS: Current evidence about the effects of hygiene and emollients in maintaining skin integrity in older people in residential and hospital settings is inadequate. We cannot draw conclusions regarding frequency of skin damage or side effects due to very low-quality evidence. Low-quality evidence suggests that in residential care settings for older people, certain types of hygiene and emollient interventions (two different standardised skin care regimens; moisturising soap bar; combinations of water soak, oil soak, and lotion) may be more effective in terms of clinical score of dryness when compared with no intervention or standard care. Studies were small and generally lacked methodological rigour, and information on effect sizes and precision was absent. More clinical trials are needed to guide practice; future studies should use a standard approach to measuring treatment effects and should include patient-reported outcomes, such as comfort and acceptability.