Clinical practice guideline for diagnosis and management of urticaria.

Urticaria is a common skin condition that can compromise quality of life and may affect individual performance at work or school. Remission is common in majority of patients with acute spontaneous urticaria (ASU); however, in chronic cases, less than 50% had remission. Angioedema either alone or with urticaria is associated with a much lower remission rate. Proper investigation and treatment is thus required. This guideline, a joint development of the Dermatological Society of Thailand, the Allergy, Asthma, and Immunology Association of Thailand and the Pediatric Dermatological Society of Thailand, is graded and recommended based on published evidence and expert opinion. With simple algorithms, it is aimed to help guiding both adult and pediatric physicians to better managing patients who have urticaria with/without angioedema. Like other recent guideline, urticaria is classified into spontaneous versus inducible types. Patients present with angioedema or angioedema alone, drug association should be excluded, acetyl esterase inhibitors (ACEIs) and non-steroidal anti-inflammatory drugs (NSAIDs) in particular. Routine laboratory investigation is not cost-effective in chronic spontaneous urticaria (CSU), unless patients have clinical suggesting autoimmune diseases. Non-sedating H1-antihistamine is the first-line treatment for 2-4 weeks; if urticaria was not controlled, increasing the dose up to 4 times is recommended. Sedating first-generation antihistamines have not been proven more advantage than non-sedating antihistamines. The only strong evidence-based alternative regimen for CSU is an anti-IgE: omalizumab; due to very high cost it however might not be accessible in low-middle income countries. Non-pharmacotherapeutic means to minimize hyper-responsive skin are also important and recommended, such as prevention skin from drying, avoidance of hot shower, scrubbing, and excessive sun exposure.

Effects of inactivated influenza vaccine on respiratory illnesses and asthma-related events in children with mild persistent asthma in Asia.

BACKGROUND: Acute asthmatic exacerbation and readmission may be associated with severe influenza infection and asthmatic children are a priority group for influenza vaccination. To date, our study is the first to evaluate the outcome of the influenza vaccine in asthmatic Asian children. OBJECTIVE: To analyze the outcomes of inactivated influenza vaccine in children with mild persistent asthma METHODS: A cross sectional non-randomized study was performed on 93 mild persistent asthmatic children who attended the Pediatric Allergy clinic between June 2012 in Chiang Rai Hospital and August 2013. Forty eight patients were immunized with 2 doses of inactivated influenza vaccine at one month interval. Respiratory illnesses and asthma-related events were compared between the immunized and the un-immunized groups. RESULTS: The two study groups had similar demographic and clinical characteristic except with regards to eczema, including asthma controllers and skin prick testing results. One year after the vaccine was administered, the immunized group had significantly reduced acute respiratory tract illnesses, asthma exacerbations, ER visits, bronchodilator usage and systemic steroid administrations. Hospitalizations (p < 0.001) and their duration (p < 0.034) were also reduced in the immunized group. CONCLUSIONS: Immunization of inactivated influenza vaccine in children with mild persistent asthma decreased respiratory illnesses and asthma-related events.

Dust mite infestation in cooking flour: experimental observations and practical recommendations.

BACKGROUND: The first documented case of oral mite anaphylaxis has recently been reported in Thailand, with mites possibly originating from cooking flour. OBJECTIVE: Our study was designed to assess the effects of cooking flours enhancement and storage conditions on mite proliferation and to provide practical recommendations to prevent mite anaphylaxis. METHODS: In a factorial experiment, six commercial brands of cooking flours were selected and either inoculated or set free of mites and stored in one of the four containers chosen for the study: original package, plastic bag, plastic box and glass bottle. The resulting experimental units where then stored at either room temperature or in a refrigerator (+4C). In order to determine levels of Der f 1 allergen, 0.1 gram of flour was sampled from each experimental unit and tested by ELISA. Sampling was carried out immediately after inoculation and subsequently at week 2, 4, 6, 8, 10, 12, 16 and 20. RESULTS: Levels of Der f 1 allergen in the inoculated samples increased significantly in all conditions 6 weeks after inoculation (p <0.001) and reached the highest levels at week 8. While experimental units left at room temperature showed higher levels of mite growth (p <0.001), no statistical differences were found among types of containers. The highest amount of Der f 1 was observed for Gogi, followed by Gold Label, tempura flour, corn flour, wheat flour and tapioca starch, respectively (p <0.01). CONCLUSIONS: In the context of our experiment, mites preferably grew in cooking flours containing high amounts of wheat at room temperature, particularly after 8 week of storage. According to our results, we thus advise to keep household cooking flour refrigerated and while the type of container does not matter, storage should not exceed 20 weeks.

