Characteristics and risk factors of axillary lymph node metastasis of microinvasive breast cancer.

PURPOSE: To select patients who would benefit most from sentinel lymph node biopsy (SLNB) by investigating the characteristics and risk factors of axillary lymph node metastasis (ALNM) in microinvasive breast cancer (MIBC). METHODS: This retrospective study included 1688 patients with MIBC who underwent breast surgery with axillary staging at the Asan Medical Center from 1995 to 2020. RESULTS: Most patients underwent SLNB alone (83.5%). Seventy (4.1%) patients were node-positive, and the majority had positive lymph nodes < 10 mm, with micro-metastases occurring frequently (n = 37; 55%). Node-positive patients underwent total mastectomy and axillary lymph node dissection (ALND) more than breast-conserving surgery (BCS) and SLNB compared with node-negative patients (p < 0.001). In the multivariate analysis, independent predictors of ALNM included young age [odds ratio (OR) 0.959; 95% confidence interval (CI) 0.927-0.993; p = 0.019], ALND (OR 11.486; 95% CI 5.767-22.877; p < 0.001), number of lymph nodes harvested (≥ 5) (OR 3.184; 95% CI 1.555-6.522; p < 0.001), lymphovascular invasion (OR 6.831; 95% CI 2.386-19.557; p < 0.001), presence of multiple microinvasion foci (OR 2.771; 95% CI 1.329-5.779; p = 0.007), prominent lymph nodes in preoperative imaging (OR 2.675; 95% CI 1.362-5.253; p = 0.004), and hormone receptor positivity (OR 2.491; 95% CI 1.230-5.046; p = 0.011). CONCLUSION: Low ALNM rate (4.1%) suggests that routine SLNB for patients with MIBC is unnecessary but can be valuable for patients with specific risk factors. Ongoing trials for omitting SLNB in early breast cancer, and further subanalyses focusing on rare populations with MIBC are necessary.

Factors influencing the quality of life in children with atopic dermatitis in Korea: A multicenter cross-sectional study.

Background: There is a lack of studies about which factors affect the quality of life (QoL) in children with atopic dermatitis (AD), although it is well known that AD has considerably negative effects on their QoL. Objective: This study aimed to measure the QoL in children with AD and identify the factors that affect their QoL. Methods: A questionnaire derived from the Children's Dermatology Life Quality Index (CDLQI) was used to measure QoL. Family history, allergic comorbidities, exacerbation-related factors, time of exacerbation, and previous and current treatment were also evaluated. The total immunoglobulin E (IgE) level and specific IgE sensitization were determined by the multiple allergen simultaneous test, allergy test, or skin-prick test. AD severity was categorized into mild, moderate, and severe based on treatments. Results: In total, 254 children (46.4 months, 53% boys) from seven hospitals completed the survey. The mean CDLQI score was 7.2 ± 5.5 (total score range of 0-30). The respondents were divided into three groups according to their QoL score distribution, with 0 - 4 points (n = 84), 5 - 9 points (n = 90), and ≥10 points (n = 80) representing good, fair, and poor QoL, respectively. The more severe AD showed the higher CDLQI score significantly (p = 0.001). Compared with other groups, children with poor QoL were more sensitized to inhalant allergens (odds ratio [OR] 1.29 [95% confidence interval {CI}], 1.03 - 1.62) and had more exacerbating factors (OR 1.26 [95% CI, 1.04 - 1.54]), which included inhalation allergen-related exacerbating factors (OR 2.54 [95% CI, 1.23 - 5.23), even after adjusting for age, total IgE, body mass index, severity, and use of moisturizer. The concordance between animal sensitization and an exacerbating factor, including dog and cat, was fair, with 0.39 κ and 0.85 accuracy. Conclusion: This study showed that impaired QoL in children with AD is associated with inhalant allergen sensitization and inhalant allergen-related exacerbation factors. Especially, dog and cat sensitization was a significant exacerbating factor. The inhalation-related exacerbation factors, including animal allergens, might be addressed to improve AD management in children.

Predicting the Outcome of Pediatric Oral Food Challenges for Determining Tolerance Development.

