Clinical implications of gallbladder enlargement in Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) presents with gallbladder enlargement (GBE) or hydrops in the acute phase. Although GBE is highly specific to KD, epidemiological data on GBE have not been updated. In this study we evaluated the occurrence rate of GBE in KD and characterized the clinical features of patients who developed GBE. METHODS: The present study was a prospective, observational study. The maximum longitudinal area of the gallbladder and the common bile duct diameter in KD patients were measured by ultrasonography at the start of initial intravenous immunoglobulin (IVIG) therapy (day 0) and on days 7, 30, and 60 of therapy. The primary outcome was the complication rate of GBE (z- score ≥2.0) on day 0. The secondary outcome was the association of GBE with cholestasis, unresponsiveness to IVIG, and coronary artery lesions (CAL). RESULTS: Gallbladder enlargement occurred in 35% (35/101) of patients on day 0. Cholestasis and severe patients (Kobayashi score [KS] ≥5) were more common in the GBE group (20.6% vs. 1.6%, p = 0.002, and 54.3% vs. 15.2%, p < 0.001, respectively). In patients with a KS of ≤4, the non-responder rate was higher in the GBE group (44% vs. 20%, p = 0.0495) but did not differ in those with a KS of ≥5 (21% vs. 20%, p = 0.95). The rate of CAL occurrence did not differ significantly between the groups (8.6% vs. 6.1%, p = 0.64). CONCLUSIONS: Gallbladder enlargement occurred in 35% of KD patients and was associated with cholestasis. Gallbladder enlargement may not only be a diagnostic finding, but also a severity marker in KD patients.

[A Case of Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma Causing Perforation of the Small Intestine].

Monomorphic epitheliotropic intestinal T-cell lymphoma(MEITL)is very rare and aggressive subtype of lymphoma with poor prognosis. A 60-year-old man complaining of abdominal pain was underwent partial resection of the jejunum for panperitonitis with a small intestinal perforation. The histopathological and immunohistochemical findings led to the diagnosis of MEITL. Postoperative course was uneventful. One month after the operation, the patient was scheduled for 6 courses of CHOP regimens. He presented with bowel obstruction twice during the 3 courses of CHOP. As the recurrence of MEITL could not be ruled out, diagnostic laparoscopy was performed. Laparoscopic findings revealed no recurrence and adhesive small bowel obstruction. The patient was followed closely without treatment after 6 courses of CHOP. The patient has been alive without recurrence 18 months after the resection. We reported a case of monomorphic epithelial intestinal T- cell lymphoma causing jejunal perforation.

Follow-Up Duration of Echocardiography in Patients with Kawasaki Disease with No Initial Coronary Aneurysms.

OBJECTIVE: To evaluate the optimal duration of echocardiographic follow-up in patients with Kawasaki disease without an initial coronary aneurysm. STUDY DESIGN: In this single-center, retrospective, observational study, we reviewed the results of follow-up echocardiography in children with Kawasaki disease enrolled in the Prospective Observational Study on Stratified Treatment with Immunoglobulin Plus Steroid Efficacy for Kawasaki Disease from a children's hospital. The main enrollment criterion was the absence of coronary aneurysms, defined as a maximum z-score (Zmax) ≥2.5, in the proximal right coronary artery and the proximal left anterior descending artery within 9 days from treatment initiation. The primary outcome was Zmax on follow-up echocardiography at up to 5 years. RESULTS: Among 386 patients, 106 (27.5%) received prednisolone with intravenous immunoglobulin for first-line therapy, and 57 (14.8%) showed a poor response. Echocardiography at 1 month detected 9 patients with a Zmax ≥2, including 3 (0.8%) with coronary aneurysms requiring additional antithrombotic treatment and observation. Of 7 patients (1.8%) with normal echocardiographic findings at 1 month but a Zmax ≥2 later, 2 were lost to follow-up and 5 experienced spontaneous resolution, but none of the 7 patients required any change in management. CONCLUSIONS: The optimal duration of echocardiographic follow-up may be 1 month in patients with no initial coronary aneurysms and a Zmax <2 at 1 month. Coronary artery abnormalities observed after 1 month are rare and mostly benign in this category of patients.

Neonatal Linear IgA Bullous Dermatosis Mediated by Breast Milk-Borne Maternal IgA.

