Palmar Hyperlinearity Research Articles

Loss of Function Filaggrin Mutations are Associated with Reduced History of Acne Vulgaris in a Cohort of Bangladeshi Atopic Eczema Patients in East London.

Acne vulgaris (AV) is the eighth most common non-fatal disease globally. Previous work identified an association between AV and increased Filaggrin (FLG) expression in the follicular epidermis, but further work did not find a clear link between loss of function (LoF) Filaggrin gene (FLG) mutations and protection from AV. In this work we aimed to explore any association between AV and FLG LoF mutations using a cohort of genotyped Bangladeshi patients with atopic eczema (AE) in East London. Retrospective notes review was performed on 245 patients who had been genotyped for FLG LoF mutations and undergone clinical assessment. The Chi squared or Fisher's exact test was used to determine differences between groups. We found a significant reduction in history of AV in AE patients with FLG LoF mutations relative to AE patients without FLG mutations (p = 0.02). We showed a non-significant reduction in AV diagnosis in patients with impaired barrier function (measured by trans epidermal water loss) and palmar hyperlinearity. We found that patients with severe AE were less likely to have a history of AV only if they had an existing FLG LoF mutation (p = 0.02). In the context of AE, our work suggests that FLG LoF mutations protect patients from developing AV.

PA14 Aquagenic palmar wrinkling in a 15-year-old swimmer

Abstract A 15-year-old girl presented with a 1-year history of recurrent palmar wrinkling on contact with water. This was associated with a burning sensation within minutes of water exposure and progressive persistent thickening of the palmar skin. She was otherwise well, with no family history of note, including cystic fibrosis (CF). She had no regular medication or newly introduced medications before the onset of wrinkling. Moderate improvement in hyperkeratosis was seen with twice-daily use of urea 10% and salicylic acid 10% creams; however, the discomfort experienced in water was negatively affecting her ability to continue competitive swimming. On examination, there was palmar hyperlinearity with focal hyperkeratosis over the thenar and hypothenar eminences. Immersion of the hands in lukewarm water resulted in wrinkling within 2 min and peaking at 3 min, at which point the patient reported a burning sensation. Wrinkling resolved within 30 min of drying her hands. Baseline laboratory investigations were normal. Biopsy of the palm in the wrinkled state showed subtle prominence and dilation of sweat gland ducts. A diagnosis of aquagenic syringeal keratoderma (ASK) was made. At the 3- and 6-month reviews, the patient reported spontaneous resolution of wrinkling on contact with water, which was confirmed clinically. Residual hyperkeratosis had similarly resolved, although subtle palmar hyperlinearity persisted. She was able to resume competitive swimming activities without symptoms. The ASK is a rare condition, classically affecting the palms of young women, in which palmar wrinkling occurs within minutes of immersion in water. It may be asymptomatic or associated with stinging, burning or paraesthesia. Palmar wrinkling typically resolves after drying of the hands without persisting signs. The mechanism for this phenomenon is unclear, with theories including acquired abnormalities in eccrine glands, an underlying primary keratoderma, or potential induction by cyclooxygenase. Aquagenic palmar wrinkling is also recognized in association with CF, both in individuals with the disease and carriers, with more rapid onset of wrinkling in the former. In this case, there was no suggestion of personal or family histories of CF, and hyperkeratosis persisted for months at a time until liberal regular use of keratolytic topical agents was introduced. Hereditary papulotranslucent acrokeratoderma, a differential diagnosis in this case, was considered; however, in this condition once papules and wrinkling appear, they typically remain and are further exacerbated by water exposure. For this patient, a diagnosis of atypical ASK was favoured due to the persisting sequelae, with probable mild atopic dermatitis reflected by palmar hyperlinearity. This case serves to highlight this rare dermatological phenomenon and its impact on a teenage swimmer.

