Netherton Syndrome in Thai Children: A Report of Two Cases With a Literature Review.

Netherton syndrome (NS) is a severe autosomal recessive disorder characterized by the triad of congenital ichthyosiform erythroderma, trichorrhexis invaginata, and atopic diathesis. We report two cases that experienced severe congenital exfoliative dermatitis, recurrent infections, and allergic conditions. Examinations of hair under the light microscope revealed trichorrhexis invaginata. Whole exome sequencing identified homologous pathogenic mutations of SPINK5. Optimal skincare and proper nutritional support could improve patients' quality of life.

Comparison efficacy of randomized nebulized magnesium sulfate and ipratropium bromide/fenoterol in children with moderate to severe asthma exacerbation.

BACKGROUND: In Thailand, nebulized ipratropium bromide/fenoterol, is commonly used in addition to salbutamol for severe asthma exacerbation. Recently, nebulized MgSO4 is indicated in GINA 2015 as an additive treatment for severe cases. However, there is limited data showed the efficacy of both drugs in childhood severe asthma. The purpose of this study to compare efficacy and safety of nebulized MgSO4 and ipratropium bromide/fenoterol in moderate to severe asthma attacks. METHODS: In this a prospective, double-blind, randomized, controlled trial study, we enrolled thirty-three children, age ranged from 2 to 15 years old, with PRAM score ≥ 4 (moderate to severe asthma exacerbation) despite 3 doses of nebulized salbutamol. Each patient was randomized to receive either three doses of nebulized MgSO4 or nebulized ipratropium bromide/fenoterol every 30 minutes. The PRAM score was measured at 0, 30, 60, 90, 120 and 240 minutes after the treatment. The adverse event and admission days were also evaluated. RESULTS: Sixteen patients received nebulized MgSO4 and seventeen received nebulized ipratropium bromide/fenoterol. Almost patients were classified as having moderate asthmatic attack. There were no statistically significant difference between the two study groups in almost baseline characteristic, PRAM score at 0, 30, 60, 90, 120, 240 minutes. The hospital length of stay was also similar between two groups (p = 0.83). There were no serious events in both groups. CONCLUSIONS: Our double blind, randomized, controlled pilot study demonstrated non-inferior outcomes including clinical benefit and safety of nebulized MgSO4 and nebulized ipratropium bromide/fenoterol among Thai children with acute moderate asthmatic.

Comparison between pediatric respiratory assessment measure (PRAM) score and Wood's asthma score to assess acute asthma exacerbation.

BACKGROUND: Wood's score, the assessment of childhood respiratory failure, has been used to assess childhood acute asthma severity in Thailand since 19th century. However, PRAM score, which is increasingly used in Western countries has not been evaluated among Thai children with asthma. OBJECTIVES: This study aims to determine whether Wood or PRAM score is better prediction of severity of childhood asthma exacerbation. METHODS: The prospective comparative study of severity asthma score was performed in asthmatic children, 2-18 years old, with acute asthma exacerbation at Queen Sirikit National Institute of Child Health. PRAM and Wood's score were separately determined by 2 physicians. The patients were further assessed at 0, 4 or 24 hours after their admissions. The asthma treatment followed GINA guideline. RESULTS: There were 80 asthmatic patients, mean aged 5.71 ± 2.95 years. The admission rate was 28.8% with the mean length of stay = 4 ± 1 days. PRAM was correlated with Wood's score (Spearman's correlation p = 0.900, p < 0.001 at triage, and = p0.981, p < 0.001). The highlight of this study is the finding that intraclass correlation of PRAM is better than Wood asthma score (ICC = 0.944; 95%CI 0.913-0.964, 0.898; 95%CI 0.841-0.935, respectively). ROC indicated Wood's score ≤ 4 and PRAM ≤ 5, in the requirement for admission. CONCLUSION: PRAM and Wood's score are both promising in prediction of severity and outcome of childhood asthma exacerbation.

Family History of Early Infant Death Correlates with Earlier Age at Diagnosis But Not Shorter Time to Diagnosis for Severe Combined Immunodeficiency.

