Pulmonary hypertension (PH) was found to be the primary cause of death in mixed connective tissue disease (MCTD). This led to investigation of the prevalence of PH in other connective tissue diseases (CTD). In 1998, the Ministry of Health and Welfare's MCTD Research Committee revealed complication of PH diagnosed by physicians in 5.02% MCTD patients, 0.90% systemic lupus erythematosus patients, 2.64% systemic sclerosis patients, and 0.56% polymyositis/dermatomyositis patients. These results have been supported by a similar survey performed in North America.
As quite a few rheumatologists find right heart catheterization difficult to perform, doppler echocardiography is frequently used for screening and diagnosing PH. The MCTD Research Committee set the revised criteria for MCTD-PH, in which the threshold of estimated pulmonary arterial systolic pressure value for diagnosis of pulmonary arterial hypertension (PAH) is set at 36mmHg, as proposed by the European Society of Cardiology. Right heart catheterization is strongly recommended for commencing the treatment. Since PH due to thromboembolism can potentially be cured surgically, lung perfusion scintigraphy should be performed for all patients diagnosed with PH.
Most CTD-PH are PAH, and since idiopathic PAH (IPAH) patients sometimes have immune disorders, treatment for IPAH may be applicable to CTD-PH. The greatest difference between the treatment strategy for CTD-PH and IPAH is the usage of corticosteroids and other immunosuppressants. The MCTD Research Committee updated its therapeutic guidelines for MCTD-PH in 2011. Validation of these guidelines is also needed.

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Connective tissue diseases (CTD), such as systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCTD), develop pulmonary hypertension (PH). Generally all PH cases associated with any CTD are classified into the same PH group. However, histological examination shows both common and specific lesions for each disease. In patients with SLE, fibrosis is generally rare and mild. The findings of PH in SLE are similar to those in primary pulmonary hypertension. Many cases of SSc are accompanied by fibrosis. MCTD is rather close to SSc. Arterial and arteriolar lesions of MCTD are characterized by fibrous intimal thickening. In this review, we describe the pathological features of PH associated with each CTD.

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Pulmonary hypertension was defined as mean pulmonary artery pressure ≥25mmHg at the 4th World Symposium on Pulmonary Hypertension. In 2009, the European Society of Cardiology and European Respiratory Society jointly created guidelines for practical pulmonary hypertension classifications and treatments based on the discussions at the 4th World Symposium. This classification is characterized by division into five groups: Pulmonary arterial hypertension (PAH); Pulmonary hypertension due to left heart disease; Pulmonary hypertension due to lung disease and/or hypoxia; Chronic thromboembolic pulmonary hypertension; and Pulmonary hypertension with unclear and/or multifactorial mechanisms.
PAH is a common and fatal complication of connective tissue disease (CTD), but pulmonary hypertension in CTD consists of PAH, pulmonary hypertension caused by myocardial involvement, pulmonary veno-occlusive disorder, pulmonary hypertension due to interstitial lung disease. PAH has been studied widely in SSc and the estimated prevalence of 7-12%. Treatment of CTD associated PAH (CTD-PAH) consists of general therapeutic options and specific treatment. Specific treatment of CTD-PAH patients is targeted to produce vasodilatation. Calcium channel blockers (CCBs) are indicated in cases where a sufficient decrease in pulmonary arterial pressure is seen in vasoreactivity testing. If vasoreactivity is absent in CTD-PAH patients, the treatment consists of the endothelin receptor antagonists, the prostacyclin analogues and phosphodiesterase-type 5 inhibitors. Few data are available to support the use of immunosuppression in CTD-PAH. However, some case reports suggested that a minority of CTD-PAH patients could benefit from immunosuppressive therapy. The treatment of CTD-PAH patients may differ from the treatment of idiopathic PAH.