BG11 Palmoplantar keratoderma with mutations in filaggrin and desmoglein-1 genes

Abstract Hereditary palmoplantar keratoderma (PPK) has many forms, and genetic testing can help distinguish diagnoses. This case demonstrates a presentation of PPK with an altered phenotype caused by a mutation in FLG. The patient was a 23-year-old woman referred with PPK since the age of 6 years. She reported dry skin on the back of her hands from infancy and no other dermatological conditions. She denied plantar pain except when there were fissures in the callus. There was no relevant past medical history, but a significant family history of individuals with PPK and curly hair, and sudden infant death (SID) in two siblings. Physical examination revealed focal plantar keratoderma bilaterally, curly hair, mild tongue leukokeratosis and generally dry skin on both legs. She had palmar hyperlinearity, small calluses on the palms and normal nails. She declined a skin biopsy. The patient was referred to cardiology to rule out cardiomyopathy associated with a desmoplakin variant. She had an unremarkable transthoracic echocardiography and cardiac magnetic resonance imaging. Twelve-lead electrocardiography showed sinus rhythm with biphasic T-wave in V2 and inverted V1. Clinically arrhythmogenic right ventricular cardiomyopathy (ARVC) was ruled out; however, given her significant family history of SID and PPK, panel testing for genes associated with ARVC was performed, which revealed a heterozygous variant of uncertain significance in MYBPC3 (p.Val639lle). This variant did not explain the patient’s PPK; therefore, a PPK panel was performed. Next-generation sequencing identified a heterozygous DSG1 [c430A>T p.(Arg.144*)] pathogenic variant and a heterozygous FLG [c2282_2285del p.(Ser761Cysfs*36)] pathogenic variant. The patient’s PPK was more severe on the plantar surface of the feet than one might expect with a DSG1 variant. This case demonstrates the interaction between two genetic variants known to be associated with skin conditions. Ichthyosis vulgaris is caused by FLG variants. Patients with heterozygous FLG variants are less severely affected and have reduced penetrance compared to homozygotes. Meanwhile, heterozygous pathogenic variants in DSG1 are associated with keratosis palmoplantaris striata I (MIM148700). We hypothesize that the coexistence of FLG and DSG1 variants may contribute to a more extensive keratoderma phenotype than usually seen with DSG1 variants. This case contributes to our understanding of PPK, demonstrates the value of genetic testing in dermatological conditions and describes a unique phenotype in the presence of multiple genetic variants. Further research is required to better understand the interaction between variants in PPK pathogenesis.

P102 Severe atopic eczema is associated with reduced acne vulgaris in Bangladeshi children and young adults: a retrospective analysis from a cross-sectional study

Abstract Atopic eczema (AE) is the most common inflammatory dermatosis, affecting up to 20% of children. Loss of function (LoF) mutations in FLG are the most strongly implicated genetic risk factor for eczema. To understand the effect of FLG on the pathobiology of AE, we knocked down FLG in primary keratinocytes using short hairpin RNA and performed phosphoproteomic analysis, which showed downregulation of the AKT signalling pathway, confirmed using Western blotting to phospho-AKT and immunostaining of biopsies from patients with AE. Given that AKT signalling is increased in acne vulgaris, we hypothesized that loss of FLG may protect patients with AE from acne. The Tower Hamlets Eczema Assessment (THEA) study is a cross-sectional study that aims to phenotype and genotype 1000 Bangladeshi children and young adults with AE. So far, 620 participants have undergone genotyping, 37% of whom have LoF mutations in FLG. We selected patients from this cohort who were older than 12 years of age. In total, 204 patients (99 FLG wild type, 86 heterozygotes, 19 compound heterozygotes) were included. We identified a diagnosis of acne or previous prescription of topical acne therapies or tetracycline antibiotics from the patients’ general practice e-health records. We stratified the patients by genotype, Eczema Area and Severity Index (EASI) score, Patient Oriented Eczema Measure (POEM) score, transepidermal water loss (TEWL) and palmar hyperlinearity groups. The χ2-test was used to determine differences between groups. A lower proportion of patients with AE with FLG mutations had acne (27% wild type vs. 19% FLG mutations), which was more pronounced, but not statistically significant, in the compound heterozygote group (16%). We saw a nonsignificant reduction in acne in patients who had the top 25% of TEWL measurements, those with the most severe form of hyperlinearity and those with higher POEM scores. Patients with severe AE, measured as an EASI score > 21, had a more reduced incidence of acne than those with lower EASI scores (9% vs. 26%; P = 0.04). Overall, this suggests that patients with more severe AE are protected from developing acne. There was insufficient evidence to establish if this was mediated by a reduction in filaggrin (FLG) and AKT signalling. This may be because the groups were too small to determine this. Given that all patients with severe AE have reduced FLG expression regardless of genotype, it is possible that this is mediated through FLG–AKT signalling.