IMPORTANCE: Neonatal linear immunoglobulin A (IgA) bullous dermatosis (LABD) is a rare disease that can be fatal when associated with respiratory failure. All previously reported cases of neonatal LABD have been in newborns with healthy asymptomatic mothers, and the pathogenic IgA was of unknown origin. OBJECTIVE: To clarify the origin of IgA associated with LABD in neonates born of healthy asymptomatic mothers. DESIGN, SETTING, AND PARTICIPANTS: This case study analyzed the laboratory findings of a single breast-fed newborn male with neonatal LABD admitted to the Keio University Hospital in Tokyo and his healthy asymptomatic mother. The healthy newborn developed life-threatening blisters and erosions of the skin and mucous membranes on day 4 after birth. Blood serum, skin, and maternal breast milk were examined for IgA autoantibodies. MAIN OUTCOMES AND MEASURES: Histopathologic and immunofluorescence analyses of specimens (serum, skin, and breast milk) from the patient and his mother. RESULTS: Histopathologic evaluation of the newborn's skin revealed subepidermal blisters with neutrophil infiltrates, and immunofluorescence testing showed linear IgA deposition along the basement membrane zone (BMZ), which lead to the diagnosis of neonatal LABD. Indirect immunofluorescence using normal human skin after treatment with 1-mol/L sodium chloride showed the patient to have circulating IgA binding to the dermal side of BMZ. Immunohistochemical staining proved the deposition of secretory IgA in the neonatal skin by demonstrating the presence of J chain-not been seen in other LABD cases-indicating that the autoantibodies producing the blisters were derived from the maternal breast milk. Although no circulating IgA against the skin was detected in mother's sera, the breast milk contained IgA that reacted with the dermal side of the BMZ. No new blister formation was observed after cessation of breastfeeding. CONCLUSIONS AND RELEVANCE: The results of this case study suggest a passive transfer of pathogenic IgA to a newborn from an asymptomatic mother via breast milk. In prior reports, no serum from asymptomatic mothers of newborns with LABD had IgA autoantibodies binding to skin components; however, in this case, we found that the maternal breast milk contained IgA autoantibodies associated with neonatal LABD. In neonatal LABD, maternal breast milk should be examined for IgA autoantibodies and breast milk feeding should be discontinued as soon as neonatal LABD is suspected.

Evaluation of a Kawasaki Disease Risk Model for Predicting Coronary Artery Aneurysms in a Japanese Population: An Analysis of Post RAISE.

OBJECTIVES: To test the performance of the Son risk score, which was created to predict coronary artery abnormalities from baseline variables in North American patients with Kawasaki disease. STUDY DESIGN: The dataset from Post RAISE, the largest prospective cohort study of Japanese patients with Kawasaki disease to date, was used for the present study. With high risk defined as ≥3 points, sensitivity, specificity, positive predictive value, and negative predictive value for coronary artery abnormality development were calculated. To evaluate the effect of each risk factor in the Son score, the OR and 95% CIs were calculated using logistic regression analysis with the presence of coronary artery abnormality at 1 month after disease onset. RESULTS: Post RAISE enrolled 2628 consecutive patients with Kawasaki disease, and 304 patients had a high-risk score, of whom 15.1% showed coronary artery abnormality. At the cutoff ≥3 points, the sensitivity was 37.7%, and the specificity was 87.2%. The maximum z score at baseline ≥2.0 (OR 3.5, 95% CI 2.3-5.2) and age <6 months at disease onset (OR 3.2, 95% CI 1.9-5.4), were significantly associated with coronary artery abnormality development. However, a high concentration of C-reactive protein was not associated with coronary artery abnormality. The area under the receiver operating characteristic curve for the Son score was 0.65 (95% CI 0.59-0.71). CONCLUSIONS: The Son score had insufficient sensitivity and good specificity in a Japanese cohort of patients with Kawasaki disease. Among the variables comprising the Son score, a large baseline z score and young age at disease onset were significant, independent predictors of coronary artery abnormality development.

Risk Factors of Coronary Artery Abnormalities and Resistance to Intravenous Immunoglobulin Plus Corticosteroid Therapy in Severe Kawasaki Disease: An Analysis of Post RAISE.