Component-resolved diagnostics for the evaluation of peanut allergy in a low-prevalence area.

BACKGROUND: Major allergenic components of peanut from distinct geographical regions are widely dispersed. Most of the diagnostic studies are from countries with a high prevalence. There have been only few reports of allergen component sensitizations from countries with a low prevalence of peanut allergy. We aimed to investigate roles of component-resolved diagnostic (CRD) to differentiate peanut allergy and peanut tolerance in the Asian population from a country with low prevalence of peanut allergy. METHODS: Participants with peanut sensitization were enrolled. Clinical reactions were determined. Skin prick test (SPT) and specific IgE (sIgE) to peanut and related allergen components were performed. RESULTS: Forty subjects with peanut sensitization were included. The mean wheal sizes of SPT and peanut sIgE were not good predictors for differentiating peanut reactions. SIgE to rAra h 2 was more often found in patients with peanut allergy and anaphylaxis. sIgE to rAra h 9 was also more frequent in the peanut-allergic group but not related to severe reactions. In the peanut-tolerant group, despite positive SPT and/or sIgE to peanut, 90% had negative sIgE to rAha h 2 and rAra h 9. Combining rAra h 2 and rAra h 9 resulted in high performance of the test with sensitivity, specificity, positive predictive value, and negative predictive value of 84%, 90%, 0.89, and 0.86, respectively. The ratio between rAra h 2 sIgE to peanut sIgE of 0.6 can be helpful in predicting patients who will develop severe reaction. SIgE to cross-reactive carbohydrate determinants (CCD) was exclusively found in the peanut-tolerant group (33.3% vs. 0%, p = 0.012). CONCLUSIONS: Our study identifies three allergen components: rAra h 2, rAra h 9, and CCD as important components in the diagnosis of peanut allergy in an Asian country with low prevalence. The ratio between rArah h 2 sIgE to peanut sIgE can be used for predicting patients who will develop anaphylaxis.

A population-based study of fish allergy in the Philippines, Singapore and Thailand.

BACKGROUND: Fish allergy is the third most common food allergy after milk and egg in parts of Europe, but there is little data about prevalence in South East Asia where it is an important part of regular diets. OBJECTIVE: We aimed to obtain an estimate of the population prevalence of fish allergy among older children in the Philippines, Singapore and Thailand. METHODS: The population prevalence of fish allergy in 14- to 16-year-old children in the 3 countries was evaluated using a structured written questionnaire which was distributed to students of randomly selected secondary schools. An extended questionnaire to determine convincing fish allergy on the basis of typical clinical manifestations within 2 h of ingestion was administered to those with positive responses. RESULTS: From a cohort of 25,842 students, responses were 81.1% in the Philippines (n = 11,434), 67.9% in Singapore (n = 6,498) and 80.2% (n = 2,034) in Thailand. Using criteria for convincing food allergy, fish allergy was much higher in the Philippines [2.29%, 95% confidence interval (CI) 2.02-2.56] than in Singapore (0.26%, 95% CI 0.14-0.79) and Thailand (0.29%, 95% CI 0.06-0.52). Weighted multiple logistic regression analyses showed that compared to the Philippines, prevalence rates were lower in Singapore [odds ratio (OR) 0.40, 95% CI 0.27-0.60, p < 0.0001] and Thailand (OR 0.13, 95% CI 0.05-0.33, p < 0.0001). Females were more likely to have fish allergy compared to males for all children combined (OR 1.32, 95% CI 1.11-1.58, p = 0.002). Most allergies appeared mild, as only 28% of cases sought medical consultation at the time of the reaction and 31.2% of cases reported continued exposure despite allergic symptoms. CONCLUSION: Fish allergy in late childhood is more common in the Philippines compared to Singapore and Thailand. Differences in food processing, dietary habits and other cultural practices might be important risk factors for the development of fish allergy in these populations.

International Cross-Sectional Survey among Healthcare Professionals on the Management of Cow's Milk Protein Allergy and Lactose Intolerance in Infants and Children.