PURPOSE: Despite the risk of anaphylaxis, oral food challenges (OFCs) are performed clinically for various indications, particularly to confirm tolerance development. This study aimed to assess OFCs by relevant indications and build an outcome prediction model to help determine when to perform OFCs in children who are likely to have developed immune tolerance. METHODS: In total, 432 pediatric OFCs were retrospectively analyzed according to indications. Clinical characteristics, serum total immunoglobulin (Ig) E, blood eosinophils, and specific IgE and IgG4 levels for food allergens were noted and compared. Machine learning was utilized to select the most important variables in determining the passage of the OFCs, and prediction models were constructed using the selected variables. RESULTS: OFCs were most commonly performed to confirm tolerance development (number, %; 267, 61.8%). The most common food allergens tested were egg (191, 44.2%) and milk (135, 31.3%). Children who passed the egg challenges for confirming tolerance acquisition had significantly lower egg white-specific IgE level (P = 0.008). Similarly, those who passed milk challenges had significantly lower cow's milk-specific IgE (P = 0.002) and casein-specific IgE levels (P = 0.005). We developed a nomogram to predict the outcome of OFCs to determine the tolerance acquisition with the selected variables; lower food-specific IgE, higher total IgE, and younger age indicated a higher probability of passage. The area under the curve (95% confidence interval) was 0.623 (0.503-0.743) for egg and 0.734 (0.628-0.840) for milk. CONCLUSIONS: Serum total IgE and food-specific IgE combined with age showed trends toward passing OFCs for confirming tolerance development. The constructed model may be used by clinicians as a practical guide for minimizing the risks of OFCs and a timely reintroduction for children with food allergies.

Rapid and long-lasting efficacy of high-dose ambroxol therapy for neuronopathic Gaucher disease: A case report and literature review.

Gaucher disease (GD) is a lysosomal storage disorder caused by a deficiency in the GBA1-encoded enzyme, ß-glucocerebrosidase. Enzyme replacement therapy is ineffective for neuronopathic Gaucher disease (nGD). High-dose ambroxol has been administered as an alternative treatment for a group of patients with nGD. However, little is known about the clinical indication and the long-term outcome of patients after ambroxol therapy. We herein report a case of a female patient who presented with a progressive disease of GD type 2 from 11 months of age and had the pathogenic variants of p.L483P (formerly defined as p.L444P) and p.R502H (p.R463H) in GBA1. A combined treatment of imiglucerase with ambroxol started improving the patient's motor activity in 1 week, while it kept the long-lasting effect of preventing the deteriorating phenotype for 30 months. A literature review identified 40 patients with nGD, who had received high-dose ambroxol therapy. More than 65% of these patients favorably responded to the molecular chaperone therapy, irrespective of p.L483P homozygous, heterozygous or the other genotypes. These results highlight the long-lasting effect of ambroxol-based chaperone therapy for patients with an expanding spectrum of mutations in GBA1.

Disparities in pediatric anaphylaxis triggers and management across Asia.

BACKGROUND: The epidemiology and management of anaphylaxis are not well-reported in Asia. METHODS: A regional pediatric anaphylaxis registry was established by the Asia-Pacific Research Network for Anaphylaxis (APRA), using standardized protocols for prospective data collection, to evaluate the triggers and management of anaphylaxis in the Asia-Pacific region. Pediatric patients below 18 years presenting with anaphylaxis across four Asian countries/cities (Thailand, Singapore, Hong Kong (HK), and Qingdao) were included. Allergen triggers, symptoms, anaphylaxis severity, and management were compared. RESULTS: Between 2019 and 2022, 721 anaphylaxis episodes in 689 patients from 16 centers were identified. The mean age at anaphylaxis presentation was 7.0 years (SD = 5.2) and 60% were male. Food was the most common trigger (62%), particularly eggs and cow's milk in children aged 3 years and below. In school-age children, nut anaphylaxis was most common in HK and Singapore, but was rare in the other countries, and wheat was the top allergen in Bangkok. Shellfish anaphylaxis was most common in children aged 7-17. Adrenaline was administered in 60% of cases, with 9% given adrenaline before hospital arrival. Adrenaline devices were prescribed in up to 82% of cases in Thailand but none in Qingdao. CONCLUSIONS: The APRA identified food as the main trigger of anaphylaxis in children, but causative allergens differed even across Asian countries. Fewer than two-thirds of cases received adrenaline treatment, pre-hospital adrenaline usage was low, and adrenaline device prescription remained suboptimal. The registry recognizes an unmet need to strengthen anaphylaxis care and research in Asia-Pacific.

Variation in the Allergenicity of Scrambled, Boiled, Short-Baked and Long-Baked Egg White Proteins.