BACKGROUND: Coronary artery abnormalities (CAAs) still occur in patients with Kawasaki disease receiving intensified treatment with corticosteroids. We aimed to determine the risk factors of CAA development and resistance to intensified treatment in Post RAISE (Prospective Observational Study on Stratified Treatment With Immunoglobulin Plus Steroid Efficacy for Kawasaki Disease)-the largest prospective cohort of Kawasaki disease patients to date. METHODS: In Post RAISE, 2648 consecutive patients with Kawasaki disease were enrolled. The present study analyzed 724 patients predicted to be intravenous immunoglobulin (IVIG) nonresponders (Kobayashi score ≥5) who received intensified treatment consisting of IVIG plus prednisolone. The association between the baseline characteristics and CAA at 1 month after disease onset was examined. The association between the baseline characteristics and treatment resistance was also investigated. RESULTS: Maximum Z score at baseline ≥2.5 (odds ratio, 3.4 [95% CI, 1.5-7.8]), age at fever onset <1 year (odds ratio, 3.4 [95% CI, 1.6-7.4]), and nonresponsiveness to IVIG plus prednisolone treatment (odds ratio, 6.8 [95% CI, 3.3-14.0]) were independent predictors of CAA development. Nonresponsiveness to IVIG plus prednisolone was significantly associated with 8 baseline variables. Baseline total bilirubin (odds ratio, 1.4 [95% CI, 1.2-1.7]) was the only significant independent predictor other than the variables included in the Kobayashi score, enabling treatment resistance to be identified at diagnosis. The area under the ROC curve was 0.74 (95% CI, 0.69-0.79). At a cutoff point of 1.0, the sensitivity and specificity for predicting treatment resistance were 71% and 65%, respectively. CONCLUSIONS: In Post RAISE, younger age at fever onset, a larger maximum Z score at baseline, and nonresponsiveness to IVIG plus prednisolone were risk factors significantly associated with CAA development. Nonresponders were able to be identified at diagnosis based on the total bilirubin value. To prevent CAA, more intensified or adjunctive therapies using other agents, such as pulsed methylprednisolone, ciclosporin, infliximab, and Anakinra, should be considered for patients with these risk factors. Registration: URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000007133.

Efficacy and safety of intravenous immunoglobulin plus prednisolone therapy in patients with Kawasaki disease (Post RAISE): a multicentre, prospective cohort study.

BACKGROUND: The RAISE study showed that additional prednisolone improved coronary artery outcomes in patients with Kawasaki disease at high risk of intravenous immunoglobulin (IVIG) resistance. However, no studies have been done to test the steroid regimen used in the RAISE study. We therefore aimed to verify the efficacy and safety of primary IVIG plus prednisolone. METHODS: We did a multicentre, prospective cohort study at 34 hospitals in Japan. We included patients diagnosed with Kawasaki disease according to the Japanese diagnostic criteria, and excluded those who were treated at other hospitals before being transferred to a participating hospital. Patients who were febrile at diagnosis received primary IVIG (2 g/kg per 24 h) and oral aspirin (30 mg/kg per day) until the fever resolved, followed by oral aspirin (5 mg/kg per day) for 2 months after Kawasaki disease onset. We stratified patients using the Kobayashi score into predicted IVIG non-responders (Kobayashi score ≥5) or predicted IVIG responders (Kobayashi score <5). For predicted non-responders, each hospital independently decided whether to add prednisolone (intravenous injection of 2 mg/kg per day for 5 days) to the primary IVIG treatment, according to their respective treatment policy, and we further divided these patients based on the primary treatment received. The primary endpoint was the incidence of coronary artery abnormalities determined by two-dimensional echocardiography at 1 month after the primary treatment in predicted non-responders treated with primary IVIG plus prednisolone. Coronary artery abnormalities were defined according to the criteria of the Japanese Ministry of Health and Welfare and of the American Heart Association (AHA). This study is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN000007133. FINDINGS: From July 1, 2012, to June 30, 2015, we enrolled 2628 patients with Kawasaki disease, of whom 724 (27·6%) were predicted IVIG non-responders who received IVIG plus prednisolone as primary treatment. 132 (18·2%) of 724 patients did not respond to primary treatment. Among patients with complete data, coronary artery abnormalities were present in 40 (incidence rate 5·9%, 95% CI 4·3-8·0) of 676 patients according to the AHA criteria or in 26 (3·8%, 2·5-5·6) of 677 patients according to the Japanese criteria. Serious adverse events were reported in 12 (1·7%) of 724 patients treated with primary IVIG plus prednisolone; two of these patients had hypertension and bacteraemia that was probably related to prednisolone. One patient died possibly due to severe inflammation from the Kawasaki disease itself. INTERPRETATION: Primary IVIG plus prednisolone therapy in this study had an effect similar to that seen in the RAISE study in reducing the non-response rate and decreasing the incidence of coronary artery abnormalities. A primary IVIG and prednisolone combination therapy might prevent coronary artery abnormalities and contribute to lowering medical costs. FUNDING: Tokyo Metropolitan Government Hospitals and the Japan Kawasaki Disease Research Center.