BACKGROUND: Severe combined immunodeficiency (SCID) is fatal unless treated with hematopoietic stem cell transplant. Delay in diagnosis is common without newborn screening. Family history of infant death due to infection or known SCID (FH) has been associated with earlier diagnosis. OBJECTIVE: The aim of this study was to identify the clinical features that affect age at diagnosis (AD) and time to the diagnosis of SCID. METHODS: From 2005 to 2016, 147 SCID patients were referred to the Asian Primary Immunodeficiency Network. Patients with genetic diagnosis, age at presentation (AP), and AD were selected for study. RESULTS: A total of 88 different SCID gene mutations were identified in 94 patients, including 49 IL2RG mutations, 12 RAG1 mutations, 8 RAG2 mutations, 7 JAK3 mutations, 4 DCLRE1C mutations, 4 IL7R mutations, 2 RFXANK mutations, and 2 ADA mutations. A total of 29 mutations were previously unreported. Eighty-three of the 94 patients fulfilled the selection criteria. Their median AD was 4 months, and the time to diagnosis was 2 months. The commonest SCID was X-linked (n = 57). A total of 29 patients had a positive FH. Candidiasis (n = 27) and bacillus Calmette-Guérin (BCG) vaccine infection (n = 19) were the commonest infections. The median age for candidiasis and BCG infection documented were 3 months and 4 months, respectively. The median absolute lymphocyte count (ALC) was 1.05 × 109/L with over 88% patients below 3 × 109/L. Positive FH was associated with earlier AP by 1 month (p = 0.002) and diagnosis by 2 months (p = 0.008), but not shorter time to diagnosis (p = 0.494). Candidiasis was associated with later AD by 2 months (p = 0.008) and longer time to diagnosis by 0.55 months (p = 0.003). BCG infections were not associated with age or time to diagnosis. CONCLUSION: FH was useful to aid earlier diagnosis but was overlooked by clinicians and not by parents. Similarly, typical clinical features of SCID were not recognized by clinicians to shorten the time to diagnosis. We suggest that lymphocyte subset should be performed for any infant with one or more of the following four clinical features: FH, candidiasis, BCG infections, and ALC below 3 × 109/L.

A comparative pilot study of the efficacy and safety of nebulized magnesium sulfate and intravenous magnesium sulfate in children with severe acute asthma.

INTRODUCTION: Severe asthma attacks are life-threatening, and require serious medical attention. Intravenous MgSO4 is an efficient medication, proven to improve outcomes. To date, most research has focused on administration of nebulized MgSO4 in adults with critical asthma. However, its benefits for treating childhood asthma has been little investigated. This study compared the clinical efficacy and adverse effects of nebulized MgSO4 and intravenous MgSO4 in the treatment of children with severe acute asthma. METHOD: A prospective, open-label, randomized, controlled pilot study was conducted in children with severe asthma exacerbation admitted at the Queen Sirikit National Institute of Child Health. Twenty-eight patients were randomized to receive three intermittent doses of nebulized or intravenous MgSO4. The Modified Wood's Clinical Asthma Score was determined prior to, and at 20, 40, 60, 120, 180 and 240 minutes after treatment administration. The length of hospital stay was also recorded. RESULTS: Fifteen patients received nebulized isotonic MgSO4 and 13 were administered intravenous MgSO4. There were no differences in the baseline characteristics of the two groups, including their initial asthma severity scores (4.87 ± 0.92 vs. 5.0 +0.82; p = 0.69). No statistically significant differences between the two groups were identified at 60 minutes (2.47 ± 0.83 vs. 2.77 ± 0.93; p = 0.37) until 240 minutes. The length of hospital stay for both groups was also similar (4.0 ±1.2 vs. 4.54 ± 2.7; p = 0.51). No adverse effects from MgSO4 administration were observed among the participants. CONCLUSIONS: In this small sample size we demonstrated that nebulized MgSO4 and intravenous MgSO4 are both clinically beneficial and safe for Thai children suffering from severe asthma exacerbation.

Paediatric rheumatology clinic population in Southeast Asia: are we different?

Objectives: To examine the descriptive epidemiology of the patient population referred to paediatric rheumatology centres (PRCs) in Southeast Asia (SEA) and to compare the frequency of conditions encountered with other PRC populations. Methods: A web-based Registry for Childhood Onset Paediatric Rheumatic Diseases was established in 2009 and seven PRCs in four SEA countries, where paediatric rheumatologists are available, participated in a prospective 24 month data collection (43 months for Singapore). Results: The number of patients analysed was 4038 (788 from Malaysia, 711 from the Philippines, 1943 from Singapore and 596 from Thailand). Over 70% of patients evaluated in PRCs in Malaysia, the Philippines and Thailand had rheumatic diseases (RDs), as compared with one-half of the proportion seen in Singaporean PRCs, which was similar to the Western PRC experience. Among RDs diagnosed (n = 2602), JIA was the most common disease encountered in Malaysia (41%) and Thailand (61%) as compared with systemic vasculitides in the Philippines (37%) and Singapore (35%) among which Henoch-Schönlein purpura was the most prevalent. SLE and related diseases were more common, but idiopathic pain syndrome and abnormal immunological laboratory tests were rarer than those seen in the West. JIA subtype distributions were different among countries. Among non-RDs (n = 1436), orthopaedic and related conditions predominated (21.7-59.4%). Conclusion: The frequencies of RDs seen by SEA PRCs were different from those in the West. Systemic vasculitides and SLE were common in addition to JIA. Paediatric rheumatologist availability and healthcare accessibility partially explain these observed discrepancies.

