The polymorphisms of interleukin 17A (IL17A) gene and its association with pediatric asthma in Taiwanese population.

BACKGROUND: The interleukin 17A (IL17A) gene, located on chromosome 6p and linked to asthma phenotype, is a highly potential candidate gene conferring asthma susceptibility. The purpose of this study was to investigate the genetic association between single nucleotide polymorphisms (SNPs) of IL17A and asthma in Taiwanese children. METHODS: We selected and performed genotyping on nine SNPs that encompass the genomic region of IL17A in Taiwanese children with or without asthma. A total of 1939 subjects containing 1027 subjects in testing group and 931 subjects in validation group were recruited in this study. RESULTS: After Bonferroni correction, SNP rs8193036 was found to have a weak association (P = 0.0074 x 9 = 0.066) in genotype frequency test. This association was confirmed by validation group. Logistic regression adjusted allergy comorbidity and gender showed a slightly weaker association. CONCLUSIONS: The results indicated an independent role of IL17A promoter polymorphism rs8193036 in the association with pediatric asthma in Taiwanese population.

Identification of variations in the human phosphoinositide 3-kinase p110delta gene in children with primary B-cell immunodeficiency of unknown aetiology.

Our recent study demonstrated that defects in p110delta result in B-cell immunodeficiency that is very similar to that observed in BTK-deficient mice. We revealed that the p110delta fit the B-cell signal transduction complex and played a non-redundant role in the development and function of B cells. In humans, most children with primary B-cell immunodeficiency have mutations in the BTK, whereas a few have defects in the components of the B-cell signal transduction complex. But little is known about the genetic variation of p110delta in children with defects in B-cell immunodeficiency of unknown aetiology. Sixteen patients from 15 unrelated families and 112 normal controls underwent sequence analysis to identify genetic variations of the p110delta. Allele frequency in each group was also analysed and compared. We identified five single base-pair polymorphic nucleotide exchanges in both patient and control groups with similar allele frequencies, which did not contribute to the immunodeficiency. Three of them are novel (m.953A>G, m.1200C>T and m.1561A>G), and the m.953A>G and m.1561A>G nucleotide exchanges are non-synonymous (N253S and T456A, respectively). The novel m.1561A>G was in complete linkage disequilibrium with the known m.873A>G in our study of Taiwanese group. In addition, one novel single base-pair missense mutation, m.3256G>A (E1021K), was identified in one boy with typical clinical features of primary B-cell immunodeficiency and could not be found in either his family or the normal control population. By atomic structural analysis of the amino acid as well as the alignment comparison between species, it resulted in the replacement of the negative-charged amino acid E with the positive-charged amino acid K at codon 1021, located in the highly conservative and important catalytic functional domain. Our findings could shed light on further understanding the polymorphisms of p110delta in B-cell immunodeficiency and different populations. Moreover, the 3256G>A missense mutation raised the attention and warranted further extensive analysis to elucidate the role of p110delta in human immunodeficiency.

Anti-leukemic immunity against U937 cells in uremic patients.

To examine anti-tumor immunity in uremic patients undergoing regular hemodialysis, we designed this study using in vitro mononuclear cell (MNC) cultures, with human leukemic U937 cells as the target. MNC were collected and cultured from uremic subjects and age- and gender-matched healthy controls. Conditioned media from the cultures (MNC-CM) were collected after stimulation with various concentrations of phytohemagglutinin (PHA). The proliferation-inhibiting and differentiation-inducing activities of the PHA-MNC-CM on U937 cells were evaluated. The growth inhibition activity of uremic patients' PHA-MNC-CM was lower than that of controls. The differentiation-inducing effects were evaluated by morphological scoring, superoxide production, and monocyte-associated antigen expression (CD14 and CD68). All three parameters demonstrated that the differentiation-inducing effect of MNC-CM increased with increasing doses of PHA. These effects, however, were significantly less in uremic patients compared to controls at higher doses of PHA. The levels of TNF-alpha and IFN-gamma in PHA-MNC-CM increased in a PHA dose-dependent manner and were much higher in the controls. We conclude that the capacity of MNC from uremic hemodialysis patients to produce anti-leukemic immunity is significantly lower than that of healthy controls.

Childhood serum sickness: a case report.

