Cell Penetrating Peptide Derived from Human Eosinophil Cationic Protein Decreases Airway Allergic Inflammation.

Cell penetrating peptide derived from human eosinophil cationic protein (CPPecp) is a 10-amino-acid peptide containing a core heparan sulfate (HS)-binding motif of human eosinophil cationic protein (ECP). It binds and penetrates bronchial epithelial cells without cytotoxic effects. Here we investigated airway-protective effects of CPPecp in BEAS-2B cell line and mite-induced airway allergic inflammation in BALB/c mice. In BEAS-2B cell, CPPecp decreases ECP-induced eotaxin mRNA expression. CPPecp also decreases eotaxin secretion and p-STAT6 activation induced by ECP, as well as by IL-4. In vivo studies showed CPPecp decreased mite-induced airway inflammation in terms of eosinophil and neutrophil count in broncho-alveolar lavage fluid, peri-bronchiolar and alveolar pathology scores, cytokine production in lung protein extract including interleukin (IL)-5, IL-13, IL-17A/F, eotaxin; and pause enhancement from methacholine stimulation. CPPecp treated groups also showed lower serum mite-specific IgE level. In this study, we have demonstrated the in vitro and in vivo anti-asthma effects of CPPecp.

Systemic lupus erythematosus and thyroid disease: A 10-year study.

BACKGROUND: This large-scale study aims to analyze the association of systemic lupus erythematosus (SLE) with thyroid diseases. METHODS: In this retrospective, nationwide cohort study, 1633 newly diagnosed SLE patients from the National Health Insurance Research Database in 2000 were examined and data on patients with diagnoses of hyperthyroidism, hypothyroidism, and autoimmune thyroiditis were collected from 2000 to 2009. We subdivided these SLE patients by the presence of overlap syndrome. Comparison with 6532 age- and sex-matched controls was performed. RESULTS: The cumulative incidence of thyroid disease in SLE patients was lower than in controls (8.1% vs. 16.9%, p < 0.001). Among SLE patients, 39.7% had overlap syndrome. The overlap syndrome group had a higher cumulative incidence of thyroid diseases (10.96% vs. 4.57%, p < 0.0001), hypothyroidism (3.86% vs. 1.93%, p = 0.017), and autoimmune thyroiditis (4.63% vs. 0.71%, p < 0.0001) than SLE patients without overlap syndrome. Comparing the data with the non-SLE-matched control group by logistic regression model revealed a decreased risk of thyroid diseases with odds ratios (ORs) of 0.25 and 0.62 [95% confidence interval (CI) 0.18-0.33, 0.48-0.80], and hyperthyroidism with ORs of 0.21 and 0.30 (95% CI 0.14-0.31, 0.20-0.45) in SLE patients without and with overlap syndrome. SLE patients without overlap syndrome had a lower risk of hypothyroidism with an OR of 0.53 (95% CI 0.53-0.86) and autoimmune thyroiditis with an OR of 0.26 (95% CI 0.12-0.56). SLE patients with overlap syndrome showed a similar risk of hypothyroidism with an OR of 0.92 (95% CI 0.66-1.53) and a higher risk of autoimmune thyroiditis with OR of 1.69 (95% CI 1.14-2.51). CONCLUSION: SLE patients had a significantly lower rate of thyroid diseases and hyperthyroidism than matched controls. Among SLE patients, risks of hypothyroidism and autoimmune thyroiditis were different in the presence of overlap syndrome. This finding is novel and important for clinical practices.

Low-molecular-weight heparin and unfractionated heparin decrease Th-1, 2, and 17 expressions.

