Distinct barrier integrity phenotypes in filaggrin-related atopic eczema following sequential tape stripping and lipid profiling

Background Filaggrin gene (FLG) loss‐of‐function mutations have been shown to represent the strongest so far known genetic risk factor for atopic dermatitis (AD). Whereas the barrier characteristics in FLG mutation carriers under baseline conditions have been investigated, there are only limited data on the permeability barrier function in filaggrin‐AD under compromised conditions. Aim We investigated: (i) stratum corneum (SC) integrity/cohesion; (ii) barrier recovery after controlled mechanical and irritant‐induced barrier abrogation; and (iii) the lipid composition of the non‐lesional and lesional skin of AD patients harbouring the European R501X, 2282del4, 3702delG, R2447X or S3247X FLG variants. Methods Thirty‐seven AD patients (14 FLG mutation carriers and 23 non‐carriers) and 20 healthy controls participated in the study. Stratum corneum integrity/cohesion was assessed by measurement of transepidermal water loss (TEWL) and amount of removed protein following sequential tape stripping. Barrier recovery was monitored by repeated measurements of TEWL and erythema up to 96 h after barrier abrogation. Samples for lipid analysis were obtained from non‐lesional and lesional skin using the cyanoacrylate method. Results Tape stripping revealed distinct genotype‐related impairment of the SC integrity/cohesion. No differences in the rate of barrier recovery among the groups were found. The SC lipid analysis revealed significant differences regarding the percentage amount of cholesterol, ceramide/cholesterol ratio and triglycerides in the uninvolved skin as well as the amounts of free fatty acids, CER[EOH] and triglycerides in the skin lesions of the AD FLG mutation carriers. Conclusions Our results provide evidence for discernible FLG‐related barrier integrity phenotypes in atopic eczema.     

Clinical severity and prognosis of hand eczema

Background  Hand eczema (HE) is a frequent, long-lasting disease with both personal and societal repercussions. Consequently, more information is needed on factors that maintain symptoms.
Objectives  In this study, patients with HE were followed for 6 months from the first visit to a dermatologist to identify factors associated with severe disease and a poor prognosis.
Methods  Study participants were 799 patients with HE from nine dermatological clinics in Denmark. Severity assessment of the HE was done at baseline and at the 6-month follow-up using the Hand Eczema Severity Index (HECSI) and by patients using a self-administered photographic guide. Additional information was obtained from a baseline questionnaire.
Results  At baseline, 60·3% assessed their HE as moderate to very severe using the self-administered photographic guide compared with 36·1% at follow-up. The mean HECSI value decreased from 19·9 points at baseline to 11·2 points at follow-up ( P  <   0·001). In a multivariable logistic regression analysis, statistically significant associations with severe HE at baseline were older age ( P  <   0·001), atopic dermatitis ( P  =   0·01) and ≥ 1 positive patch test ( P  <   0·001). Being an unskilled worker was a predictor for a poor prognosis at follow-up ( P  =   0·04), and the presence of frequent symptoms during the previous 12 months was associated with severe initial disease ( P  =   0·02) and a poor prognosis ( P  =   0·04).
Conclusions  Overall, the disease had improved 6 months after the dermatological examination: nevertheless, many patients continued to have significant symptoms. Dermatologists should pay special attention to patients with frequent eruptions and to unskilled workers.     

Staphylococcus aureus and hand eczema severity

Background  The role of bacterial infections in hand eczema (HE) remains to be assessed.
Objectives  To determine the prevalence of Staphylococcus aureus in patients with HE compared with controls, and to relate presence of S. aureus , subtypes and toxin production to severity of HE.
Methods  Bacterial swabs were taken at three different visits from the hand and nose in 50 patients with HE and 50 controls. Staphylococcus aureus was subtyped by spa typing and assigned to clonal complexes (CCs), and isolates were tested for exotoxin-producing S. aureus strains. The Hand Eczema Severity Index was used for severity assessment.
Results  Staphylococcus aureus was found on the hands in 24 patients with HE and four controls ( P  <   0·001), and presence of S. aureus was found to be related to increased severity of the eczema ( P  <   0·001). Patients carried identical S. aureus types on the hands and in the nose in all cases, and between visits in 90% of cases. Ten different CC types were identified, no association with severity was found, and toxin-producing strains were not found more frequently in patients with HE than in controls.
Conclusions  Staphylococcus aureus was present on hands in almost half of all patients with HE, and was significantly related to severity of the disease. This association indicates that S. aureus could be an important cofactor for persistence of HE.     