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Background: Tree nut allergy is characterized by a high frequency of life-threatening reactions and is typically lifelong persistent. Some people with a pistachio nut allergy, which is common in the pistachio rich area of Iran, develop a hypersensitivity to other tree nuts as well. The aim of this study was to investigate the prevalence of pistachio nut allergy in Iran, the major pistachio cultivation region in the world. The study also addressed the presence of allergenic cross-reactivity between pistachio and other nuts, including almond, peanut, and cashew in pistachio allergic patients.
Methods: A survey was conducted to determine whether the prevalence of pistachio allergy is affected by exposure to this nut in pistachio cultivation regions, as well as possible cross-reactivity between pistachio and other nuts including cashew, almond, and peanut. Inhibition Western blot and inhibition ELISA studies were conducted to assess the presence of allergenic cross-reactivity between pistachio and the other tree nuts.
Results: Our results revealed that the prevalence of pistachio allergy is twice as much in pistachio cultivation regions than other areas. Western blotting and inhibition ELISA presented high percentages of inhibition with pistachio and cashew, followed by almond and, to some degree, peanut which indicates different levels of allergenic cross-reactivity.
Conclusions: The results indicate that exposure of people to pistachio significantly affects the prevalence of its allergic reactions. In addition, it was observed that, among pistachio allergic subjects, such exposure may affect the co-sensitivities with other nuts, including cashew and almond. The plant taxonomic classification of pistachio and other tree nuts does appear to predict allergenic cross-reactivity.

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Background: Treatment strategy that reduces dependence on long-term medication for chronic asthma is preferable. The purpose of the study is to investigate the efficacy of an early intensive intervention for inducing inactive asthma in adults and identify factors that affect the efficacy.
Methods: A prospective study was conducted on subjects who had asthma for two years or less. An intensive intervention consisting of systemic corticosteroid treatment for two weeks followed by inhaled corticosteroid for further 16 weeks with concomitant administration of bronchodilator(s) was administrated on 109 subjects. As a control group, 33 subjects were treated according to the current asthma treatment guidelines for 18 weeks. The primary outcome of the intervention was assessed with symptomatology and use of medication during 12 months after the cessation of treatment period.
Results: At one year after the intervention, significantly more patients in the intensive intervention group (41%) than in the control group (24%) had no respiratory symptoms and were medication-free or had experienced minor upper respiratory symptoms (inactive asthma)(P = 0.01). The intensive intervention maintained a significant factor associated with one-year inactive asthma (adjusted odds ratio: 3.61, 95% confidence interval: 1.20-10.84; P = 0.02). Infection as onset cause, asthma duration and pre-treatment %FEV_1.0 were also identified independently associated with inactive asthma. As the limitation, the study was not randomized trial.
Conclusions: Intensive therapy in the early stage is very likely to contribute to increasing one-year asthma inactivity, which may reduce patients' dependence on long-term management by medical treatment.

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Background: The burden of asthma is recognized as an important public health problem worldwide. In most countries, the prevalence of asthma has been reported to increase in the last few decades. However, more recent epidemiological studies have shown that the prevalence of asthma has been flat or even decreasing after the 1990s in some developed countries. The recent time trend in the prevalence of adult asthma in Japan is unknown.
Methods: Population-based surveys were conducted three times in the same region, in 1985, 1999, and 2006, at Fujieda City, Shizuoka, Japan, and the results were reported previously. We compared the results of these surveys to reveal the time trend in the prevalence of adult asthma. Although the questionnaires used in these surveys were not exactly the same, the time trend was assessed by comparing the responses to relevant questions between questionnaires.
Results: The prevalences of wheeze following a common cold and dyspneal feeling at night increased significantly from 1985 to 1999 (4.2% to 7.6%, and 3.2% to 5.3%, respectively). The prevalences of lifetime asthma and current asthma also significantly increased from 1999 to 2006 (5.1% to 6.7%, and 1.5% to 3.4%, respectively).
Conclusions: The prevalences of asthma among adults in Fujieda City consistently increased from 1985 to 2006. There was no evidence that the prevalences were in plateau or decreasing. These findings suggest that more efforts are required to stop the increase in the burden of this disease in Japan.

