Immunoglobulin G (IgG) subclass deficiency in Thai children.

Background: Patients with Immunoglobulin G (IgG) subclass deficiency may suffer from recurrent infections, mainly sino-pulmonary infection. Objective: To determine the epidemiology of IgG subclass deficiency in Thai children at a tertiary care hospital and to compare the differences between children who were diagnosed with IgG subclass deficiency by using low level criteria [less than 2 standard deviation (SD) of normal levels for age] and by using low percentage criteria (proportion of each IgG subclasses/total IgG). Methods: The study was a descriptive study of 55 children up to 15 years old with recurrent infections diagnosed as having IgG subclass deficiency but no acquired or other primary immune deficiencies except for IgA and/or IgM deficiency. Result: Isolated IgG3 subclass deficiency was the most common IgG subclass deficiency (56.4%). IgG3 subclass deficiency, either isolated or combined with other IgG subclass deficiency, was found in 85.5% of the cases. The common age of onset was between birth and five years of age. The most common presenting symptom was recurrent sinusitis (83.6%). Majority of the cases (89.3%) were diagnosed by low percentage criteria while 12.7% were diagnosed by low level criteria. All cases with low levels of IgG subclass antibodies also had low percentages. There were no statistically significant differences in the clinical manifestations and management methods between the children who were diagnosed by low level and low percentage. Conclusion: IgG3 subclass deficiency was the most common IgG subclass deficiency in Thai children. The most common presenting symptom was recurrent sinusitis. Although the diagnosis could be made in the patients with recurrent upper respiratory infection by using low level criteria, but the diagnosis should be considered when the low percentage criteria are met.

The effect of montelukast on bronchial hyperreactivity and lung function in asthmatic children aged 6-13 years.

Background: Cysteinyl leukotrienes have been shown to play an important role in the pathogenesis of asthma. The effect of the leukotriene receptor antagonist, montelukast, on bronchial hyperreactivity (BHR) as measured by the methacholine challenge test in school children has not been reported. Objective: To determine the effect of montelukast (Singulairâ) on BHR measured by methacholine challenge and lung function tests in Thai asthmatic children aged 6-13 years. Materials and methods: This was a randomized, double-blind, placebo-controlled, crossover study performed in 29 mild to moderate persistent asthmatic children aged 6-13 years. Each child received crossover treatment with 6 weeks of montelukast (5 mg/day) and 6 weeks of placebo separated by a two-week washout period. Results: The improvement of FEV1 and FEV1/FVC after 6 weeks of treatment was significantly higher in montelukast group compared to those of placebo group (p<0.05). After 6 weeks of treatment, mean (+ SEM) PC was 20 in the placebo group (5.7 + 1.41 mg/ml) which was lower than in montelukast group (6.8 + 1.74 mg/ml) but there was no significant difference (p=0.79). Conclusion: Montelukast significantly improved FEV1 and FEV1/FVC but not BHR in mild to moderate persistent asthmatic children aged 6-13 years after the 6 weeks of treatment.

In-vivo allergenic potency of Siriraj Mite Allergen Vaccine (SMAV) comparing with standardized vaccine in mite-sensitive patients.

Background: The prevalence of allergic diseases, particularly asthma and allergic rhinitis, has increased tremendously in Thailand and worldwide. House dust mite (HDM) is the major IgE sensitizer among allergic children and adults. We have developed local standardized mite allergen extracts, Siriraj Mite Allergen Vaccine (SMAV) from Dermatophagoides pteronyssinus (Dp) and Dermatophagoides farinae (Df) from our source materials which were highly purified (99%). Objective: To compare in-vivo allergenic potency of both SMAV Dp and Df with commercial standardized mite allergen vaccine by using skin prick testing in mite-sensitive individuals. Methods: This was a double-blind, randomized, self controlled study comparing SMAV and commercial standardized mite allergen vaccine (Dp and Df) by using skin prick testing in mite-sensitive adult volunteers, 18 – 60 years of age. Results: The study was performed in 54 adult volunteers (19 males, mean age 26.6 + 5.5 years old) who had positive skin test to commercial Dp and Df. Seventeen of them had no allergic disease. The most common allergic disease among the volunteers was allergic rhinitis (21/37). Mean wheal diameter of SMAV Dp and commercial Dp at the concentration of 10,000 and 5, 000 AU/ml were equivalent but at the concentration of 2,500 AU/ml was inequivalent. Mean wheal diameter of SMAV Dp was significantly larger than commercial Dp at concentration of 2,500 AU/ml (p < 0.05). Mean wheal diameter of SMAV Df and commercial Df at all 3 concentrations were equivalent. There was no systemic side effect in all subjects. Conclusion: The study demonstrated that in mite-sensitive adults, SPT using SMAV Dp (10,000 AU) and Df (10,000 AU) had equivalent allergenic potency to the commercial comparator without any systemic side effect.