BACKGROUND: Hen's egg white (HEW) is the most common cause of food allergy in children which induces mild to fatal reactions. The consultation for a proper restriction is important in HEW allergy. We aimed to identify the changes in HEW allergenicity using diverse cooking methods commonly used in Korean dishes. METHODS: Crude extract of raw and 4 types of cooked HEW extracts were produced and used for sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE), enzyme-linked immunosorbent assay (ELISA), and ELISA inhibition assays using 45 serum samples from HEW allergic and tolerant children. Extracts were prepared; scrambled without oil for 20-30 seconds in frying pan without oil, boiled at 100°C for 15 minutes, short-baked at 180°C for 20 minutes, and long-baked at 45°C for 12 hours with a gradual increase in temperature up to 110°C for additional 12 hours, respectively. RESULTS: In SDS-PAGE, the intensity of bands of 50-54 kDa decreased by boiling and baking. All bands almost disappeared in long-baked eggs. The intensity of the ovalbumin (OVA) immunoglobulin E (IgE) bands did not change after scrambling; however, an evident decrease was observed in boiled egg white (EW). In contrast, ovomucoid (OM) IgE bands were darker and wider after scrambling and boiling. The IgE binding reactivity to all EW allergens were weakened in short-baked EW and considerably diminished in long-baked EW. In individual ELISA analysis using OVA+OM+ serum samples, the median of specific IgE optical density values was 0.435 in raw EW, 0.476 in scrambled EW, and 0.487 in boiled EW. Conversely, it was significantly decreased in short-baked (0.406) and long-baked EW (0.012). Significant inhibition was observed by four inhibitors such as raw, scrambled, boiled and short-baked HEW, but there was no significant inhibition by long-baked HEW (IC50 > 100 mg/mL). CONCLUSION: We identified minimally reduced allergenicity in scrambled EW and extensively decreased allergenicity in long-baked EW comparing to boiled and short-baked EW as well as raw EW. By applying the results of this study, we would be able to provide safer dietary guidence with higher quality to egg allergic children.

Comparative Evaluation of Recombinant and Acellular Pertussis Vaccines in a Murine Model.

Since the 2000s, sporadic outbreaks of whooping cough have been reported in advanced countries, where the acellular pertussis vaccination rate is relatively high, and in developing countries. Small-scale whooping cough has also continued in many countries, due in part to the waning of immune protection after childhood vaccination, necessitating the development of an improved pertussis vaccine and vaccination program. Currently, two different production platforms are being actively pursued in Korea; one is based on the aP (acellular pertussis) vaccine purified from B. pertussis containing pertussis toxoid (PT), filamentous hemagglutin (FHA) and pertactin (PRN), and the other is based on the recombinant aP (raP), containing genetically detoxified pertussis toxin ADP-ribosyltransferase subunit 1 (PtxS1), FHA, and PRN domain, expressed and purified from recombinant E. coli. aP components were further combined with diphtheria and tetanus vaccine components as a prototype DTaP vaccine by GC Pharma (GC DTaP vaccine). We evaluated and compared the immunogenicity and the protective efficacy of aP and raP vaccines in an experimental murine challenge model: humoral immunity in serum, IgA secretion in nasal lavage, bacterial clearance after challenge, PTx (pertussis toxin) CHO cell neutralization titer, cytokine secretion in spleen single cell, and tissue resident memory CD4+ T cell (CD4+ TRM cell) in lung tissues. In humoral immunogenicity, GC DTaP vaccines showed high titers for PT and PRN and showed similar patterns in nasal lavage and IL-5 cytokine secretions. The GC DTaP vaccine and the control vaccine showed equivalent results in bacterial clearance after challenge, PTx CHO cell neutralization assay, and CD4+ TRM cell. In contrast, the recombinant raP vaccine exhibited strong antibody responses for FHA and PRN, albeit with low antibody level of PT and low titer in PTx CHO neutralization assay, as compared to control and GC DTaP vaccines. The raP vaccine provided a sterile lung bacterial clearance comparable to a commercial control vaccine after the experimental challenge in murine model. Moreover, raP exhibited a strong cytokine response and CD4+ TRM cell in lung tissue, comparable or superior to the experimental and commercial DTaP vaccinated groups. Contingent on improving the biophysical stability and humoral response to PT, the raP vaccine warrants further development as an effective alternative to aP vaccines for the control of a pertussis outbreak.

Clinical Manifestations and Genotype of Primary Ciliary Dyskinesia Diagnosed in Korea: Multicenter Study.

