Search

Prurigo chronica multiformis is a commonly used diagnostic designation for a peculiar subtype of prurigo in Japan, although the disease entity might not be well-recognized in other countries. Experts approved by the Japanese Dermatological Association attempted to build a common consensus on prurigo chronica multiformis, agreeing that it is a unique and important disease entity in elderly patients. Skin lesions are characterized by intensely pruritic, edematous, urticarial papules, or small macules, which gradually become solid papules/small nodules. The papules tend to aggregate and occasionally coalesce into polygonal lichenified plaques. The most commonly affected sites are the lower abdomen and lower back, although the chest, thighs, and upper back might also be involved. Common histopathological features of prurigo chronica multiformis include infiltration of lymphocytes and eosinophils in the upper dermis, with minimal epidermal changes. Basophil infiltration is also observed. The epidemiological incidence, differences in clinical manifestations by geographical location, and disease placement among other forms of prurigo and/or related skin diseases need to be further elucidated. Dermatologists should be aware of the clinical characteristics of prurigo chronica multiformis., (© 2024 Japanese Dermatological Association.)

Background: Vitiligo is an acquired pigmentary disorder characterized by depigmented patches on the skin that majorly impact patients' quality of life. Although its etiology involves genetic and environmental factors, the role of microorganisms as environmental factors in vitiligo pathology remains under-researched., Objectives: Our study explored the presence of characteristic bacterial and fungal flora in vitiligo-affected skin and investigated their potential roles in vitiligo pathogenesis., Methods: We sequenced bacterial 16S rRNA and the fungal ITS1 region from skin swabs collected at frequently affected sites, namely the forehead and back, of patients with vitiligo. We analyzed bacterial and fungal flora in lesional and non-lesional areas of patients with vitiligo compared with corresponding sites in age- and sex-matched healthy subjects., Results: Our findings revealed elevated α-diversity in both bacterial and fungal flora within vitiligo lesions compared with healthy controls. Notably, bacterial flora exhibited a distinctive composition in patients with vitiligo, and the proportional representation of Enterococcus was inversely correlated with the degree of vitiligo progression. Gammaproteobacteria, Staphylococcus spp., and Corynebacterium spp. were more abundant in vitiligo patients, with notable Staphylococcus spp. prevalence during the stable phase on the forehead. Conversely, the proportion of Malassezia sympodialis was lower and that of Malassezia globosa was higher in the progressive phase on the back of vitiligo patients., Conclusion: Our study identified some characteristic bacterial and fungal groups associated with vitiligo activity and prognosis, highlighting the potential roles of microorganisms in pathogenesis and offering insights into personalized disease-management approaches., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Surgery for acute type A aortic dissection (type AAD) in non-agenarians is usually contraindicated due to advanced age. The aim of this study was to assess and compare outcomes after surgical or conservative treatment for acute type AAD in non-agenarians by evaluating frailty., Methods: Between October 2012 and September 2018, 273 patients underwent open repair for type AAD at the Shonan Kamakura General Hospital and the Shonan Fujisawa Tokushukai Hospital, and here, we retrospectively reviewed the case reports of 10 surgically treated non-agenarians and 15 conservatively treated non-agenarians. Exclusion criteria for surgery were the patient's refusal of surgery, severe dementia and coma. In patients considered to be at a high risk, our judgements were based on the results of comprehensive evaluation., Results: Both in-hospital mortality and 30-day mortality in the surgical group were zero, while in-hospital mortality in conservatively treated non-agenarians was 73.3%. Importantly, 1-year survival in the surgical group and conservative group was 90% and 25%, respectively. The 5-year survival in the surgical group and conservative group was 49.2% and 25%, respectively (log-rank test, P = 0.0105). Four of 6 patients with preoperative clinical frailty scores not higher than 4 were still alive at 1 year with the same level of preoperative frailty., Conclusions: Surgery for acute type AAD in non-agenarians can be performed with acceptable outcomes in carefully selected patients, particularly in those with preoperative clinical frailty scores not higher than 4., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion, which is frequently encountered in clinical practice. Skin barrier dysfunction leads to enhanced skin irritability to non-specific stimuli and epicutaneous sensitization. In the lesion site, a further inflammation-related reduction in skin barrier function, enhanced irritability and scratching-related stimuli deteriorate eczema, leading to vicious cycle of inflammation. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice., (Copyright © 2020 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Pediatric atopic dermatitis (PAD) is a pluricausal disease and is frequently seen in dermatological and pediatric practice. Therefore, it is important to find common views in clinical practice and to promote consensus among practitioners. Aiming to obtain common views among dermatologists and pediatricians and to disseminate them widely in clinical practice, we held the PAD Consensus Forums described herein., Methods: Questionnaire surveys of treatment goals and drug therapy were conducted to prepare topics for discussion at the PAD Consensus Forums. Reaching consensus was defined as agreement among at least 70% of the participants., Results: As a result of discussion among 24 dermatologists and 25 pediatricians, consensus was obtained on 7 topics. These topics configure 3 consensus of treatment goals (Attainment targets were divided into the short/medium term and the long term. Attainment targets were associated with the primary evaluation domains of the Harmonising Outcome Measures for Eczema (HOME) roadmap, etc.) and 4 consensus of drug therapy (The number of applications of topical anti-inflammatory drugs in the acute phase and selection and ideal intervals between applications of topical anti-inflammatory drugs in proactive therapy, etc.)., Conclusions: The consensus is expected to help practitioners set appropriate treatment goals in clinical practice and facilitate the choice of drugs for treatment., (Copyright © 2019 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Erdheim-Chester disease is a rare histiocytosis with insufficient clinical data. To clarify the clinical features and prognostic factors of Erdheim-Chester disease, we conducted a nationwide survey to collect the detailed data of 44 patients with Erdheim-Chester disease in Japan. The median age of onset of the participants was 51 (range: 23-76) years, and the median number of involved organs per patient was 4 (range: 1-11). The existence of central nervous system disease was correlated with older age ( P =0.033), the presence of cardiovascular lesions ( P =0.015), and an increased number of involved organs ( P =0.0042). The median survival from the onset was 10.4 years, and >3.0 mg/dL C-reactive protein level at onset was associated with worse outcome (median survival, 14.6 vs. 7.4 years; P =0.0016). In a multivariate analysis, age >60 years (hazard ratio, 25.9; 95% confidence interval, 2.82-237; P =0.0040) and the presence of digestive organ involvement (hazard ratio, 4.74; 95% confidence interval, 1.05-21.4; P =0.043) were correlated with worse survival. Fourteen patients had available histological samples of Erdheim- Chester disease lesions. BRAF V600E mutation was detected in 11 patients (78%) by Sanger sequencing. A correlation between BRAF mutation status and clinical factors was not observed. Our study revealed that age and digestive organ involvement influence the outcome of Erdheim-Chester disease patients, and an inflammatory marker, such as C-reactive protein, might reflect the activity of this inflammatory myeloid neoplasm., (Copyright© 2018 Ferrata Storti Foundation.)