Clinical characteristics of children with non-allergic rhinitis vs with allergic rhinitis.

Background: Allergic rhinitis (AR) and nonallergic rhinitis (NAR) are major causes of chronic rhinitis. Knowledge about children with non-allergic rhinitis is limited. Objective: To study clinical characteristics differentiating NAR and AR among children with chronic rhinitis. Methods: This is a retrospective, descriptive study of 302 children (with ages of 14 years or less) with chronic rhinitis evaluated at the pediatric allergy clinic, Siriraj Hospital between January and December 2006. Based on the results of skin prick test (SPT), they were classified into 2 groups, i.e., AR and NAR. Their medical records were reviewed with respect to clinical data on rhinitis and related symptoms. Results: There were 222 patients with AR and 80 with NAR (73.5% and 26.5%). Median age of onset of the disease among patients with NAR was younger than AR (p = 0.04) while the duration of disease among AR cases was longer than in NAR (p < 0.01). Severity of rhinitis, based on Allergic Rhinitis and its Impact on Asthma (ARIA), was not different between the two groups. Nasal pruritus, sneezing and eye symptoms were more commonly observed in AR than in NAR (p <0.01), whereas snoring and sinusitis were more common in NAR than in AR (p < 0.01). The presence of nasal pruritus, sneezing and eye symptoms strongly suggested AR (adjusted OR 2.73, 2.96, 1.49) while snoring was a risk factor for NAR

A combination of intravenous immunoglobulin and pulse methylprednisolone extended survival in pulmonary alveolar proteinosis with chronic interstitial pneumonitis: a case report.

Pulmonary alveolar proteinosis (PAP) is characterized by intra-alveolar accumulation of lipoproteinaceous material. The severe chronic pulmonary disease and susceptibility to pulmonary infection is a prominent feature of the disease. We reported a case of postnatal-onset PAP and chronic interstitial pneumonitis in a girl with chronic respiratory distress since she was 5 months of age. A lung biopsy confirmed the diagnosis. The therapeutic bronchoalveolar lavages, a short trial of granulocyte colony-stimulation factor (G-CSF) and a combination of low dose methylprednisolone and hydroxychloroquine were used at different times without noting satisfactory improvement. Intravenous immunoglobulin (IVIG) and pulse methylprednisolone were given monthly with gradual recovery. She did not require oxygen supplement after 21 months of this combination. Our report suggested that IVIG and pulse methylprednisolone might have a potential role in the treatment of PAP with chronic interstitial pneumonitis.

The accumulation of dust mite allergens on mattresses made of different kinds of materials.

Background: Different mattress materials may affect the accumulation of allergens. Objective: To compare the amount of group 1 dust mite allergens (Der p1 + Der f1) on mattresses made of different kinds of materials before and after use. Methods: Sixty new mattresses made of kapok, synthetic fiber, coconut fiber and sponge-like polyurethane, were placed in the house officers’ dormitory at Siriraj hospital, Thailand. The dust samples were collected before (0), 1, 2, 3, 6, 9 and 12 months after the mattresses were used. Group 1 dust mite allergens were analyzed using two-site monoclonal antibody ELISA. Results: Der f1 made up 86.7 % of group 1 allergens found in the matress dust. After the 2nd month, only the mean level in sponge-like polyurethane mattress was under 2 µg/g dust (sensitized level). At the 6th month, the mean levels were 13.1 in coconut, 21.7 in kapok and 17.3 µg/g dust in synthetic fiber, all of which were more than 10 µg/g dust (symptomatic level). At the 9th month, the level in sponge-like polyurethane mattress was increased to 11.2 µg/g. At 12th month the level in coconut fiber, sponge-like polyurethane synthetic fiber and kapok mattresses were 20.2, 22.4, 28.9 and 32.2 µg/g dust respectively. Conclusions: The accumulation rate in kapok and synthetic mattresses was significantly higher than coconut and sponge-like polyurethane mattresses. The mean level of group 1 mite allergens exceeded 10 µg/g dust after the 6th month of use in coconut fiber, kapok and synthetic fiber and at the 9th month in sponge-like polyurethane mattress.

Determination of storage conditions for shrimp extracts: Analysis of specific IgE-allergen profiles.

