Complete Myeloperoxidase Deficiency: Beware the "False-Positive" Dihydrorhodamine Oxidation.

Myeloperoxidase deficiency is the most common inherited phagocyte disorder (1:2000) and causes an abnormal dihydrorhodamine oxidation test, which also is seen in chronic granulomatous disease. A patient with Candida meningitis and low dihydrorhodamine oxidation signal was diagnosed with chronic granulomatous disease but actually had compound heterozygous myeloperoxidase deficiency.

Asthma in Urban Children: Epidemiology, Environmental Risk Factors, and the Public Health Domain.

Asthma is the most commonly reported chronic condition of childhood in developed countries, with 6.5 million children affected in the USA. A disparate burden of childhood asthma is seen among socioeconomically disadvantaged youth, often concentrated in urban areas with high poverty rates. Host factors that predispose a child to asthma include atopy, male gender, parental history of asthma, and also race, ethnicity, and genetic and epigenetic susceptibilities. Environmental factors, such as improved hygiene, ambient air pollution, and early life exposures to microbes and aeroallergens, also influence the development of asthma. With greater than 90% of time spent indoors, home exposures (such as cockroach, rodent, and indoor air pollution) are highly relevant for urban asthma. Morbidity reduction may require focused public health initiatives for environmental intervention in high priority risk groups and the addition of immune modulatory agents in children with poorly controlled disease.

Uncontrolled asthma: a retrospective cohort study in Japanese patients newly prescribed with medium-/high-dose ICS/LABA.

Many asthma patients remain uncontrolled despite guideline-based therapies. We examined real-life asthma control in Japanese patients prescribed with inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA). Patients (≥12 years) with ≥2 asthma diagnoses, newly initiated on medium-/high-dose ICS/LABA (Japanese asthma guidelines), from 01 April 2009 to 31 March 2015 were included, using Japan Medical Data Center Claims Database. Primary objective: proportion of patients with uncontrolled asthma in the year following ICS/LABA initiation. Secondary objectives: predictors of uncontrolled asthma and healthcare resource utilization. In medium-dose (N = 24,937) and high-dose (N = 8661) ICS/LABA cohorts, 23% and 21% patients, respectively, were uncontrolled. Treatment step up and exacerbation were most common indicators of uncontrolled asthma. Predictors of uncontrolled asthma, analyzed by multivariable Cox model, included systemic corticosteroid use, exacerbation history, comorbidities, and being female. In both cohorts, healthcare resource utilization was higher in patients with uncontrolled asthma. Over 20% patients with persistent asthma who initiated medium- or high-dose ICS/LABA were uncontrolled, highlighting unmet need for novel therapies in these patients.

Omalizumab and unmet needs in severe asthma and allergic comorbidities in Japanese children.

Childhood asthma is one condition within a family of allergic diseases, which includes allergic rhinitis, atopic dermatitis, and food allergy, among others. Omalizumab is an anti-IgE antibody therapy that was approved in Japan for children with asthma and added to the Japanese pediatric asthma guidelines in 2017. This review highlights the Japanese clinical perspectives in pediatric allergic asthma, and consideration for allergic comorbidities, and reflects on omalizumab clinical trials in progress to present comprehensive future opportunities.

A retrospective cohort study evaluating healthcare resource utilization in patients with asthma in Japan.