Background: Allergic diseases are an important health problem for children and adults. It is important to know how allergic diseases develop and remit from infancy to adolescence. Early intervention is effective in treating allergic diseases., Objective: We performed a large-scale questionnaire survey of high school students in Fukui Prefecture, Japan, and analyzed the factors associated with the development and remission of allergic diseases., Methods: A total of 21,802 students participated in the epidemiologic survey, and the valid response rate was 89.3% (19,461). We applied an inverse probability weighting method with propensity scores., Results: The present prevalence rate of allergic rhinitis (AR) was 19.2%. The remission rate of AR was 15.3%. Only children and firstborns had a significantly higher risk of developing symptoms of allergic diseases [only child: AR, 1.37; bronchial asthma (BA), 1.30; food allergy (FA), 1.33 and firstborn: AR, 1.38; BA, 1.10]. Constipation was an associated factor for development of atopic dermatitis (AD) (1.17) and AR (1.17), regular intake of lactic acid bacteria was not an associated factor for development of allergic diseases but was a factor for remission of AD (1.22). Hypohidrosis was an associated factor for development of AD (1.25). High academic performance was an associated factor for development of AR (1.20) but was a negative factor for development of BA (0.89). The values in parentheses are significant adjusted odds ratios., Conclusion: This epidemiologic survey showed that the hygiene hypothesis and intestinal bacterial flora might influence the development of symptoms and remission of allergic diseases.