The consumption of shrimp is a common cause of food hypersensitivity reactions. Shrimp allergy is diagnosed using a skin prick test (SPT) as well as by food challenges. Due to the lack of a wide variety of commercial shrimp extracts for SPTs, we selected various shrimp species for the preparation of local shrimp extracts. However, optimal storage conditions for the shrimp extracts which also maintains allergenic potency has not yet been identified. The objective of the present study was to determine the potency of the shrimp extracts under different storage conditions and durations. Specific IgE-allergen profiles of eight shrimp-allergic patients were investigated by using sera incubated with extracts prepared from lyophilized raw or boiled shrimp, which were stored at 4oC or -20oC for up to 4 weeks. When stored at -20oC, most allergens were preserved after 4 weeks. However, storage at 4oC results in few allergens remaining after 2 weeks. Boiled-shrimp extracts stored at 4oC and -20oC contained higher amounts of IgE-allergen complexes than raw-shrimp extracts. Moreover, in both raw and boiled shrimp extracts, the IgE bound 36-40 kDa allergens constituted the major proteins since they were observed in all IgE–allergen profiles. In conclusion, we recommend that shrimp extracts are stored at -20oC for 4 weeks to prevent the loss of allergens.

Comparison between siriraj mite allergen vaccine and Standardized Commercial mite vaccine by skin prick testing in normal Thai adults.

House dust mite is a major cause of allergic asthma and rhinitis in Thai population. Skin prick test (SPT) is a useful tool for the diagnosis of the IgE-mediated reactions. The imported commercial mite vaccine for SPT is available but it is relatively expensive. Aim of this studyis to compare Siriraj Mite Allergen Vaccine (SMAV) with standardized commercial mite allergen vaccine by skin prick testing in normal Thai adults. A double blind, self-controlled study between the SMAV and standardized commercial mite allergen vaccine was performed by SPT in 17 normal Thai adult males and non-pregnant or non-lactating females aged 18-60 years. The study showed that35.29 % of non atopic adults had positive SPT reaction to Dp and Df of both SMAV andstandardized commercial mite allergen vaccine. Mean wheal and flare diameters from SPT of Dp and Df of SMAV showed strong correlation with standardized commercial mite allergen vaccine (r = 0.768 and 0.897 in Dp and Df respectively, p <0.001). The intraclass correlation was also excellent (0.893 and 0.775 in Dp and Df respectively). There was no significant difference in wheal and flare diameter between SMAV andstandardized commercial mite allergen vaccine. No systemic or large local reaction was found in any of the study cases.

Immediate type hypersensitivity to chemotherapeutic agents in pediatric patients.

Nine patients (3 boys and 6 girls) with a median age of 9.5 years, with immediate type hypersensitivi-ty reactions to chemotherapeutic agents were reviewed. The presenting symptoms were urticaria (4/9) and ana-phylaxis (5/9). The causative agents were vincristine (2/9), L-asparaginase (2/9), mesna (1/9), cyclosporine (1/9), carboplatin (2/9) and cyclophosphamide (1/9). Three of the five patients with anaphylaxis were changed to alterna-tive chemotherapeutic agents. In two cases alternative drugs were not available and the patients underwent safe and successful desensitization. Three of the 4 patients with urticaria were successfully exposed to graded chal-lenges with cyclosporine, carboplatin and cyclophosphamide, respectively. In the other case with generalized urti-caria, mesna was withdrawn due to a positive intradermal test. In patients with immediate type hypersensitivity reactions to chemotherapeutic drugs, if effective alternative chemotherapeutic agents are not available and/or the skin test is negative, a careful drug challenge and/or desensitization should be performed.

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 chal-lenge 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 con-sumed more than 100 grams of wheat prior to the exercise. The three-day challenge protocol is a definitive diag-nostic tool to confirm the diagnosis of WDEIA. However, the amount of wheat used for challenging should be at least 100 grams. Abbreviations: WDEIA, wheat-dependent, exercise-induced anaphylaxis; FDEIA, food-dependent, exercise-induced anaphylaxis; SPT, skin prick test.

Is silent sinusitis a cause of chronic urticaria in children.

The etiologies of chronic urticaria (CU) comprise a wide variety of disorders including chronic infec-tions. The association of sinusitis and CU is controversial due to the lack of a control group. The objective of this study was to investigate the role of silent sinusitis as a cause of CU in children. A sinus X-ray (SXR) was performed in 107 children with CU. SXR abnormalities were found in 52.3% of the patients. Nine patients (8.4%) had symp-toms of sinusitis and were treated with amoxicillin/clavulanate. Five of these patients (55.6%) had CU remission. Forty-seven patients (43.9%) who had an abnormal SXR without sinusitis symptoms were randomized into treated (23 patients) and control (24 patients) groups. Eighteen patients (78.3%) in the treated group and 15 patients (62.5%) in the control group had CU remission (p = 0.24). These data did not support a causal relationship of si-nusitis and CU in children.