PURPOSE: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder that leads to secondary ciliary dysfunction. PCD is a rare disease, and data on it are limited in Korea. This study systematically evaluated the clinical symptoms, diagnostic characteristics, and treatment modalities of pediatric PCD in Korea. METHODS: This Korean nationwide, multicenter study, conducted between January 2000 and August 2022, reviewed the medical records of pediatric patients diagnosed with PCD. Prospective studies have been added to determine whether additional genetic testing is warranted in some patients. RESULTS: Overall, 41 patients were diagnosed with PCD in 15 medical institutions. The mean age at diagnosis was 11.8 ± 5.4 years (range: 0.5 months-18.9 years). Most patients (40/41) were born full term, 15 (36.6%) had neonatal respiratory symptoms, and 12 (29.3%) had a history of admission to the neonatal intensive care unit. The most common complaint (58.5%) was chronic nasal symptoms. Thirty-three patients were diagnosed with transmission electron microscopy (TEM) and 12 patients by genetic studies. TEM mostly identified outer dynein arm defects (alone or combined with inner dynein arm defects, n = 17). The genes with the highest mutation rates were DNAH5 (3 cases) and DNAAF1 (3 cases). Rare genotypes (RPGR, HYDIN, NME5) were found as well. Chest computed tomography revealed bronchiectasis in 33 out of 41 patients. Among them, 15 patients had a PrImary CiliAry DyskinesiA Rule score of over 5 points. CONCLUSIONS: To our knowledge, this is the first multicenter study to report the clinical characteristics, diagnostic methods, and genotypes of PCD in Korea. These results can be used as basic data for further PCD research.

Comparison of COVID-19-associated multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease shock syndrome: case reports and literature review.

Multisystem inflammatory syndrome in children (MIS-C) is a serious post-infectious complication of COVID-19 characterized by hyperinflammation and multi-organ dysfunction including shock. Shock is also seen in a severe form of Kawasaki disease (KD) called KD shock syndrome (KDSS). Here, we present one MIS-C and one KDSS case and compare similarities and differences between them. Both MIS-C (case 1) and KDSS (case 2) showed hyperinflammation, KD-related features, gastrointestinal problems, hypotension, and coagulopathy. The extent of systemic inflammation and organ dysfunction was more severe in KDSS than in MIS-C. Case 1 was diagnosed as MIS-C because SARS-CoV-2 was confirmed, and case 2 was diagnosed as KDSS because no pathogen was identified in microbiological studies. We believe that the most important difference between MIS-C and KDSS was whether SARS-CoV-2 was identified as an infectious trigger. Organ dysfunction is a hallmark of MIS-C and KDSS, but not KD, so MIS-C shares more clinical phenotypes with KDSS than with KD. Comparison of MIS-C and KDSS will be an interesting and important topic in the field of KD-like hyperinflammatory disease research.

A booster administration of the OKA/SK strain causes fatal disseminated varicella in an immunocompetent child.

Live varicella vaccines are known to provide robust immunity against varicella zoster virus (VZV) infections. However, problems with viral attenuation have led to pathogenic VZV vaccine strains causing varicella-like rash and herpes zoster in immunocompetent children after immunization. We report the first fatal case of VZV infection caused by OKA/SK strain contained in the vaccine administrated as a booster shot in an immunocompetent child, which has been independently developed from any currently available varicella vaccines that are OKA strain or MAV/06 strain based. The patient died due to sudden pulmonary alveolar hemorrhage as a secondary complication of VZV pneumonitis. Sequencing of the four SNPs unique to the OKA/SK strain (SNP loci 14 035T; 32 626C; 58 777G; 70 319G) enabled discrimination of the strain responsible for the disseminated infection. OKA/SK strain does not have any SNPs in ORF62 postulated to be responsible for the attenuation of varicella vaccines which have been safely and effectively used world-wide or locally, and exclusively enriches a virulent factor in ORF31 identified in parental OKA strain, thus possibly resulting in disseminated VZV infection leading to mortality. Therefore, actions need to be taken to prevent vaccine related morbidity and mortality in children.

Similarities and Differences between Multisystem Inflammatory Syndrome in Children (MIS-C) and Kawasaki Disease Shock Syndrome.