BACKGROUND: We evaluated the effects of T helper cell differentiation in a mite-allergic animal model treated with inhaled heparins of different molecular weight. METHOD: BALB/c mice were divided into four groups: 1. Control, 2. Mite intratracheal (mIT), 3. Inhaled heparin (hIN), 4. Inhaled low-molecular-weight heparin (lmwhIN). Groups 2, 3, and 4 were sensitized twice with Der p allergen subcutaneously on day 1 and day 8. Der p allergen was administered intratracheally on day 15. Groups 3 and 4 were treated with heparin or low-molecular-weight (lmw) heparin intranasally from day 1 to 22. Splenocytes from sacrificed mice stimulated with 16 µg/ml of Der p were cultured for 72 hours. Supernatants of splenocyte were collected to analyze the effect of Interleukin (IL)17-A/F, Interferon(IFN)-γ, IL-4, IL-13, and IL-10. Serum was also collected for Der P-specific IgE level on day 23. Total RNA was extracted from spleen tissue for mRNA expression. Gene expression of Foxp3, IL-10 IFN-γ, GATA3, IL-5, and RORγt were analyzed. RESULTS: Both hIN and lmwhIN groups had lower serum IgE level than that of the mIT group (both p<0.0001). Both hIN and lmwhIN groups showed significantly decreased transcripts of GATA-3, IFN-γ, IL-5, and RORγt mRNA in their spleen. Regarding the supernatant of splenocyte culture stimulated with Der p, compared with the mIT group, there were significant decreases in IL-17A/F, IFN-γ, IL-4, IL-13, and IL-10 secretion in inhaled hIN and lmwhIN groups. CONCLUSIONS: From this balb/c mice study, the analyses of mRNA and cytokines revealed that both intranasal heparin and lmw heparin treatment decreased the expression of Th1, Th2, and Th17 in spleen. The underlying mechanism(s) warrant further studies.

Evaluation of the effect of Lactobacillus paracasei (HF.A00232) in children (6-13 years old) with perennial allergic rhinitis: a 12-week, double-blind, randomized, placebo-controlled study.

INTRODUCTION: Dietary supplementation with probiotics alters intestinal microflora of children and may have immunomodulatory effects in prevention of allergic diseases. The aim of this study was to evaluate the effects of Lactobacillus paracasei (LP), strain HF.A00232, as a supplementary agent to levocetirizine in treating children with perennial allergic rhinitis (AR). METHODS: This study was a 12-week, double-blind, randomized, placebo-controlled trial. Sixty children with AR aged 6-13 years with nasal total symptoms score (NTSS) ≥5 who fulfilled the inclusion criteria were enrolled. Patients were randomized into two groups with 28 participants receiving levocetirizine plus placebo and 32 participants receiving regular levocetirizine plus LP (HF.A00232) for the first 8 weeks, with a shift to levocetirizine as rescue treatment during the following 4 weeks. Parameters evaluated, including nasal, throat, and eye TSS (NTSS, TTSS, and ETSS, respectively), TSS and levocetirizine use, were recorded daily. Physical examinations and Pediatric Rhinoconjunctivitis Quality of Life Questionnaires (PRQLQs) were administered at each visit. In addition, blood samples were obtained for evaluation of cytokines including interleukin-4, interferon-γ, interleukin-10, and transforming growth factor-ß at baseline, Week 8, and Week 12. RESULTS: The LP (HF.A00232) group had significantly lower PRQLQ scores even after discontinuing regular levocetirizine from Week 9 to Week 12 (p < 0.01). There was more improvement in individual parameters in the PRQLQ, including sneezing (p = 0.005), itchy nose (p = 0.040), and swollen puffy eyes (p = 0.038), in the LP (HF.A00232) group. No significant differences in TSS, NTSS, TTSS, ETSS, or cytokine levels were found between the two groups. CONCLUSION: Dietary supplementation with LP (HF.A00232) provided no additional benefit when used with regular levocetirizine in treating AR in the initial 8 weeks of our study, but there was a continuing decrease in PRQLQ scores, as well as a significant improvement in individual symptoms of sneezing, itchy nose, and swollen eyes, after discontinuing regular levocetirizine treatment.

The natural course of eczema from birth to age 7 years and the association with asthma and allergic rhinitis: a population-based birth cohort study.

Although "atopic march" is a popular concept, the relationship between eczema and subsequent asthma is far from clear. However, some cohort studies have shown the possibility of two different allergic phenotypes in those who present with early eczema in terms of their persistency. We checked the cohort data from 308,849 children born in 2000 in Taiwan, to evaluate the different courses of eczema and their relationships to subsequent asthma and allergic rhinitis (AR) at age 7 years. We examined the age prevalence of eczema, asthma, and AR up to 7 years of age. We grouped all cases according to their course of eczema, as well as wheezing, and determined the rates of asthma and AR at age 7 years. We checked the adjusted risk factors by multiple logistic regression model. We also examined the distributions of wheezing types in different eczema groups. We found the "atopic march" pattern of allergic diseases based on their age prevalence. Early eczema was associated with asthma and AR at the age of 7 years. Those with eczema symptoms persisting after 36 months of age had a higher risk than those with transient eczema. Early wheeze also contributed to asthma and AR later in childhood. In addition, late-onset eczema had a completely different wheeze distribution compared with other groups and also had a higher risk for asthma and AR than transient eczema. In conclusion, different eczema phenotypes could be found in this population-based cohort. This article emphasizes the special attention to the persistency and late-onset eczema in clinical practice.