Childhood serum sickness is a rare allergic disease that follows the administration of a foreign antigenic material, most commonly caused by injecting a protein or haptenic drug. The disease is a type III hypersensitivity reaction mediated by deposits of circulating immune complexes in small vessels, which leads to complement activation and subsequent inflammation. The clinical features are fever, cutaneous eruptions, lymphadenopathy, arthralgias, albuminuria, and nephritis. Serum sickness is an acute self-limited disease. We report a 3-year-old child who presented with fever and a rash; an invasive bacterial infection was strongly suspected. He was therefore given penicillin and gentamicin and responded well. At day 4 after admission, he developed a serum sickness reaction and showed symptoms of arthralgias, generalized edema, purpura, and gross hematuria. The white blood cell count was 12 190/mm3 with 7% eosinophils. Urinalysis revealed red blood cell above 100 per high power field, white blood cell 10 to 15 per high power field, and proteinuria. The antibiotics were discontinued and hydrocortisone (20 mg/kg/d), diphenhydramine HCl (4 mg/kg/d), aspirin (66 mg/kg/d) was administered, plus 1 dose of epinephrine (0.01 mL/kg) administered intramuscularly. On day 7, the 3rd day after withholding antibiotics, his condition dramatically improved. The clinical symptoms resolved progressively and his urinalysis returned to normal.

Steroid allergy: report of two cases.

Corticosteroid preparations have anti-inflammatory and immunosuppressive properties and are widely used in the treatment of asthma and allergic disorders. Steroids themselves, however, can induce hypersensitivity reactions. The number of reports on contact allergy or anaphylactic reactions is increasing. Steroid hypersensitivity should be considered in any patient whose dermatitis becomes worse with topical steroid therapy, or in patients who develop systemic allergic reactions after the use of systemic steroids. The diagnosis can be confirmed by skin testing, in vitro evidence of specific IgE, oral or parenteral challenge, or an allergic patch test. The latter may be positive within 20 min, which indicates immediate contact urticaria, or at 72 to 96 h, which indicates delayed contact hypersensitivity. In this article we report two cases of steroid allergy. Case 1 was a 5-year-old asthmatic boy with an anaphylactic reaction to steroids and aspirin. Case 2 was a 2-year-old boy with atopic dermatitis and steroid contact urticaria. Both cases 1 and 2 showed positive results to triamcinolone, dexamethasone, hydrocortisone, and methylprednisolone in the immediate skin allergy test. Case 2 had immediate contact urticaria to hydrocortisone and clobetasone butyrate. Case 1 had a positive systemic allergic reaction to cortisone acetate, prednisolone, and dexamethasone on the oral steroid challenge test, and also had aspirin induced angioedema and urticaria 10 min after challenge with 50 mg aspirin.

Ataxia telangiectasia: report of two cases.

Ataxia telangiectasia (A-T) is a rare autosomal recessive multisystem disease. The diagnosis of A-T is based on the typical clinical picture: ataxia and telangiectasia. However, an increase in (alpha-fetoprotein (AFP) level and the identification of the A-T mutated gene (ATM) assist in an early diagnosis. Here we report two cases of A-T diagnosed in our hospital (case 1: a 7-year-old boy; case 2: an 8-year-old girl). Both of these patients had typical clinical pictures of ataxia and telangiectasia, AFP was also increased (case 1:471.2 ng/dL; case 2: 196 ng/dL). T-cell dysfunction was noted in both patients. Case 1 had IgG2 deficiency and case 2 had IgA, IgG2 and IgG3 deficiency. Case 2 developed malignant lymphoma at 9 years of age and died of pneumonia with respiratory failure at 10 years of age. Because of rhe rarity of A-T in Taiwan, we report two cases to help pediatricians make an early diagnosis of A-T if they have a patient with progressive ataxia and oculocutaneous telangiectasia.

Fish allergy in atopic children.

The prevalence of fish allergy among 11 atopic children with elevated levels of specific immunoglobulin (Ig) E for cod was determined. None of the children had a history of fish allergy. All of the children had asthma and allergic rhinitis and 5 of them had also atopic dermatitis. The children underwent allergy skin tests (codfish, tuna, catfish, salmon, flounder, and bass), specific IgE tests (salmon, trout, tuna, eel, and mackerel), and food challenge tests. Skin tests in cod-specific IgE-positive children were positive for codfish in 4 children, tuna in 2, catfish in 2, salmon in 6, flounder in one, and bass in 2. Three children had elevated specific IgE for salmon, 5 for trout, 8 for tuna, 4 for eel, and 4 for mackerel. Oral fish challenge with 10 g of fish did not result in positive reaction in any of the children. In conclusion, a positive food challenge test provided the only definitive confirmation of fish allergy, whereas positive allergy skin tests or positive specific IgE tests were less reliable. Skin tests and in vitro specific IgE assays were not correlated with clinical symptoms of fish allergy, and the results of these 2 tests did not correlate with each other in this study.