This study aimed to investigate the characteristics of COVID-19-associated multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease shock syndrome (KDSS) and to compare the similarities and differences between the two diseases. The incidence of KDSS and MIS-C was also estimated. Medical records of patients diagnosed with MIS-C or KDSS at four hospitals from January 2013 to December 2022 were retrospectively reviewed. Thirty-one patients were enrolled in the study in either an MIS-C group (n = 22) or a KDSS group (n = 9). The incidence of KDSS in KD was 0.8% (9/1095) and the incidence of MIS-C versus KD was 10.2% (22/216). Compared with the MIS-C group, the KDSS group had longer hospital stays and more severe systemic inflammation (e.g., anemia, elevated C-reactive protein, hypoalbuminemia, and pyuria) and organ dysfunction (e.g., number of involved organs, shock, vasoactive infusion, and intensive care unit admission). All patients in the MIS-C group, but none in the KDSS group, including two patients during the COVID-19 pandemic, had laboratory evidence of SARS-CoV-2 infection. MIS-C and KDSS shared demographic, clinical, and laboratory characteristics; organ dysfunction; treatment; and outcomes. Overall severity was more severe in patients with KDSS than in those with MIS-C. The most important difference between MIS-C and KDSS was whether SARS-CoV-2 was identified as an infectious trigger.

Natural course of IgE-mediated food allergy in children.

The prevalence of food allergy and food-induced anaphylaxis in children is increasing worldwide. Cow's milk, hen's eggs, and wheat allergies in young children have a more favorable prognosis with a relatively early outgrow, while allergies to peanuts, tree nuts, and seafood are more likely to be persistent. Although our understanding of the mechanism underlying the resolution of food allergy is incomplete, the roles of dendritic cells, regulatory T cells, and regulatory B cells are important. Many past studies on the natural course of food allergy were retrospective analyses of specific study groups, but large-scale population-based prospective studies are now being published. This review summarizes recent studies of the natural course of cow's milk, hen's eggs, wheat, peanuts, tree nuts, soy, sesame, and seafood allergies. The potential factors affecting the natural course of food allergy include symptom severity on ingestion, age at diagnosis, allergic comorbidities, skin prick test reaction size or serum food-specific immunoglobulin (Ig) E levels, changes in sensitization degree, IgE epitope specificity, ratio of food-specific IgE to IgG4, food-specific IgA levels, component-resolved diagnostic profile, diet, gut microbiome, and interventions such as immunotherapy. Since food allergy places a significant burden on patients and their caregivers in daily life, clinicians should be able to provide relevant knowledge on the natural course of food allergy, appropriately evaluate its resolution, and offer therapeutic options whenever possible.

Clinical significance of microinvasive breast cancer across the different subtypes and human epidermal growth factor receptor 2 expression levels.

PURPOSE: The clinical behavior, prognosis, and management of microinvasive breast cancer (MiBC) is controversial. We aimed to clarify its significance across different subtypes and the role of human epidermal growth factor receptor 2 (HER2) expression in MiBC. METHODS: We analyzed 1530 patients with T1mi (tumor size ≤ 0.1 cm), node-negative breast cancer who underwent breast conserving surgery or total mastectomy between 2001 and 2020 at the Asan Medical Center (AMC). RESULTS: When divided into four subtypes, hormone receptor (HR)+/HER2-, HR+ /HER2+ , HR-/HER2+ , and HR-/HER2-, HR-/HER2+ had the highest prevalence rate of 38.5% in MiBC patients. In a median follow-up period of 74 months (0-271 months), 103 (6.7%) patients had recurrent tumor, and 95 (6.2%) had local recurrence. Disease-free survival (DFS) and local recurrence-free survival (LRFS) were worst in the HR-/HER2+ group. The five-year DFS for the HR-/HER2+ group was 92.2%, while it was 97.1% for the HR+/HER2- group (p = 0.024 The five-year LRFS for HER2- patients were better than that of HER2+ MiBC patients, which were 97.1 and 93.8%, respectively (p = 0.010). Univariate and multivariate Cox regression analyses showed that the HR-/HER2+ group had relatively higher risk of recurrence compared to the HR+/HER2- group (hazard ratio [HR] = 2.332, 95% confidence interval [CI] 1.412-3.852, p = 0.001 unadjusted; HR = 3.346, 95% CI 1.408-7.953, p = 0.006 adjusted). CONCLUSION: HER2 overexpression was significantly associated with adverse clinicopathologic parameters and increased local recurrence risk in MiBC. Therefore, more understanding of the clinical behavior of HER2 in MiBC will enable tailoring of adjuvant therapy for these patients.

Pharmacokinetic Comparison of Ginsenosides between Fermented and Non-Fermented Red Ginseng in Healthy Volunteers.

