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Hereditary angioedema (HAE) is a rare genetic disease with significant mortbidity and mortality for which early diagnosis and effective therapy are critical. Many Asia-Pacific (AP) countries still lack access to diagnostic tests and evidence-based therapies. Epidemiological data from the AP is needed to formulate regional guidelines to improve standards of care for HAE.To investigate the estimated minimal prevalence, needs and potential interventions for the diagnosis and management of HAE in the AP.A structured questionnaire was distributed to representative experts from member societies of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI). Patient profiles and presence of diagnostic facilities/ tests, regional / national HAE guidelines and patient support groups were reported and compared.Completed questionnaires were received from 14 representatives of 12 member countries/territories, representing 46% of the world population. Overall minimal prevalence of HAE in the AP region was 0.02 per 100,000 population, with significant heterogeneity across different centres. Only half and one-third had registered on-demand and prophylactic medications, respectively. Few had patient support groups (58%) or regional guidelines (33%), and their existence was associated with availability of HAE-specific medications. Availability of C1-inhibitor level testing was associated with a lower age of HAE diagnosis (p=0.017).HAE in the AP differs from Western countries. HAE-specific medications were only registered in a minority of countries/territories, but those with patient support groups or regional guidelines were more likely to have better access. AP specific consensus and guidelines are lacking and urgently needed.

Generalised morphea (GM) is a subtype of localised scleroderma that usually manifests with bilateral involvement. Unilateral generalised morphea (UGM) is a rare variant of GM. This is a case report of a Taiwanese girl with UGM over the left side of her body. She presented with hyperpigmentation, tightness, and skin atrophy over the left extremities and trunk. Mild range of motion (ROM) limitation over the left knee was also noted. At the clinic, the patient was given oral prednisolone, oral methotrexate (MTX), and oral D-penicillamine. topical emollient and topical glucocorticoids were also given. The dose of oral prednisolone was tapered gradually. All symptoms were improved under the treatment and regular rehabilitation program. To date, there is very little evidence to form the basis for treatment recommendations. This case report provides a treatment option for UGM in the paediatric group without the use of intravenous methylprednisolone pulse therapy.

Background The EHF and ELF5 genes, located on chromosome 11p and linked to asthma phenotypes, are high-potential candidate genes conferring asthma susceptibility. The purpose of this study was to investigate the genetic association among single nucleotide polymorphisms (SNPs) of EHF and ELF5 , and their relationship with asthma in the Taiwanese population. Methods We selected and performed genotyping on 16 SNPs that encompass the genomic region of EHF and ELF5 in Taiwanese children with or without asthma. A total of 1983 children, 523 in the test group and 619 and 842 in two validation groups, were recruited for this study. Results The SNP rs3910901, located in the 5′ upstream region of ELF5 , was found to have a weak association ( p = 0.043) with asthma in the odds ratio analysis. The genotype distribution was similar in all comparison groups, but the CC genotype was more frequent in asthma patients. Logistic regression adjusted allergy comorbidity showed obviously diluted association. Conclusion The results indicated that SNP rs3910901 may have a minor impact on pediatric asthma in the Taiwanese population.

Background The recurrence rate of Henoch-Schönlein purpura (HSP) is 2.7%–30%, with varied average intervals between the first and second episodes. Few studies have explored the incidence and risk factors for recurrent HSP. Methods We used a 16-year nationwide database to analyze the incidence of recurrent HSP. Patients with HSP were identified, and risk factors for recurrent HSP were explored. Kaplan-Meier and Cox regression model analyses were performed, and covariates were adjusted in the multivariate model. Results From January 1, 1997 to December 31, 2012, among 2,886,836 individuals in the National Health Insurance Research Database, 1002 HSP patients aged 10 days (adjusted hazard ratio, 8.13; 95%CI, 2.51–26.36; p 10 days should be notified regarding the possibility of recurrence. Electronic supplementary material The online version of this article (10.1186/s12969-018-0247-8) contains supplementary material, which is available to authorized users.

Buckwheat anaphylaxis is commonly recognized in Europe and Asia, and there is only one case reported in Taiwan so far. Here, we report a case of biphasic buckwheat anaphylaxis in a 57 year-old male patient who lost consciousness twice in the same day after having buckwheat noodles. The serum test shows that Dermatophagoides pteronyssinus (Dp)immunoglobulin E (IgE) (42.4 kU/L) and buckwheat-specific IgE (81.5 kU/L) are unusually high. Although biphasic buckwheat anaphylaxis is rare, we should still be aware the second episode could be life-threatening and happen within a day after the exposure to the buckwheat antigen.