Macrohematuria as initial presentation in a girl with factor VIII and factor IX inhibitors associated with systemic lupus erythematosus.

Acquired hemophilia is rarely observed in a pediatric population. We report a case of a 14-year-old girl presented with ecchymoses and macrohematuria. She developed factor VIII and factor IX inhibitors, and was diagnosed with simultaneous acquired hemophilia and systemic lupus erythematosus (SLE). Recombinant-activated FVII and corticosteroid were prescribed due to macrohematuria-related hypovolemia and anemia, which resolved satisfactorily. This case is a reminder that the rare concurrent presence of factor VIII and factor IX inhibitors could be associated with SLE in a pediatric population. Children with SLE-associated-acquired hemophilia may develop macrohematuria as well.

Prevalence of attention-deficit/hyperactivity disorder in patients with pediatric allergic disorders: a nationwide, population-based study.

BACKGROUND: Allergic disorders are common, chronic conditions in pediatric populations. The characteristic symptoms of allergic disorders mainly include bronchial asthma (BA), allergic rhinitis (AR), and atopic dermatitis (AD), all of which may disturb sleep, leading to daytime inattention, irritability, and hyperactivity, which are also components of attention-deficit/hyperactivity disorder (ADHD). Conflicting data exist in the literature regarding the relationship between ADHD and allergic disorders. The aim of this nationwide, population-based study is to examine the prevalence and risk of developing ADHD among allergic patients in a pediatric group. METHODS: Data from a total of 226,550 pediatric patients under 18 years of age were collected from Taiwan's National Health Insurance Research Database recorded from January 1 to December 31, 2005 and analyzed. We calculated the prevalence of allergic diseases based on various demographic variables, including ADHD. We also used multivariable logistic regression to analyze the risk factors of ADHD. RESULTS: In 2005, the period prevalence rates of allergic disorders and ADHD in persons under the age of 18 were 21.5% and 0.6%, respectively. Pediatric patients with allergic disorder(s) had a substantially increased rate of developing ADHD (p < 0.001) in terms of period prevalence and odds ratio (OR). This significance existed across various demographic groups regardless of age, gender, location, or degree of urbanization of their residence. BA and AR, but not AD, were determined to be risk factors for ADHD. Co-morbidities of allergic disorders, including AR+AD, AR+BA and AR+BA+AD, but not BA+AD, were also determined to increase the risk of ADHD. CONCLUSION: Allergic disorders appear to increase the risk of ADHD in pediatric patients. Our detailed analysis shows that the main contributing factor is AR. Co-morbidity with AD, BA, and BA+AD in AR patients further increases the risk of ADHD.

Treatment with propranolol for infantile hemangioma in 13 Taiwanese newborns and young infants.

BACKGROUND: Hemangioma in infants has a benign self-limited course, but the 10% of cases with complications need further treatment. Successful treatment with propranolol in western countries has been reported over the past few years. We evaluated the efficacy of propranolol for treating infantile hemangioma in Taiwanese newborns and young infants. METHODS: Patients below 1 year of age treated with propanolol between November 2009 and March 2011 were enrolled. Demographic data, clinical features, imaging findings, treatment regimens of propranolol, and outcome were investigated. RESULTS: Thirteen patients were treated with propranolol at a dose of 2-3 mg/kg/day. Seven (53.8%) patients had solitary hemangioma and six had multiple ones. The indications for treatment were risk of local event in nine patients, functional risk in four, local complication in one, and life-threatening complication in one. The median age for starting propranolol was 4 months (range: 1-11 months). Responses to propranolol, such as decolorization, regression in tumor size, or improvement of hemangioma-associated complications were observed in all patients within 1-2 weeks after treatment. Propranolol-associated adverse effects occurred in two patients. One infant had occasional tachypnea, and the other had occasional pale-looking appearance. The symptoms resolved after dosage tapering. CONCLUSION: Propranolol may be a promising therapeutic modality for infantile hemangioma. Therapeutic strategies are needed to evaluate the optimal treatment protocol and long-term adverse effects.

Juvenile diffuse systemic sclerosis/systemic lupus erythematosus overlap syndrome--a case report.