Background: Recent studies have suggested that epidermal barrier dysfunction contributes to the development of atopic dermatitis (AD) and other allergic diseases., Objective: We performed a prospective, randomized controlled trial to investigate whether protecting the skin barrier with a moisturizer during the neonatal period prevents development of AD and allergic sensitization., Methods: An emulsion-type moisturizer was applied daily during the first 32 weeks of life to 59 of 118 neonates at high risk for AD (based on having a parent or sibling with AD) who were enrolled in this study. The onset of AD (eczematous symptoms lasting >4 weeks) and eczema (lasting >2 weeks) was assessed by a dermatology specialist on the basis of the modified Hanifin and Rajka criteria. The primary outcome was the cumulative incidence of AD plus eczema (AD/eczema) at week 32 of life. A secondary outcome, allergic sensitization, was evaluated based on serum levels of allergen-specific IgE determined by using a high-sensitivity allergen microarray of diamond-like carbon-coated chips., Results: Approximately 32% fewer neonates who received the moisturizer had AD/eczema by week 32 than control subjects (P = .012, log-rank test). We did not show a statistically significant effect of emollient on allergic sensitization based on the level of IgE antibody against egg white at 0.34 kUA/L CAP-FEIA equivalents. However, the sensitization rate was significantly higher in infants who had AD/eczema than in those who did not (odds ratio, 2.86; 95% CI, 1.22-6.73)., Conclusion: Daily application of moisturizer during the first 32 weeks of life reduces the risk of AD/eczema in infants. Allergic sensitization during this time period is associated with the presence of eczematous skin but not with moisturizer use., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Given the importance of appropriate diagnosis and appropriate assessment of cutaneous symptoms in treatment of atopic dermatitis, the basics of treatment in this guideline are composed of (1) investigation and countermeasures of causes and exacerbating factors, (2) correction of skin dysfunctions (skin care), and (3) pharmacotherapy, as three mainstays. These are based on the disease concept that atopic dermatitis is a inflammatory cutaneous disease with eczema by atopic diathesis, multi-factorial in onset and aggravation, and accompanied by skin dysfunctions. These three points are equally important and should be appropriately combined in accordance with the symptoms of each patient. In treatment, it is important to transmit the etiological, pathological, physiological, or therapeutic information to the patient to build a favorable partnership with the patient or his/her family so that they may fully understand the treatment. This guideline discusses chiefly the basic therapy in relation to the treatment of this disease. The goal of treatment is to enable patients to lead an uninterrupted social life and to control their cutaneous symptoms so that their quality of life (QOL) may meet a satisfactory level. The basics of treatment discussed in this guideline are based on the "Guidelines for the Treatment of Atopic Dermatitis 2008" prepared by the Health and Labour Sciences Research and the "Guidelines for the Management of Atopic Dermatitis 2012 (ADGL2012)" prepared by the Atopic Dermatitis Guidelines Advisory Committee, Japanese Society of Allergology in principle. The guidelines for the treatment of atopic dermatitis are summarized in the "Japanese Guideline for the Diagnosis and Treatment of Allergic Disease 2013" together with those for other allergic diseases.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with multi-system involvement and variable manifestations. There has been significant progress in TSC research and the development of technologies used to diagnose this disorder. As a result, individuals with mild TSC are now being diagnosed, including many older adults who have not developed seizures or cognitive abnormalities. We conducted a statistical analysis of the frequency of TSC manifestations in a population of Japanese adults and children, comparing our findings with historical data. The chi-square test was used to examine the frequency of each manifestation by age. A total of 166 outpatients at the Department of Dermatology of Osaka University Hospital during the period from January 2001 to March 2011 were included in the study. Compared to previous reports, the frequency of neurologic manifestations (excepting autism) was lower in this cohort, and the frequency of skin manifestations (excepting hypomelanotic macules) was higher in this cohort. The frequencies of pulmonary lymphangioleiomyomatosis and renal manifestations were not significantly different from those previously reported. Regarding the association of each manifestation with age, the frequency of neurologic manifestations (excepting subependymal giant cell astrocytoma) was significantly higher in younger patients than in older patients. The frequency of skin manifestations and renal angiomyolipoma were significantly higher in older patients than in younger patients. Because of their high frequency and visibility, skin manifestations are useful in the diagnosis of TSC. Moreover, uterine perivascular epithelioid cell tumor was also characterized as a new findings associated with TSC.

Vitiligo is an acquired pigment disorder in which depigmented macules result from the loss of melanocytes from the involved regions of skin and hair. The color dissimilarity on the cosmetically sensitive regions frequently induces quality of life impairment and high willingness to pay for treatment in patients with vitiligo. The Vitiligo Japanese Task Force was organized to overcome this situation and to cooperate with the Vitiligo Global Issues Consensus Conference. This guideline for the diagnosis and treatment of vitiligo in Japan is proposed to improve the circumstances of Japanese individuals with vitiligo. Its contents include information regarding the diagnosis, pathogenesis, evaluation of disease severity and effectiveness of treatment, and evidence-based recommendations for the treatment of vitiligo. The therapeutic algorithm based on the proposed recommendation is designed to cure and improve the affected lesions and quality of life of individuals with vitiligo., (© 2013 Japanese Dermatological Association.)