[Analysis of clinical features of community-acquired pneumonia caused by pediatric respiratory syncytial virus and human metapneumovirus].

We retrospectively reviewed the background, clinical features, blood tests, and complications in the 720 children seen for acute respiratory tract infection from July 2004 to December 2005. Of these, 75 (10.5%) were diagnosed with pneumonia due to respiratory syncytial virus (RSV) and 19 (2.6%) with pneumonia due to human metapneumovirus (hMPV) based on multiplex PCR analysis of nasopharyngeal samples. RSV was PCR-positive mostly in winter, -from November to January-, and hMPV mostly in spring, -from March to June. The mean RSV pneumonia group age was 1.3 +/- 1.4 years and in the hMPV pneumonia group 3.0 +/- 3.1 years, showing a statistically significant differences in the age of virus onset. Clinically the RSV group showed more rhinorrhea and wheezing (p < 0.05) and the hMPV group a higher maximum body temperature and a longer wheezing duration (p < 0.05). Fever, cough, vomiting, diarrhea, fever frequency, and C-reactive protein level were similar in both groups (p > 0.05). Complication prevalence was 49.3% in the RSV group and 42.1% in the hMPV group. Acute otitis media was seen more often in the RSV group (32.0%) and febrile convulsion more often in the hMPV group (15.8%) (p > 0.05). These findings may be helpful in clinically diagnosing community-acquired pneumonia due to RSV or hMPV.

[A 14-year-old healthy boy with splenic abscess due to Salmonella enterica serovar Senftenberg].

Salmonella enterica serovar Senftenberg may very rarely cause splenic abscess, which can be diagnosed using gallium scintigraphy and drained. A 14-year-old boy admitted for stomachache, diarrhea and fever and diagnosed from his symptoms as having enteritis did not respond when treated with fosfomycin, meropenem, and clindamycin. A low-density splenic area seen in abdominal computed tomography on admission did not show contrast medium enhancement. Gallium scintigraphy on hospital day 10, however, showed abnormal splenic accumulation confirming the splenic abscess diagnosis, after which we punctured and drained the abscessout. S. Senftenberg was isolated from pus aspirated pus from the abscess, after which responded well to ceftriaxone and levofloxacin. Follow-up gallium scintigraphy on hospital day 24 showed that the abnormal splenic accumulation had disappeared, after which he has been followed up with abdominal ultrasonography and blood tests as an outpatient. He has experienced no relapse of splenic abscess.

A comparative clinical study of macrolide-sensitive and macrolide-resistant Mycoplasma pneumoniae infections in pediatric patients.

In recent years, the increased prevalence of macrolide-resistant Mycoplasma pneumoniae (MR-M. pneumoniae) has become a significant issue in Japan. We isolated 94 strains of M. pneumoniae, and determined the minimum inhibitory concentrations (MICs) of macrolides and other antimicrobial agents for these strains. We also performed a comparative clinical evaluation of macrolide efficacy for cases of MR-M. pneumoniae infections and cases of macrolide-sensitive Mycoplasma pneumoniae infections (MS-M. pneumoniae). Of the 94 isolates of M. pneumoniae, 64 (68.1%) were classified as MS-M. pneumoniae and 30 (31.9%) as MR-M. pneumoniae strains. The clinical study included an assessment of 47 pediatric cases of MS-M. pneumoniae and 22 pediatric cases of MR-M. pneumoniae. The patient demographics, such as sex, age, the period from the onset of the infection to the first examination, laboratory findings, diagnosis, and the severity of symptoms, showed no significant difference between the two study groups. However, the efficacy of macrolide treatment was 91.5% for MS-M. pneumoniae and 22.7% for MR-M. pneumoniae, a statistically significant difference (P < 0.01). Although M. pneumoniae infection is generally considered a treatable condition, the increasing prevalence of macrolide-resistant strains of M. pneumoniae has become a significant clinical issue in pediatric patients, and it is therefore necessary to give careful consideration to the appropriate antimicrobial therapy for MR-M. pneumoniae infection.