Table S2. The percentage and duration of steroid use in each episode. (DOCX 18 kb)

Table S1. The generic name of steroid used in current cohort. (DOCX 133 kb)

Background Aeroallergen sensitization may predict higher fractional exhaled nitric oxide (FeNO) levels. Objective We evaluate cut-off values of FeNO in asthmatic children with and without positive specific immunoglobulin E (IgE) to at least one of 5 aeroallergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat, dog, and cockroach). Methods 564 patients with asthma and allergic rhinitis (AR) aged 5 to 18 years were enrolled into two groups. Sensitized group included 378 children with positive IgE to at least one of 5 inhaled allergens. Non-sensitized group included 186 children. Pulmonary function tests, FeNO, eosinophil counts, and IgE levels were examined. Patients were divided into preschool age (5~6 years old), elementary school children (7~11 years old) and adolescents (12~18 years old). Results In preschool children, FeNO≥15.5 ppb differentiates between non-sensitized and sensitized groups. (sensitivity 54.3%; specificity 87.5%; positive predictive value (PPV) 86.2%; negative predictive value (NPV) 57.1%; area under receiver operating characteristic curve (AUC) 0.72) Among elementary school children, the cut-off value of FeNO≥19.5 ppb showed sensitivity 66.4%; specificity 85.8%; PPV 90.5%; NPV 55.7%; AUC 0.81. In adolescents, FeNO≥27.5 ppb showed sensitivity 60.2%; specificity 85.4%; PPV 91.2%; NPV 46.1%; AUC 0.76. Conclusion In asthmatic children, aeroallergen sensitization appears to contribute to higher FeNO levels than those not sensitized. Cut-off values of FeNO which well discriminate asthmatic children with and without aeroallergen sensitization should be chose according to different ages.

Patients with X-linked hyperimmunoglobulin M syndrome (XHIGM) have a defective CD40-CD40 ligand system and further immunoglobulin class-switching. They may present with recurrent infection and malignancy involving the liver, pancreas or biliary tract. We report here a case of poorly differentiated transitional cell carcinoma in a young man with XHIGM even on regular treatment and discuss the possible pathogenesis. Given that the triggering of the CD40-CD40 ligand system has been found to improve tumor immunogenicity in recent studies, future immunotherapy targeting the CD40 ligand for these patients may be feasible to prolong their survival.

Cystic fibrosis (CF) is one of the most common autosomal recessive inherited disorders among Caucasians. Comparatively, it is considered to be a rare disease among Asians. To date, only a few cases of Taiwanese CF have been published. We report four CF cases from three families. Case 1 was the first report of CF associated with a homozygosity for the CF transmembrane conductance regulator gene (CFTR gene) mutation 3849+10kb C->T in a Taiwanese patient. Cases 2 and 3 had heterozygous c. 1898+5 G->T and heterozygous p. I1023R (novel mutation) for the CFTR gene mutation. Case 4 was homozygous for the CFTR gene mutation R553X being reported in 2005 and complicated with cor pulmonale. These four patients had received 300 mg bid aerosolized tobramycin treatment every other month.

We report a 3-year-old girl with Kawasaki disease who presented with retropharyngeal edema and shock syndrome. This is the first reported case in Taiwan. The patient initially presented with fever, cough, and pyuria followed by rapidly progressive enlarged bilateral cervical lymphadenopathy. On the third day of the fever, computed tomography for airway compression sign found widening of the retropharyngeal space mimicking a retropharyngeal abscess. Later, an endotracheal tube was inserted for respiratory distress. A skin rash over her trunk was also noted. On the fifth day of the fever, the clinical course progressed to hypotension and shock syndrome. Because of more swelling of bilateral neck lymph nodes, computed tomography was arranged again and revealed partial resolution of the edematous changes in the retropharyngeal space. Edema of the hands and feet, bilateral bulbar conjunctivitis, and fissured lips were subsequently found. The diagnosis of Kawasaki disease was confirmed on the eighth day of fever. There was no evidence of bacterial infection. She was administered intravenous immunoglobulin (2 mg/kg) and high dose aspirin (100 mg/kg/day). One day later, the fever subsided, and her blood pressure gradually became stable. Heart echocardiography on the Day 13 revealed dilated left coronary artery and mitral regurgitation. Follow-up echocardiography six months later showed normal coronary arteries. To date, the patient has not experienced any complications. This case illustrates that retropharyngeal edema and shock syndrome can be present in the same clinical course of Kawasaki disease. Clinicians and those who work in intensive care units should be aware of unusual presentations of Kawasaki disease to decrease rates of cardiovascular complications.