Purpose: The present international survey among healthcare providers aimed to collect data on theoretical knowledge and clinical practices in the diagnosis and management of cow's milk protein allergy (CMPA) and lactose intolerance (LI) in infants. Methods: A global survey was conducted in several countries with diverse health care settings. The survey consisted of multiple-choice questions in 3 main domains: (1) understanding and clinical practices around CMPA and LI; (2) case scenarios; and (3) disease-specific knowledge and potential educational needs. Results: Responses were available from 1,663 participants. About 62% of respondents were general practitioners or general pediatricians, and the remainder were pediatric allergists/gastroenterologists (18%) or other health practitioners (20%). The survey identified knowledge gaps regarding the types of CMPA (IgE-mediated vs. non-IgE-mediated) and the clinical overlap with LI. The survey suggested diverse clinical practices regarding the use of hypoallergenic formulas, as well as misconceptions about the prebiotic benefits of lactose in extensively hydrolyzed formulas in non-breastfed infants with CMPA. Responses to the two case scenarios highlighted varying levels of awareness of the relevant clinical practice guidelines. While respondents generally felt confident in managing infants with CMPA and LI, about 80% expressed an interest for further training in this area. Conclusion: The current survey identified some knowledge gaps and regional differences in the management of infants with CMPA or LI. Local educational activities among general and pediatric healthcare providers may increase the awareness of clinical practice guidelines for the diagnosis and treatment of both conditions and help improve clinical outcomes.

Comparison of salbutamol efficacy in children--via the metered-dose inhaler (MDI) with Volumatic spacer and via the dry powder inhaler, Easyhaler, with the nebulizer--in mild to moderate asthma exacerbation: a multicenter, randomized study.

BACKGROUND: Beta(2) agonist administered via a nebulizer is the standard treatment for acute asthma exacerbation. There are some limitations for the use of nebulization. We conducted a study to determine the efficacy of salbutamol administered via the pMDI with Volumatic spacer and the Easyhaler (DPI) compared to nebulization in mild to moderate asthma exacerbations in children. METHODS: A multicenter, randomized, controlled study was conducted in children between 5 and 18 years of age who presented at an emergency or outpatient department. They were randomized to receive either 6 puffs of salbutamol via the pMDI with Volumatic spacer, or via the Easyhaler, or 0.15 mg/kg of salbutamol nebulized via oxygen (or compressed air). The primary outcome was the clinical response which was assessed using the modified Wood's asthma score. The secondary outcomes were: hospitalization, asthma revisit within 3 days, systemic corticosteroid use and adverse events. The clinical score, oxygen saturation, PR, RR, BP and adverse events were recorded at time 0 (before treatment) and 20, 40 and 60 minutes after drug administration. RESULTS: There were no statistically significant differences in the clinical response between the three groups at the 1st, 2nd or 3rd dose or for the SpO(2) or the respiratory rate while the children in the Easyhaler group had significantly less tachycardia after the 2nd dose. No significant adverse events were noted among the three groups. CONCLUSIONS: Salbutamol administered via pMDI with Volumatic spacer or DPI (Easyhaler) are as effective as salbutamol given via a nebulizer in providing effective relief of mild to moderate severity acute asthma exacerbation in children between 5 and 18 years of age.

Prevention of recurrent wheezing in young children by loratadine compared with ketotifen.

BACKGROUND: Various trials showed benefit of the prophylactic agent ketotifen in prevention of recurrent wheezing in young children, but no such clinical trial with loratadine or comparison trial is available. OBJECTIVE: To study the efficacy and safety of loratadine syrup compared with ketotifen and placebo in prevention of recurrent wheezing in young children. MATERIAL AND METHOD: Randomized double-blind placebo controlled trial on 90 recurrent wheezing children aged less than 6 years old was done. Children were randomized to receive loratadine, ketotifen syrup, or placebo with dose of 0.25 cc/kg once a day for four months. Blood biochemistry (CBC, LFT) and EKG were performed pre and post treatment period. Assessment of symptoms--wheezing and night cough including use of bronchodilators was done daily via patient diary card. Subjects were asked to do monthly visits to the clinic for physical examination. At those visits, the doctors questioned the patients about adverse event. RESULT: Of the 90 children enrolled, 12 dropped out. Thus, 27 children remained in the loratadine, 26 in the placebo, and 25 in the ketotifen group. The demographic data were comparable among the three treatment groups. It was noted that wheezing decreased significantly at 2 months in the ketotifen (p = 0.008) and at 3 months in the loratadine (p = 0.029) but not in the placebo group. Coughing at night decreased significantly at 3 months in both the loratadine (p = 0.005) and the ketotifen (p = 0.036) group. The use of bronchodilator drug was significantly decreased at 2 months in the ketotifen (p = 0.028) and placebo (p = 0.025) group, and at 3 months in the loratadine (p = 0.009) group. Only a few patients had mild adverse events in all groups. CONCLUSION: Loratadine and ketotifen are safe and effective significantly in prevention of recurrent wheezing in young children.