Although the global economic burden of asthma is well described, detailed data regarding Asia, particularly for Japan, are relatively scarce. This retrospective study aims to fill this evidence gap by evaluating asthma-associated healthcare resource utilization (HCRU) and economic burden in Japanese patients aged ≥16 years, identified using anonymized patient data from the Japan Medical Data Center (JMDC) database from April 2009 to March 2015. Asthma severity was classified according to asthma treatment guidelines from the Japanese Society of Allergology. HCRU was calculated based on hospitalizations, emergency room visits, outpatient visits, and prescriptions. Incidence rate ratios (IRRs) for HCRU and per-patient-per-year direct costs were reported. In addition, differences across HCRU and cost variables for severe versus non-severe asthma patients were also compared. Of 541,434 asthma cases identified from the JMDC database during the study period, 54,433 patients who met the inclusion criteria were included in this analysis. HCRU and costs were heavily concentrated within severe asthma, a subgroup comprising 12.7% of total study population. Moreover, patients with severe asthma had significantly higher all-cause hospitalizations, outpatient visits, outpatient prescriptions (IRR [95% CI], 1.60 [1.46-1.76]; 1.43 [1.41-1.45]; 1.24 [1.22-1.25], respectively), and total medical costs (mean ± SD costs, US$ 4345 ± 11,104 versus US$ 1528 ± 3989, P < 0.001 (t-test); US$ 1 = 110 JPY) compared with those with non-severe asthma. The burden of asthma is significantly and disproportionately concentrated in Japanese severe asthma patients, suggesting clinical failure to achieve adequate disease control. This study highlights the unmet needs for severe asthma in Japan and provides a catalyst for important dialogues in advancing public health.

Real-world safety and efficacy of omalizumab in patients with severe allergic asthma: A long-term post-marketing study in Japan.

BACKGROUND: Omalizumab (anti-IgE monoclonal antibody) is an approved add-on therapy for Japanese patients with severe allergic asthma. As directed by the Ministry of Health, Labor and Welfare Japan, a post-marketing surveillance (PMS) study on omalizumab was conducted between 2009 and 2017. METHODS: The PMS observed safety and efficacy of omalizumab in patients treated with open-label omalizumab for 52 weeks (with optional 2-year extension period). Primary safety outcomes included incidence and severity of adverse events (AEs) and adverse drug reactions (ADRs). Primary efficacy outcomes included physician-assessed global evaluation of treatment effectiveness (GETE). Asthma-exacerbation-related events including requirement for additional systemic steroid therapy, hospitalization, emergency room visits, unscheduled doctor visits, and absenteeism were also evaluated. RESULTS: Of 3893 patients registered, 3620 (age [mean ±â€¯SD] 59.3 ±â€¯16.11 years) were evaluated for 52 weeks; 44.12% were aged ≥65 years and 64.45% were women. Overall, 32.24% reported AEs and 15.30% reported serious AEs. ADRs were seen in 292 (8.07%) patients. GETE results showed that the majority of patients experienced clinical improvements (58.29% at 16 weeks and 62.40% at 52 weeks). Nearly half of all patients (47.96%) were free from asthma exacerbations after therapy. Omalizumab also reduced all events related to asthma exacerbations. No specific ADRs were observed in the elderly population. CONCLUSIONS: This post-marketing study confirmed the clinically meaningful benefits of omalizumab in a majority of patients from Japan, and showed safety and efficacy in a real-life clinical setting to be consistent with previous reports.

Gastric ulcers due to varicella-zoster reactivation.

We report on an 18-year-old man with common variable immunodeficiency presenting with abdominal pain and vomiting due to gastric ulcers caused by reactivation of varicella-zoster virus (VZV). Endoscopy revealed multiple ulcers in the gastric antrum. Fever and rash developed the next day. Skin biopsy showed multinucleated cells with intranuclear inclusions highly suggestive of VZV infection, and high-dose intravenous acyclovir was started. VZV was detected on direct immunofluorescence from skin biopsy and polymerase chain reaction from endoscopic biopsy. His course was complicated by encephalopathy, pancreatitis, hepatitis, renal impairment, and hyponatremia. After 3 weeks of antiviral therapy, he gradually improved. Skin lesions cleared within a week. He remained well on follow-up 1 year later. Disseminated zoster presenting as gastric ulcers in the absence of the classic rash is unusual but has been reported in immunosuppressed patients with a history of bone marrow and stem cell transplant. We report this rare presentation in a patient with common variable immunodeficiency and highlight the importance of considering zoster as a cause for severe abdominal pain and of seeking endoscopic diagnosis to facilitate early therapy and reduced mortality risk.