Hyper IgM syndrome (HIGM), characterized by recurrent infections, low serum IgG and IgA, normal or elevated IgM, defective class switch recombination and somatic hypermutation, are heterogeneous disorders with at least 6 distinct molecular defects, including the CD40 ligand (CD40L) and the nuclear factor κB essential modulator (NEMO, also known as IKKγ) genes (both X-linked), the CD40, activation-induced cytidine deaminase (AICDA or AID), uracil-DNA glycosylase genes (autosomal recessive) and IκBα (IKBA) (autosomal dominant). Our objective was to determine the molecular basis and clinical features of Taiwanese patients with the HIGM phenotype.Clinical manifestations and candidate genes were analyzed in a nationwide population-based study.Among 14 patients (12 unrelated families) since 2003, 10 patents were identified (8 families) with CD40L mutations, including 2 novel deletions of "A" nucleotide (Del 347A and Del 366A), both frameshift and stop at the 127th location; 1 novel AID deletion mutation lack of the 37thAsp and 38th Ser; 1 ataxia-telangiectasia mutation; and 1 deletion of chromosome 1q42. An adult-onset patient with mutant (Thr254Met)CD40L had approximately 30% detectable affinity and therefore less severity. Memory B cells decreased in patients with CD40L and activation-induced cytidine deaminase mutations. Three mortalities encompassed renal cell carcinoma in 1 patient with (Tyr169Asn)CD40L, pneumothorax in 1 with (Tyr140Stop)CD40L and pneumonia after chemotherapy in an ataxia-telangiectasia patient. One patient without detectable genetic defects but normal lymphocyte proliferation resembled the mild form of common variable immune deficiency phenotype.In contrast to those with AICDA mutation, small chromosome 1 q42 deletion and unknown genetic defect, the majority (10/14; 71.4%) with CD40L mutations except (Thr254Met) and an ataxia-telangiectasia patient had the severe form of HIGM phenotype.

As a member of orthomyxoviridae family, influenza viruses are enveloped viruses containing eight RNA segments. The main antigenic determinants of influenza A and B viruses are two surface glycoproteins, the hemagglutinin (H) and the neuraminidase (N). A genetic reassortment between influenza A viruses from different animal hosts may lead to an antigenic shift and thereby increase the risk of a potential pandemic. H1N1 and H3N2 subtypes of influenza A have been circulating all over the world as seasonal influenza since the last H3N2 pandemic in 1968.1 In April 2009, the Centers for Disease Control and Prevention of the United States identified two cases of human infection with the H1N1 novel influenza virus. The greatest initial burden of critical illness and deaths occurred in Mexico between March and June 2009. The virus is a triple-reassortant containing gene segments from swine influenza virus, human influenza virus, and avian influenza virus. Genes for hemagglutinin and neuraminidase come from swine influenza virus.2 On June 11th, 2009, the World Health Organization raised the level of influenza A (H1N1) pandemic alert from phase 5 to 6, as sustained communitylevel transmission of the virus is taking place in more than one region of the world. Recommendations for the Management of Children With H1N1 Novel Influenza Infection

Our aims were to evaluate the performance of an automated microfluidic immunoassay system for measuring allergen-specific IgE (sIgE) in sera against an established in vitro assay and to assess the systems diagnostic accuracy against objective clinical criteria for identifying sensitization to specific allergens in daily practice of allergy clinics. Using both the automated microfluidic-based immunoassay system (BioIC) and ImmunoCAP, we measured sIgE in serum samples from 212 children who visited allergic clinics in two medical centers. Outcomes of skin prick tests (SPT) served as the clinical comparison method. The assay results of targeted allergen of BioIC have a good correlation with ImmunoCAP in the diagnosis of allergen sensitivity by patients clinical history. When comparing the test results of the sIgE against overall allergens, in either two tests among the three assays performed showed high percentage of agreement between BioIC and ImmunoCAP (77.8%, 95% CI: 72–83.3%) but not with SPT (BioIC 64.9%, 95% CI: 58–72%; ImmunoCAP 67.5%, 95% CI: 61–74%). Using ROC analysis and SPT as quasi-standard, BioIC and ImmunoCAP have nearly the same performance of sensitivity and specificity in the confirmation of SPT results. The total and within one-class agreements of each allergen test result between BioIC and ImmunoCAP ranged between 55.2% and 99.5% with an overall average of 80.9%. Laboratory testing for sIgE can be performed on a fully automated, microfluidic cartridge system with advantages of low sample volume, simultaneously tested allergens, and with diagnostic accuracy for representative allergens equivalent to the semi-automated CAP technology.

We previously reported an association between genetic differences of pediatric asthma subtypes and a short tandem repeat (STR) marker, D9S286. It has been known that the protein-tyrosine phosphatase receptor-type delta (PTPRD) gene is located downstream of D9S286 and that the physical distance between them is about 0.25 Mb. We selected and conducted genotyping on 76 single-nucleotide polymorphisms (SNPs) that encircle the genomic region of PTPRD in Taiwanese children with or without asthma. A total of 996 subjects were divided into testing group (674 subjects) and validation group (322 subjects). The results were further validated with the third subject group (611 subjects) recruited from different geographical regions. After Bonferroni correction, 3 out of 80 SNPs were found to be strongly significant (P < 0.05/76 = 0.000658) in the allele frequency test. This association was confirmed by validation groups. The results indicate that polymorphisms of PTPRD are strongly associated with pediatric bronchial asthma in the Taiwanese population.