Atopic dermatitis: Correlation of distinct risk factors with age of onset in adulthood compared to childhood.

Atopic dermatitis (AD) has long been regarded as a primarily pediatric disease. However, there is growing evidence for a high rate of adult-onset AD. We aimed to characterize factors associated with adult-onset versus childhood-onset AD and controls. We analyzed cross-sectional data of the CK-CARE-ProRaD cohorts Bonn, Augsburg, Davos, Zürich of 736 adult patients stratified by age of AD onset (childhood-onset <18 years: 76.4% (subsets: 0 to 2; ≥2 to 6; ≥7 to 11; ≥12 to 18); adult-onset ≥18 years: 23.6% (subsets: ≥18 to 40; ≥41 to 60; ≥61) and 167 controls (91 atopic, 76 non-atopic)). We identified active smoking to be associated with adult-onset AD versus controls (adjusted Odds Ratio (aOR) = 5.54 [95% Confidence Interval: 1.06-29.01] vs. controlsnon-atopic , aOR = 4.03 [1.20-13.45] vs. controlsatopic ). Conjunctivitis showed a negative association versus controlsatopic (aOR = 0.36 [0.14-0.91]). Food allergy (aOR = 2.93 [1.44-5.96]), maternal food allergy (aOR = 9.43 [1.10-80.95]), palmar hyperlinearity (aOR = 2.11 [1.05-4.25]), and academic background (aOR = 2.14 [1.00-4.54]) increased the odds of childhood-onset AD versus controlsatopic . Shared AD-associated factors were maternal AD (4-34x), increased IgE (2-20x), atopic stigmata (2-3x) with varying effect sizes depending on AD onset and control group. Patients with adult-compared to childhood-onset had doubled odds of allergic rhinitis (aOR = 2.15 [1.12-4.13]), but reduced odds to feature multiple (3-4) atopic comorbidities (aOR = 0.34 [0.14-0.84]). Adult-onset AD, particularly onset ≥61 years, grouped mainly in clusters with low contributions of personal and familial atopy and high frequencies of physical inactivity, childhood-onset AD, particularly infant-onset, mainly in "high-atopic"-clusters. The identified associated factors suggest partly varying endo- and exogeneous mechanisms underlying adult-onset versus childhood-onset AD. Our findings might contribute to better assessment of the individual risk to develop AD throughout life and encourage prevention by non-smoking and physical activity as modifiable lifestyle factors.

Association of Adult Atopic Dermatitis Severity With Bacterial, Viral, and Fungal Skin Infections.

