Regional brain activity and neural network changes in cognitive-motor dual-task interference: A functional near-infrared spectroscopy study.

Previous neuroimaging studies have reported dual-task interference (DTi) and deterioration of task performance in a cognitive-motor dual task (DT) compared to that in a single task (ST). Greater frontoparietal activity is a neural signature of DTi; nonetheless, the underlying mechanism of cortical network in DTi still remains unclear. This study aimed to investigate the regional brain activity and neural network changes during DTi induced by highly demanding cognitive-motor DT. Thirty-four right-handed healthy young adults performed the spiral-drawing task. They underwent a paced auditory serial addition test (PASAT) simultaneously or independently while their cortical activity was measured using functional near-infrared spectroscopy. Motor performance was determined using the balanced integration score (BIS), a balanced index of drawing speed and precision. The cognitive task of the PASAT was administered with two difficulty levels defined by 1 s (PASAT-1 s) and 2 s (PASAT-2 s) intervals, allowing for the serial addition of numbers. Cognitive performance was determined using the percentage of correct responses. These motor and cognitive performances were significantly reduced during DT, which combined a drawing and a cognitive task at either difficulty level, compared to those in the corresponding ST conditions. The DT conditions were also characterized by significantly increased activity in the right dorsolateral prefrontal cortex (DLPFC) compared to that in the ST conditions. Multivariate Granger causality (GC) analysis of cortical activity in the selected frontoparietal regions of interest further revealed selective top-down causal connectivity from the right DLPFC to the right inferior parietal cortex during DTs. Furthermore, changes in the frontoparietal GC connectivity strength between the PASAT-2 s DT and ST conditions significantly correlated negatively with changes in the percentage of correct responses. Therefore, DTi can occur even in cognitively proficient young adults, and the right DLPFC and frontoparietal network being crucial neural mechanisms underlying DTi. These findings provide new insights into DTi and its underlying neural mechanisms and have implications for the clinical utility of cognitive-motor DTs applied to clinical populations with cognitive decline, such as those with psychiatric and brain disorders.

Effects of Heart Rate Variability Biofeedback Training on Anxiety Reduction and Brain Activity: a Randomized Active-Controlled Study Using EEG.

Heart rate variability biofeedback (HRVBF) is a promising anxiety-reducing intervention that increases vagally-mediated heart rate variability (vmHRV) through slow-paced breathing and feedback of heart rhythm. Several studies have reported the anxiety-reducing effects of HRVBF; however, some studies have reported such training as ineffective. Furthermore, the effects of training and underlying brain activity changes remain unclear. This study examined the anxiety-reducing effects of HRVBF training and related brain activity changes by randomly assigning participants, employing an active control group, and measuring anxiety-related attentional bias using the emotional Stroop task and electroencephalography (EEG). Fifty-five healthy students with anxiety were randomly assigned to the HRVBF or control groups, and 21 in the HRVBF group and 19 in the control group were included in the analysis. Both groups performed 10 training sessions of 20 min each within 3 weeks. They were assessed using resting vmHRV, event-related potential (ERP), time-frequency EEG, attentional bias, and the State-Trait Anxiety Inventory-JYZ (STAI-JYZ) before and after training. The results demonstrated increased resting vmHRV in the HRVBF group compared to the control group after training. However, no differences were observed in ERP, time-frequency EEG, attentional bias, and STAI-JYZ. Participants with higher pre-training resting vmHRV achieved higher heart rhythm coherence in HRVBF training and had reduced attentional bias. This study suggests that individuals with higher resting vmHRV are more likely to be proficient in HRVBF training and benefit from its anxiety-reducing effects. The findings contribute to participant selection to benefit from HRVBF training and modification of the training protocols for non-responders.Clinical trial registrationOrganization: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), JapanRegistration number: UMIN000047096Registration date: March 6, 2022.

Transcranial direct current stimulation to the left dorsolateral prefrontal cortex enhances early dexterity skills with the left non-dominant hand: a randomized controlled trial.