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Background: Interleukin-19 (IL-19), a member of the IL-10 family, is characterized as the cytokine suppressing the release and function of several proinflammatory cytokines. For regulation of local reaction in allergic rhinitis (AR), IL-19 might play an especially important role.
Methods: We examined effects of IL-19 on IL-4-induced eotaxin production by human nasal fibroblasts. Early receptor-mediated events (expression of the suppressors of cytokine signaling (SOCS) and phosphorylation of signal transducer and activator of transcription 6 [STAT6]) by IL-19 was examined. Knockdown methods by RNAi were administered to investigate the involvement of those signal transductions.
Results: Pretreatment with IL-19 downregulates IL-4-induced eotaxin production, but not interferon-γ (IFN-γ)-induced RANTES. Pretreatment with IL-19 suppressed the IL-4-induced STAT6 phosphorylation. The IL-19 induced SOCS-1, but not SOCS-3 or SOCS-5. The SOCS-1 knockdown by RNAi diminished pretreatment with IL-19-induced down-regulation of eotaxin production.
Conclusions: These results suggest that IL-19 down-regulates IL-4-induced eotaxin production via SOCS-1 in human nasal fibroblasts. In non-hematopoietic cells in AR, IL-19 might be an immunosuppressive factor.

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Background: The effect of inhaled corticosteroid (ICS) on the bone status of asthmatic patients is still uncartain, becuase it can differ by race and because there have been few cases in Japan. In this study, the bone status of ICS users with asthma was evaluated in an actual clinical setting in Japan.
Methods: In 7 participating hospitals, ICS users with asthma and control subjects were age- and gender-matched and recruited into this study. To assess bone status, ultrasound measurements of each individual's calcaneus were made using an AOS-100. The ratio of the osteo sono-assessment index (OSI) to the average OSI corrected for age and gender was denoted as %OSI and used for quantitative assessment. The second %OSI measurement was performed 6 months after the first %OSI one. During the study period, individual treatment remained unchanged.
Results: There were no significant differences in the 1st and 2nd %OSI between the ICS users and control subjects. However, the 2nd %OSI significantly decreased compared with 1st %OSI in female ICS users, although there were no significant changes in the male and female control subjects and male ICS users.
Conclusions: The 6 month manegement of asthma in the actual clinical setting, including regular ICS use, might have a harmful influence on the bone status of female asthmatic patients. It may be necessary to manage and treat female patients for potent corticosteroid-induced osteoporosis, although further analyses of bone status in asthma patient ICS users will be required.

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Background: Respiratory syncytial virus (RSV) is a major respiratory pathogen which causes bronchiolitis with dyspnea and wheezing in children less than 2 years old. RSV bronchiolitis in infancy severe enough to cause hospitalization might be a risk factor for allergic sensitization and bronchial asthma in future. However, the pathophysiology behind this development has not been clearly characterized. To evaluate the existence of airway inflammation and characteristic of RSV bronchiolitis, we analyzed and compared the concentrations of eosinophilic cationic protein (ECP) in nasal fluid and plasma.
Methods: From 69 infants (aged <2 years) hospitalized for possible lower respiratory tract infections including RSV infection, we collected nasal fluid and plasma and determined the ECP concentrations.
Results: ECP concentrations in nasal fluid were significantly higher in patients with wheezing and/or bronchial rales than in patients without them (1733 ± 660ng/mL vs 680 ± 450ng/mL, p = 0.018), and those of the respiratory syncitial virus-infected group were significantly higher than those of the uninfected group (p = 0.04). Meanwhile, there was no significant difference in plasma ECP levels between patients with wheezing and patients without wheezing, and no significant difference between RSV-infected and other pathogen-infected patients. There were significant correlations between nasal fluid ECP concentrations and both neutrophil and eosinophil counts in the peripheral blood.
Conclusions: Nasal fluid ECP concentrations are increased in infants with lower respiratory infections including RSV infection accompanied with wheezing. ECP probably originates from neutrophils as well as eosinophils migrated into airways. The monitoring of ECP concentration in nasal fluid may be useful for evaluating leukocyte (including eosinophils and neutrophils)-mediated airway inflammation during infancy and its severity.

