Exploring the benefits of full-time hospital facility dogs working with nurse handlers in a children's hospital.

OBJECTIVE: To examine the benefits of full-time hospital facility dogs (HFDs) working with qualified nurse handlers for inpatients in a pediatric medical facility. METHODS: A questionnaire survey on the evaluation of HFD activities was conducted in a hospital that had introduced HFDs for the first time in Japan and has been using them for 9 years. Of the 626 full-time medical staff, 431 responded, of which 270 who observed HFD activities were included in the analysis. The Questionnaire contained 20 questions, and nine questions were selected for presentation in this paper because they focused on the situations in which HFD activities were thought to have a strong impact on inpatients. A comparison of the respondents' evaluations for each question was made, and differences in the respondents' attributes (such as profession, length of clinical experience and experience of dog ownership) for those items were examined. RESULTS: The impact of HFDs in terminal care was ranked highest among the respondents. Similarly, HFDs increased patient cooperation for clinical procedures. The responses to these two items did not differ statistically depending on the respondents' attributes. The results imply that patients were more cooperative even for highly invasive examinations and procedures with the support of HFD activities. CONCLUSIONS: Healthcare providers considered that HFDs were useful, especially for providing support during the terminal phase and for gaining patients' cooperation for procedures. The fact that the handler was a nurse and the HFD team worked full-time may have enhanced the effectiveness of the program.

Cytokine profile after oral food challenge in infants with food protein-induced enterocolitis syndrome.

BACKGROUND: Although food protein-induced enterocolitis syndrome (FPIES) is supposed to be caused by inflammation, the role of cytokines has not yet been clarified. METHODS: To elucidate the role of cytokines in the development of symptoms and abnormal laboratory findings at an oral food challenge (OFC), changes in serum cytokine levels were analyzed for 6 OFCs in 4 patients with FPIES. The result of OFC was judged positive if any gastrointestinal (GI) symptoms (vomiting, diarrhea, or bloody stool) were induced. RESULTS: Among 11 cytokines profiled, serum levels of interleukin (IL)-2, IL-5, and IL-8 were clearly increased in all 4 positive OFCs in which elevations of the serum level of C-reactive protein (CRP) and peripheral blood neutrophilia were also seen. The level of serum IL-10 also rose in 2 positive OFCs. Remarkable increases in the serum level of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), IL-6, and IL-12 were observed in a positive OFC where the serum level of CRP rose markedly (6.75 mg/dL). The serum levels of IL-5 were also elevated in 2 negative OFCs. No apparent specific correlations were found between cytokines and GI symptoms. CONCLUSIONS: These results suggest that IL-2 and IL-8 are involved in the antigen-specific immune responses in most patients with FPIES. Further studies are needed to elucidate the significance of these cytokine in the pathogenesis of FPIES.

Targeted use of prednisolone with the second IVIG dose for refractory Kawasaki disease.

BACKGROUND: Prednisolone (PSL) has been suggested to be useful for the treatment of Kawasaki disease (KD) resistant to i.v. immunoglobulin (IVIG), but much remains to be elucidated regarding its use. METHODS: A total of 1087 subjects were involved in a two-study multicenter prospective investigation of the effects of acute phase therapy on IVIG-resistant KD. Subjects resistant to the first dose of IVIG were classified into high (≥10 mg/dL) and low (<10 mg/dL) serum C-reactive protein (CRP) groups after the first dose of IVIG. RESULTS: In the first study, the efficacy of the second dose of IVIG in the high CRP group was significantly lower than in the low CRP group (47.8% vs 76.8%, P < 0.005). In the second study, PSL was co-administered with the second dose of IVIG to the high CRP patients (intensified regimen). The efficacy of the intensified regimen was similar to that of the second dose of IVIG in the low CRP group (79.4% vs 83.3%). Although the difference in the incidence of persistent coronary artery lesions (CAL) between the high and low CRP groups was significant in the first study (19.6% vs 3.0%, P < 0.005), it was not significant in the second study (8.8% vs 2.4%). CONCLUSIONS: The targeted use of PSL with the second dose of IVIG in KD patients resistant to the first dose of IVIG and who are predicted to be resistant to the second dose of IVIG, appears to be effective.

Eosinophilia in infants with food protein-induced enterocolitis syndrome in Japan.