Association of allergy with Tourette's syndrome.

In our clinical practice, we often encounter signs and symptoms of allergy, such as rhinitis and asthma, in patients with Tourette's syndrome (TS). Some of the allergic manifestations are similar to the oral tics or motor tics found in TS patients. To clarify the association between TS and allergy, we evaluated 72 consecutive patients with TS from 1 September 1996 through 31 August 1997. The diagnosis of TS was based on the Diagnostic and Statistical Manual of Mental Disorders diagnostic criteria. Sixty-five boys and 7 girls, 4 to 17 years old (9.4 +/- 3.1 yr) were evaluated using the Multiple Allergens Simultaneous Tests (MAST) for the detection of total and specific immunoglobulin. Forty-five patients had positive results, of whom 41 (56.9%) had clinical evidence of allergy. The prevalence of allergy in the local population as reported by The International Study of Asthma and Allergy in Childhood Taiwan Group (1994) was 44.3% (33.5% with allergic rhinitis and 10.8% with asthma). These subjects served as controls. Comparing the number of patients with clinical evidence of allergy in the MAST positive group (56.9%) of TS patients with the control group (44.3%), the difference was significant++ (p < 0.05). The prevalence of allergy in TS patients in our study was significantly higher than in the general population. TS had an association with allergy.

Comparison of antileukemic immunity against U937 cells in atopic asthmatics versus healthy controls.

To assess the antitumor effects in atopic asthmatics versus healthy adults, we designed this study using in vitro mononuclear cells (MNC) culture as an immunity model with human leukemic U937 cells as the target. MNCs were collected from asthmatic subjects and healthy controls. Conditioned media from the MNC cultures (MNC-CM) were collected after stimulation with various concentrations of phytohemagglutinin (PHA). We treated U937 cells with these MNC-CMs, then assayed their proliferation and differentiation after 5 days of culture. At lower PHA doses (1.25 microg/ml), as well as in absence of PHA, the asthmatic MNC-CMs inhibited U937 cells growth to a slightly greater extent than did the MNC-CMs from controls. In contrast, when higher doses of PHA were used (5, 10 microg/ml), this growth-inhibiting effect was dramatically reversed. The dual effect of MNC-CM in these two groups was also shown in U937 cell differentiation assay, assessed as follows: morphological change by Liu's staining, functional change by NBT reduction test and CD 14 expression by flow cytometric detection. We suggest that the antileukemic effects of MNCs from asthmatic patients result from a slightly immunopotentiated status. This immunity may be dramatically reversed, however, after marked activation of MNCs.

Eczema herpeticum in children with atopic dermatitis.

Eczema herpeticum (EH), a form of disseminated cutaneous herpes simplex virus (HSV) infection, is a potentially life-threatening disease. It usually occurs in individuals with atopic dermatitis (AD) or other preexisting dermatosis. The resulting disruption of the skin barrier decreases the ability of such individuals to localize an HSV infection. We report eight AD cases with eczema herpeticum, seen from February 1989 to January 1996. Their ages ranged from 5 months to 6 years (mean age 2.5 years), There were 5 boys and 3 girls. Their laboratory data showed: IgE: 39 to 474, mean 197 IU/ml; eosinophil count 139 to 560, mean 314/mm3; Tzanck smear positive in 6 out of 6 patients; vesicle fluid culture positive for Herpes simplex type I in 4 out of 4 patients. All patients were treated with acyclovir and recovered.

X-linked agammaglobulinemia presenting as juvenile chronic arthritis: report of one case.

Bruton agammaglobulinemia (X-linked agammaglobulinemia, XLA), transmitted by X-linked recessive inheritance, affects only males. Twenty percent of patients with XLA may have arthritis. Septic arthritis may occur, but there is also a form of arthritis that is similar to rheumatoid arthritis or juvenile chronic arthritis. Here we report one case of XLA in a boy with non-erosive chronic right knee arthritis. There was no evidence of septic arthritis. Regular intravenous gammaglobulin replacement therapy and oral naproxen resulted in dramatic improvement in the arthritis. This case illustrates that XLA should be considered as a possible underlying cause of juvenile chronic arthritis in males.