BACKGROUND: The left dorsolateral prefrontal cortex (DLPFC) is involved in early-phase manual dexterity skill acquisition when cognitive control processes, such as integration and complexity demands, are required. However, the effectiveness of left DLPFC transcranial direct current stimulation (tDCS) on early-phase motor learning and whether its effectiveness depends on the cognitive demand of the target task are unclear. This study aimed to investigate whether tDCS over the left DLPFC improves non-dominant hand dexterity performance and determine if its efficacy depends on the cognitive demand of the target task. METHODS: In this randomized, double-blind, sham-controlled trial, 70 healthy, right-handed, young adult participants were recruited. They were randomly allocated to the active tDCS (2 mA for 20 min) or sham groups and repeatedly performed the Purdue Pegboard Test (PPT) left-handed peg task and left-handed assembly task three times: pre-tDCS, during tDCS, and post tDCS. RESULTS: The final sample comprised 66 healthy young adults (mean age, 22.73 ± 1.57 years). There were significant interactions between group and time in both PPT tasks, indicating significantly higher performance of those in the active tDCS group than those in the sham group post tDCS (p < 0.001). Moreover, a greater benefit was observed in the left-handed assembly task performance than in the peg task performance (p < 0.001). No significant correlation between baseline performance and benefits from tDCS was observed in either task. CONCLUSIONS: These results demonstrated that prefrontal tDCS significantly improved early-phase manual dexterity skill acquisition, and its benefits were greater for the task with high cognitive demands. These findings contribute to a deeper understanding of the underlying neurophysiological mechanisms of the left DLPFC in the modulation of early-phase dexterity skill acquisition. TRIAL REGISTRATION: This study was registered in the University Hospital Medical Information Network Clinical Trial Registry in Japan (UMIN000046868), Registered February 8, 2022 https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053467.

Occupational ionizing radiation-induced skin injury among orthopedic surgeons: A clinical survey.

BACKGROUND: This study aimed to assess orthopedic surgeons' attitudes and behaviors toward occupational radiation exposure and investigate the prevalence of occupational radiation-induced skin injury among orthopedic surgeons. Similarly, risk factors for the presence of radiation-induced skin injury were investigated. METHODS: Overall, 108 orthopedic surgeons were administered self-reported questionnaires about occupational radiation exposure, and their hands were then photographed. Their fields of expertise were classified into spine, arthroplasty, sports medicine, hand, oncology, rheumatoid arthritis, pediatric orthopedic, and resident. Dermatologists evaluated the surgeons' skin conditions and classified into 3 grades of injury: grade 0, no clinical symptoms; grade 1, careful observation required; and grade 2, detailed examination required. Logistic regression analysis was performed to investigate the factors related to the presence of radiation-induced skin injury. Crude and adjusted logistic regression analysis using the backward stepwise selection method was similarly conducted. Receiver operating characteristic curve (ROC) analysis was performed to estimate the predictive power of exposure time, occupational period, and accumulated annual exposure time for radiation-induced skin injury. RESULTS: In total, 93.5% of the surgeons were careful about occupational radiation exposure, of which 76.8% used a dosimeter. Skin changes in the hands were self-reported by 42.5% of the surgeons, and radiation-induced skin injury was diagnosed in 31.4%. The accuracy of the self-reported skin changes was 100% for grade 2 and 61.5% for grade 1. Adjusted regression analysis showed that dermatologists' diagnosis-related factors were self-reported skin changes (odds ratio [OR] 3.1) and spine surgeons (OR 3.2). ROC analysis demonstrated that an occupational period >21 years and an accumulated exposure time >6696 min were considered risk factors, with ORs of 4.07 and 5.99, respectively. CONCLUSIONS: Orthopedic surgeons, particularly spine surgeons, should be regularly examined by dermatologists early in their careers for early detection of radiation-induced skin injury on the hands.

Availability of mRNA Obtained from Peripheral Blood Mononuclear Cells for Testing Mutation Consequences in Dystrophic Epidermolysis Bullosa.