Background Hereditary angioedema (HAE) is a rare disorder characterized by recurrent attacks of localized subcutaneous or submucosal edema. It is inherited in an autosomal dominant fashion and caused by a deficiency of C1 inhibitor (C1 INH). Most patients with HAE have an absolute deficiency of C1 INH (type I HAE), whereas the rest (approximately 15%) synthesize a dysfunctional C1 INH protein (type II HAE). Mosaicism is rare in HAE. Objective To describe the clinical manifestations, laboratory findings, and molecular genetic studies in a Taiwanese family with type I HAE with paternal mosaicism. Methods A family that included a 34-year-old man (index patient) and his 25-year-old brother who both had recurrent peripheral angioedema was evaluated. A younger sister had died of an unexplained cause at 18 years of age. We analyzed blood levels of C3, C4, and C1 INH and sequenced the SERPING1 ( C1NH ) gene that codes for C1 INH in 5 family members, including the parents and 3 brothers. Results The 4 men in the family had a novel mutation c.3_73del, p.N1fsX34 in exon 3 of the C1INH gene, resulting in C1 INH deficiency. Although the father carried this mutant gene, he had normal serum levels of C1 INH. Based on quantitative analysis of allele dosage by DNA fragment analysis (GeneScan), the father was determined to have genetic mosaicism. Conclusion Parental mosaicism is a possible explanation for normal C1 INH plasma concentrations in both parents despite clinically apparent HAE in the children.

An 8-month-old boy developed a disseminated cutaneous mycobacterial infection at 6 months of age that responded poorly to treatment. Further immunologic study and sequence analysis showed the presence of a missense mutation in the IL2RG gene, and X-linked severe combined immunodeficiency was diagnosed. To identify the strain of the microorganism causing the cutaneous infection, polymerase chain reaction with four pairs of primers was performed on skin biopsy specimens positive for acid-fast bacilli. Sequence analysis showed 99.36% homology with a bacilli Calmette-Guerin positive control. Disseminated bacilli Calmette-Guerin disease must be considered in any infant with cutaneous mycobacterial lesions, especially those with atypical histologic findings or who are immunocompromised. Testing by polymerase chain reaction using the proper primers may help in making a precise diagnosis.

Background X-linked agammaglobulinemia (XLA), characterized by a profound deficiency of all immunoglobulins and the absence of mature B cells, is caused by mutations in the gene encoding Bruton tyrosine kinase (BTK). Most patients have recurrent sinopulmonary infection. Infections usually occur in multiple locations across time, but single infection may be limited to one anatomic location. Objectives To report a case of atypical XLA with recurrent pyoderma and to observe the immunologic changes in the patient in 10 years. Methods Immunologic investigations, skin wound culture, and molecular study with DNA sequencing were performed. Results The patient was originally diagnosed as having common variable immunodeficiency disease because of the presence of circulating B cells (CD19+ B cells: 7%) at 11 years old. On further evaluation at the age of 20 years, flow cytometric analysis of lymphocytes showed only 0.4% B cells. The molecular study with DNA sequencing of the patient showed a point mutation in complementary DNA 1630 A>G(p.R544G) in the BTK gene, indicating that the patient has XLA. The mutation analysis of the BTK gene revealed a normal DNA sequence in the other family members. Conclusions This case is an important example of a possible presentation of XLA with a predominant skin manifestation, and it demonstrates that maintaining a high level of clinical suspicion is essential for the diagnosis of XLA in a child with recurrent pyoderma.

Trisomy 18 is the second most common autosomal trisomy in newborns. The birth prevalence of this disorder is approximately 1 in 3,000 to 1 in 8,000, and the life span of the majority of patients is less than 1 year. As information regarding outcome in trisomy 18 is rather fragmentary in the literature, this study is aimed at investigating the survival and natural history of trisomy 18. We also evaluated the survival age and management of trisomy 18 in two different periods, before and after the implementation of National Health Insurance (NHI) program. Thirty-nine cases of trisomy 18 were collected in Mackay Memorial Hospital in a 17-year period, from 1988 to 2004. Delivery data, survival age, management before and after the implementation of NHI program, structural defects, image findings and cytogenetic results were analyzed by medical and nurse's records. The diagnosis of trisomy 18 was based on the prenatal amniocentesis or postnatal chromosome analysis. Three patients had trisomy 18 mosaicism. Since cardiovascular and central nervous systems are the most common organ systems involved in this disorder, 31 patients received brain ultrasonography and heart ultrasonography for evaluation of their multiple anomalies after admission. All patients except one died in their first year due to severe malformations of the cardiovascular or central nervous systems. The median survival age was 6 days. We found a longer survival with female patients than with male patients (P < 0.05). Implementation of NHI program in the more recent decade of this study period was associated with longer survival of trisomy 18 (P < 0.05). The three most common structural defects were clenched hands (95%), rocker bottom feet (90%), and low set or malformed ears (90%). Low birth weight was present in 90%. By cardiac ultrasonography, the top four heart defects were ventricular septal defect (94%), patent ductus arteriosus (77%) and atrial septal defect (68%). However, ten cases (32%) had complex congenital heart defects. By brain ultrasonography, the most common brain lesion was cerebellar hypoplasia (32%), followed by brain edema (29%), enlarged cisterna magna (26%) and choroid plexus cysts (19%). Although most patients with trisomy 18 die within the first few weeks after birth, it is important to recognize that a small but notable percentage of these patients will survive the first year. When prenatal or postnatal decisions need to be made, the possibility of long-term survival should be included in any discussion to enable families to make the most appropriate decision.