Fish induced anaphylactic reaction: report of one case.

In the past 2 years, a 4 year-old boy has had an anaphylactic reaction whenever he contacted food prepared with fish. The symptoms included intense itching in the throat and eyes, which progressed to generalized urticaria and facial angioedema. This was accompanied by cough, wheezing and dyspnea. Many fish preparations caused these episodes including several different kinds of fish (cod, tuna, salmon, trout, eel...), fish soup, chopsticks contaminated with fish preparations and canned fish. Elevated levels of total serum IgE (224 IU/ml) and specific IgE for cod (93.1 IU/ml), tuna (> 100 IU/ml), salmon (> 100 IU/ml), trout (64.4 IU/ml), mackerel (41.2 IU/ml) and eel (28.1 IU/ml) were found by the Pharmacia CAP system RAST FEIA in our allergy clinic. A skin prick test for mixed fish extracts (contain flounder, cod and halibut) was positive. A fish challenge test for cod, tuna, salmon, trout and eel all showed anaphylactic reactions. His allergic symptoms stabilized gradually after strictly avoiding ingestion of fish and using drug treatment. He also had a similar anaphylactic reaction to frogs. The best treatment for fish allergy is avoidance. Avoidance of fish may need to include both ingestion and inhalation of cooking vapors.

Whey and casein specific IgE and the cow's milk challenge test for atopic children.

We studied 30 atopic children who suspected of milk allergy by past history (age ranging from 1 yr 4 mo to 9 yr 6 mo, mean age: 5.03 yr.) diagnosed as having asthma, atopic dermatitis and/or allergic rhinitis. These 30 atopic children had been screened from the patients at our outpatient clinic by the Pharmacia CAP system RAST FEIA. All of them showed the presence of at least Class II (greater than 0.7 ku/l) IgE specific to proteins in cow's milk. Further analysis found IgE specific to alpha-lactoalbumin (alpha-LA) elevated in 1 patient (3.3%), 1 patient (3.3%) to beta-lactoglobulin (beta-LG), 4 patients (13.3%) to alpha-LA and beta-LG, 5 patients (16.7%) to casein, 8 patients (26.7%) to casein and alpha-LA, 11 patients (36.7%) to casein, alpha-LA and beta-LG. After 3 weeks' cow-milk-free diet, the patient's milk challenge test was performed at our outpatient clinic. According to the test result, none of these 30 atopic children showed clinical evidence of significant allergic reaction to cow's milk in the skin, the gastrointestinal tract or the respiratory tract either within two hours after the challenge test or within 3 days after they went home. We therefore conclude that: (1) No single major allergen is apparent in cow's milk: casein, alpha-LA and beta-LG all show a high proportion of positive reaction. (2) Many atopic children fully tolerate cow's milk, although they have high titer of IgE antibodies specific to cow's milk. The RAST test is only the first step to screen patients with suspected IgE-mediated allergies. To make sure, any positive reaction must be confirmed by the "golden standard" for diagnosis, i.e., the double-blind placebo-controlled food challenge.

Severe combined immunodeficiency with B-lymphocytes (T-B+SCID): report of two cases.

Severe combined immunodeficiency (SCID) is a rare pediatric medical emergency in Taiwan. The early diagnosis of infants with SCID is very important because it can save the life of these critical infants. The essential clues important for early diagnosis of SCID patients include positive family history of early infant death, paucity of tonsil and lymphoid tissue, cutaneous fungal infection and lymphopenia. Severe combined immunodeficiency is a heterogeneous group of inherited disorders characterized by the failure of both cellular and humoral immunity. It can be categorized into SCID with B-lymphocytes predominant (T-B+SCID) and SCID with paucity of B-lymphocytes (T-B-SCID), according to the number of B-lymphocytes in the patient's peripheral circulation. We report two male infants with T-B+SCID who had been suffering from severe pulmonary distress with persistent O2 desaturation when they were transferred to our pediatric intensive care unit. Tracing back these infant's family histories, it was discovered that both of them had an elder brother who had died to overwhelming infection within the first year of life, and Pneumocystis carinii pneumonitis (PCP) was confirmed in the elder brother of case 2. After hospitalization, the immune condition of these two infants were evaluated which showed a decrease in T-cell and NK cell number, an increase in B-cell number, and decreased serum levels of all the Igs except IgM, which was elevated in case 1. These were the diagnostic immunological findings for T-B+SCID, which included X-linked SCID and Jak-3-deficient SCID. During hospitalization, severe mucocutaneous candidiasis and PCP were noted and confirmed in case 1 and PCP was highly suspected in case 2. Bone marrow transplantation, the only curable treatment for T-B+SCID at present, could not be performed in these two patients because of their grave clinical condition. Both of them expired due to their progressively downhill pulmonary conditions.