The utility of the World Health Organization-The Uppsala Monitoring Centre (WHO-UMC) system for the assessment of adverse drug reactions in hospitalized children.

Although the World Health Organization-The Uppsala Monitoring Centre (WHO-UMC) system has been suggested as a practical tool for classifying adverse drug reactions (ADRs), verification of such system has not been examined. The objective of this study was to evaluate the usefulness of the WHO-UMC classification for the diagnosis of ADRs. The gold standard was the results of drug challenges and serum tryptase in cases of anaphylaxis. Twenty-seven children had ADRs classified by the WHO-UMC system. The causality terms were 'certain' in 4/27, 'probable' in 6/27, 'possible' in 10/27 and 'unlikely' in 7/27 of the patients. Skin prick tests and intradermal tests were positive in 1/20 and 1/5 of the patients, respectively. Drug challenges and serum tryptase were positive in 8/26 and 1/3 of the patients, respectively. After complete evaluation, the positive and negative ADRs were documented in 9/27 patients (33.33%) and 18/27 patients (66.67%), respectively. The multi-level likelihood ratios for ADRs using the WHO-UMC system were infinity in causality term 'certain', 2 in 'probable', 0.5 in 'possible', and 0 in 'unlikely'. In conclusion, causality term 'certain' and 'unlikely' of the WHO-UMC system had large impact on the likelihood of ADRs. In contrast, the causality term 'probable' and 'possible' had small impact on the likelihood of ADRs. Drug challenges and serum tryptase were helpful to confirm ADRs categorized by WHO-UMC system.

Association between ADAM33 polymorphisms and asthma in a Thai population.

ADAM33 (A Disintegrin And Metalloprotease 33) is an asthma susceptibility gene found across several human populations. However, no information on ADAM33 exists for Thai population. The objective of this study was to determine the association, if any, between ADAM33 polymorphisms and asthma in Thai subjects. Genotyping revealed 8 single nucleotide polymorphisms (SNPs) within the 3' region of the ADAM33 gene among 200 asthmatics and 100 control subjects. Asthmatic subjects were further sub-categorized into high and low severity groups. Multiple genetic model statistic tests for single-marker and haplotype association were carried out. Differences in allele frequencies at the SNPs rs528557/S2, rs598418 and rs44707/ST+4 in asthmatics were statistically significant compared to controls. The SNP rs528557/S2 could also be linked to the low severity group and the SNPs rs598418 and rs44707/ST+4 with the high severity group. Two-SNP haplotype analysis at the SNPs rs528557/S2 and rs598418 revealed a significant association with asthma. This study in a Thai population confirmed a positive association between ADAM33 polymorphisms and asthma susceptibility.

Successful treatment of disseminated BCG infection in a SCID patient with granulocyte colony stimulating factor.

Severe combined immunodeficiencies (SCID) are disorders with impairment of humoral and cellular immune functions. The prognosis of disseminated bacillus Calmette-Guérin (BCG) infection in immunocompromised host is unfavorable since response to standard therapy is poor. We report a successful treatment of disseminated BCG infection with granulocyte colony stimulating factor (G-CSF) in a patient with severe combined immunodeficiency. The patient failed to response to intensive anti-tuberculous (anti-TB) therapy. After 2 months of G-CSF, in addition to anti-TB treatment, the clinical signs of disseminated BCG infection were improved. Since serious BCG infections in SCID are not uncommon in developing countries, where BCG vaccination is mandatory to all newborns, the combination of G-CSF and anti-TB drugs should be considered in immunocompromised patients with protracted mycobacterial infection.

A novel mutation of the CYBB gene resulting in severe form of X-linked chronic granulomatous disease.

We evaluated a boy who had multiple Salmonella septicemia, Aspergillus pneumonia and brain abscesses. His nitroblue tetrazolium (NBT) test was reportedly abnormal. The dihydrorhodamine (DHR) flow cytometry assay was compatible with typical X-linked chronic granulomatous disease (X-CGD). CYBB analysis revealed a novel complex mutation atggacg --> ttca in exon 12 (base pairs 1532-1538). As a result, 3 amino acids Tyr 511, Gly 512 and Arg 513 were deleted and replaced by 2 amino acids, Phe and Gln. The DHR and mutation analysis of his mother showed normal DHR pattern and no mutations in exon 12 of CYBB gene. In conclusion, any children with multiple Salmonella and Aspergillus infection should be suspected of CGD. NBT test, DHR assay and gene analysis are helpful toolsto confirm the diagnosis e v en i n the case of de novo mutation.