Background Hyper-IgM1 syndrome is a rare genetic primary immunodeficiency disease caused by mutations of the CD40 ligand gene. It is characterized by normal or elevated levels of IgM and markedly decreased serum IgG, IgA, and IgE levels. Patients with this syndrome often easily develop infections. During the past decade, it has become clear that enteroviral infections may also occur as a manifestation of hyper-IgM1 syndrome. Objective To report a case of hyper-IgM1 syndrome in a 3-month-old boy who had interstitial pneumonia and intractable diarrhea. Methods Chest radiography, bronchoscopy, immune studies, and open lung biopsy were performed. Results Chest radiography revealed diffuse bilateral infiltrates. Immune studies revealed the following proportions of lymphocyte markers: CD3, 5,976/μL; CD4, 5,015/μL; CD8, 866/μL; CD19, 1,325/μL; CD16 + 56, 935/μL; and active T cells, 225/μL. The IgG level was 190 mg/dL; IgA, 2 mg/dL; IgM, 34 mg/dL; IgE, 1 IU/dL; and CH 50 , 23.8/mL. CD40L expression was less than 1%, and a Tyr 169 Asn (t526a) mutation in the exon 5 tumor necrosis factor domain of the CD40L gene was found. The patient was treated with intravenous immunoglobulin and had a dramatic improvement in symptoms. Open lung biopsy failed to demonstrate pneumocystis, and there was no evidence of cryptosporidium in the stool. However, coxsackievirus B4 was isolated by viral throat culture. Conclusion Interstitial pneumonia and diarrhea caused by coxsackievirus B4 may be a complication of hyper-IgM1 syndrome.

Hereditary angioedema (HAE) due to C1 inhibitor deficiency (C1-INH) is a rare complement immunodeficiency disease. It is an autosomal dominant condition with an estimated prevalence of approximately 1:50,000 to 100,000 in Western countries and 1: 1,000,000 in Taiwan. HAE can be categorized into three different types. Type I HAE results from low antigenic and functional levels of C1INH. Type II HAE is associated with a normal C1-INH protein level but impaired function. Type III HAE has been described in women only and presents normal C1-INH levels and function. In Taiwan, all of the reported cases were type I HAE. In this report,wedescribe thefirst caseof type II HAE inTaiwan. A 37-year-old man visited Mackay Memorial Hospital, Taipei, becauseof recurrent abdominal painwith syncope for 2 months. He suffered from spontaneous lip, limbs, and perineum eruption with nonpitting edema since 2009, but there was no identified trigger. The skin lesion onset was about three to five times a year and the usual duration was 3e4 days, afterwhich the symptoms resolved spontaneously. Severe abdominal pain with syncope occurred in July 2014. Physical examination showed periumbilical tenderness with muscle guarding noted but no rebounding pain. Abdominal computed tomography showed edematous of the duodenum

Background Systemic anaphylaxis after the ingestion of mite-contaminated food has rarely been reported. Objective To describe an 8-year-old boy in whom systemic anaphylaxis developed shortly after the ingestion of pancakes prepared with commercial pancake flour. Methods The patient underwent skin prick testing for house dust mites and with uncontaminated and mite-contaminated pancake flour. Specific IgE for mites and the main ingredients of the pancake flour were also evaluated, with titers for Der p 1, Der f 1, and Blo t 5 quantitated using immunochemical methods. A sample of pancake flour was examined microscopically for mites. Results The patient had positive skin prick test results to contaminated pancake flour extract (1 g/5 mL), Dermatophagoides pteronyssinus , and Dermatophagoides farinae but a negative skin test response to uncontaminated pancake flour. The patient's serum specific IgE analysis was positive for antibodies to dust and storage mite allergens. There was no response, however, to the main ingredients of the pancake mix. Microscopic examination of the pancake flour revealed the storage mite Blomia freemani . Using an immunochemical assay, we found that the contaminated flour contained 5.4 μg/g of the allergen Blo t 5 but no Der p 1 or Der f 1. Conclusions This patient's anaphylactic episode was the result of ingestion of the storage mite B freemani . To our knowledge, this is the first reported systemic hypersensitivity reaction caused by this mite anywhere in the world.