Epidermal innervation correlates with severity of photodamage

Abstract Intraepidermal nerve fibers were studied by electron microscopy in chronically photodamaged preauricular skin and in paired sun-protected postauricular sites of 20 Caucasian women aged 56–70 years. As previously reported, basal keratinocytes in the sun-exposed skin showed various degrees of degenerative changes including intracellular vacuolar structures and widened intercellular spaces. Neurites were frequently closely apposed to basal keratinocytes in preauricular sun-exposed skin, but were observed less than 10% as often in sun-protected postauricular skin. When degree of epidermal photodamage was quantified by means of the number of degenerated keratinocytes per 100 keratinocytes in the basal layer, the number of intraepidermal nerve libers was significantly correlated by linear regression analysis to the severity of epidermal photodamage (r=0.913) independent of anatomical sites. These results demonstrate for the first time a correlation between degree of epidermal innervation and chronic photodamage and suggest the possibility of neural involvement in the pathophysiology and/or repair of photodamaged skin.     

Outcome measures of disease severity in atopic eczema

BACKGROUND: An essential component of evidence-based medicine is the use of valid and reliable outcome measures in clinical trials. There is much confusion in the field of atopic eczema regarding how to best measure disease severity objectively. OBJECTIVE: To establish the extent to which existing objective clinical scales for atopic eczema have been tested for validity, reliability, sensitivity to change, and acceptability. DESIGN: An electronic bibliographic search was performed for published data on all currently available named atopic eczema scales. RESULTS: Thirteen scales were identified in total. Data on construct or criterion validity were available for 10 scales. Only 5 scales had been tested for reliability (interobserver variability, intraobserver variability, or internal consistency). Data on responsiveness to change were available for 8 scales. An estimated time to administer the measure had been given for 3 scales. The only severity scale for which published data could be found on validity, reliability, sensitivity, and acceptability testing was the Severity Scoring of Atopic Dermatitis index, although problems occurred with interobserver variation of the index. CONCLUSION: The rapidly increasing number of severity scales for atopic eczema, many of which have been inadequately tested, has made the interpretation of patient outcomes confusing, and comparison of results between studies almost impossible. Consensus among clinicians and researchers on the use of severity scales for atopic eczema should be based on evidence of adequate validity), reliability, sensitivity to change, and ease of use.     

Sensitive skin is highly frequent in extrinsic atopic dermatitis and correlates with disease severity markers but not necessarily with skin barrier impairment

Background

Sensitive skin is a condition of cutaneous hypersensitivity to environmental factors. Lactic acid stinging test (LAST) is commonly used to assess sensitive skin and composed of four distinct sensations (pain, burning sensation, itch, and crawly feeling). A link between sensitive skin and barrier dysfunction has been proposed in atopic dermatitis (AD) patients. However, clinical and laboratory factors that are associated with sensitive skin remain unelucidated.

Eczema workshops reduce severity of childhood atopic eczema

An intervention study was conducted to assess the effectiveness of a nurse-led eczema workshop in reducing the severity of atopic eczema in infants, children and adolescents. Ninety-nine new patients referred to the Dermatology Department of The Royal Children's Hospital in Melbourne, Australia, for the management of atopic eczema were randomized to receive care from an eczema workshop or a dermatologist-led clinic. Patients were followed-up 4 weeks after the intervention. The primary outcome was the severity of eczema as determined by scores obtained using the Scoring of Atopic Dermatitis (SCORAD) index at a 4-week follow-up visit. The secondary outcome was a comparison of treatments used in both clinics. At the 4-week review the mean improvement in SCORAD was significantly greater in those patients attending the eczema workshop than those attending the dermatologist-led clinic (−9.93, 95% confidence interval −14.57 to −5.29, P  < 0.001). Significantly more patients from the eczema workshop improved from moderate severity eczema at baseline to mild at review. There was greater adherence to eczema management in the eczema workshop compared with the dermatologist-led clinic. In this study, patients attending the eczema workshop had a greater improvement in eczema severity thanpatients attending a dermatologist-led clinic, supporting collaborative models of service provision.     