In vitro correction of a novel splicing alteration in the BTK gene by using antisense morpholino oligonucleotides.

A novel sequence variant, c.240+109C>A, in the Bruton's tyrosine kinase (BTK) gene was identified in a patient with X-linked agammaglobulinemia. This alteration resulted in an incorporation of 106 nucleotides of BTK intron 3 into its mRNA. Administration of the 25-mer antisense morpholino oligonucleotide analog in the patient's cultured peripheral blood mononuclear cells was able to restore correctly spliced BTK mRNA, a potential treatment for X-linked agammaglobulinemia.

Latex allergy in dental students: a cross-sectional study.

BACKGROUND: Latex allergy is a major occupational health problem in health care workers who regularly use latex gloves. Dentists are one of the high risk groups for latex allergy and sensitization as it is generally found that healthcare workers (HCW) have 3 times greater prevalence of latex allergy. There are very few studies of latex allergy in HCW in Thailand. OBJECTIVE: To study the prevalence of latex-related symptoms, latex-sensitization and possible risk factors in dental students. MATERIAL AND METHOD: A cross-sectional study was performed on all dental students of the Faculty of Dentistry, Chulalongkorn University, during Dec 2007 to May 2008, using questionnaires and skin prick tests (SPT), using 3 latex extracts prepared from Proglove, Doctor Plus gloves and a commercial latex allergen (Stallergenes, France). SPT was done only in those who were willing and signed informed consents. RESULTS: There were 617 completed questionnaires (87.3%). The mean age of the volunteers was 20.9 +/- 1.7 years with 29.3% male and 70.7% female. The prevalence of latex glove-related symptoms was 5.0%. These symptoms were all local, cutaneous symptoms, ranging from hand pruritus (64.5%), hand eczema (19.4%) and contact urticaria (16.1%). Eight subjects (1.3%) reported pruritus or urticaria on exposure to other rubber products while 12 subjects (1.9%) reported reactions to some fruits. The risk factors for latex-glove allergy were personal history of allergic diseases (atopic dermatitis, urticaria, pruritus and rubber allergy), duration of using gloves more than 18 hours per week, more than 3 pairs of gloves used per day and timing of glove exposure. The 4th to 6th year students were observed significantly more prevalence of symptoms than the 1st to 3rd year students (OR, 3.69; 95% CI, 1.73-7.87; p = 0.0003). SPT for 3 extracts of latex was done in 247 cases (40.0%); overall latex sensitization rate was 14.2%. The commercial extract had higher incidence of latex sensitization compared to the 2 gloves extract. The 1st year students had the lowest percentage of latex sensitization (3.2%) and positive skin test was significantly found in the 2nd year students (20.8%; OR, 6.46; 95% CI, 1.87-47.98; p = 0.04). CONCLUSION: The prevalence of latex allergy in dental students is 5% and the signs and symptoms were local cutaneous reaction; pruritus, eczema and contact urticaria. The latex sensitization rate in dental students was14.2%, which is higher than the general population. The possible risk factors included personal history of allergic diseases, duration and frequency of exposure. Therefore, primary prevention of the occupational latex allergy should be carefully considered especially concerning high risk factors.

Anti-N-methyl-D-aspartate receptor encephalitis: a newly recognized inflammatory brain disease in children.

OBJECTIVE: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a newly recognized antineuronal antibody-mediated inflammatory brain disease that causes severe psychiatric and neurologic deficits in previously healthy children. The present study was undertaken to describe characteristic clinical features and outcomes in children diagnosed as having anti-NMDAR encephalitis. METHODS: Consecutive children presenting over a 12-month period with newly acquired psychiatric and/or neurologic deficits consistent with anti-NMDAR encephalitis and evidence of central nervous system (CNS) inflammation were screened. Children were included in the study if they had confirmatory evidence of anti-NMDAR antibodies in the serum and/or cerebrospinal fluid. Features at clinical presentation and results of investigations were recorded. Type and duration of treatment and outcomes at last followup were documented. RESULTS: Seven children were screened, and 3 children with anti-NMDAR encephalitis were identified. All patients presented with neurologic and/or psychiatric abnormalities, seizures, speech disorder, sleep disturbance, and fluctuating level of consciousness. The 2 older patients had more prominent psychiatric features, while the younger child had significant autonomic instability and prominent involuntary movement disorder. None had an underlying tumor. Immunosuppressive therapy resulted in near or complete recovery; however, 2 of the patients had early relapse necessitating re-treatment. CONCLUSION: Anti-NMDAR encephalitis is an important cause of neuropsychiatric deficits in children, which must be included in the differential diagnosis of CNS vasculitis and other inflammatory brain diseases. Early diagnosis and treatment are essential for neurologic recovery.