Dystrophic epidermolysis bullosa (DEB) is an inheritable blistering disease caused by mutations in COL7A1, which encodes type VII collagen. To address the issue of genotype-phenotype correlations in DEB, analyzing the consequences of COL7A1 mutations using mRNA is indispensable. Herein we established a novel method for testing the effect of mutations in DEB using COL7A1 mRNA extracted from peripheral blood mononuclear cells (PBMCs). We investigated the consequences of four COL7A1 mutations (c.6573 + 1G > C, c.6216 + 5G > T, c.7270C > T and c.2527C > T) in three Japanese individuals with recessive DEB. The novel method detected the consequences of two recurrent COL7A1 mutations (c.6573 + 1G > C, c.6216 + 5G > T) and a novel COL7A1 mutation (c.7270C > T) accurately. In addition, it detected aberrant splicing resulting from a COL7A1 mutation (c.2527C > T) which was previously reported as a nonsense mutation. Furthermore, we revealed that type VII collagen-expressing cells in PBMCs have similar cell surface markers as mesenchymal stem cells; they were CD105+, CD29+, CD45-, and CD34-, suggesting that a small number of mesenchymal stem cells or mesenchymal stromal cells are circulating in the peripheral blood, which enables us to detect COL7A1 mRNA in PBMCs. Taken together, our novel method for analyzing mutation consequences using mRNA obtained from PBMCs in DEB will significantly contribute to genetic diagnoses and novel therapies for DEB.

Psychological Impact of COVID-19 on Occupational Therapists: An Online Survey in Japan.

IMPORTANCE: Coronavirus disease 2019 (COVID-19) has had a severe psychological impact on frontline and second-line medical workers. However, few empirical reports have been published on its impact on occupational therapists. Clarifying the mental health status of occupational therapists is important to maintain care quality and prevent psychological problems in this population. OBJECTIVE: To investigate the psychological impact of COVID-19 on Japanese occupational therapists in prefectures with and without severe pandemic-related restrictions and elucidate factors associated with psychological problems such as anxiety, depression, and insomnia. DESIGN: A cross-sectional online survey using region-stratified two-stage cluster sampling conducted May 28-31, 2020. PARTICIPANTS: The sample included 371 participants (63.1% women) in the prefectures under specific cautions (i.e., where residents were strictly advised to refrain from outings) and 1,312 in the prefectures without such cautions (61.9% women). RESULTS: The increase in workload due to the pandemic was significantly related to an increase in anxiety, depression, and insomnia, and an attempt to avoid talking face to face with others was significantly related to an increase in anxiety regardless of area. In prefectures under specific cautions as of May 25, 2020, the provision of sufficient information on COVID-19 by the workplace significantly reduced the risk of insomnia. In other prefectures, the provision of sufficient information significantly reduced the risk of depression. CONCLUSIONS AND RELEVANCE: These results demonstrate the severe negative psychological impact of the increase in workload resulting from COVID-19 and suggest the importance of psychological support for occupational therapists, such as the provision of sufficient information by the workplace. What This Article Adds: This study highlights the importance of providing psychological support for occupational therapists worldwide.

The role of the ventromedial prefrontal cortex in automatic formation of impression and reflected impression.

Previous neuroimaging studies demonstrated that ventromedial prefrontal cortex (vmPFC) activity reflects how much an individual positively views each person (impression). Here, we investigated whether the degree to which individuals think others positively view them (reflected impression) is similarly tracked by activity in the vmPFC by using fMRI and speed-dating events. We also examined whether activity of the vmPFC in response to the faces of others would predict the impression formed through direct interactions with them. The task consisted of three sessions: pre-speed-dating fMRI, speed-dating events, and post-speed-dating fMRI (not reported here). During the pre-speed-dating fMRI, each participant passively viewed the faces of others whom they would meet in the subsequent speed-dating events. After the fMRI, they rated the impression and reflected impression of each face. During the speed-dating events, the participants had 3-min conversations with partners whose faces were presented during the fMRI task, and they were asked to choose the partners whom they preferred at the end of the events. The results revealed that the value of both the impression and reflected impression were automatically represented in the vmPFC. However, the impression fully mediated the link between the reflected impression and vmPFC activity. These results highlight a close link between reflected appraisal and impression formation and provide important insights into neural and psychological models of how the reflected impression is formed in the human brain.

Microstructural Alterations in Bipolar and Major Depressive Disorders: A Diffusion Kurtosis Imaging Study.