Background: Increases in allergic diseases have been reported from various epidemiological surveys. However, a few reports demonstrate the comorbidity of food allergy (FA) and allergic march. The aim of this study was to assess the prevalence and comorbidity of allergic diseases in Japanese students., Methods: First-year students (n = 3,321; 2,209 male and 1,112 female) at Osaka University were asked about allergic diseases using postal interview sheets. Personal and family histories of doctor-diagnosed allergic diseases, clinical courses, and aggravating factors were included in the questionnaires., Results: The lifetime prevalence of allergic rhinitis (AR), atopic dermatitis (AD), bronchial asthma (BA), and FA was 35.7%, 16.5%, 9.9%, and 7.0%, respectively. Disease-specific family histories existed for AR, AD, and BA. There was a positive correlation between the number of family histories of allergic disease and comorbidity (R = 0.370, P < 0.001). Comorbidity with AD significantly lowered the onset age of both BA (P = 0.010) and AR (P < 0.001). In addition, the onset age of AD was remarkably lowered by comorbidity with FA (P < 0.001). Comorbidity with FA was the highest risk factor for the progression of allergic march. Although most students showed improvement in AD, BA, and AR over time, the peak recurrence period was observed in adolescence., Conclusions: These findings indicate that AD associated with FA accelerates the subsequent progression of allergic march. Early appropriate management for genetically high-risk groups is important for the prevention of allergic march.

Given the importance of appropriate diagnosis and appropriate assessment of cutaneous symptoms in treatment of atopic dermatitis, the basics of treatment in this guideline are composed of (1) investigation and countermeasures of causes and exacerbating factors, (2) correction of skin dysfunctions (skin care), and (3) pharmacotherapy, as three mainstays. These are based on the disease concept that atopic dermatitis is a inflammatory cutaneous disease with eczema by atopic diathesis, multi-factorial in onset and aggravation, and accompanied by skin dysfunctions. These three points are equally important and should be appropriately combined in accordance with the symptoms of each patient. In treatment, it is important to transmit the etiological, pathological, physiological, or therapeutic information to the patient to build a favorable partnership with the patient or his/her family so that they may fully understand the treatment. This guideline discusses chiefly the basic therapy in relation to the treatment of this disease. The goal of treatment is to enable patients to lead an uninterrupted social life and to control their cutaneous symptoms so that their quality of life (QOL) may meet a satisfactory level.

Background: The impairment that pruritic skin diseases have on patient productivity at work, in the classroom, and in daily activities is substantial and needs to be characterized. The objective of this study was to determine how pruritic skin diseases impact patient productivity and quality of life (QOL), in order to improve the measurement of these endpoints to allow the influence of treatment options including sedative and non-sedative antihistamines to be analyzed., Methods: The impact of pruritic skin diseases and the effect of antihistamine therapy on work, classroom, and daily productivity were evaluated using the Work Productivity Assessment Index-Allergy Specific Questionnaire. The intensity of itch and patient QOL were assessed using a visual analogue scale and Skindex-16, respectively., Results: Pruritic skin diseases resulted in significant impairment of work, classroom, and daily productivity. The severity of overall work impairment in atopic dermatitis (AD), urticaria, and prurigo was higher than for other diseases analyzed. However, classroom activity was more adversely affected in patients with urticaria relative to other diseases. All pruritic diseases in this study negatively impacted daily activity to a similar degree. Impaired productivity was significantly improved in patients taking non-sedative antihistamines for 1 month, and the improvements correlated with the alleviation of itch and improved QOL., Conclusions: These results indicate that pruritic skin diseases reduce patient productivity at work, in the classroom, and during daily activities, and that non-sedative antihistamines may offer an advantage over sedative antihistamines for alleviating certain negative consequences of these skin diseases.