Background: Little is known about the relationship of atopic dermatitis (AD) severity, phenotype, and persistence on different types of skin infections. Objective: To evaluate the relationship of AD characteristics and skin infections over time in adults. Methods: We performed a prospective dermatology practice-based study (n = 559). History of infection was assessed using questionnaires. AD severity was evaluated using Scoring Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), and Patient-reported Global Assessment (PtGA). Results: At baseline, 160 (21.4%) patients reported history of ≥1 skin infection, including 14.3% with bacterial infections. In multivariable repeated measures logistic regression models, ≥1 cutaneous infection was associated with moderate (adjusted odds ratio [95% confidence interval]: 2.67 [1.67-4.28]) and severe (6.35 [3.36-12.01]) versus mild SCORAD; as well as severe SCORAD-itch; moderate and severe versus clear-mild EASI; moderate and severe versus clear-mild PtGA; mild, moderate, and severe versus clear-almost clear IGA. Cutaneous infections were not associated with ichthyosis, palmar hyperlinearity, nummular eczema, cheilitis, or hand eczema. Specific infections varied by AD severity and body site. Persistent moderate-severe disease was associated with higher odds of skin infection. Conclusion: Skin infections were associated with AD severity but not phenotype, and may be mitigated by improved AD severity.

A Cross-Sectional Study Comparing Application of Hanifin and Rajka Criteria in Indian Pediatric Atopic Dermatitis Patients to that of Other Countries.

Hanifin and Rajka criteria are considered to be the gold standard for atopic dermatitis diagnosis. However, the exhaustive nature limits its use in clinical settings. To determine the frequency of Hanifin and Rajka criteria commonly found in Indian pediatric atopic dermatitis patients and variation from the findings of other studies. An observational, descriptive study with a sample size of 52 pediatric atopic dermatitis patients. Patients were divided into infantile, childhood, and adolescent. Overall, xerosis, early age of onset, Dennie-Morgan fold, aggravation because of environmental factors, palmar hyper-linearity, ichthyosis vulgaris, keratosis pilaris, pityriasis alba, and orbital darkening were found in more than 50% of patients. Dennie-Morgan fold was more commonly found in Indian pediatric atopic dermatitis patients. Peri-follicular accentuation was less prevalent in Indian patients as compared to other Asian studies. None of the parents reported food intolerance, which was seen in studies from other countries. A small sample size and ophthalmological evaluation was not performed in all patients. The frequency of different Hanifin and Rajka minor criteria varies widely among different study populations. Hence, the criteria specifically applicable to the Indian population need to be derived for ease of diagnosis.

Risk factors for food sensitization in children with atopic dermatitis: a single-center cross-sectional study.

To study the risk factors for food sensitization and the influence of food sensitization on quality of life and clinical signs in children with atopic dermatitis (AD). A retrospective analysis was performed on the medical data of 241 children with AD, including demographic features, age of onset, severity of AD, quality of life, physical examination results, skin prick test (SPT) results, serum total IgE levels, and eosinophil count. According to the results of SPT, the children were divided into a food sensitization group (n=127) and a non-food sensitization group (n=114). The multivariate logistic regression analysis was used to identify the risk factors for food sensitization in children with AD. The prevalence rate of food sensitization was 52.7% (127/241) in the children with AD. The multivariate logistic regression analysis showed that birth in autumn or winter, age of onset of AD<12 months, severe AD, and total IgE>150 IU/mL were risk factors for food sensitization (P<0.05). Compared with the non-food sensitization group, the food sensitization group had a significantly poorer quality of life (P=0.008) and significantly higher prevalence rates of non-specific hand/foot dermatitis and palmar hyperlinearity (P<0.05). Compared with the single food sensitization group, the multiple food sensitization group had more severe AD and a significantly higher proportion of children with exclusive breastfeeding or total IgE>150 IU/mL (P<0.05). The AD children born in autumn or winter, or those with early onset (<12 months), severe AD or total IgE>150 IU/mL have a higher risk of food sensitization. The AD children with food sensitization have a poorer quality of life and are more likely to develop non-specific hand/foot dermatitis and palmar hyperlinearity.

Factors associated with severity of atopic dermatitis - a Finnish cross-sectional study.