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Background: Bronchial asthma is a chronic inflammatory disease that has a severe impact on health worldwide.
Methods: A survey of 10,771 patients with bronchial asthma in the Tama region, Tokyo was conducted for 5 years to examine treatment and quality of life (QOL). Subjects were patients aged ≥16 years and their physicians who replied to a questionnaire sent in November from 2002 to 2006. Symptoms of bronchial asthma, visits to an emergency room, use of drugs, and severity of asthma were investigated.
Results: Asthmatic symptoms improved over the 5 years, with a reduction in the number of emergency room visits. Since inhaled corticosteroids (ICS) were used by >80% of patients in 2002, we suspected that increased use of concomitant leukotriene receptor antagonists (LTRA) and long-acting β₂ agonists (LABA) might have contributed to these findings. The effects of these drugs were compared between ICS + LTRA (n = 45) and ICS + LABA (n = 54) groups of patients. There was no significant difference in the ICS dose between these groups. In the ICS + LABA group, 18.5% and 22.2% of patients visited an emergency room before and after initiation of combination therapy, respectively, with no statistically significant difference. In contrast, the rate of emergency room visits in the ICS + LTRA group decreased from 24.4% to 6.6% after addition of LTRA.
Conclusions: These results suggest that the frequency of visits to an emergency room was decreased by complementing the anti-inflammatory effect of ICS with further treatment of inflammation, particularly with LTRA.

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Background: Leukotriene receptor antagonists (LTRAs) are effective for prophylactic treatment of pollinosis based on studies showing that administration of LTRAs prior to or at the start of the pollen season reduces symptoms and QOL disturbance at the peak of pollen dispersal. Two goals of prophylactic treatment of pollinosis are use of fewer types of drugs and delay of onset of symptoms and impairement of QOL. Therefore, this study was performed to determine if pranlukast, a LTRA, met these goals in treatment of pollinosis.
Methods: Pranlukast or placebo was administered to patients who visited our hospital immediately before the start of Japanese cedar pollen dispersal. The study was performed for 4 weeks as a double blind randomized trial. Subsequently, all patients were given pranlukast for a further 4 weeks from the peak until the end of pollen dispersal. The incidence of symptoms and use of concomitant drugs were investigated from daily nasal allergy records kept by patients. QOL was evaluated using the JRQLQ questionnaire.
Results: In the double blind period of the study, the percentage of patients who used concomitant drugs for nasal symptoms was significantly lower in the pranlukast group compared to the placebo group. Development of nasal symptoms (sneezing, runny nose and nasal congestion) and disturbance of daily activities were significantly delayed in the pranlukast group. No serious adverse reactions occurred in the pranlukast group and no patient withdrew from treatment with pranlukast.
Conclusions: Pranlukast is effective for prophylactic treatment of pollinosis.

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Background: The relationship between chronic rhinosinusitis (CRS) and asthma has been known for a long time. However, no large studies on the relationship between CRS and lower airway diseases have been reported to date in Japan. Additionally, eosinophilic chronic rhinosinusitis (ECRS) in Japan is considered to be a subgroup of CRS with nasal polyps (CRSwNP) characterized by eosinophil-dominant inflammation. However, the diagnostic criteria of ECRS have not been established.
Methods: To investigate clinical and epidemiological features of patients with CRS from the aspect of their associations with lower airway diseases, 553 patients with CRS who visited one of six local university hospitals were examined and interviewed. Local eosinophilic infiltration was evaluated pathologically by exmining NPs.
Results: The prevalences of olfactory dysfunction (OD) in the patients with nasal polyps (NPs) and those without NPs were 57.0% and 13.7%, respectively (p < 0.0001). The prevalence of asthma in all patients was 23.1%. Furthermore, the prevalences of NPs and OD in the patients with asthma and those without asthma were 81.0% and 50.1% (p < 0.0001) and 64.2% and 35.7% (p < 0.0001), respectively. 97.4% of the patients with asthma had ≥15% mucosal eosinophils, and 87.9% of the patients without asthma had <15% mucosal eosinophilis.
Conclusions: Similar to the relationship between nasal allergy and asthma, CRSwNP may be applicable to the concept of "one airway, one disease".