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.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.

Hereditary angioedema (HAE) is a rare, autosomal dominant inherited disease which is caused by a genetic deficiency of C1 esterase inhibitor (C1 INH). There have only been a few case reports in Taiwan to date.To describe the clinical features of type I HAE in Taiwanese patients.Three unrelated Taiwanese families with type I HAE are reported, and one case of a family from a review of PubMed was reviewed. Clinical manifestations, diagnostic examinations, management and genetic studies were analyzed.Including this report, 19 patients had low C1 INH and low C4 levels and were diagnosed with type I HAE. Only 11 (57.9%) patients were symptomatic. Recurrent skin swelling and edema over the four extremities or trunk were reported in all symptomatic patients (100%). 45.5% of the patients recalled laryngeal attacks and one patient died from asphyxia. 18.2% of the patients experienced abdominal symptoms. The age at the beginning of clinical symptoms ranged from 5 to 30 years (mean +/- SD: 20.82 +/- 7.88 years). The diagnosis tended to be delayed (range from 1 to 39 years; mean +/- SD: 8.45 +/- 11.04 years). Nine patients had a mutant C1 INH gene, and two patients received long-term prophylaxis with danazol.The prevalence of hereditary angioedema in Taiwan is low. Persons with low levels of C1 INH who were clinically symptomatic accounted for only 57.9% of the cases in our study, which is far lower than previous reports from other countries. Ethnic differences may be the reason for this finding. Further genomic studies are needed to elucidate the genetic penetrance of C1 INH deficiency in Taiwan.

X-linked agammaglobulinemia (XLA, also called Bruton's disease) is is an X-linked recessive disorder characterized by recurrent bacterial infections, usually occurring in the first few years of life. Here, we report the results of a BTK gene mutation screening study that was performed in Taiwanese families with the BTK gene defect to further understand the inheritance patterns of XLA patients in Taiwan and to avoid new cases of XLA within families.In this study, 52 members of 4 unrelated Taiwanese families with the BTK gene defect were enrolled. We studied the immunologic reports of 6 symptomatic living male patients with confirmed BTK gene defects and correlated the findings with their clinical symptoms. The genomic DNA of the subjects was subjected to direct sequencing mutation analysis.We screened 52 members of 4 unrelated Taiwanese families with the BTK gene defect for BTK gene mutation and found that there were 6 symptomatic living patients with a confirmed defect, 7 symptomatic deceased patients highly suspected to have had the defect and 11 asymptomatic female carriers.This is the first report in a series of the thorough screening for the BTK mutation and its carrier status in 4 unrelated Taiwanese families. One pedigree of our study comprises 4 generations. A complete BTK gene mutation study for the patient's family members is strongly suggested.

Patients with X-linked hyperimmunoglobulin M syndrome (XHIGM) have a defective CD40-CD40 ligand system and further immunoglobulin class-switching. They may present with recurrent infection and malignancy involving the liver, pancreas or biliary tract. We report here a case of poorly differentiated transitional cell carcinoma in a young man with XHIGM even on regular treatment and discuss the possible pathogenesis. Given that the triggering of the CD40-CD40 ligand system has been found to improve tumor immunogenicity in recent studies, future immunotherapy targeting the CD40 ligand for these patients may be feasible to prolong their survival.

Primary immunodeficiency diseases (PIDs) are a group of rare diseases with wide geographic and ethnic variations in incidence, prevalence, and distribution patterns. The aim of this study was to examine the distribution pattern and clinical spectrum of PIDs in Taiwan at a national referral institute. From 1985 to 2010, 215 patients from 183 families were diagnosed and grouped according to the updated classification of PIDs. Eighty-one (37.7%) patients had “other well-defined immunodeficiency syndromes”, followed by “predominantly antibody deficiencies” (54 patients; 25.1%), “T- and B-cell immunodeficiencies” (34; 15.8%), “congenital defects of phagocytes” (25; 20.2%), “complement deficiencies” (15; 7.0%), and “disease in immune dysregulation” (5; 2.3%). The last category included two patients with Chediak–Higashi syndrome, and one each with familial hemophagocytosis, IPEX, and hypogammaglobulinemia and albinism. One female had cold-induced auto-inflammatory disease. There were no cases of “defects in innate immunity”. Pseudomonas and Streptococcus pneumoniae were the two most identified microorganisms in septicemia (42.7%; 44/103 episodes). Stem cell transplantation was successful in 13 of 22 patients, while 34 patients (15.8%) died. Molecular defects were identified in 109 individuals (from 90 families). There were relatively fewer cases of “predominantly antibody deficiencies” due to there being only a few patients with adult-onset PIDs, implying certainty bias rather than ethnic variation. Awareness of under-diagnosis among physicians rather than pediatricians is vital for timely diagnosis and consequently adequate treatment.