Fermentation of red ginseng (RG) produces fermented red ginseng (FRG), thereby increasing the relative amount of downstream ginsenosides, including compound Y (CY), F2, Rh2, compound K (CK), compound O, protopanaxadiol (PPD), and protopanaxatriol (PPT). These downstream ginsenosides have beneficial pharmacological effects, and are easily absorbed by the human body. Based on these expectations, a randomized, single-dose, two-period, crossover clinical trial was planned to compare the pharmacokinetic characteristics of seven types (Rb1, CY, F2, CK, Rh2, PPD, and PPT) of ginsenoside components after FRG and RG administration. The safety and tolerability profiles were assessed in this clinical trial. Sixteen healthy Korean male subjects were administered 6 g of FRG or RG. All ginsenosides except Rb1 showed higher systemic exposure after FRG administration than after RG administration, based on comparisons of ginsenoside Cmax and area under the concentration-time curve (AUC) between FRG and RG. CK, the main ginsenoside component produced during the fermentation process, had 69.23/74.53-fold higher Cmax/AUClast after administration of FRG than RG, and Rh2 had 20.27/18.47-fold higher Cmax/AUClast after administration of FRG than RG. In addition, CY and F2 were detected in FRG; however, all plasma concentrations of CY and F2, except in one subject, were below the lower limit of quantification in RG. There were no clinically significant findings with respect to clinical laboratory tests, blood pressures, or adverse events. Therefore, regular administration of FRG may exert better pharmacological effects than RG.

Maternal Posttraumatic Stress Symptoms and Psychological Burden in Mothers of Korean Children With Anaphylaxis.

PURPOSE: Anaphylaxis is a severe allergic reaction that is potentially life-threatening, but post-traumatic stress symptoms (PTSS) in the caregivers of children with anaphylaxis have not been evaluated. This study aimed to investigate the psychological burden on mothers of children with recent anaphylaxis. METHODS: A total of 188 children with recent anaphylaxis was recruited from 13 hospitals in Korea. Validated questionnaires, including the Korean versions of the Beck Anxiety Inventory (K-BAI), the Beck Depression Inventory (K-BDI), and the Impact of Event Scale Revised-Korean version (IES-R-K), were used to evaluate maternal anxiety, depression, and PTSS. RESULTS: The median ages of children and their mothers were 4 and 36 years, respectively. PTSS (IES-R-K ≥ 25) were identified in 56.9% of mothers, and 57.9% of them showed severe PTSS. The proportions of mothers who had anxiety (K-BAI ≥ 22) and depression (K-BDI ≥ 17) were 18.6% and 33.0%, respectively. Multivariable logistic regression analysis indicated that the patient's history of asthma (adjusted odds ratio [aOR], 5.46; 95% CI, 1.17-25.59) and the presence of central nervous symptoms (aOR, 3.27; 95% CI, 1.07-9.96) were associated with PTSS. Age of 2 or older (aOR, 2.87; 95% CI, 1.10-7.52) and eggs, milk, or wheat as the cause of anaphylaxis (aOR, 2.87; 95% CI, 1.10-7.52) increased the risk of severe PTSS. CONCLUSIONS: The rate of PTSS among mothers of children with recent anaphylaxis was high at 56.9%. Clinicians who care for pediatric anaphylaxis patients should be aware of the psychological burden on their caregivers.

Under-Recognized Macrophage Activation Syndrome in Refractory Kawasaki Disease: A Wolf in Sheep's Clothing.

Recognition of macrophage activation syndrome (MAS) in patients with refractory Kawasaki disease (KD) can be challenging. This study aimed to investigate the incidence of MAS in patients with refractory KD and to compare the characteristics of refractory KD and MAS. Medical records of 468 patients diagnosed with KD from January 2010 to December 2019 were retrospectively reviewed. Of the 468 KD patients, 63 were enrolled in the study as a refractory KD group (n = 59) and an MAS group (n = 4). The incidence of MAS was 0.8% (4/468) in patients with KD and 6.3% (4/63) in patients with refractory KD. Compared to the refractory KD group, the MAS group had higher frequencies of incomplete KD, hepatosplenomegaly, third-line treatment, and MAS screening, and showed lower levels of albumin. No significant differences were found in other clinical and laboratory findings. In addition to four patients with MAS, five patients with refractory KD who received third-line treatment showed severe systemic inflammation and organ dysfunction, but only one in five patients underwent MAS screening, including ferritin levels. In conclusion, given the relatively high incidence of MAS in children with refractory KD and the similar phenotype between refractory KD and MAS, we propose that MAS screening should be included in routine laboratory tests for refractory KD.