We report a rare case of diffuse systemic sclerosis (SSc) evolving into diffuse SSc/systemic lupus erythematosus (SLE) overlap syndrome. A 15-year-old boy was diagnosed as diffuse SSc with initial presentations of Raynaud's phenomenon and skin tightening. He underwent Chinese herbal treatment and clinical symptoms deteriorated in the following 3 years. On admission to our ward, serositis with pleural effusion, severe pulmonary fibrosis with moderate pulmonary hypertension, swallowing difficulty, and polyarthritis were observed. Autoantibody profiles revealed concurrence of anti-double-stranded DNA, anti-Smith, anti-topoisomerase I, and anti-ribonucleoprotein antibodies. The patient fulfills the criteria for both diffuse SSc and SLE. After drainage for pleural effusion accompanied by oral prednisolone and sildenafil, there were improvement of respiratory distress, swallowing difficulty, and pulmonary hypertension. In conclusion, connective tissue diseases may overlap with each other during the disease course. Serial follow-up for clinical symptoms as well as serological changes is recommended.

Reduced expression of transforming growth factor-ß1 and correlated elevation of interleukin-17 and interferon-γ in pediatric patients with chronic primary immune thrombocytopenia (ITP).

BACKGROUND: Dysregulated T helper (Th) cells are considered important in the pathophysiology of chronic primary immune thrombocytopenia (ITP). The present study investigated whether levels of Th cytokines in pediatric patients with chronic ITP were different compared with healthy controls. PROCEDURES: Fifty-seven pediatric patients with chronic ITP and 28 healthy controls were enrolled. Patients were divided into three groups based on their platelet counts at the time of the study: (i) active disease <50 × 10(9) /l (n = 23), (ii) stable disease 50-150 × 10(9) /l (n = 23), and (iii) in remission >150 × 10(9) /l (n = 11). Plasma concentration of Th1 [interferon gamma (INF-γ), interleukin 2 (IL-2)], Th2 (IL-4, IL-10), Th3 [transforming growth factor-ß1 (TGF-ß1)], and Th17 (IL-17) cytokines were investigated by enzyme-linked immunosorbent assay. RESULTS: IFN-γ was increased in patients with active (P < 0.001) and stable disease (P = 0.026) when compared with controls. The IL-17 level was significantly higher in all of the 3 patient groups. In addition, there was a positive correlation between IL-17 and IFN-γ levels in chronic ITP patients (r = 0.640, P < 0.001). Reduced TGF-ß1 expression was observed in patients with active (P < 0.001) and stable disease (P = 0.001) in comparison with controls. Moreover, TGF-ß1 level in patients was positively correlated with the platelet count (r = 0.355, P = 0.007). CONCLUSIONS: Elevation of IL-17 and IFN-γ may be an important dysregulation of cellular immunity in pediatric patients with chronic ITP. The disease activity is associated with reduced production of TGF-ß1.

Are empiric antibiotics for acute exudative tonsillitis needed in children?

BACKGROUND: Empiric antibiotics are frequently given for children with acute exudative tonsillitis. A few studies have investigated the causative agent of acute "exudative" tonsillitis in children to evaluate the necessity of antibiotic therapy. This study tried to explore the common causative agent of acute exudative tonsillitis among children. METHODS: From April 2009 to March 2010, throat swabs were obtained and cultured for viruses and bacteria from children who visited the pediatric emergency rooms of two medical centers in central Taiwan with acute exudative tonsillitis. Demographic data and microbiological results were analyzed. RESULTS: A total of 294 children with acute exudative tonsillitis were enrolled during the 1-year prospective study, and 173 (58.8%) of them were younger than 7 years. Group A streptococci were isolated from only three (1.0%) children, and they were all older than 6 years. A total of 143 viruses were isolated from 140 (47.6%) children. Adenovirus (18.7%) and enterovirus (16.3%) were the most common viral etiologies, followed by influenza virus (5.4%), parainfluenza virus (5.1%), herpes simplex virus Type 1 (2.7%), and respiratory syncytial virus (0.3%). Group A streptococcus only contributed to a minimal portion of acute exudative tonsillitis. CONCLUSION: Routine or immediate antibiotic therapy for acute exudative tonsillitis in children is not necessary.

Sodium sulfite aggravated allergic sensitization and airway inflammation in mite allergen sensitized BALB/c mice.