Background: Undiagnosed diabetes mellitus (DM) and impaired glucose tolerance (IGT) have important health consequences., Methods and Results: To examine the prevalence of undiagnosed glucose intolerance, oral glucose tolerance tests were administered to 1,142 consecutively enrolled middle-aged subjects (age range 40-55 years; 914 men, mean 50.7 years; 228 women, mean 49.4 years) who worked in a company and underwent a health check in 2006. No subject had a history of glucose intolerance. Fasting glucose levels increased with age in both men and women, with the levels being higher in men than women at every age. Glucose intolerance was more common in men compared with women (fasting glucose 100.1 +/-19.7 vs 92.9 +/-9.6, P<0.01; 1-h 170.7 +/-52.1 vs 139.7 +/-11.6, P<0.01; 2-h 136.0 +/-50.1 vs 119.8 +/-31.5 mg/dl, P<0.01). The prevalence of IGT and DM was also higher in men than in women (IGT: 24.1 vs 16.7, P<0.01; diabetes 10.7 vs 1.4%, P<0.01)., Conclusions: Fasting glucose levels increased with age in both men and women, with levels being higher in men than in women at every age. The prevalences of undiagnosed IGT and type 2 DM were also higher in men than in women.

X-linked hypohidrotic ectodermal dysplasia (XLHED), which is characterized by hypodontia, hypotrichosis, and hypohidrosis, is caused by mutations in ED1, the gene encoding ectodysplasin-A (EDA). This protein belongs to the tumor necrosis factor ligand superfamily. We analyzed ED1 in two Japanese patients with XLHED. In patient 1, we identified a 4-nucleotide insertion, c.119-120insTGTG, in exon 1, which led to a frameshift mutation starting from that point (p.L40fsX100). The patient's mother was heterozygous for this mutation. In patient 2, we identified a novel missense mutation, c.1141G>C, in exon 9, which led to a substitution of glycine with arginine in the TNFL domain of EDA (p.G381R). This patient's mother and siblings showed neither symptoms nor ED1 mutations, so this mutation was believed to be a de novo mutation in maternal germline cells. According to molecular simulation analysis of protein structure and electrostatic surface, p.G381R increases the distance between K375 in monomer A and K327 in monomer B, which suggests an alteration of overall structure of EDA. Thus, we identified two novel mutations, p.L40fsX100 and p.G381R, in ED1 of two XLHED patients. Simulation analysis suggested that the p.G381R mutation hampers binding of EDA to its receptor via alteration of overall EDA structure.

Background: Although dermatomyositis (DM)-associated facial erythema was noted in the nasolabial folds of Japanese patients, DM-associated facial erythema other than heliotrope rash has drawn little attention in previous studies., Objectives: To characterize phenotypical features and frequencies of erythema, especially those in the seborrheic area of the head, in DM patients., Methods: A retrospective study on skin manifestations in 33 DM patients followed up at our department during the past 15 years was conducted., Results: Macular violaceous erythema (MVE) in the seborrheic area of the face was most frequent (67%). Patients with facial MVE had also MVE in the scalp significantly more frequently than those without facial MVE. The pathology of the facial MVE was dominated by DM-associated changes with slight changes compatible with seborrheic dermatitis (SD)., Conclusions: Japanese DM patients had MVE frequently in the seborrheic area of the head. Its phenotypical features suggested that it might be triggered by SD., (2008 S. Karger AG, Basel.)

Background: The comparative studies of the prevalence of atopic dermatitis and skin barrier functions in Japanese and Chinese were performed., Methods: Clinical investigations were performed in 68 elementary school students in Lhasa, Tibet Autonomous Region and 67 students in Yixing, Jiangsu Province in China, and 99 students in Nishinomiya, Hyogo in Japan. Transepidermal water loss (TEWL) and capacitance were measured. Questionary survey about bathing frequency was also performed for students in Lhasa, Yixing and Osaka., Result: The prevalence rate of atopic dermatitis was 0% in Lhasa, 2.63% in Yixing, 4.26% in Nishinomiya. TEWL of students in Nishinomiya was higher than that in Yixing and Lhasa. Capacitance of students in Lhasa was lower than that in Nishinomiya and Yixing. The frequency of taking a bath in Lhasa was about 2.2 times per month and fewer than that in Nishinomiya and Yixing., Conclusion: There was tendency that the prevalence of atopic dermatitis increased according to increase of TEWL. It was thought that more investigations are necessary whether the development of habitat and environment influence the prevalence of atopic dermatitis and skin barrier function.

