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.

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.

Multisystem disorder associated with a pathogenic variant in CLCN7 in the absence of osteopetrosis.

BACKGROUND: We clinically and genetically evaluated a Taiwanese boy presenting with developmental delay, organomegaly, hypogammaglobulinemia and hypopigmentation without osteopetrosis. Whole-exome sequencing revealed a de novo gain-of-function variant, p.Tyr715Cys, in the C-terminal domain of ClC-7 encoded by CLCN7. METHODS: Nicoli et al. (2019) assessed the functional impact of p.Tyr715Cys by heterologous expression in Xenopus oocytes and evaluating resulting currents. RESULTS: The variant led to increased outward currents, indicating it underlies the patient's phenotype of lysosomal hyperacidity, storage defects and vacuolization. This demonstrates the crucial physiological role of ClC-7 antiporter activity in maintaining appropriate lysosomal pH. CONCLUSION: Elucidating mechanisms by which CLCN7 variants lead to lysosomal dysfunction will advance understanding of genotype-phenotype correlations. Identifying modifier genes and compensatory pathways may reveal therapeutic targets. Ongoing functional characterization of variants along with longitudinal clinical evaluations will continue advancing knowledge of ClC-7's critical roles and disease mechanisms resulting from its dysfunction. Expanded cohort studies are warranted to delineate the full spectrum of associated phenotypes.

Respiratory-syncytial virus immunoprophylaxis on asthma symptoms development in prematurity with bronchopulmonary dysplasia.

Background: Infants with respiratory-syncytial virus bronchiolitis hospitalization are more likely to develop wheezing and subsequent asthma. Reportedly, palivizumab prophylaxis effectively prevents respiratory-syncytial virus hospitalization in high-risk children-such as premature infants or infants with bronchopulmonary dysplasia (BPD). Objective: We sought to explore the effect of respiratory-syncytial virus immunoprophylaxis on the risk of asthma development in premature infants with BPD in subtropical areas. Methods: This case-control study included preterm children with BPD born at Mackay Memorial Hospital, Taipei, Taiwan, from 1999 to 2015. Overall, medical records of 616 eligible participants were retrospectively collected from their birth to the time they attained an age of 5 to 20 years. The primary outcome was onset of active asthma. Results: Overall, 576 consecutive cases met the inclusion criteria. Of these, 306 (53.2%) patients had palivizumab exposure and 191 (33.2%) were diagnosed with asthma. Patients with history of respiratory-syncytial virus bronchiolitis hospitalization had a higher risk of developing asthma in the future (adjusted odds ratio, 3.77; 95% CI, 2.30-6.20, P < .001; hazard ratio, 2.56; 95% CI, 1.81-3.62, P < .001). Palivizumab prophylaxis reduced future asthma development through the inhibition of respiratory-syncytial virus bronchiolitis hospitalization (coefficient, -0.021; 95% CI, -0.031 to -0.011, P = .027). Asthmatic children who received palivizumab immunoprophylaxis had a lesser active asthma duration than those who did not (P = .005). Conclusions: Children with BPD with hospitalization for respiratory-syncytial virus bronchiolitis had higher risk of developing asthma compared with those without respiratory-syncytial virus infection. Prophylactic palivizumab might reduce later asthma development through inhibition of respiratory-syncytial virus bronchiolitis hospitalization. For those already developing asthma, palivizumab could reduce active asthma duration.

Case report: Presentations and cytokine profiles of inflammatory non-pulmonary COVID-19 and related diseases in children.

The coronavirus disease 2019 (COVID-19) pandemic has evolved to dynamic waves of different SARS-CoV-2 variants. Initially, children diagnosed with COVID-19 presented pulmonary involvement characterized by mild diseases. In the later waves of the COVID-19 pandemic, life-threatening non-pulmonary inflammatory diseases such as (1) aseptic meningoencephalitis (ME), (2) acute necrotizing encephalopathies (ANE), and (3) multisystem inflammatory syndrome in children (MIS-C) have been reported, affecting the pediatric population. To alert timely identification and prevention of the life-threatening non-pulmonary COVID-19, we present the cases of ME, ANE, and MIS-C in terms of clinical manifestation, cytokine profile, and follow-up consequences. Based on the immunopathogenesis and risk factors associated with non-pulmonary COVID-19, we delineate strategies for an early diagnosis and treatment to reduce morbidity and mortality in children.

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.

Pseudomonas aeruginosa sepsis with ecthyma gangrenosum and pseudomembranous pharyngolaryngitis in a 5-month-old boy.

Pseudomonas aeruginosa infection that induced pseudomembranous laryngopharyngitis and ecthyma gangrenosum simultaneously in a healthy infant is rare. We reported on a previously healthy 5-month-old boy with initial presentation of fever and diarrhea followed by stridor and progressive respiratory distress. P. aeruginosa sepsis was suspected because ecthyma gangrenosum over the right leg was found at the emergency department, and the diagnosis was confirmed by the blood culture. Fiberscope revealed bacterial pharyngolaryngitis without involvement of the trachea. Because of early recognition and adequate treatment, including antimicrobial therapy, noninvasive ventilation, incision, and drainage, he recovered completely without any complications.

Unusual manifestations of Kawasaki disease with retropharyngeal edema and shock syndrome in a Taiwanese child.

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.

Cystic fibrosis: experience in one institution.

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.