Cow's milk allergy in Thai children.

Cow's milk allergy (CMA) is nowadays a common problem in Thai children. We reviewed medical records of patients with CMA from the Department of Pediatrics at King Chulalongkom Memorial Hospital of the past 10 years, from 1998 to 2007. The criteria for the diagnosis of CMA included: elimination of cow's milk formula resulting in improvement of symptoms, and: recurrence of symptoms after reintroduction of cow's milk by oral challenge or by accidental ingestion. Of the 382 children with a diagnosis of CMA, 168 were girls and 214 were boys. The average age at the time of diagnosis was 14.8 months (7 days-13 years). The average duration of symptoms before diagnosis was 9.2 months. A family history of atopic diseases was found in 64.2% of the patients. All of the mothers reported an increased consumption of cow's milk during their pregnancy. The most common symptoms were respiratory (43.2%) followed by gastrointestinal (GI) (22.5%) and skin manifestations (20.1%). Less common symptoms included failure to thrive (10.9%), anemia (2.8%), delayed speech due to chronic serous otitis media (0.2%) and anaphylactic shock (0.2%). A prick skin test with cow milk extract was positive in 61.4%. Exclusively breast-fed was found in 13.2% of the patients. Successful treatment included elimination of cow's milk and milk products and substitution with soy formula in 42.5%, partial hydrolysate formula (pHF) in 35.7%, extensive hydrolysate formula (eHF) in 14.2%, and amino acid formula in 1.7%. Continued breast feeding was successful in 5.9% (with maternal restriction of cow's milk and milk products). Our study demonstrates the variety of clinical manifestations of CMA in Thai children especially respiratory symptoms which are usually overlooked.

Nonsense mutations of the CYBB gene in two Thai families with X-linked chronic granulomatous disease.

X-linked chronic granulomatous disease (X-CGD) is an immunodeficiency disorder characterized by defective intracellular killing of microorganisms due to the neutrophils' inability to generate superoxide ions. Although it is always caused by mutations in the CYBB gene, clinical and molecular characteristics vary in different ethnic backgrounds. Two unrelated Thai boys presented with severe persistent pulmonary infections at the age of two months. Their abnormal dihydrorhodamine (DHR) flow cytometry assays supported the diagnosis of X-CGD. Mutation analysis was performed by polymerase chain reaction (PCR) amplification and sequencing of the entire coding regions of CYBB. Mutations identified were confirmed by restriction enzyme analyses. PCR-sequencing of the entire coding regions of CYBB identified nonsense mutations, 271C>T (R91X) in exon 4 and 456T>A (Y152X) in exon 5, in probands of each family. Both of the patients' mothers were found to be carriers. This observation supports that CYBB is the gene responsible for X-CGD across different populations and nonsense mutations are associated with severe phenotypes.

Lactose intolerance and gastrointestinal cow's milk allergy in infants and children - common misconceptions revisited.

Lactose is the main carbohydrate in human and mammalian milk. Lactose requires enzymatic hydrolysis by lactase into D-glucose and D-galactose before it can be absorbed. Term infants express sufficient lactase to digest about one liter of breast milk daily. Physiological lactose malabsorption in infancy confers beneficial prebiotic effects, including the establishment of Bifidobacterium-rich fecal microbiota. In many populations, lactase levels decline after weaning (lactase non-persistence; LNP). LNP affects about 70% of the world's population and is the physiological basis for primary lactose intolerance (LI). Persistence of lactase beyond infancy is linked to several single nucleotide polymorphisms in the lactase gene promoter region on chromosome 2. Primary LI generally does not manifest clinically before 5 years of age. LI in young children is typically caused by underlying gut conditions, such as viral gastroenteritis, giardiasis, cow's milk enteropathy, celiac disease or Crohn's disease. Therefore, LI in childhood is mostly transient and improves with resolution of the underlying pathology. There is ongoing confusion between LI and cow's milk allergy (CMA) which still leads to misdiagnosis and inappropriate dietary management. In addition, perceived LI may cause unnecessary milk restriction and adverse nutritional outcomes. The treatment of LI involves the reduction, but not complete elimination, of lactose-containing foods. By contrast, breastfed infants with suspected CMA should undergo a trial of a strict cow's milk protein-free maternal elimination diet. If the infant is not breastfed, an extensively hydrolyzed or amino acid-based formula and strict cow's milk avoidance are the standard treatment for CMA. The majority of infants with CMA can tolerate lactose, except when an enteropathy with secondary lactase deficiency is present.