BACKGROUND: Identifying structural and functional abnormalities in bipolar (BD) and major depressive disorders (MDD) is important for understanding biological processes. HYPOTHESIS: Diffusion kurtosis imaging (DKI) may be able to detect the brain's microstructural alterations in BD and MDD and any differences between the two. STUDY TYPE: Prospective. SUBJECTS: In all, 16 BD patients, 19 MDD patients, and 20 age- and gender-matched healthy volunteers. FIELD STRENGTH/SEQUENCE: DKI at 3.0T. ASSESSMENT: The major DKI indices of the brain were compared voxel-by-voxel among the three groups. Significantly different voxels were tested for correlation with clinical variables (ie, Young Mania Rating Scale [YMRS], 17-item Hamilton Depression Rating Scale [17-HDRS], Montgomery-Åsberg Depression Rating Scale, total disease duration, duration of current episode, and the number of past manic/depressive episodes). The performance of the DKI indices in identifying microstructural alterations was estimated. STATISTICAL TESTS: One-way analysis of variance (ANOVA) was used for group comparison of DKI indices. The performance of these indices in detecting microstructural alterations was determined by receiver operating characteristic (ROC) analysis. Pearson's product-moment correlation analyses were used to test the correlations of these indices with clinical variables. RESULTS: DKI revealed widespread microstructural alterations across the brain in each disorder (P < 0.05). Some were significantly different between the two disorders. Mean kurtosis (MK) in the gray matter of the right inferior parietal lobe was able to distinguish BD and MDD with an accuracy of 0.906. A strong correlation was revealed between MK in that region and YMRS in BD patients (r = -0.641, corrected P = 0.042) or 17-HDRS in MDD patients (r = -0.613, corrected P = 0.030). There were also strong correlations between a few other DKI indices and disease duration (r = -0.676 or 0.626, corrected P < 0.05). DATA CONCLUSION: DKI detected microstructural brain alterations in BD and MDD. Its indices may be useful to distinguish the two disorders or to reflect disease severity and duration. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3 J. Magn. Reson. Imaging 2020;52:1187-1196.

Erythropoietic Protoporphyria in a Japanese Population.

Erythropoietic protoporphyria is caused by a partial deficiency of ferrochelatase, which is the last enzyme in the heme biosynthesis pathway. In a typical erythropoietic protoporphyria, photosensitivity initially appears, following the first exposure to the sun in early infancy or childhood. Erythropoietic protoporphyria has been reported worldwide, but there is a regional variation in its epidemiology. Approximately 20% of the Japanese patients were recognized to have symptoms of erythropoietic protoporphyria after 10 years of age. Physicians occasionally encounter Japanese patients with erythropoietic protoporphyria, mild symptoms and no FECH gene mutations. The homozygous IVS3-48C polymorphism may cause a mild phenotype of the erythropoietic protoporphyria via a slight increase in protoporphyrin. The frequency of the homozygous IVS3-48C polymorphism in the Japanese population is higher than that observed in European countries. Japanese type of erythropoietic protopor-phyria shows a characteristic phenotype of the late onset and mild symptoms compared to the Caucasian erythropoietic protoporphyria. This review describes the characteristics of erythropoietic protoporphyria in Japanese patients.

Subcutaneous dermoid cysts on the eyebrow and neck.

We report a case of dermoid cysts on the right lateral eyebrow and anterior neck. Multiple concurrent dermoid cysts, as in the present case, are very rare. The differential diagnosis of dermoid cyst includes epidermoid (epidermal inclusion) cyst, trichilemmal cyst, pilomatrixoma, lymphatic malformation, and lipoma. In particular, thyroglossal duct cyst and midline anterior neck inclusion cyst are part of the differential diagnosis when the lesion is in the anterior neck.

Extracellular cleavage of collagen XVII is essential for correct cutaneous basement membrane formation.

In skin, basal keratinocytes in the epidermis are tightly attached to the underlying dermis by the basement membrane (BM). The correct expression of hemidesmosomal and extracellular matrix (ECM) proteins is essential for BM formation, and the null-expression of one molecule may induce blistering diseases associated with immature BM formation in humans. However, little is known about the significance of post-translational processing of hemidesmosomal or ECM proteins in BM formation. Here we show that the C-terminal cleavage of hemidesmosomal transmembrane collagen XVII (COL17) is essential for correct BM formation. The homozygous p.R1303Q mutation in COL17 induces BM duplication and blistering in humans. Although laminin 332, a major ECM protein, interacts with COL17 around p.R1303, the mutation leaves the binding of both molecules unchanged. Instead, the mutation hampers the physiological C-terminal cleavage of COL17 in the ECM. Consequently, non-cleaved COL17 ectodomain remnants induce the aberrant deposition of laminin 332 in the ECM, which is thought to be the major pathogenesis of the BM duplication that results from this mutation. As an example of impaired cleavage of COL17, this study shows that regulated processing of hemidesmosomal proteins is essential for correct BM organization in skin.