Scleroderma is a chronic connective tissue disease characterized by hardened or scaly skin and widespread abnormalities of the viscera, which is rare in the pediatric age group.In this study, we retrospectively reviewed 23 pediatric patients suffering systemic (SSc) and localized (LS) scleroderma.Twenty-three patients were enrolled and were diagnosed with SSc or LS from March 1993 to September 2009 in the Department of Pediatrics at Mackay Memorial Hospital in Taipei, Taiwan. These diagnoses were based on the criteria of the American College of Rheumatology and the clinical manifestations of hard skin. Data recorded included sex, age-at-onset, age-at-diagnosis, laboratory data, family history, trauma history, treatment, and outcomes.Three patients suffered SSc and 20 patients had LS, including 16 girls and 7 boys. Mean age-at-onset was 6.55 +/- 3.28 years old. Antinuclear antibodies were positive in 15 patients. Tests for anti-Scl-70 antibodies were positive in 1 patient with SSc. One boy had en coup de sabre combined with a posterior fossa tumor. Twenty-two patients were treated with D-penicillamine. Oral prednisolone and methotrexate were added, if indicated. One girl with LS developed proteinuria after D-penicillamine treatment. All patients with localized disease ultimately documented a softening of their skin lesions.While scleroderma is rare in children, the prognosis of SSc is poor but better than for adults. The prognosis for LS is usually benign, however, the skin may become progressively indurated and it may not only be a skin disease. No progression from LS to SSc was observed in our study.

This report is of a healthy 3-year-old boy with bilateral parotitis caused by Mycobacterium chelonae. He was treated with antibiotics, but the symptoms did not improve. The biopsy pathology report revealed chronic caseating granulomatous inflammation. After 2 weeks, Mycobacterium chelonae was identified from the biopsy specimen culture. The antibiotics were changed to amikacin and clarithromycin, according to the susceptibility test. Two weeks later, he underwent debridement surgery. Only partial excision of the infected tissue was performed because of the possibility of facial nerve injury. After another 2 weeks of treatment with amikacin and clarithromycin, parotidectomy was performed. The patient then received a 6-month course of oral clarithromycin. At the 1-year follow up, he was well and without residual mass. His immunologic examinations were all within normal limits. This is the first report of bilateral parotitis caused by Mycobacterium chelonae in an immunocompetent boy in the English-language literature.

Our aims were to evaluate the performance of an automated microfluidic immunoassay system for measuring allergen-specific IgE (sIgE) in sera against an established in vitro assay and to assess the system's diagnostic accuracy against objective clinical criteria for identifying sensitization to specific allergens in daily practice of allergy clinics. Using both the automated microfluidic-based immunoassay system (BioIC and ImmunoCAP, we measured sIgE in serum samples from 212 children who visited allergic clinics in two medical centers. Outcomes of skin prick tests (SPT) served as the clinical comparison method. The assay results of targeted allergen of BioIC have a good correlation with ImmunoCAP in the diagnosis of allergen sensitivity by patients' clinical history. When comparing the test results of the sIgE against overall allergens, in either two tests among the three assays performed showed high percentage of agreement between BioIC and ImmunoCAP (77.8%, 95% CI: 72-83.3%) but not with SPT (BioIC 64.9%, 95% CI: 58-72%; ImmunoCAP 67.5%, 95% CI: 61-74%). Using ROC analysis and SPT as quasi-standard, BioIC and ImmunoCAP have nearly the same performance of sensitivity and specificity in the confirmation of SPT results. The total and within one-class agreements of each allergen test result between BioIC and ImmunoCAP ranged between 55.2% and 99.5% with an overall average of 80.9%. Laboratory testing for sIgE can be performed on a fully automated, microfluidic cartridge system with advantages of low sample volume, simultaneously tested allergens, and with diagnostic accuracy for representative allergens equivalent to the semi-automated CAP technology.

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 × 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.

The aim of this study was to evaluate the clinical and immunologic effects of sublingual-swallow immunotherapy (SLIT). A six-month, multicenter, double-blind, placebo-controlled trial was carried out in 59 patients aged 6 to 18 years with allergic rhinitis who were sensitized to mites only. Patients were randomly assigned to placebo or SLIT with a standardized Dermatophagoides pteronyssinus (D.p.)/D. farinae (D.f) 50/50 extract. Nasal symptom scores and use of medications were recorded. Skin sensitivity, mite-specific IgE, IgG4, and IgG4/IgE were evaluated before and after treatment. The skin sensitivity, total nasal symptom scores and medication consumption did not differ significantly after treatment. Specific IgG4 (both p0.001) and IgG4/IgE to D.p. and D.f (p = 0.010, p = 0.001, respectively) increased significantly in the treatment group. Specific IgE increased significantly in both placebo and SLIT groups after treatment but did not differ between the two groups. The medication was well tolerated. SLIT did not significantly improve clinical manifestations of allergic rhinitis when used for 6 months. We demonstrated SLIT did significantly increase specific IgG4 and IgG4/IgE compared to treatment with placebo.