Montelukast in general pediatric practices.

Allergic diseases, e.g., allergic rhinitis, atopic dermatitis and asthma, are common problems in children. Researches on the pathogenesis of allergic diseases have led to the development of new specific antiinflammatory medications, including Montelukast, which blocks the interaction of cysteinyl leukotrienes to their receptors and resulting downstream events. Several studies have demonstrated the effect of regular Montelukast therapy on asthma, allergic rhinitis, viral-induced wheezing in bronchiolitis and chronic rhinitis symptoms. Evidence base medicine now shows that Montelukast can be used as a monotherapy in mild persistent asthma and can be an add-on drug to inhaled corticosteroid (ICS) in moderate to severe persistent asthma. Even in allergic rhinitis, Montelukast has a role in controlling rhinitis symptoms. Montelukast demonstrated a safety profile similar to placebo and more safety than ICS. Moreover Montelukast can improve quality of life in patients with asthma and comorbid allergic rhinitis.

Recurrent purpura fulminans associated with drug-resistant Streptococcus pneumoniae infection in an asplenic girl.

We report a case of purpura fulminans associated with drug-resistant Streptococcus pneumoniae that responded to ceftriaxone therapy. Ultrasonography of the abdomen and splenic scan revealed the absence of a spleen.

Peak inspiratory flow rate and the ability to use the Turbuhaler in Thai children aged 3-7 years.

A Turbuhaler is a dry powder inhaler device commonly used by asthmatic patients. Its superiority over a metered-dose inhaler device includes easy technique, convenience in handling and absence of chloro fluoro carbon (CFC). However, the use of this device has some limitations in young children who may not be able to generate the inspiratory flow rate high enough to assure adequate medication delivery. Even though the Turbuhaler has been used in Thailand for many years, the study of inspiratory flow rate and the ability to use this device in Thai preschool children is lacking. In the present study, the authors aimed to evaluate the ability to use the Turbuhaler in Thai preschool children by measuring the peak inspiratory flow rate, peak inspiratory flow rate through the Turbuhaler as well as positive test of the Turbutester. Subjects included 468 Thai preschool children, aged 3-7 years old. They were assigned to perform the test with In-Check Dial, Mini-Wright Peak Flow Meter and Turbutester. The authors found that the ability to use the device correlated directly with age and children with age of 5 years or more could perform significantly better. Children weight of 20 kilograms or more, or a height of 113 centimeters or more were also able to generate adequate inspiratory flow rate for medication delivery. The authors concluded that children from the age of five years, or with a weight from 20 kilograms or a height from 113 centimeters were able to generate adequate inspiratory flow rate for effective medication delivery by the Turbuhaler.

Direct medical costs associated with atopic diseases among young children in Thailand.

OBJECTIVE: Allergic diseases are the most common childhood illness in Thailand. Their prevalence has been rising over time, with several studies having revealed substantial economic burden. However, no such study had yet been conducted for Thailand. The aim of this study was to estimate direct medical costs associated with atopic diseases among children aged 0-5 years in Thailand. RESEARCH DESIGN AND METHODS: A cost-of-illness model was constructed to estimate the total direct medical costs of atopic diseases comprising atopic dermatitis, chronic rhinitis, asthma (i.e., recurrent wheeze), and cow's milk allergy. The model employed a prevalence-based approach, considering a total number of atopic cases in 2010. Direct medical costs were estimated using a bottom-up analysis with the estimation of the quantity of healthcare resource use and the unit costs. Epidemiological data were obtained from literature and Thai surveys, whereas treatment unit costs were from either a hospital database or Thai standard cost list. Expert opinion informed type, frequency, and quantity of medical resources utilized. Key limitations included lack of data-driven evidences on severity distribution for this particular age group, indirect costs, and medical resource use associated with each condition. RESULTS: Total direct cost was estimated to be THB 27.8 billion (US$899 million). Treatments contributed largest to the total costs (46%), followed by inpatient care (37%), outpatient care (12%), and monitoring and labs (5%). Costs per treated patient were highest in cow's milk allergy (THB 64,383; US$2077), followed by rhinitis (THB 12,669; US$409), asthma (THB 9633; US$312), and atopic dermatitis (THB 5432; US$175). CONCLUSION: Atopic diseases in young children are associated with substantial burden in direct medical costs to Thailand. These costs can be diminished through nutritional intervention recognized to effectively decrease the incidence of atopic diseases.