Modulation of Stimulator of Interferon Genes (STING) Expression by Interferon-γ in Human Keratinocytes.

Infection of microbial pathogen triggers the innate immune system, and the induction of interferons (IFNs) play a vital role in host antiviral response. Stimulator of interferon genes (STING) was identified as a crucial regulator of the DNA sensing pathway, and activates both nuclear factor-κB and interferon regulatory factor 3 transcription pathways to evoke IFNs production. In this study, we studied the upregulation of STING mRNA expression, induced by IFN-γ in human keratinocytes (HaCaT). STING promoter assays clarified that a gamma-activated sequence (GAS), located at - 7 to - 15-bp, is required for IFN-γ-upregulated promoter activity. Furthermore, an electrophoretic mobility shift assay showed that signal transducers and activators of transcription 1 (STAT1) attach to the GAS motif on the human STING promoter region. This indicates that IFN-γ/Janus kinases/STAT1 signaling is essential for the STING upregulation in human keratinocytes.

Clinical utility of neuropsychological tests for employment outcomes in persons with cognitive impairment after moderate to severe traumatic brain injury.

OBJECTIVE: To retrospectively examine the clinical utility of neuropsychological tests (NPTs) for predicting employment outcomes in persons with cognitive impairment after moderate to severe traumatic brain injury (TBI). METHODS: 132 individuals of working age with cognitive impairment after moderate to severe TBI were classified into three groups by employment status: competitive employment (CE); supported employment (SE); and unemployed (UE). NPT scores were compared among groups. Using multinomial logistic regression with group allocation as the dependent variable, significant variables were identified, and receiver operating characteristic (ROC) curves were calculated. RESULTS: Comparison of NPT results among the three groups showed significant differences for all NPTs (all items, p < 0.01). Using multinomial logistic regression analysis, Rivermead Behavioral Memory Test (RBMT) and Behavioral Assessment of the Dysexecutive Syndrome from CE versus SE and Trail Making Test-B and RBMT from SE versus UE were identified. ROC curve analysis indicated small to moderate accuracy (area under the curve, 0.63-0.84). CONCLUSION: NPT scores can predict future employment status in patients with cognitive impairment after TBI. These findings may lead to improved clinical assessments when providing work support. Future research should consider occupational categories, managerial categories, and types of re-employment.

Prevalence of skin infections caused by Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus in Japan, particularly in Ishigaki, Okinawa.

The prevalence of Panton-Valentine leukocidin gene (pvl)-positive community-acquired methicillin-resistant Staphylococcus aureus USA300 clone, which is designated as the ST8-staphylococcal cassette chromosome (SCC) mec type IV (ST8-IV) lineage, is a major public health concern worldwide. Thus, to elucidate the prevalence and characteristics of pvl-positive community-onset MRSA in Japan, we conducted a molecular epidemiological analysis for 854 S. aureus isolates obtained from outpatients with skin infections during 2013 and 2014. The isolation rate of MRSA was 25.6% (219 isolates), and the ratio of pvl-positive MRSA was 13.2% (29 isolates). Notably, the proportion (93.8%) of pvl-positive isolates was particularly high among MRSA isolates from Ishigaki island in Okinawa. Pulsed-field gel electrophoresis and multilocus sequence typing showed that the pulsotype C isolates (11 isolates) were typical USA300 clones with arginine catabolic mobile element (ACME) type I-CC8-IV lineages and prevalent on the main island of Japan (Honshu). Pulsotypes A (11 isolates) and B (four isolates) consisted of ACME-negative CC8-IV clones and were specific for Ishigaki island. Both USA300 and Okinawa-Ishigaki specific clones were associated with deep-seated skin infections, such as furuncle and cellulitis. Pulsotypes D (two isolates) and E (one isolate) were ACME-negative clonal complex (CC) 59-IV clones and were related to superficial skin infections, such as impetigo. Our findings revealed that pvl-positive MRSA associated with deep-seated skin infections are spreading in Japanese communities, particularly in Ishigaki, Okinawa.