Severity-associated factors in atopic dermatitis (AD) have focussed on early onset, concomitant atopic diseases, markers of Th2-shifted inflammation and filaggrin mutations. To investigate factors associated with severe AD in Finnish patients. We conducted a single-centre, cross-sectional observational study with 502 AD patients aged 4.79 to 79.90 years (mean 32.08 years). Disease severity was assessed with the Rajka-Langeland severity score and EASI and associated clinical signs were evaluated. Data regarding onset, relatives, atopic and other comorbidities was gathered retrospectively. We investigated total serum IgE-levels, a panel of filaggrin null mutations and functional variants of genes associated with skin barrier defects. Factors more frequent in severe AD included early onset (P = 0.004, 95%CI 0.000-0.024), male sex (P = 0.002, 95%CI 0.000-0.11), history of smoking (P = 0.012, 95%CI 0.000-0.024), concomitant asthma (P = 0.001, 95%CI 0.000-0.011), palmar hyperlinearity (P = 0.013, 95%CI 0.014-0.059), hand dermatitis (P = 0.020, 95%CI 0.000-0.029) and history of contact allergy (P = 0.042, 95%CI 0.037-0.096). Body mass indices (P < 0.000, 95%CI 0.000-0.011) and total serum IgE-levels (P < 0.000, 95%CI 0.000-0.011) were higher in severe AD. No differences were observed for allergic rhinitis, allergic conjunctivitis, food allergy, peanut allergy, prick positivity, keratosis pilaris, history of herpes simplex infections, filaggrin null mutations and other gene variants. Severity determinants in Finnish patients seem to be early-onset, male sex, smoking, overweight, concomitant asthma, palmar hyperlinearity, hand dermatitis and high IgE-levels. A sub-typing of patients in relation to confirmed severity determinants may be useful for course prediction, prognosis and targeted AD management.

Keratosis pilaris and filaggrin loss‐of‐function mutations in patients with atopic dermatitis – Results of a Finnish cross‐sectional study

Keratosis pilaris (KP) associates with epidermal barrier defects in atopic dermatitis (AD) but its role in disease severity and concomitant atopic diseases seems to vary between populations. We performed a cross‐sectional observational study with 502 randomly selected AD patients of a Finnish tertiary health care center. At a single clinical examination, disease severity (Rajka Langeland severity score and EASI), clinical signs and patient history were evaluated and total IgE levels and frequent filaggrin (FLG) loss‐of‐function mutations were investigated. There was no link with disease severity (p = 0.649, 95% CI 0.569–0.654), asthma (p = 0.230, 95% CI 0.206–0.281) or atopic sensitization (p = 0.351, 95% CI 0.309–0.392). Keratosis pilaris was significantly associated with palmar hyperlinearity (p < 0.000, 95% CI 0.000–0.006, OR 4.664, 95% CI 2.072–10.496) and the filaggrin loss‐of‐function mutation 2282del4 (p < 0.000, 95% CI 0.000–0.009, OR 4.917, 95%CI 1.961–12.330). The prevalence of KP in the cohort was generally low and KP seems to be infrequent in Finnish AD patients. This may be explained by the fact that the tested FLG loss‐of‐function mutations are rarer in the Finnish population compared for example, with central Europe or Asia. Mutations in other locations of the FLG gene or other genes of the epidermal barrier may play a more important role.

054 Machine learning prediction of filaggrin mutation status from palmar images: a proof-of- concept study

Palmar hyperlinearity has been identified in 68%-85% of individuals with heterozygous filaggrin gene (FLG) mutations and up to 100% of individuals with homozygous FLG mutations. However, the definition of palmar hyperlinearity used in studies has varied. We aimed to standardize prediction of FLG status from palmar images using machine learning. Palmar images and FLG genotyping were available for 342 individuals with atopic dermatitis from the Tower Hamlets Eczema Assessment study. There were 97 individuals (28%) with FLG mutations (10 homozygous or compound heterozygous and 87 heterozygous) and 245 wild type individuals (72%).

