Factors associated with the development and remission of allergic diseases in an epidemiological survey of high school students in Japan.

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.

Sweat, the driving force behind normal skin: an emerging perspective on functional biology and regulatory mechanisms.

The various symptoms associated with excessive or insufficient perspiration can significantly reduce a patient's quality of life. If a versatile and minimally invasive method could be established for returning sweat activity to normalcy, there is no question that it could be used in the treatment of many diseases that are believed to involve perspiration. For this reason, based on an understanding of the sweat-gland control function and sweat activity, it was necessary to conduct a comprehensive search for the factors that control sweating, such as the central and peripheral nerves that control sweat-gland function, the microenvironment surrounding the sweat glands, and lifestyle. We focused on the mechanism by which atopic dermatitis leads to hypohidrosis and confirmed that histamine inhibits acetylcholinergic sweating. Acetylcholine promotes the phosphorylation of glycogen synthesis kinase 3ß (GSK3ß) in the sweat-gland secretory cells and leads to sensible perspiration. By suppressing the phosphorylation of GSK3ß, histamine inhibits the movement of sweat from the sweat-gland secretory cells through the sweat ducts, which could presumably be demonstrated by dynamic observations of the sweat glands using two-photon microscopy. It is expected that the discovery of new factors that control sweat-gland function can contribute to the treatment of diseases associated with dyshidrosis.

Decreased sudomotor function is involved in the formation of atopic eczema in the cubital fossa.

BACKGROUND: Eczema in the cubital fossa, which is susceptible to sweat, is frequently observed in atopic dermatitis (AD). However, there has been no direct evidence that sweating causes eczema in the cubital fossa. METHODS: To investigate this issue, axon reflex-mediated sweating volume (AXR) and skin barrier function in the cubital fossa were measured in subjects with AD and in healthy volunteers, and were applied to clinical feature of the cubital fossa. RESULTS: AXR in the cubital fossa decreased in AD subjects; it positively correlated only with water-holding capacity in healthy subjects but not in patients with in AD. Furthermore, AD subjects with lichenoid eczema and either prurigo or papules over the cubital fossa showed extremely decreased AXR. CONCLUSIONS: These results suggest that decreased sweating is a major source of water in the stratum corneum, and decreased sudomotor function may be involved in both the cause and aggravation of representative atopic eczema in the cubital fossa.

Prevalence and impact of past history of food allergy in atopic dermatitis.

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.

Prevalence and Impact of Past History of Food Allergy in Atopic Dermatitis.

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.

Abnormal axon reflex-mediated sweating correlates with high state of anxiety in atopic dermatitis.

BACKGROUND: Sweating plays a key role in skin homeostasis, including antimicrobial and moisturizing effects, and regulation of skin surface pH. Impaired axon reflex-mediated (AXR) sweating has been observed in patients with atopic dermatitis (AD). However, the mechanism of such abnormal sudomotor axon reflex remains to be revealed. METHODS: To investigate this mechanism, sudomotor function was analyzed using a quantitative sudomotor axon reflex test (acetylcholine iontophoresis) in patients with AD (n = 26) and healthy volunteers (n = 12). Correlation between sudomotor function and certain background factors, including Spielberger State Trait Anxiety Inventory score, Severity Scoring of Atopic Dermatitis (SCORAD) score, number of circulating eosinophils, and serum concentrations of thymus and activation-regulated chemokine and immunoglobulin E radioimmunosorbent test, was validated. RESULTS: Latency time was significantly prolonged in AD (p = 0.0352), and AXR sweating volume (mg/0-5 min) was significantly lower in AD patients than in healthy controls (p = 0.0441). Direct sweating volume (mg/0-5 min) was comparable in AD patients and healthy controls. A significant correlation between the evaluation results of quantitative sudomotor axon reflex tests and certain background factors was not observed. The latency time in non-lesioned and lesioned areas for AD patients versus continuous anxiety value in the Spielberger State Trait Anxiety Inventory and the AXR versus SCORAD showed significant correlations (p = 0.0424, p = 0.0169, and p = 0.0523, respectively). CONCLUSIONS: Although the number of study subjects was little, abnormal AXR sweating in patients with AD was observed. Correlative analysis suggests possible involvement of continuous anxiety and the immune system in such abnormal sudomotor function.

Four cases of atopic dermatitis complicated by Sjögren's syndrome: link between dry skin and autoimmune anhidrosis.