Neurogenic diabetes insipidus in children with hypoxic encephalopathy: six new cases and a review of the literature.

UNLABELLED: Hypoxic encephalopathy is rarely mentioned as a cause of neurogenic diabetes insipidus (DI) in children. We here report six cases of DI which occurred after severe hypoxic/ischaemic brain damage and include a review of the literature on 28 paediatric cases of neurogenic DI due solely to severe hypoxia/ischaemia. Airway obstruction, haemorrhagic shock and sudden infant death syndrome are the three major causes of hypoxia/ischaemia. The ages (25/28) ranged from 0.03 to 18 years (mean 7.27 years, median 5 years). The intervals between the hypoxic insult and the onset of DI (23/28) ranged from 0.08 days (2 h) to 13 days (mean 4.07 days, median 3.5 days). Linear regression analysis revealed no significant correlation between the age and the interval. Nineteen cases (82.6%) developed DI within 6 days after the hypoxic/ischaemic insult. Only two neonates survived with developmental delay. The remaining 26 cases died. CONCLUSION: Neurogenic DI can be caused by hypoxia/ischaemia and is an ominous sign of severe brain damage in children with hypoxic encephalopathy. It is important to recognize this potential sequel by regularly monitoring intake and output, plasma sodium level, and urine specific gravity.

Continuous infusion of vasopressin in comatose children with neurogenic diabetes insipidus.

Three comatose children with neurogenic diabetes insipidus were treated with intravenous infusion of vasopressin. The infusion of vasopressin was started at a dose of 1.3 to 2.7 mU/kg/h as soon as diabetes insipidus was diagnosed. The effect (urine flow < 2 ml/kg/h with increased specific gravity) was noted in 1 to 6 hours. The infusion rate of vasopressin was adjusted according to urine flow rate which was usually kept around 65 ml/100 kcal metabolized/day. Hypernatremia was corrected 17 to 53 hours after the initiation of infusion of vasopressin. The levels of sodium stayed between 127 and 151 mmol/l during a period of 2.5 to 22 days until the patients' death due to the termination of respiratory support or cardiac decompensation. A continuous infusion of vasopressin offered the advantage of rapid onset and termination of effect and therefore could be easily titrated. It seems a rational therapy for comatose children with neurogenic diabetes insipidus.

Neurogenic diabetes insipidus in a child with fatal Coxsackie virus B1 encephalitis.

A 5 year-old boy presented with fever, sore throat, diarrhea, and general soreness which evolved into encephalitis. His cerebrospinal fluid showed a cell count of 3 mononuclear cells/microliters, protein 2800 mg/l, and growth of Coxsackie virus B1. Cardiorespiratory arrest was noted after a convulsion and infusion of diazepam. Although he was immediately resuscitated, he remained unconscious with a modified Glasgow coma score of 4 or 3. He developed neurogenic diabetes insipidus 169 hours after the convulsion and died the next day. We conclude that although Coxsackie virus infection is usually benign it may become overwhelming and be complicated with neurogenic diabetes insipidus. It is important to recognize this potential sequel by regularly monitoring weight, intake and output, plasma sodium level, and urine specific gravity.

Juvenile scleroderma: report of a case.

Scleroderma is a rare connective tissue disease in children. A 12-year-old boy suffered from progressive increasing skin tension with erythematous changes in his left leg for a period of 3 months. This limited the range of motion in his left first and second metatarsophalangeal joints. A skin biopsy showed hypertrophic collagen bundles with atrophic skin appendages and lymphocytic infiltration. Based on the clinical manifestations and typical histopathologic findings, juvenile linear scleroderma was diagnosed. He was successfully treated with a short course of oral prednisolone in addition to long-term therapy with D-penicillamine and a topical emollient.