Contact dermatitis caused by airborne antigen is a well-recognized problem. Previously, airborne contact dermatitis after contact with Japanese cedar pollen [Japanese cedar pollen dermatitis (JCPD)] has been reported in Japan. However, there is still no diagnostic test to evaluate contact dermatitis due to Japanese cedar pollen. Skin tests with Japanese cedar pollen have been used to investigate these patients. A histological analysis was also conducted to clarify the mechanism of JCPD. We performed a scratch-patch test, scratch test and assays for total immunoglobulin E (IgE) and specific IgE in 13 patients suspected to have skin symptoms from Japanese cedar pollen, 5 patients with Japanese cedar pollinosis and 15 control normal subjects. All subjects were tested with Japanese cedar pollen allergen extract. A skin biopsy was performed from a Japanese cedar pollen-scratch-patch-test positive in patients with JCPD. The result after 48 hr of scratch-patch test was compared with the patient's history and the findings of corresponding scratch test and specific IgE. 100% of the 13 patients with JCPD showed a positive scratch-patch-test reaction to Japanese cedar pollen extract. However, 20% of the patients with the Japanese cedar pollinosis without any eruptions showed a positive scratch-patch-test reaction. The percentage of positive results for specific IgE and the scratch test did not differ substantially between Japanese cedar pollionosis patients with a history of chronic erythema after contact with Japanese cedar pollen and those without such a history. No side-effects were observed regarding the scratch-patch test. Control subjects showed 7% positive reaction. Histological examination showed that eczematous change (spongiosis, intracellular oedema and acanthosis), and infiltration of lymphocytes and eosinophils were all observed at the scratch-patch-test-positive sites. We therefore concluded that the use of the scratch-patch test with Japanese cedar pollen extract was useful for accurately diagnosing JCPD.

Generalized atrophic benign epidermolysis bullosa (GABEB), a subtype of epidermolysis bullosa (EB), is an autosomal recessive skin disease characterized by derm-epidermal separation leading to skin fragility and atrophy and other associated abnormalities. Although a few reports demonstrated that eosinophils are infiltrating beneath bullas in infants with some types of EB, no such condition in adult GABEB patients has been known. Here we report on three adult patients with GABEB from a Japanese family, whose bullous skin lesions showed massive eosinophil infiltration. One of the three patients showed amyloid deposition at the intestine, kidney, and skin. Linkage analysis revealed that GABEB in the family was linked to COL17A1 with a maximum LOD score of 3.08. Mutation analysis identified in the three patients a homozygous insertional mutation, 209-210insCA, in exon 5 of COL17A1. The expression of mutated COL17A1 was confirmed by semiquantitative RT-PCR, but no signals for truncated COL17A1 protein were detected by the immunohistochemical studies using antibodies against BP180. Furthermore, no autoantibody against the mutant protein was detected by western blot analysis. It is thus less likely that autoantibody and/or a local immune reaction in their skin has a primary role in eosinophil infiltration in these patients.

Over 30 years have passed since the accidental polychlorinated biphenyls (PCB) poisoning in Japan and yet high concentrations of PCB are still detected in the serum of the victims. PCB produces superoxide and thus victims of PCB poisoning are in a persistent state of oxidative stress. To examine the antioxidative state, we measured the serum concentrations of Cu, Zn-superoxide dismutase (SOD) and Mn-SOD in 38 victims and 20 age-matched control subjects. The mean serum concentration of Cu, Zn-SOD was significantly lower and that of Mn-SOD higher than those of the control. Such an antioxidative state is indicative of an imbalance of Redox regulation mechanism. Persistence of imbalance could result in serious ailments in the future.

We report a 66-year-old woman with localized argyria caused by embedding of acupuncture needles. Ten years after she had received acupuncture, she noticed two asymptomatic bluish macules on her right arm. A biopsied specimen from the macule revealed many brownish-black granules mainly located around the sweat glands and the blood vessels in the dermis. The X-ray examination of the extremities revealed numerous needle-like fragments around her extremities. "Embedding of needles" induces some serious adverse events. We should know the adverse events for the safety and health of patients.

To identify the correlation between the house dust mite-specific lymphocytes proliferation and other clinical parameters and clinical features, we conducted a lymphocytes stimulation test in 37 patients with atopic dermatitis. A total of 12 patients showed positive reactions (positive patients) and 25 showed no reaction (negative patients). Both the number and percentage of peripheral blood eosinophils were significantly lower in positive patients than in negative patients. Stimulation index measured by lymphocytes stimulation test showed no correlation with the total IgE level, nor the number and percentage of eosinophils. Stimulation index weakly correlated with mite-specific IgE-RAST scores both in positive patients and in negative patients. Only in positive patients, stimulation index weakly correlated with the severity measured by the clinician score method. Three out of four positive patients showed an increased stimulation index in accordance with increased clinician scores during their clinical course. These results could suggest that, in positive patients, a house dust mite allergy might be an active cause that exacerbates clinical symptoms at the time of their clinical course. Therefore, the stimulation index of the lymphocytes stimulation test might become one of the effective parameters that reflect the involvement of a house dust mite allergy in adult atopic patients.