Multiple Milia as an Isolated Skin Manifestation of Dominant Dystrophic Epidermolysis Bullosa: Evidence of Phenotypic Variability.

We report a Japanese pedigree with dominant dystrophic epidermolysis bullosa (DDEB) harboring the p.G2251E mutation of COL7A1. The proband of this pedigree presented with multiple milia as an isolated skin manifestation without a history of blistering and subsequently developed generalized intractable blisters, suggesting that multiple milia could be a primary manifestation of DDEB. Her mother exhibited nail dystrophy and pruritic nodules and her elder sister was unaffected, despite having the same COL7A1 mutation. Inter- and intrafamilial clinical variability are often observed in DDEB, so we should be aware of this factor to provide appropriate genetic counselling.

Modified sympathetic nerve regulation in AKAP5-null mice.

Genetic analyses have revealed an important association between A-kinase anchoring proteins (AKAPs) and the intracellular calcium modulating system. AKAP5, also known as AKAP79/150, is an anchoring protein between PKA and voltage-dependent calcium channels, ryanodine receptor-2, phospholamban and other molecules. The aim of the present study was to elucidate the physiological importance of AKAP5 in the creation of cardiac rhythm using AKAP5-null mice. ECG analysis showed a normal sinus rhythm and a decreased responsiveness to isoproterenol in AKAP5-null mice compared with wild-type mice. Analysis of heart rate variability revealed that the R-R interval was unstable in AKAP5-null mutants and that the low-frequency components had decreased, indicating that the tonus of the sympathetic nervous system was affected. Furthermore, the atrium of the AKAP5-null mice showed a decreased positive inotropic response to isoproterenol, indicating the involvement of AKAP5 in a PKA-dependent pathway. Thus, our present study revealed that AKAP5 plays a significant role in the regulation of sympathetic nerve activities.

Involvement of the histamine H1 receptor in the regulation of sympathetic nerve activity.

The histamine system is involved in the regulation of the autonomic nervous system. We used gene-targeted mice to investigate the role of histamine receptors in the regulation of the sympathetic nervous system. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed histamine H1, H2, and H3 receptor expression in the superior cervical ganglion, which contains sympathetic nerve cell bodies. We measured the heart rate variability (HRV), the changes in the beat-to-beat heart rate, which is widely used to assess autonomic activity in the heart. H1 blockade attenuated the baroreflex-mediated changes in heart rate in wild-type (WT) mice, whereas the heart rate response to H2- and H3-specific blockers was unaffected. l-Histidine decarboxylase (HDC) expression in the superior cervical ganglion of H1R-null mice was higher than that in WT controls, whereas the enzyme levels in H2R- and H3R-null mice were not significantly different from those in the WT. All mutant mice (H1R-, H2R-, and H3R-null mice) showed normal electrocardiogram (ECG) patterns with little modification in ECG parameters and the expected response to the ß-adrenergic blocker propranolol. Similar to our findings in WT mice, H1 blockade attenuated the baroreflex-mediated heart rate change in H1R-null mice, whereas the heart rate response was unaffected in H2R- and H3R-null mice. The HRV analysis revealed relatively unstable RR intervals, an increased standard deviation of the interbeat interval (SDNN), and low-frequency (LF) component in H1R-null mice compared with the other groups, suggesting that sympathetic nerve activity was altered in H1R-null mice. Taken together, our findings indicate that H1 receptors play a major role in the regulation of sympathetic nerve activity.

Atopic diathesis in hypohidrotic/anhidrotic ectodermal dysplasia.

Recently, patients with hypohidrotic/anhidrotic ectodermal dysplasia (H/AED) have been reported to have a higher prevalence of symptoms suggestive of atopic disorders than the general population. To better understand atopic diathesis in H/AED, 6 cases of clinically or genetically diagnosed H/AED were examined. The following criteria were evaluated with patient consent: sweating, blood test results, histopathology and filaggrin staining. Five of 6 H/AED cases displayed atopic dermatitis-like manifestations, and 3 of these 5 cases experienced periorbital lesions. H/AED patients tended to present with atopic dermatitis-like eruptions with characteristics potentially indicative of periorbital lesions. Atopic diathesis in H/AED appeared not to be associated with filaggrin. We could speculate that hypohidrosis or anhidrosis itself might impair skin barrier function and contribute to atopic diathesis.