BACKGROUND: Many Japanese infants with food protein-induced enterocolitis syndrome (FPIES) show eosinophilia, which has been thought to be a characteristic of food protein-induced proctocolitis (FPIP). METHODS: To elucidate the characteristics of eosinophilia in Japanese FPIES patients, 113 infants with non-IgE-mediated gastrointestinal food allergy due to cow's milk were enrolled and classified into FPIES (n = 94) and FPIP (n = 19). RESULTS: The percentage of peripheral blood eosinophils (Eo) was increased in most FPIES patients (median, 7.5%), which was comparable with that in FPIP patients (9.0%). Among FPIES patients, Eo was the highest in patients who had vomiting, bloody stool, and diarrhea simultaneously (12.9%) and lowest in patients with diarrhea alone (3.2%). Eo showed a significant positive correlation with the incidence of vomiting (Cramer's V = 0.31, p < 0.005) and bloody stool (Cramer's V = 0.34, p < 0.0005). A significant difference was found in Eo between early- (≤10 days, n = 56) and late-onset (>10 days, n = 38) FPIES (median, 9.8% vs. 5.4%; p < 0.005). IL-5 production by peripheral blood T cells stimulated with cow's milk protein in early-onset FPIES was significantly higher than that in late-onset FPIES (67.7 pg/mL vs. 12.5 pg/mL, p < 0.01), and showed a significant positive correlation with Eo (rs = 0.60, p < 0.01). CONCLUSIONS: This study demonstrated two types of eosinophilia in Japanese FPIES infants: conspicuous and mild eosinophilia in early- and late-onset FPIES patients, respectively. Conspicuous eosinophilia in early-onset FPIES is suggested to be caused by abnormally high IL-5 production.

Serum C-reactive protein in food protein-induced enterocolitis syndrome versus food protein-induced proctocolitis in Japan.

BACKGROUND: Some infants with food protein-induced enterocolitis syndrome (FPIES) have increased serum C-reactive protein (CRP) and fever in Japan. The aim of this study was therefore to clarify and compare the incidence of this in patients with FPIES versus patients with food protein-induced proctocolitis (FPIP). METHODS: One hundred and sixteen infants with non-IgE-mediated gastrointestinal food allergies were enrolled in this study and classified into three phenotypes: FPIES presenting with vomiting and/or diarrhea (n = 47); FPIP with bloody stool alone (n =19); and the mixed phenotype (MP), bloody stool with vomiting and/or diarrhea (n = 50). RESULTS: Serum CRP was increased in 55.3% of the FPIES group, similar to that in the MP group (54.0%), and significantly higher than in the FPIP group (15.8%; P < 0.01). Fever was observed in 29.8% of the FPIES group, significantly higher than in the MP group (8.0%; P < 0.01) and in the FPIP group (0%; P < 0.05). Patients with fever had significantly higher serum CRP than patients without fever (median, 12.8 vs <0.2 mg/dL, P < 0.00001). CONCLUSIONS: Serum CRP was significantly higher in the FPIES group than in the FPIP group. This suggests that serum CRP is a useful marker for differentiating the pathogenesis of FPIES from FPIP. From the perspective of serum CRP, the pathology of the intestinal inflammation in MP subjects is suggested to be similar to that of FPIES.

Chronic active EBV infection with features of granulomatosis with polyangiitis.

Herein, we report the case of a 13-year-old boy with multiple recurrent ulcers on his legs. He developed severe sinusitis at 10 years of age and had significant weight loss (6 kg) in the 2 months prior to admission. Histology of tissue biopsied from the ulcer indicated small vessel vasculitis and granulomatous inflammation. Given that these findings met the diagnostic criteria for granulomatosis with polyangiitis (GPA), he was treated with immunosuppressive agents. Further pathology, however, indicated Epstein-Barr virus (EBV)-encoded RNA (EBER) in most lymphocytes in the same sample. The EBER-positive lymphocytes were mainly CD4-positive T cells. The EBV-DNA load in the peripheral blood was also abnormally increased (1.0 × 10(4) copies/µg DNA). Thus, the diagnosis was established as chronic active EBV infection (CAEBV). This case illustrates the necessity of careful differential diagnosis of CAEBV owing to its clinical resemblance and pathological overlap with GPA.

Increased C-reactive protein and fever in Japanese infants with food protein-induced enterocolitis syndrome.

BACKGROUND: Increased C-reactive protein (CRP) and fever are observed in some infants with food protein-induced enterocolitis syndrome (FPIES) in Japan, but the reproducibility of these findings has not yet been confirmed on oral food challenge (OFC). METHODS: Fourteen infants with FPIES induced by cow's milk (CM) formula were enrolled. OFC using CM formula was performed on each infant once or repeatedly (total 18 tests), with a stepwise incremental protocol in an infection-controlled setting. CRP was measured 24 h after the last ingestion of the CM formula. RESULTS: Increased CRP was observed in 11 of the 18 OFC conducted (median, 2.60 mg/dL; range, 0.22-4.84 mg/dL). Fever was induced in six occasions during OFC. Serum CRP in the patients with fever increased to median 3.76 mg/dL (range, <0.7-4.84 mg/dL), which was significantly higher than that of the patients without fever (median <0.1 mg/dL; range, <0.1-2.6 mg/dL; P < 0.001). CRP during OFC significantly correlated with that at disease onset (rs = 0.62, P < 0.02). Three of the four patients with fever at disease onset also had fever during OFC. CONCLUSIONS: Increased CRP and fever are reproducible during OFC in some infants with FPIES, suggesting that these are not accidental phenomena, but instead are associated with FPIES itself in Japanese patients.

Close Positive Correlation between the Lymphocyte Response to Hen Egg White and House Dust Mites in Infants with Atopic Dermatitis.

