Cytomegalovirus Pneumonia in a Patient with X-Linked Agammaglobulinemia: A Case Report.

X-linked agammaglobulinemia (XLA) is a hereditary immune disorder that predisposes patients to frequent and severe bacterial infections caused by encapsulated bacteria (such as Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae). Otitis media, sinusitis, and pneumonia are common complications of XLA that require prompt diagnosis and treatment. Cytomegaloviruses (CMV) cause widespread and severe infections in immunocompromised individuals, affecting the respiratory tract, and consequently, leading to pneumonia, which is associated with a high mortality rate. However, CMV-induced pneumonia is rarely reported in patients with XLA. This case study details a 37-year-old male patient with XLA presenting with fever, productive cough, and dyspnea. The patient was diagnosed with CMV pneumonia and recovered after treatment. To the best of our knowledge, this is the first reported case of CMV pneumonia in a patient with XLA in Taiwan. This case study emphasizes that CMV pneumonia in patients with XLA is a treatable condition if diagnosed promptly, and that a shorter duration of treatment with the antiviral agent, in combination with immunoglobulin replacement therapy, can resolve symptoms.

Unusual presentation of linear wrist blisters associated with hereditary angioedema: The first case report in Taiwan.

Hereditary angioedema (HAE) is an autosomal dominant disease characterized clinically by recurrent episodes of swelling in the tissues of the extremities, face, abdomen, and respiratory tract. It is most often caused by C1 esterase inhibitor (C1 INH) gene mutation. This swelling may lead to bradykinin release, resulting in recurrent, paroxysmal, painful angioedema. Blister formation is an uncommon cutaneous manifestation of HAE. Herein, we report a case of a patient with HAE who developed linear wrist blisters on her skin, with swelling, as a rare complication of HAE. She was treated with attenuated androgens (Danazol) for two weeks at our clinic, after which the blisters showed dramatic improvement. To date, only a few HAE cases have been reported across the world. Therefore, it is important to focus on and recognize the development of edema blisters as a flare of HAE, which could consequently avoid unnecessary dermatological diagnostic workup and treatment.

Unilateral generalized morphea: First case report in Taiwan.

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.

Biphasic buckwheat anaphylaxis:Case report and systematic review.

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.

Exhaled nitric oxide helps discriminating asthmatic children with and without positive specific IgE to aeroallergens.

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.

Transitional cell carcinoma in a patient with X-linked hyperimmunoglobulin M syndrome.

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.

Epidemiology, Management, and Treatment Access of Hereditary Angioedema in the Asia Pacific Region: Outcomes From an International Survey.

BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disease with significant morbidity 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. Epidemiologic data from the AP is needed to formulate regional guidelines to improve standards of care for HAE. OBJECTIVE: To investigate the estimated minimal prevalence, needs, and potential interventions for the diagnosis and management of HAE in the AP. METHODS: A structured questionnaire was distributed to representative experts from member societies of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology. Patient profiles and the presence of diagnostic facilities or tests, regional and national HAE guidelines, and patient support groups were reported and compared. RESULTS: Completed questionnaires were received from 14 representatives of 12 member countries and territories, representing 46% of the world population. Overall minimal prevalence of HAE in the AP region was 0.02/100,000 population, with significant heterogeneity across different centers. Only one-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 the availability of HAE-specific medications. Availability of C1-inhibitor level testing was associated with a lower age at HAE diagnosis (P = .017). CONCLUSIONS: Hereditary angioedema in the AP differs from that in Western countries. Hereditary angioedema-specific medications were registered in only a minority of countries and territories, but those with patient support groups or regional guidelines were more likely to have better access. Asia Pacific-specific consensus and guidelines are lacking and urgently needed.

Type I hereditary angioedema in Taiwan -- clinical, biological features and genetic study.

BACKGROUND: 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. OBJECTIVE: To describe the clinical features of type I HAE in Taiwanese patients. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Clinical manifestations and BTK gene defect in 4 unrelated Taiwanese families with Bruton's disease.

BACKGROUND AND OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Determination of multiple allergen-specific IgE by microfluidic immunoassay cartridge in clinical settings.

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.

Factors for high-risk asthma in Taiwanese children.