Wheat-dependent, exercise-induced anaphylaxis in Thai children: a report of 5 cases.

Wheat is not an uncommon cause of food-dependent, exercise-induced anaphylaxis. This study aims to describe common clinical characteristics and laboratory manifestations of the disease. Five children, aged 8-14 years were evaluated. An atopic history was found in 20% of the patients. All patients had symptoms which involved the skin and three had hypotension. Serum specific IgE for wheat was measured and showed a positive result in 2 patients. A three-day challenge protocol with an open challenge for wheat on day 1, an exercise challenge test on day 2 and another exercise challenge test on day 3 after a meal containing wheat was performed. Four patients completed the three-day challenge protocol. Anaphylaxis occurred in 2 out of 4 patients who consumed more than 100 grams of wheat prior to the exercise. The three-day challenge protocol is a definitive diagnostic tool to confirm the diagnosis of WDEIA. However, the amount of wheat used for challenging should be at least 100 grams.

Allergen sensitization to aeroallergens including Blomia tropicalis among adult and childhood asthmatics in Thailand.

To study prevalence of allergen sensitization among asthmatics in Thailand, skin prick tests (SPT) were performed in 84 pediatric, 71 adult asthmatics and 71 adult volunteers. Allergen extracts used for testing included common allergens in Thailand and in Singapore. The incidence of positive SPT to any allergen among the three groups (childhood, adult patients and adult controls) were 64.3%, 43.7% and 35.2%, respectively. Dermatophagoides were the most common allergens sensitized by both pediatric (58.3%) and adult asthmatics (40.8%). Twenty-four children (28.6%) and 8 adult patients (11.3%) were sensitized to storage mites (Blomia tropicalis and/or Austroglyciphagus malaysiensis). All patients sensitized to Blomia tropicalis were sensitized to Dermatophagoides. Twenty-seven percent and 15.5% of childhood and adult asthmatics were sensitized to cockroach allergens. The rates of sensitization to oil palm pollen in childhood and adult asthmatics were 8.3% and 5.6%, respectively. Sensitization to other pollens and spores were less than 5%. This study confirms the importance of Dermatophagoides among Thai asthmatics.

How do Thai children and adolescents describe asthma symptoms?

Prevalence of childhood asthma appears to be increasing worldwide. In Thailand, the prevalence of childhood asthma increased from 4.2% to 13% within the past decade. The last epidemiologic survey in Thailand utilized the International Study of Asthma and Allergies in Childhood (ISAAC) phase I questionnaire translated into Thai language. Language in the questionnaire can affect the reliability and validity of results of the survey. The purpose of this study is to determine common Thai wordings actually used by Thai children and adolescents to describe wheeze, chest tightness, shortness of breath and dyspnea. Sixty asthmatic Thai children, aged 9.2-18 years with asthmatic attacks less than 1 yr prior to the study, and 178 age-matched controls were recruited into the study. Asthmatic children spontaneously expressed their terms describing their asthma symptoms (in Thai) and then answered a preoutlined questionnaire regarding asthma terminology during an interview session after viewing the severe attack scene of the International ISAAC video questionnaire. Controls responded only to the preoutlined questionnaire after viewing the video scene. Of the 60 asthmatic children (38 males and 22 females, mean age 11.9 yr), 75% had their last asthmatic attacks within 2 months prior to the study. Wheeze was referred to as " and '/wi:d/' in 50% and 33% of patients, respectively, and " in 93.8% among controls. Using only the word '/wi:d/' in our previous ISAAC-I survey, as it sounded like the English word 'wheeze', it appears that up to 67% of the cases could have been missed. Dyspnea was referred to as rapid breathing and feeling tired in 78.2% of cases and as rapid and difficult breathing in 76.3% of controls. Chest tightness was referred to as chest discomfort in 65.7%. Shortness of breath was referred to as not being able to catch a breath, too short a breath, not enough breath and feeling suffocated in 88.8%. Local terms for asthma symptoms should be established and validated into each language to obtain reliable epidemiologic data.