Many patients with severe atopic dermatitis (AD) in Japan are afflicted with persistent erythema of the face (atopic red face) that is not only resistant to topical corticosteroid, but often becomes worse with its use. During a three-year period (1991-1993), we treated 79 inpatients with severe AD by a combination of careful daily skin care, use of emollients, and exclusion of exacerbating factors. Occular complications before and after treatment were examined in these cases. After withdrawal of topical corticosteroid, almost all of the patients showed a temporary worsening of their skin condition. Immediately thereafter, their occular symptoms did not change. Cataract was found in 20 cases (25.3%), and retinal detachment in 9 (11.4%). After 2 months, 11 cases of cataract and 5 cases of retinal detachment in the peripheral retina were observed. However, these incidences were similar to the numbers reported in Japan during conventional treatment with topical corticosteroid. The development of cataract or retinal detachment had no relationship to serum IgE levels, personal history of respiratory atopy, the duration of topical corticosteroid use on the face, or treatment with systemic corticosteroid. Our observations suggest that patients who habitually tap or rub their faces strongly tend to develop cataract or retinal detachment at a statistically significant higher frequency. Patients with AD should have ophthalmologic examinations every one to two months for at least one year after a facial oozing attack or withdrawal of corticosteroid.

Only a few cases of Post-kala-azar dermal leishmaniasis have been reported in Japan, especially recently. We describe a case of a 32-year-old woman who developed rose-colored nodules on her forearms two years after Kala-azar. A skin biopsy specimen from a nodule revealed not only granulomatous changes but also many amastigotes of Leishmania donovani in macrophages. Rose-colored nodules were also distributed on her face and neck. Treatment with antimony compound was very effective.

Clinical analysis was performed on non-steroidal ointment therapy for 70 patients with refractory adult-type atopic dermatitis by the clinical data and patient's own evaluation of the therapy obtained through enquiries after discharge from the hospital. Forty cases (57%) were between 20 and 30 years old and the male and female ratio was 39/31. The clinical evaluations were subdivided into five groups; conditions worsened (n = 9), no-change (n = 9), slightly improved (n = 14), much improved (n = 29) and cured (n = 9). Although statistically not significant, the age of onset of atopic dermatitis and the start of use of steroid ointment was much higher while the duration of the atopic dermatitis was much shorter in the remission patients. The duration of steroid ointment therapy for the facial skin was significantly shorter in the remission group when compared to groups with worsened symptoms and no-change in symptoms. Family history and complications of atopic diseases, laboratory data including IgE titer, eosinophils and RAST score were not statistically significant in any group except for a higher prevalence of IgE antibodies against inhalant and food allergens in the group with worsened symptoms. Most patients still used steroid ointment on the trunk lesions while they ceased using from the topical steroid on the facial lesions after discharge. Most frequent precipitating factors pointed out by the patients were emotional stress, irritation by sweat or UV light and longstanding use of steroid ointment. Complications of cataracta and retinopathy were found in 12 cases. These results suggest that remission of adult-type refractory atopic dermatitis can be achieved by the combination of careful daily skin care, use of non-steroidal topical ointment and minimizing the precipitating factors.

For the first time, we performed an epidemiological study of SSc in Japan to study the factors influencing prognosis, survival rate and cause of death of Japanese SSc patients and to compare our data with those from foreign countries. Prognosis of 496 Japanese patients with progressive systemic sclerosis (SSc) was analyzed based on clinical data described in case cards provided by the members of the Scleroderma Research Committee of the Japanese Ministry of Health and Welfare. The essential observation period was from 5 to 20 years, at ending in 1994. Ninety patients died (males 11, females 79). The age of onset of the deceased patients was significantly higher than that of surviving patients (deceased, 45.6 yrs, surviving 41.3 yrs). Statistically significant factors for a poor prognosis were as follows: Barnett type III > type II > type I, positive for anti-Scl-70 antibody, negative for anti-centromere antibody. The survival rate at 5 years after the onset of the disease was 0.937, followed by 0.82 at 10 years, 0.567 at 20 years and 0.40 at 30 years after the onset. Sex was not a predictor for prognosis, although male patients died at an earlier stage of the disease. The most common causes of death were heart failure, pulmonary insufficiency, lung fibrosis, and renal failure. Twenty-four patients had cancer of which 13 were lung cancers. The current status of the survival rate and prognostic factors of 496 Japanese SSc patients is summarized. In future, more well-controlled studies using the same criteria should be performed for the better understanding and management of SSc.