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Background: The leukocyte migration test (LMT) is effective in identifying the causative drug in drug allergies. Both leukocyte migration activating activity (LMAA) and leukocyte migration inhibitory activity (LMIA) are involved in the development of drug allergies. However, no cytokines associated with LMIA have been identified to date. Because CXCL8 played an important role in neutrophil infiltration and activation, we performed the LMT and measured CXCL8 levels in patients with hypersensitivity to beta-lactam antibiotics (beta-lactams) and antipyretic analgesics (APAs) and investigated the pathogenic mechanism of hypersensitivity to these drugs.
Methods: The LMT was performed according to an improved version of the agarose plate method and CXCL8 levels in the reacted solution that had been stored as described were measured using a solid-phase sandwich enzyme-linked immunosorbent assay.
Results: Migration index (MI) values for the LMT were 77.7 ± 11.7 for patients with hypersensitivity to beta-lactams and 83.6 ± 1.9 for those with hypersensitivity to APAs. The CXCL8 concentrations were significantly higher in patients after beta-lactams administration (175.9 ± 71.2ng/mL) than those without beta-lactams administration (48.3 ± 34.9ng/mL). The CXCL8 concentrations were significantly lower in patients after APAs administration (41.7 ± 24.3ng/mL) than those without APAs administration (63.1 ± 30.2ng/mL).
Conclusions: Increased CXCL8 levels produced by beta-lactams administration were accompanied by LMIA. CXCL8 may be involved in LMIA and play a role in beta-lactam allergies. In contrast, the LMIA detected in patients with allergies to APAs may be a cytokine or chemokine other than CXCL8.

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Background: Generalized vitiligo is an acquired disorder in which depigmented macules result from the autoimmune loss of melanocytes from the involved regions of skin. Generalized vitiligo is frequently associated with other autoimmune diseases, particularly autoimmune thyroid diseases (Hashimoto's thyroiditis and Graves' disease), rheumatoid arthritis, adult-onset type 1 diabetes mellitus, psoriasis, pernicious anemia, systemic lupus erythematosus, and Addison's disease.
Methods: One hundred and thirty-three Japanese patients with generalized vitiligo were enrolled in this study to investigate the occurrence of autoimmune diseases in Japanese patients with generalized vitiligo and their families.
Results: Twenty-seven of the patients with generalized vitiligo (20.3%) had autoimmune diseases, particularly autoimmune thyroid disease (sixteen patients, 12%) and alopecia areata (seven patients, 5.3%). Thirty-five patients (26.3%) had a family history of generalized vitiligo and/or other autoimmune diseases. Familial generalized vitiligo was present in fifteen (11.3%), including four families with members affected by autoimmune disorders. Twenty (15.0%) had one or more family members with only autoimmune disorders.
Conclusions: Among Japanese vitiligo patients, there is a subgroup with strong evidence of genetically determined susceptibility to not only vitiligo, but also to autoimmune thyroid disease and other autoimmune disorders.

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Background: The International Study of Asthma and Allergies in Childhood (ISAAC) has reported the prevalence of asthma and allergic diseases in many countries.
Methods: We used the ISAAC core written questionnaire to examine the prevalence of asthma and allergic diseases in 6- to 14-year old schoolchildren in Tokyo. In 2005, we conducted a cross-sectional survey of all schoolchildren in all public schools located in the Setagaya area of Tokyo.
Results: Data were collected from 27,196 children in 95 schools. Prevalence ranged from 10.5% to 18.2% for asthma symptoms and from 10.9% to 19.6% for atopic dermatitis, with both conditions tending to decrease with age. As has been previously reported for all age groups, significantly higher rates of current asthma are observed in boys than in girls. The prevalence of allergic rhinoconjunctivitis exhibited a different pattern from that of asthma and atopic dermatitis, peaking at the age of 10 (34.8%). Prevalence of allergic rhinoconjunctivitis was 1.5 to 2-fold higher than the previous ISAAC studies that were performed in Tochigi and Fukuoka. In all age groups, symptoms of allergic conjunctivitis were more frequent from February to May, which coincides with the Japanese cedar pollen season, and were less frequent between June to September.
Conclusions: The prevalence of asthma and atopic dermatitis was higher in younger schoolchildren. Tokyo schoolchildren appear to have extremely high prevalence rates of seasonal allergic rhinoconjunctivitis.