A Cross-Sectional Evaluation of the Usefulness of the Minor Features of Hanifin and Rajka Diagnostic Criteria for the Diagnosis of Atopic Dermatitis in the Pediatric Population.

Background:Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease. Hanifin and Rajka's criteria is the most common diagnostic criteria used for the clinical diagnosis of this condition. However, many find that it is too exhaustive to be used in routine practice, and the specificity of many of the minor criteria poses challenges, particularly from Asian countries with type III, IV, and V skin.Aims and Objectives:The aim of the study is to evaluate the effectiveness of the minor features of the Hanifin and Rajka criteria for AD in comparison to the UK working party's diagnostic criteria in pediatric populations of India.Methodology:A hospital-based cross-sectional study of 100 patients in the pediatric age group (3 months–12 years) with AD was conducted based on history, clinical, and laboratory evaluation. An age-matched control group of 100 pediatric patients who did not have a personal or family history of atopic dermatitis was included after obtaining informed consent to find out the prevalence of minor criteria among the control group.Results:Mean of the number of minor clinical criteria found positive in our study population in the infantile and toddler (below 2 years) and childhood groups (2–12 years) was (4.72 ± 1.75) and (5.67 ± 1.78), respectively. Early-onset of disease was the most consistent feature among the minor criteria found in 83% of patients, followed by xerosis (71%), hyperlinearity of palm (56%), pityriasis alba (54%), Denny Morgan fold (52%), elevated serum IgE (47%), perifollicular accentuation (37%), and tendency toward cutaneous infections (37%).Conclusion:We found that though some of the minor criteria are highly sensitive and specific to the diagnosis of AD (xerosis, ichthyosis, palmar hyperlinearity, tendency of cutaneous infections, Dennie–Morgan infraorbital fold, pityriasis alba, and perifollicular accentuation), some other criteria were either very rare or nonspecific for AD. We suggest that many of the minor criteria of Hanifin and Rajka may not have much significance for Indian patients and a multicentric nationwide study with a larger patient pool is required to create a trimmed and improved version of Hanifin and Rajka criteria.

Natural History and Risk Factors of Infantile Atopic Dermatitis: A Case Report and Literature Review

Atopic dermatitis (AD) or atopic eczema is one of the most common forms of pediatric dermatological skin conditions, primarily beginning in childhood with a variable natural course characterized by intense pruritus and eczematous lesions. This condition requires multifactorial interplay and risk factors to explain the pathogenesis. We hereby report a case of a two-month-old male who presented with widespread erythematous lesions, excoriations, and dry skin since one day before admission. The antenatal history showed use of antibiotics during pregnancy, familial history of atopy, and non-exclusive breastfeeding which are all known risk factors. Dermatological examination revealed skin phototype III with diffuse erythematous patches scattered on the face, trunk, upper and lower limbs, and groin followed with excoriations and palmar hyperlinearity. Further laboratory and histopathological examinations were not conducted. The patient was treated with topical corticosteroid and emollients, resulting in a notable improvement without any further flares. A thorough history taking and physical examination must be conducted to establish the diagnosis based on the Hanifin and Rajka criteria and identify risk factors such as genetic factors, impaired skin barrier, and environmental factors and microbial exposure, which may play a protective or harmful role in AD development. Holistic treatments consist of pharmacological and non-pharmacological treatments, with significant emphasis on education to the patient and caregiver(s) to improve quality of life and prevent exacerbations and infectious complications while minimizing potential medication side effects.