Recurrent Campylobacter lari bacteremia in X-linked agammaglobulinemia: a case report and review.

X-linked agammaglobulinemia (XLA) is a primary immune deficiency disease with a B-cell defect. We present the first XLA patient who had recurrent Campylobacter lari bacteremia. High dose intravenous immunoglobulin combined with azithromycin once per week, and a complete avoidance of bacterial reservoirs may be helpful for the prevention of C. lari bacteremia.

Chronic rhinosinusitis and recurrent nasal polyps in two children with IgG subclass deficiency and review of the literature.

Chronic rhinosinusitis (CRS) is a chronic inflammatory disorder of mucosa of the nose and the paranasal sinuses. Two major forms of CRS can be differentiated; CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). The pathophysiology and etiology of nasal polyps (NPs) are partly understood. IgG subclass deficiency was shown to be associated with an increased susceptibility to infections. However the association between NPs and IgG subclass deficiency has never been reported. OBJECTIVES: To report two cases of recalcitrant CRS and recurrent NPs with IgG subclass deficiency. CASE REPORT: Two children (6 and 8 year-old boys) were referred to the Pediatric Allergy/Immunology Clinic, Siriraj Hospital due to a prolonged history of CRS and recurrent NPs. Both of them were treated with aggressive medical (topical and systemic corticosteroids, antibiotics, leukotriene antagonist, nasal irrigation) as well as surgical therapy, without significant improvement. Immunologic investigation in both patients showed that IgG, IgA, and IgM level were normal. IgG subclasses level in patient No. 1 were IgG1 1,235 (280-1120) mg/dl (79%), IgG2 235 (30-630) mg/dl (23.5%), IgG3 27.3 (40-250) mg/dl (1.74%), and IgG4 92.4 (11-620) mg/dl (5.9%). IgG subclasses level in patient No. 2 were IgG1 1,139 (280-1120) mg/dl (82.5%), IgG2 170 (30-630) mg/dl (12.3%), IgG3 5.6 (40-250) mg/dl (0.4%), IgG4 65.7 (11-620) mg/dl (4.8%). The diagnosis of CRS and recurrent NPs with IgG3 subclass deficiency in the first patient and IgG2/IgG3 subclass deficiency in the second patient were made. Patient No. 1 was given monthly IVIG therapy for the total of 7 courses and medications were gradually tapered. Currently, the patient is doing well after the cessation of IVIG therapy for 3 months. Patient No. 2 denied the IVIG treatment and was lost to follow up. CONCLUSION: We reported two cases of recalcitrant CRS and recurrent NPs in children. Immunologic work up revealed IgG subclass deficiency. The treatment with monthly IVIG improved CRS and NPs in treated patient which brought up the possibility of association between NPs and IgG subclass deficiency. Further study on the direct role of IVIG in NPs will be needed in the future.

Medical charge of asthma care in admitted Thai children.

BACKGROUND: Asthma is one of the most common chronic diseases in children. Due to high admission rate for acute asthmatic attack, children often miss their schools and parents have to stop working to take care of them. These affect both mental and physical health as well as socioeconomic status of the family and the country. OBJECTIVES: To evaluate medical charge of asthma care in children admitted to the Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University. MATERIAL AND METHOD: The study was a retrospective and descriptive study. Data were collected from children with asthmatic attack admitted to the Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand from January 1st, 2000 to June 30th, 2003. Cost of room, food, drugs, devices, laboratory study and service charge were recorded. Total medical charges per year, per patient per admission and per patient per day were calculated. Data were analyzed with Chi square test, ANOVA and Post Hoc test. A p value of < 0.05 was considered statistical significant. RESULTS: Numbers of children with asthmatic attack admitted to the Department of Pediatrics, Siriraj Hospital increased between 2000-2002 (113,147 and 176 in 2000, 2001, and 2002). Seventy two percent of the patients were < or = 5 years of age. Most were mild intermittent asthma. The average duration of hospitalization was 4 days (95% CI, 3.6-4.3). Average medical charge per patient per admission and per day was 3236.20 and 998.60 Bahts respectively. There was no significant difference in the medical charge per patient among the admitted years. Medical charge of admission was significantly associated with the asthma severity. (p < or = 0.05) CONCLUSION: The rate of admission from asthmatic attack in children at Siriraj Hospital and the total medical charge per year increased between 2000-2002. Nevertheless, medical charge of asthma admission per person was unchanged. Main expense in medical charge of asthma admission was the cost of medication and room. Severity of asthma was related directly to medical charge.

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.