Skin barrier function, epidermal proliferation and differentiation in eczema

Skin permeability barrier function is impaired in eczema, particularly in contact and atopic dermatitis (AD). In contact dermatitis disruption of the barrier by irritants and allergens is the primary event, followed by sensitization, inflammation, increased epidermal proliferation and changes in differentiation. Genetically impaired skin barrier function is already present in non-lesional and more pronounced in lesional skin in AD. Increased epidermal proliferation and disturbed differentiation, including changes in lipid composition, cause impaired barrier function in AD. Defective permeability barrier function enables the enhanced penetration of environmental allergens into the skin and initiates immunological reactions and inflammation. Barrier dysfunction is therefore crucially involved in the pathogenesis of AD. The atopic syndrome represents a genetically impaired skin barrier function as well as impaired nasal, bronchial, and intestinal mucous membranes leading to AD, allergic rhinitis, bronchial asthma or aggravation of AD. Common treatment strategies for eczema include the application of lipid-based creams and ointments, which aim toward the restoration of the defective permeability barrier, thus helping to normalize proliferation and differentiation.     

Anxiety, depression and impaired health-related quality of life in patients with occupational hand eczema

Background. Occupational hand eczema is one of the most frequent occupational diseases. Few data about the prevalence of mental comorbidities are available. Objectives. We aimed to investigate the prevalence of anxiety, depression symptoms, the impairment of health-related quality of life (HRQoL) and their correlates in patients with occupational hand eczema. Patients and methods. A test battery consisting of the German versions of the Hospital Anxiety and Depression Scale, the Dermatology Life Quality Index (DLQI) as a specific instrument and the Short Form Health Survey-36 (SF-36) as a generic instrument for HRQoL was applied in 122 patients. The severity of hand eczema was assessed with the Osnabrueck Hand Eczema Severity Index (OHSI). Results. Twenty per cent of patients had a positive anxiety score, and 14% had a positive depression score. Higher anxiety levels, a greater impairment in the SF-36 mental component summary score and a higher DLQI category score for symptoms and feelings was detected in females than in males. The OHSI correlated with the impairment in HRQoL, and an association of severe hand eczema with symptoms of anxiety and depression was found in males. Conclusions. We found a high prevalence of anxiety and depression in our study population of patients with occupational hand eczema. Preventive measures should consider the psychosocial implications of occupational hand eczema.     

Filaggrin loss-of-function mutations are associated with early-onset eczema, eczema severity and transepidermal water loss at 3 months of age

Background Filaggrin loss‐of‐function (FLG) mutations are associated with eczema and skin barrier impairment, but it is unclear whether skin barrier impairment precedes phenotypic eczema in FLG mutation carriers. Objectives To study the association between FLG mutations, skin barrier impairment and clinical eczema at 3 months of age. Methods A total of 88 infants were examined for eczema. Disease severity was determined by the SCORAD eczema severity score. Transepidermal water loss (TEWL) was measured on unaffected forearm skin. Venous blood samples were screened for the four most common FLG mutations found in the U.K. white population (R501X, 2282del4, R2447X and S3247X). Median SCORAD and TEWL measurements in children with and without eczema and FLG mutations were compared. Results Thirty‐three per cent (29/88) of children had clinical eczema. Median SCORAD was 10·6 (range 3·5–31·0). TEWL (g m^?2 h^?1) was higher in children with eczema compared with unaffected infants (median TEWL 14·24 vs. 11·24, P < 0·001). Higher TEWL was associated with more severe disease (r = 0·59, P < 0·001, median TEWL, SCORAD < 15, 13·1 vs. 29·6, SCORAD ≥ 15, P = 0·029). Clinically dry skin was associated with higher TEWL, even in the absence of eczema (median TEWL 17·55 vs. 11·08, P = 0·008). Seventeen per cent (15/88) of children carried at least one FLG mutation. FLG mutation carriers were significantly more likely to have clinically dry skin, even in the absence of eczema [odds ratio (OR) 8·50, 95% confidence interval (CI) 1·09–66·58, P = 0·042]. FLG mutation carriers were also more likely to have eczema by 3 months of age (OR 4·26, 95% CI 1·34–13·57, P = 0·014). FLG mutations were significantly associated with higher median TEWL (all children, FLG‘yes’ 21·59 vs. FLG‘no’ 11·24, P < 0·001), even without clinical eczema (FLG‘yes’ 15·99 vs. FLG‘no’ 10·82, P = 0·01). Conclusions By the age of 3 months, FLG mutations are associated with an eczema phenotype, dry skin and TEWL. The observation that TEWL is elevated in unaffected FLG mutation carriers suggests that skin barrier impairment precedes clinical eczema.     