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Background: East Asian desert dust storms that occur during mainly spring are called Asian dust storms (ADS). Our objective was to study the association of pollen and ADS with symptoms of adult asthma patients in Japan.
Methods: We designed a telephone survey to investigate the upper and lower respiratory, ocular, and skin symptoms of asthma patients during ADS in February, March, and December on 2009. Peak expiratory flow (PEF) was also measured from February to May.
Results: We surveyed 106 patients in February, 101 patients in March, and 103 patients in December. In February and March, Japanese cedar and/or cypress pollen was also in the atmosphere during ADS, but no pollen was identified during December survey. Worsening of upper or lower respiratory, ocular, or skin symptoms was noted by 20.8% of patients in February, 33.7% in March, and 16.5% in December. Worsening of symptoms was significantly more common in March than in February or December. Two patients needed emergency treatment for exacerbation during ADS in March, but no patient needed hospitalization in any period. There was no significant difference of the daily morning PEF/personal best PEF ratio between ADS days and control days. However, in patients with worsening of upper and/or lower respiratory tract symptoms, the daily morning PEF/personal best ratio was significantly associated with the atmospheric level of particulate matter, but not with levels of pollen or other air pollutants.
Conclusions: Pollen augmented symptoms in adult asthma patients, but ADS on its own also were able to aggravate symptoms and pulmonary function.

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Background: Stevens-Johnson syndrome (SJS) associated with Mycoplasma pneumoniae (M. pneumoniae) infection is mainly observed in children. In adults, drugs are a major cause of SJS, but some adult patients with SJS are infected with M. pneumoniae. We analyzed patients with SJS associated with M. pneumoniae infection to elucidate the differences between drug-induced SJS and M. pneumoniae-associated SJS and also to study differences between M. pneumoniae-associated SJS in children and adults.
Methods: This is a retrospective review of Japanese patients who have been reported as M. pneumoniae-associated SJS in medical Journals published from 1981 to 2009, compared with data of Japanese patients with drug-induced SJS reported from 2000 to 2009.
Results: Thirty-eight cases of M. pneumoniae-associated SJS and 78 cases of drug-induced SJS were analyzed in this study. Ocular lesions were observed more frequently in M. pneumoniae-associated SJS than in drug-induced SJS (p < 0.01), and adult patients showed a higher ratio of sequelae in their eyes than did patients under 20 years of age (p < 0.01). Sixty-six percent of adult patients with M. pneumoniae-associated SJS developed fever/respiratory symptoms and mucocutaneous lesions on the same day. In contrast, most of the patients under 20 years of age developed fever/respiratory symptoms before mucocutaneous involvement. This means that these adult patients were infected and immunized previously and developed allergic reactions to M. pneumoniae soon after the later infection.
Conclusions: In order to prevent ocular sequelae in adult patients when M. pneumoniae infection is suspected, more intensive treatment may be needed in adult patients than in younger patients.

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Background: We previously built a pollen challenge test unit (allergen challenge chamber: ACC) to collect objective data about Japanese cedar pollinosis. In this study, we investigated adequate conditions for pollen challenge using the ACC.
Methods: The study consisted of two parts. The first part was conducted in November, which is not in pollen season. Subjects were exposed to Japanese cedar pollen at a concentration of 50,000grains/m³ in the chamber for 120 min each day over the course of three consecutive days. The second part was conducted in April, which is just after pollen season. Subjects were exposed to Japanese cedar pollen at the same concentration (50,000grains/m³) in the chamber for 90 min on a single day. Subjects recorded nasal and ocular symptoms before challenge and every 15 min after challenge initiation. The minimum cross-sectional area in the nasal cavity was measured using acoustic rhinometry before and after challenge as an indicator of nasal obstruction. Inflammatory markers in nasal lavage fluid and serum were also measured before and after challenge.
Results: Nasal and ocular symptoms were significantly exacerbated after challenge on all days of the single and 3-consecutive-day challenge tests, particularly on the third day of the consecutive challenge test. Nasal and ocular symptoms were also quickly induced with challenge immediately after the end of pollen season. No significant changes in inflammatory markers were seen.
Conclusions: Care is needed with regard to pollen challenge conditions in the ACC, including timing of the challenge, to induce pollinosis symptoms that accurately reflect chronic inflammation.