BACKGROUND: Asthma is one of the major causes of death in otherwise healthy young individuals. However, many of these deaths may have been prevented by more aggressive treatment. To determine factors correlated with a high risk of death in Taiwanese children with atopic asthma. METHODS: Taiwanese children aged 5-18 years, diagnosed with atopic asthma were enrolled in the study. Atopic asthma was diagnosed and immunoglobulin E (IgE) specific to antigens from any 1 of 8 allergens was measured (i.e. Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat and dog dander, cockroach, egg white, milk and fish). High-risk asthma was defined as asthma requiring admission to a hospital or a visit to an emergency department. The study tried to determine the association of high-risk asthma with allergy-related parameters (e.g. asthma severity, asthma score, total serum IgE levels, serum levels of allergen-specific IgE, eosinophil count) and pulmonary function in Taiwanese children. RESULTS: One thousand one hundred and twenty-two Taiwanese children were evaluated. Those with higher asthma severity, asthma symptom score, serum levels of IgE specific to D. pteronyssinus and D. farinae, higher total serum IgE levels, and lower FEF25-75% (forced expiratory flow, 25-75%) values were considered to be members of the high-risk asthma group. CONCLUSIONS: The characterization of risk factors has enabled us to identify high-risk asthma in Taiwanese children, which will facilitate the treatment of these children in the future.

Juvenile scleroderma: experience in one institution.

BACKGROUND: 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. OBJECTIVE: In this study, we retrospectively reviewed 23 pediatric patients suffering systemic (SSc) and localized (LS) scleroderma. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The polymorphisms of protein-tyrosine phosphatase receptor-type delta gene and its association with pediatric asthma in the Taiwanese population.

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.

Changes in serum specific IgG4 and IgG4/ IgE ratio in mite-sensitized Taiwanese children with allergic rhinitis receiving short-term sublingual-swallow immunotherapy: a multicenter, randomized, placebo-controlled trial.

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 p <0.001) 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.

The risk of hospitalization for respiratory tract infection (RTI) in children who are treated with high-dose IVIG in Kawasaki Disease: a nationwide population-based matched cohort study.

BACKGROUND: Kawasaki disease (KD) is an immune-mediated systemic vasculitis, and infection plays an important role in the pathophysiology of KD. The susceptibility to infectious disease in patients with KD remains largely unclear. This study aimed to investigate the risk of respiratory tract infection (RTI)-related hospitalizations in children with KD. METHODS: Data from the Taiwanese National Health Insurance Research Database was analyzed. We excluded patients with history of congenital abnormality, allergic diseases, or hospitalization history. Children with KD were selected as KD group and age- and sex-matched non-KD patients were selected as control group with 1:4 ratio. Both cohorts were tracked for one year to investigate the incidences of RTI-related hospitalizations. Cox regression hazard model was used to adjust for confounding factors and calculate the adjusted hazard ratio (aHR). RESULTS: Between January 1996 and December 2012, 4,973 patients with KD were identified as the KD group and 19,683 patients were enrolled as the control group. An obviously reduced risk of RTI-related hospitalizations was observed in KD patients (aHR: 0.75, 95% CI [0.66-0.85]). The decreased risk persisted through the first six-months follow-up period with a peak protection in 3-6 months (aHR: 0.49, 95% CI [0.37-0.64]). CONCLUSIONS: KD patients had approximately half reduction of risk for RTI-related hospitalizations. The protective effects persisted for at least six months. Further studies are warranted to elucidate the entire mechanism and investigate the influences of intravenous immunoglobulin.

Incidence and risk factors for recurrent Henoch-Schönlein purpura in children from a 16-year nationwide database.

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 < 18 years were identified. Among them, 164 had ≥2 HSP episodes (recurrence rate, 16.4%; incidence of recurrent HSP, 7.05 per 100 person-years); 83.6% patients with one HSP episode remained free of secondary HSP. The average time intervals between the first and second and second and third HSP episodes were 9.2 and 6.4 months, respectively. After adjusting for demographic parameters, comorbidities, and socioeconomic status, recurrent HSP was found to occur more frequently in patients who had renal involvement (adjusted hazard ratio, 2.41; 95% confidence interval [CI], 1.64-3.54; p < 0.001), were receiving steroid therapy for > 10 days (adjusted hazard ratio, 8.13; 95%CI, 2.51-26.36; p < 0.001), and had allergic rhinitis (adjusted hazard ratio, 1.63; 95%CI, 1.06-2.50; p = 0.026). CONCLUSIONS: The annual incidence of recurrent HSP was low. However, children who had underlying allergic rhinitis, presented with renal involvement, and received steroid treatment for > 10 days should be notified regarding the possibility of recurrence.

Hereditary angioedema: a Taiwanese family with a novel gene mutation.

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.

Prednisolone oral solution plus inhaled procaterol for acute asthma in children: a double-blind randomized controlled trial.

BACKGROUND: To evaluate the efficacy of prednisolone sodium phosphate oral solution plus inhaled procaterol in the treatment of acute asthma in children. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.