We report four adult cases of atopic dermatitis (AD) complicated by Sjögren's syndrome (SS). The patients fulfilled diagnostic criteria for AD and SS. All cases showed persistent itchy dry skin and eczematous lesions complicated by sicca symptoms including dry eyes and dry mouth with moderate joint pain. One case manifested annular erythema and another manifested widespread discoid erythema. To investigate the underlying cause of dry skin in these cases, sweating function was evaluated using a quantitative sudomotor axon reflex test (QSART) in which the axon reflex is stimulated by acetylcholine iontophoresis. The sweating latency time was significantly prolonged in eczematous skin of AD and AD/SS compared to normal controls. Axon reflex (AXR) sweat volume was also significantly reduced in AD (normal and eczematous skin) and AD/SS (normal and eczema) compared to normal control. In contrast, the direct sweat volume of lesional or non-lesional AD skin induced by direct stimulation with acetylcholine was only slightly reduced compared to that in normal controls, but not in SS and lesional skin of AD/SS patients. These results suggest that the impaired sweat response in AD is attributable to an abnormal sudomotor axon reflex, which is accelerated and modulated when complicated by SS resulting in dry skin in the present cases.

Cedar pollen aggravates atopic dermatitis in childhood monozygotic twin patients with allergic rhino conjunctivitis.

We report a case of 7-year-old monozygotic twin patients with atopic dermatitis. The HLA haplotypes were HLA A2, A11, B27, B61, DR1, and DR4. Both serum IgE levels and cedar pollen radioallergosorbent test (RAST) scores were high in the twins (elder/younger sister: IgE: 5170/3980 IU/ml and Japansese cedar pollen: >100/64.0) in contrast to low mite and food RAST scores (Dermatophagoides Pterygonium; 0.59/0.4 and egg white 9.24/4.6). The patients showed positive immediate (20 min in both sisters) and delayed (24 hours in elder sister, 24, 48, 72 hours in younger sister) reactions to a scratch test with Japanese cedar pollen. Skin lesions on the face were aggravated and extended to the trunk and extremities during the Japanese cedar pollen season and gradually subsided in summer. Oral provocation with egg white or cow milk showed no exacerbations, and topical corticosteroid did not improve the eczema. In contrast, successful protection from severe scratching behaviors was achieved by use of topical anti-allergic eye drops and wearing nightgowns made by the mother.

A case of disseminated DLE complicated by atopic dermatitis and Sjögren's syndrome: link between hypohidrosis and skin manifestations.

We report an unusual case of disseminated discoid lupus erythematosus (DLE) complicated by pre-existing atopic dermatitis (AD) and late-onset Sjögren's syndrome (SS). Disseminated DLE lesions were sparse on the expected sites for AD, such as the medial region of the extremities or v-neck area. The patient fulfilled the diagnostic criteria for AD and SS but not for systemic lupus erythematosus. Histopathological analysis of the crusted erythematous lesions revealed typical DLE with few FoxP3(+) cells and a moderate number of IL-17(+) cells. A quantitative sweating test showed impaired sweating of both lesional and non-lesional skin due to underlying hypohidrosis that was related to AD and SS. This finding suggests that dissemination of DLE was triggered by scratching and a Köbner phenomenon-like effect related to hypohidrotic and xerotic skin. To the best of our knowledge, this is the first reported case of disseminated DLE complicated by AD and SS.

[A case of AIDS with Pneumocystis jirovecii pneumonia which required differentiation from ANCA-related lung disease].

A 41-year-old man with fever, diarrhea and skin rash received a diagnosis of drug-induced lupus. He was given corticosteroids for 3 months and was subsequently admitted to a local hospital due to dyspnea. Pneumonia was then diagnosed and he was given a new quinolone antibacterial agent. Despite this treatment, his symptoms and signs gradually worsened and he was referred to our hospital. High resolution CT (HRCT) of the chest showed diffuse ground-glass opacities, reticular shadows, parenchymal abnormalities, traction bronchiectasis, a subpleural curvilinear shadow and septal lines. Serological examinations were positive for anti-myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) and subsequent HRCT findings were consistent with ANCA-related lung disease. However, the patient had complications such as previous syphilis infection, oral candidiasis, herpes zoster, hepatitis B virus and cytomegalovirus infection. Additionally, his serum was positive for HIV antibody and HIV-1 RNA, and therefore we diagnosed AIDS. His bronchoalveolar lavage fluid revealed Pneumocystis jirovecii. It is known that HIV infection is associated with many types of autoantibodies including MPO-ANCA. Therefore, in HIV/AIDS patients with interstitial lung diseases, it is important to differentiate opportunistic Pneumocystis pneumonia infection from collagen vascular disease-associated interstitial lung diseases.

[Type 1 allergy to formaldehyde in root canal sealant after dental treatment: two case reports and review of the literature].

Two cases of generalized urticaria after the dental treatment were reported. These cases had clearly positive RAST to formaldehyde, whereas skin prick testings were negative. We diagnosed them as type I allergy due to formaldehyde. Immediate type formaldehyde allergy is not widely recognized as a major allergic complication of dental treatment. Previous reports of immediate allergy to formaldehyde in dental treatment were reviewed. The characteristics are the followings, first, it tends to represent severe symptom like anaphylaxis, second, the symptom often appears a few hours later than usual cases of anaphylaxis. Allergen tests show highly positive ratio to formaldehyde RAST, whereas skin prick test often shows false negative. Assessment of specific IgE to formaldehyde is a useful and a diagnostic measurement, and is recommended in patients at risk.