178例泛发性湿疹临床分析

目的：回顾性分析178例泛发性湿疹患者的临床资料,寻找相关发病因素。结果：泛发性湿疹好发于中老年男性,既往过敏史者27％,伴发高血糖20．2％、高血脂65．2％、高血压40．4％、高尿酸19．1％、冠心病50．6％及实验室指标异常（嗜酸粒细胞增高65．2％、血清IgE水平增高14．6％、低血钙者13．5％、高血磷16．9％、低血磷1．1％、转氨酶升高14．6％、脂蛋白a15．7％、乳酸脱氢酶增高50．5％、碱性磷酸酶增高23．6％、总胆汁酸增高10．1％）。结论：泛发性湿疹易伴发引起代谢综合征的疾病。     

Urinary leukotriene E4 correlates with severity of atopic dermatitis in children

Leukotriene E4 (LTE(4)) is elevated in adults with atopic dermatitis (AD). We evaluated whether urinary LTE(4) as a noninvasive marker correlates with clinical indices of disease activity in children with AD. AD patients aged 18 years or younger were eligible for inclusion in the study. Disease severity over the preceding 3 days was evaluated by the SCORing Atopic Dermatitis (SCORAD) index. Severity of AD over the past 12 months was evaluated by the Nottingham Eczema Severity Score (NESS) in Chinese. Urinary LTE(4) concentration was measured by competitive enzyme immunoassay. One hundred and twenty-six children with AD (82 boys and 44 girls) and 45 controls were recruited. The mean +/- SD urinary log-transformed LTE(4) concentration in AD patients and controls was 2.94 +/- 0.32 and 2.62 +/- 0.20 pg/mg creatinine, respectively (P < 0.0001). SCORAD significantly correlated with NESS (r = 0.681, P < 0.0001). There were significant correlations between urinary LTE(4) concentration and overall SCORAD score (r = 0.270, P = 0.002) and its extent (r = 0.185, P = 0.038) and intensity components (r = 0.247, P = 0.005), but not with NESS. When compared with mild AD, urinary LTE(4) concentrations were higher in patients with moderate-to-severe disease (P = 0.049). Urinary LTE(4) measurement is noninvasive and may be useful in supplementing the SCORAD for following longitudinal changes in AD severity in children. However, the practical value of this assay in a clinical setting remains to be determined.     

Hand eczema severity and quality of life: a cross-sectional, multicentre study of hand eczema patients

Background and Objectives:  Hand eczema is a chronic disease with negative impact on quality of life (QoL). In this study, QoL in hand eczema patients is assessed and related to age, sex, severity, and diagnostic subgroups.
Methods:  A total of 416 patients with hand eczema from 10 European patch test clinics participated in the study. Data on QoL were obtained from a self-administered questionnaire using the Dermatology Life Quality Index (DLQI). Severity was assessed by a scoring system (Hand Eczema Severity Index, HECSI) as well as frequency of eruptions and sick leave due to hand eczema.
Results:  No significant difference was found between males and females with respect to QoL [DLQI median values and 25/75 percentiles for males and females being 7.0 (3–14) and 8.0 (3–13), respectively], although males were more severely affected than females ( P < 0.025). A significant positive correlation was found for hand eczema severity and age ( P < 0.001), while no significant correlation was found for QoL and age. QoL was found increasingly reduced when sick leave was getting higher ( P < 0.001). A statistically significant correlation between QoL (as measured by DLQI) and hand eczema severity as measured by HECSI was found ( P < 0.001). No significant difference in QoL was found between diagnostic subgroups.
Conclusions:  QoL was found markedly negatively affected in hand eczema patients and was significantly correlated to disease severity. No significant difference in QoL was found between males and females, in spite of significantly more severe eczema in males, indicating that QoL in female patients is more easily affected.