Palm reading and water divining: A cross-sectional study of the accuracy of palmar hyperlinearity and transepidermal water loss to identify individuals with a filaggrin gene null mutation

Palm reading and water divining: A cross-sectional study of the accuracy of palmar hyperlinearity and transepidermal water loss to identify individuals with a filaggrin gene null mutation

A study to estimate the frequency of Hanifin and Rajka's minor criteria in children for diagnosis of atopic dermatitis in a tertiary care center in South India

Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease characterized by intense pruritus. Hanifin and Rajka's criteria is the most common diagnostic criteria used in the hospital setup, which consists of 4 major and 23 minor criteria. The frequency of minor criteria may vary population wise. Aims: The aim of the study is to estimate the frequency of minor diagnostic criteria of Hanifin and Rajka in children with AD. Methodology: A hospital-based cross-sectional study of 174 children (≤16 years) with AD, was conducted based on history, clinical, and ophthalmological examination. Blood test to assess serum immunoglobulin E (IgE) level was conducted. Results: The most common minor criteria observed were Dennie–Morgan infraorbital fold (71.8%), early age of onset (67.8%), palmar hyperlinearity (67.8%), xerosis (67.2%), pityriasis alba (57.5%), and perifollicular accentuation (47.7%). Out of 143 cases whose serum was tested for IgE level, elevation was seen in 92. History of winter exacerbation was seen in 8% of the cases, while summer exacerbation was seen in none. On the ophthalmological examination of 111 cases, “high reading with no obvious keratoconus” was present in two cases while three cases were labeled as “keratoconus suspect.” Conclusion: Clinical features of AD vary with geographical location. The prevalence and severity of AD are influenced by several factors such as ethnic/racial, environmental, and dietary factors. Therefore, it is relevant for dermatologists to have a knowledge regarding common clinical features of AD in a given population for the diagnosis and thereby provide treatment to reduce the morbidity along with appropriate counseling.

儿童特应性皮炎2 620例疾病严重程度相关因素分析

Objective To investigate factors influencing disease severity in children of Han nationality with atopic dermatitis (AD) in China, and to provide scientific evidences for prevention and treatment of AD in children. Methods From November 2005 to May 2015, data were collected from AD children aged 0-12 years in Department of Dermatology, The First Affiliated Hospital of Anhui Medical University and AD sample collection collaboration network in China. Statistical analysis was carried out with SPSS16.0 software by using univariate and multivariate ordinal logistic regression analysis to investigate factors influencing the severity of AD. Results A total of 2 620 children with AD were enrolled into the study, including 230 (8.8%) with mild AD, 1 379 (52.6%) with moderate AD and 1 011 (38.6%) with severe AD. As univariate analysis showed, factors influencing the severity of AD included region, early onset, itching during sweating, xeroderma, ichthyosis, palmar hyperlinearity, lichen pilaris, orbital darkening, scalp dermatitis and infra-auricular fissure (all P 0.05) . Multivariate ordinal logistic regression analysis showed that southern region (OR = 2.10, 95% CI: 1.76 - 2.51) , early onset (OR = 1.32, 95% CI: 1.01 - 1.71) , itching during sweating (OR = 1.70, 95% CI: 1.42 - 2.02) , xeroderma (OR = 2.57, 95% CI: 2.10 - 3.15) , ichthyosis (OR = 1.49, 95% CI: 1.19 - 1.87) , palmar hyperlinearity (OR = 2.03, 95% CI: 1.61 - 2.57) , lichen pilaris (OR = 1.44, 95% CI: 1.17 - 1.78) , orbital darkening (OR = 1.53, 95% CI: 1.24 - 1.89) , scalp dermatitis (OR = 2.38, 95% CI: 2.01 - 2.82) and infra-auricular fissure (OR = 1.55, 95% CI: 1.31 - 1.85) were positively correlated with the severity of AD (all P<0.05) . Conclusion The severity of AD is associated with patients′ region, early onset, itching during sweating, xeroderma, and other concomitant symptoms. Key words: Dermatitis, atopic; Severity of illness index; Children; Logistic models

Palmar hyperlinearity in early childhood atopic dermatitis is associated with filaggrin mutation and sensitization to egg.