We reviewed 111 clinical and pathological materials of patients who had been entered as mycosis fungoides (MF) or Sézary syndrome (SS) in the Annuals of the Pathological Autopsy Cases in Japan during the 29-year-period since the Annuals' inception in 1958. One hundred and seven patients were classified. Of these, 64 were in Group 1 (mycosis fungoides, MF), 23 in Group II (Sézary syndrome, SS), and 20 in Group III (non-Hodgkin's lymphoma, NHL). The clinicopathologic features of Groups I and II (MF, SS) were similar to those of cutaneous T cell lymphoma (CTCL) in Europe and the United States. Those of Group III (NHL) were indistinguishable from primary cutaneous non-Hodgkin's lymphoma. It was suggested that some patients with adult T cell leukemia/lymphoma (ATLL) with skin lesions used to be misdiagnosed as MF or SS in earlier years when ATLL was still unknown. It was concluded that CTCL in Japan has clinicopathologic features quite like those of CTCL in Europe and the United States and that they are probably the same disease.

Recently the Lymphoma Study Group of Japan (LSGJ) proposed a new classification of non-Hodgkin's lymphomas (NHLs), diving NHLs into the follicular group consisting of three subsets and the diffuse group, 7. Each subset of the diffuse group is further divided into B or T cell types according to immunologic markers and/or morphologic prediction. In the review of 118 malignant lymphomas, the authors studied the 109 cases of NHLs, attempting to assess the clinicopathologic utility of this classification. Morphologic criteria, enzyme histochemistry, and immunoperoxidase technique were used to ensure the accuracy of the immunologic phenotyping. The results suggest that the LSGJ classification is easily reproducible and yields a more precise clinicopathologic correlation than traditional, morphologic classifications. Consistent with similar studies in Japan, this study demonstrated a low incidence of Hodgkin's disease (7.6% of all lymphomas) and follicular lymphomas (8.3% of all NHLs) and a high incidence of T cell lymphomas (34.9% of all NHLs). The incidence (45.9%) of extranodal presentation was high. These four features seem characteristic of lymphomas in Japan.

Sera from 11 Japanese patients with hairy cell leukemia and 4B122, an anti-hairy cell serum produced by the authors, were surveyed by Western blot analyses for cross-reacting antibodies to human T cell leukemia virus (HTLV)-I and -II virions released, respectively, from Lma-66 and Mo-T cell lines. Sera from the majority of the patients showed positive reactions with p15, p19, and/or p24 of HTLV-I and with p21 and/or p22 or HTLV-II. 4B122 was weakly cross-reactive with HTLV-II but not with HTLV-I. These results militate against the involvement of HTLV-I or -II but may implicate a role by a cross-reacting, previously unrecognized retrovirus in the pathogenesis of hairy cell leukemia in Japanese patients.

Using a panel of monoclonal antibodies and three anti-hairy cell sera (alpha HC1 and alpha HC2 of Posnett and 4B122 prepared by the authors), hairy cells were phenotyped on frozen sections of cell pellets from blood and spleen of 11 Japanese patients with hairy cell leukemia (HCL). The results were quite similar to those reported for HCL of non-Japanese patients inasmuch as hairy cells in the majority of these patients were B1+, B2-, FMC7+, and IL-2R1+. However, they were more often than not J5+, Leu-1+, alpha HC1-, alpha HC2-, and 4B122+ in contrast to the pattern reported for non-Japanese patients. In conclusion, HCL in the Japanese constitutes a special variant of HCL because of its rareness, unusual immunophenotype, and atypical clinicohematologic features.

Using SDS polyacrylamide gel electrophoresis (SDS-PAGE), several coworkers isolated a unique membrane protein that they named p35 from hairy cells of white patients with hairy cell leukemia. In the current study using a similar technique, p35 was identified in hairy cells from 2 of 4 Japanese patients with hairy cell leukemia. Further, p35 was immunoprecipitated from the leukemic membrane proteins of one of these two Japanese patients with an anti-hairy cell serum prepared against hairy cells of a typical white patient. Because both Japanese and white patients share the unique membrane antigen, it is proposed that the Japanese have the hairy cell leukemia as whites despite some differences in laboratory features.