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Background: Oral antihistamines are considered the gold standard therapy for allergic rhinitis to date. The goal of this investigation is to make an indirect comparison between loratadine, an oral antihistamine available over-the-counter (OTC) in the USA, and the more modern antihistamine levocetirizine. Only double-blind, placebo-controlled (DBPC) studies involving monotherapy with the active substances levocetirizine and loratadine were included in the meta-analysis.
Methods: The medical databases EMBASE and Medline were searched systematically for all relevant studies completed by the end of 2009. Only DBPC studies conducted in normal environmental settings were included. Furthermore, the Jadad scale was used to guarantee the quality of the studies involved. The "standardized mean difference" (SMD) method was applied for calculating the study-specific effects to neutralize the variability between studies.
Results: The results of a total of seven published DBPC studies met all criteria for inclusion in meta-analysis. The meta-analysis showed that levocetirizine was significantly more effective than loratadine in improving the total symptom score (TSS)(p < 0.01). The effect sizes were calculated as -0.59 (95% confidence interval -0.89, -0.29) for levocetirizine and -0.21 (95% confidence interval -0.31, -0.1) for loratadine when compared to placebo.
Conclusions: The results of this meta-analysis illustrate greater effectiveness for treatment with the active substance levocetirizine as monotherapy in reducing allergic symptoms when compared to treatment with loratadine.

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Background: Dermographic urticaria (DU) is characterized by strong itch and wheals induced by mechanical scratching. H₁-receptor antagonists may reduce symptoms of DU to some extent, but other treatments being used for chronic spontaneous urticaria, such as H₂-receptor antagonists and corticosteroids, are not usually effective for DU.
Case Summary: We here report six cases of antihistamine-resistant DU treated with oral ciclosporin. Four cases suffering from severe itches that spontaneously occurred before the appearance of wheals in response to scratching were substantially improved by use of ciclosporin for 21, 16, 32, and 8 months, and one of them reached complete remission. Two cases did not obtain a benefit from the treatment, because of insufficient effects and/or side effects.
Discussion: Oral ciclosporin may be of value as a potential treatment of anti-histamine-resistant DU.

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Background: Eosinophilic pneumonia comprises a group of lung diseases in which eosinophils appear in increased numbers in the lungs. The distinct etiology of eosinophilic pneumonia is unknown, although the previous case series have indicated a relationship between acute eosinophilic pneumonia and the exposure to exogenous substances including the constituents of cigarettes.
Case Summary: A 60-year-old nonsmoking female, who had started to harvest and sort tobacco leaves two months before presentation, was admitted because of persistent coughing, breathlessness, and general malaise. Her laboratory findings revealed eosinophilia. Chest computed tomography showed nonsegmental airspace consolidations bilaterally. A bronchoalveolar lavage fluid analysis also revealed that the numbers of total cells and eosinophils had increased. Although the urine level of cotinine was within the normal range, positive findings were found in the skin scratch-patch tests using tobacco leaf and its extracts, and a biopsy specimen obtained from the positive site demonstrated infiltration of eosinophils in the dermis. The patient was successfully treated with corticosteroids.
Discussion: Green tobacco sickness, a type of nicotine poisoning caused by the dermal absorption of nicotine, is a well known occupational illness of tobacco harvesters. Although it is unclear whether the present case could be identified as a subtype of green tobacco sickness, this is the first report of eosinophilic pneumonia occurred in a tobacco harvester which was possibly induced by tobacco leaf exposure.

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Trimebutine maleate [2-dimethylamino-2-phenylbutyl 3,4,5-trimethoxybenzoic acid] has been demonstrated to be active for relieving abdominal pain and it is widely used for patients with irritable bowel syndrome. Adverse drug reactions are mostly mild and well-tolerated. To our knowledge, only two cases of trimebutine induced hypersensitivity have been reported, and both were delayed type reactions. Here, we report the first case of trimebutine maleate-induced anaphylaxis.

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