Sulfur dioxide is a typical air pollutant. Sulfite, which is formed at the bronchial mucosa from inhaled sulfur dioxide, might play a role in the exacerbation of asthma. In this study, we investigated the effects of sodium sulfite and its interaction with a house dust mite (Dermatophagoides pteronyssinus, Der p) on allergic sensitization and airway inflammation. BALB/c mice were divided into four groups: control (n = 10), mite intranasal (mIN, n = 12), sodium sulfite intranasal (sIN, n = 12) and mIN + sIN (n = 12). In non-control groups, the mice were sensitized on day 8 and day 15 with mite allergen subcutaneously. Mite allergen was then administrated intranasally from day 15 to day 22 in mIN and mIN+sIN groups. Sodium sulfite was administrated in sIN and mIN + sIN groups intranasally from day 1 to day 22. Plasma Der p-specific IgE, IgG2a, lung histopathology and cytokine levels (IL-5 and IFN-γ) were analyzed. In comparison between mIN (or sIN) and mIN + sIN group, Der p-specific IgE levels were significantly higher in mIN + sIN group (p < 0.01). Besides, Der p-specific IgG2a level was significantly lower in mIN + sIN group than mIN (or sIN) group (p < 0.01). The peribronchiolar, alveolar and total inflammatory scores were increased in the mIN + sIN group comparing with the control group (p < 0.05, p < 0.01, p < 0.01, respectively). Lung supernatant in mIN + sIN group has higher IL-5/IFN-γ ratio than control, mIN or sIN group (all p < 0.05). Our study concluded sodium sulfite may enhance allergic sensitization as well as airway inflammation in mite allergen sensitized BALB/c mice.

Recurrent hemarthrosis in a boy with synovial hemangioma: a case report.

We describe an unusual case of hemarthrosis caused by a synovial hemangioma in an 11-year-old boy. The initial presentations were sudden onset of spontaneous knee swelling and painful sensation accompanied by limitation of joint movement. The patient had a history of recurrent swelling with spontaneous remission over the same location in the past year. In addition, diffuse cutaneous hemangioma since infancy was also noted. Synovial involvement of a cutaneous hemangioma was confirmed by multidetector computed tomography and arthroscopy. The patient was started on oral corticosteroid and ß-blocker. No recurrence was noted on multidetector computed tomographic images or clinical examination at the 2-month follow-up.

Prevalence of attention deficit/hyperactivity disorder in pediatric allergic rhinitis: a nationwide population-based study.

Allergic rhinitis (AR) is the most common chronic condition in pediatric populations. Characteristic symptoms in AR may bother daily activities and disturb sleep, leading to daytime inattention, irritability, and hyperactivity, which are also components of attention deficit/hyperactivity disorder (ADHD). Conflicting data exist in the literature regarding the relationship between ADHD and AR. The aim of this nationwide population-based study was to examine the prevalence and risk of ADHD among AR patients in a pediatric group. Data from a total of 226,550 pediatric patients <18 years old were collected from Taiwan's National Health Insurance Research Database from January 1 to December 31, 2005 and analyzed. We calculated the prevalence of allergic diseases based on various demographic variables, as well as in ADHD patients. We also used multivariable logistic regression to analyze the risk factors of ADHD. In 2005, the period prevalence rates of atopy and ADHD in patients <18 years of age were 15.35 and 0.6%, respectively. Pediatric patients with AR had a substantially increased rate of ADHD (p < 0.001) in terms of period prevalence and odds ratio. This significance existed across various demographic groups regardless of age, gender, area, or degree of urbanization. Neither comorbidity of atopic dermatitis nor bronchial asthma carried high risk for ADHD in AR patients. The present study revealed an increased rate of ADHD among AR patients. Therefore, evaluation of ADHD is advised for treatment of AR children.

Concurrence of Incontinentia Pigmenti and Behçet's Disease.

We report here a rare case of incontinentia pigmenti (IP) in a 10-year-old girl who developed Behçet's disease. IP was diagnosed in infancy and Behçet's disease was diagnosed at 10 years of age. The initial presentations of Behçet's disease were spiking fever and recurrent painful oral and genital ulcers that were refractory to antibiotics. After corticosteroid treatment, her fever subsided and ulcers subsequently healed. The patient's mother and sister were also diagnosed with IP. Her mother had suffered from Behçet's disease since her teenage years and it was complicated with colon perforation. Although there are several reports on the combination of IP and Behçet's disease, this is the first reported case of a family with such concurrence.