To evaluate the efficacy of prednisolone sodium phosphate oral solution plus inhaled procaterol in the treatment of acute asthma in children.Forty-three patients aged 6 to 12 years with an acute exacerbation of asthma were double-blind randomized into one of two treatment groups in a 1:1 ratio:1) prednisolone oral solution +placebo tablets + procaterol MDI or 2) prednisolone tablets +placebo oral solution + procaterol MDI, all given three times daily for 7 days. Peak expiratory flow rate (PEFR), 24-hour reflective asthma symptom scores, spirometry and pulmonary index score (PIS) were recorded before and after treatment. Net changes in PEFR, symptom score, PIS, Forced Expiratory Volume in the first second (FEV1), FEV1/forced vital capacity (FVC), forced expiratory flow between 25 and 75 percent of the forced vital capacity (FEF(25-75%)) (before and after treatment) and global assessment by the investigator and the subjects or their parents were analyzed.The two groups were statistically similar at baseline values of these parameters. After a 7-day course of treatment, the net change of PEFR before and after treatment was significantly improved in both groups, but there was no significant difference in the net change of PEFR between the two groups (57.27+/-31.44 L/min vs. 54.29 +/-30.04 L/min, difference 2.99 +/-30.76 L/min, mean +/-SD, P=0.752). The net change in PIS and total symptom score did not differ between the two groups (P=0.091 and 0.827, respectively). Similarly, the FEV1, FEV1/FVC and FEF25-75% all improved with either treatment, and neither group was significantly superior to the other group (P=0.162, 0.48 and 0.081, respectively). Global assessment by the investigator and the subjects or their parents at the end of study indicated an essentially comparable result.Prednisolone sodium phosphate oral solution plus inhaled procaterol is as efficacious as prednisolone tablets plus inhaled procaterol in the management of acute asthma in children.

Hereditary angioedema (HAE) is an autosomal dominant disorder caused by a deficiency of C1 esterase inhibitor (C1-INH). Affected individuals have attacks of swelling involving almost any part of the body. We studied a family with 15 living members, including a 16-year-old girl who had 3 attacks of angioedema in 2 years. Her paternal uncle had died of asphyxiation during an attack 15 years previously. We analyzed the blood of each family member for C3, C4, and C1-INH levels and sequenced the SERPING1 (formerly C1NH) gene that codes for C1-INH. Six individuals had decreased serum levels of C4 and C1-INH, and they were all found to have a single nucleotide A deletion at codon 210 of the gene, 1210fsX210, a novel mutation that accounts for the HAE in this family.

An 8-month-old boy developed a disseminated cutaneous mycobacterial infection at 6 months of age that responded poorly to treatment. Further immunologic study and sequence analysis showed the presence of a missense mutation in the IL2RG gene, and X-linked severe combined immunodeficiency was diagnosed. To identify the strain of the microorganism causing the cutaneous infection, polymerase chain reaction with four pairs of primers was performed on skin biopsy specimens positive for acid-fast bacilli. Sequence analysis showed 99.36% homology with a bacilli Calmette-Guérin positive control. Disseminated bacilli Calmette-Guérin disease must be considered in any infant with cutaneous mycobacterial lesions, especially those with atypical histologic findings or who are immunocompromised. Testing by polymerase chain reaction using the proper primers may help in making a precise diagnosis.

IgE-mediated hypersensitivity to buckwheat is common in Korea, Japan, and some other Asian countries. However, buckwheat is not a common allergen in Taiwan. We report a woman with asthma who had anaphylactic shock, generalized urticaria, and an acute exacerbation of asthma five minutes after ingesting buckwheat. The patient underwent skin prick and Pharmacia CAP testing (Uppsala, Sweden) for specific IgE to buckwheat, white sesame and soybean as well as other common allergens in Taiwan including Dermatophagoides pteronyssinus (Dp), D. farinae (Df), cat and dog dander, cockroach, egg white, cow milk and codfish. The patient had a strongly positive skin prick test response to buckwheat and positive reactions to Dp and latex. Specific IgE results were class 6 for buckwheat, class 4 for Dp and Df, and class 2 for dog dander, wheat, sesame and soybean. Results of an open food challenge with white sesame and soybean were negative. Although buckwheat is a rare allergen in Taiwan, it can cause extremely serious reactions and should be considered in patients presenting with anaphylaxis after exposure to buckwheat.