Palmar hyperlinearity is a typical clinical feature of Filaggrin gene (FLG) null mutations. There are reports of FLG mutations and allergic sensitization; however, reports on the relationship between palmar hyperlinearity to sensitization are limited. This study aimed to examine the association between palmar hyperlinearity and sensitization in atopic dermatitis (AD) children. This cross-sectional, case-control study included children ˂ 6years old with moderate-severe AD whose parents consented for mutation analysis and photographic documentation. Each child underwent genotyping to detect the eight most prevalent FLG mutations in the Japanese population: R501X, 3321delA, S1695X, Q1701X, S2554X, S2889X, S3296X, and K4022X. Clinical features and parameters including egg-specific IgE were examined, and palm photographs were evaluated by 12 trained dermatologists blinded to genotyping results. Of the 57 patients (age range, 2months to 5years; median, 22months), 16 were heterozygotes and three were compound heterozygotes. Palmar hyperlinearity, as recognized by more than two-thirds of dermatologists, was significantly associated with FLG mutation (P=0.002, OR=6.98, 95% CI=2.1-23.7), and this association was observed especially in children over 2years. Cross-shaped crease of the thenar eminence, as known in previous reports, also demonstrated significant correlation with FLG mutation. When the children were divided according to the presence or absence of palmar hyperlinearity, the egg white-specific IgE was significantly higher in the hyperlinearity group (55.9 vs 18.3IU/mL, P<0.05). Palmar hyperlinearity indicates possible inherited barrier abnormalities of the skin in early childhood. Its identification may help to predict a more accurate prognosis, such as sensitization.

Novel and Recurrent PNPLA1 Mutations in Spanish Patients with Autosomal Recessive Congenital Ichthyosis; Evidence of a Founder Effect

Autosomal recessive congenital ichthyosis (ARCI) is a group of rare non-syndrome diseases that affect cornification. PNPLA1 is one of the 12 related genes identified so far. Mutation screening of this gene has resulted in the identification of 13 individuals, from 10 families, who carried 7 different PNPLA1 mutations. These mutations included 2 missense, 2 frame-shift and 3 nonsense, 3 of them being novel. One of the identified variants, c.417_418delinsTC, was highly prevalent, as it was found in 6 out of 10 (60%) of our ARCI families with PNPLA1 mutations. Clinical manifestations varied significantly among patients, but altered sweating; erythema, palmar hyperlinearity and small whitish scales in flexor-extensor and facial areas were common symptoms. Haplotype analyses of c.417_418delinsTC carriers confirmed the existence of a common ancestor. This study expands the spectrum of the PNPLA1 disease, which causes variants and demonstrates that the c.417_418delinsTC mutation has founder effects in the Spanish population.

A systematic review and meta-analysis of the regional and age-related differences in atopic dermatitis clinical characteristics

Previous studies found conflicting results about the commonality of different atopic dermatitis (AD) signs and symptoms. To determine the prevalences of AD characteristics and differences by region and age. A systematic review was performed of all publishedstudies in MEDLINE, EMBASE, SCOPUS, LILACS, Cochrane, China National Knowledge Infrastructure, Taiwan Electronic Periodical Services, and CiNii that analyzed the proportion of AD characteristics. Two reviewers performed a review study titles and/or abstracts and data abstraction. In all, 101 studies reported proportion of AD features with sufficient data for meta-analysis. The most prevalent AD features were pruritus, lichenification, and xerosis. There were differences in AD characteristics by study region. Flexural involvement was less commonly reported in India, the Americas, and Iran. Studies from East Asian reported more erythroderma and truncal, extensor, scalp, and auricular involvement. Studies from Southeast Asia reported more exudative eczema, truncal involvement, lichenification, and prurigo nodularis. Studies from Iran reported more head, face, and neck involvement; pityriasis alba; and xerosis. Studies from Africa reported more papular lichenoid lesions, palmar hyperlinearity, ichthyosis, and orbital darkening. Heterogeneity between studies and limited reporting of certain AD clinical characteristics. AD characteristics are heterogeneous and vary by region and age.

Ichthyosis Vulgaris

Ichthyosis Vulgaris