BACKGROUND: It was recently hypothesized that food allergens sensitize infants with atopic dermatitis (AD) via the skin. If this is the case, an intimate positive correlation should be observed between immune responses to both food and indoor allergens. METHODS: One hundred and seven infants with AD and 32 controls were enrolled. The proliferation of lymphocytes stimulated with hen egg white (EW) or house dust mite (HDM) allergens was measured by means of an allergen-specific lymphocyte stimulation test (ALST). Cytokine production was measured in 13 patients and 4 controls. RESULTS: ALST responses for EW (EW-ALST) were significantly higher in AD infants than in control subjects (stimulation index: 7.98 vs. 2.54, p < 0.0001). HDM-ALST responses were also significantly higher in AD infants than in controls (stimulation index: 5.09 vs. 1.44, p < 0.0001). A significant positive correlation was seen between HDM-ALST and EW-ALST responses in AD infants aged 5-6 months (rs = 0.77, p < 0.000001). Serum levels of EW-specific IgE (EW-IgE) were significantly correlated with both EW-ALST (rs = 0.43, p < 0.05) and HDM-ALST levels (rs = 0.47, p < 0.05) in AD patients aged 3-4 months. Serum EW-IgE levels in AD infants were significantly correlated with the ratio of IL-4/IFN-γ production from lymphocytes stimulated with EW (rs = 0.62, p < 0.01) and with HDM (rs = 0.67, p < 0.005). CONCLUSIONS: This study describes the close positive correlation between EW- and HDM-specific immune responses in infants with AD. These results may support the hypothesis that both food and indoor allergens concurrently sensitize infants via the skin.

Follow-up of pediatric patients treated by IVIG for Langerhans cell histiocytosis (LCH)-related neurodegenerative CNS disease.

The follow-up of eight Japanese children with Langerhans cell histiocytosis (LCH)-related neurodegenerative central nervous system (ND-CNS) disease who were treated with intravenous immunoglobulin (IVIG) for >3 years is described. The patients developed ND-CNS disease at a median age of 5.2 (range 3.5-10.0) years and received IVIG treatment for a median duration of 6.5 + (range 3.7 to 10+) years. After a median follow-up period of 11.6 + (8.3+ to 13.9+) years after ND-CNS disease diagnosis, the median Expanded Disability Status Scale (EDSS) score of the eight patients was 4.0 (range 2.0-9.5). At the last follow-up as of March 2014, three patients have low EDSS scores (<3.0) and can walk without any assistance. Another three patients have EDSS scores of 3.5-4.5 and can walk by themselves, albeit occasionally with supports. However, the remaining two patients are wheelchair bound or bed ridden. The school performance of seven of the eight patients was below average. IVIG appeared to be most beneficial when it was administered soon after ND-CNS disease diagnosis when the EDSS scores were low (1.0-2.5). The patients who began receiving IVIG when their high EDSS scores were higher (4.5-7.0) appeared to obtain less benefit. To prevent progression of ND-CNS disease in patients with LCH, it is recommended to introduce IVIG early and to continue this therapy for >3 years.

[Evaluation of the allergenicity of ß-casein in Japanese children with cow milk allergy by using the basophil activation test].

BACKGROUND: Among the casein components, αs-casein (αs-CAS) is considered the major allergen in Japan, and there are very few reports on the allergenicity of ß-casein (ß-CAS). In this study, we compared the allergenicity of ß-CAS with that of αs-CAS in Japanese children with cow milk allergy (CMA). METHOD: The allergenicity of αs-CAS and ß-CAS in 29 CMA patients and 11 control subjects was assessed using the basophil activation test (BAT). The accuracy of the BAT to distinguish the patients with CMA from the control subjects was estimated using a receiver operating characteristic (ROC) analysis and was expressed as the area under the curve (AUC). RESULTS: BAT results for CM were positive in 93.1% of the CMA patients. The results of the ß-CAS-BAT and αs-CAS-BAT were found to be positive in 86.2% and 69.0% of the CMA patients, respectively, however, the difference was not significant. The AUC for the ß-CAS-BAT was 0.893, which was not significantly different from that for the αs-CAS-BAT (0.859). CONCLUSIONS: These results suggest that the allergenicities of ß-CAS and αs-CAS are similar in Japanese patients with CMA.

Association of age and family history with supplement use in pediatric patients with allergy.

This study was conducted to determine the frequency and characteristics of supplement use in pediatric patients with allergic disorders in Japan. A total of 229 patients with various allergic disorders aged between 0 and 15 years were enrolled. Supplements were defined as preparations that provided nutritional content in the form of a tablet, capsule, powder, liquid, or jelly. The parents of each subject were asked to complete a questionnaire on their child's use of supplements over the previous year. Demographic information, parents' perceived view of the child's health status over the previous month, and family history of both allergic disorders, and supplement use were collected. Four hundred eight age- and sex-matched healthy children served as the controls. Twenty-nine (12.7%) patients had used supplements. This frequency was not significantly different from that in the control group (15.0%). The types of supplements most commonly used were vitamins, followed by minerals, probiotics, and chlorella. Univariate analysis revealed that older age and a positive family history of supplement use were associated with patients' supplement use. The types of allergic disorders, health status from the point of view of the parents, and a family history of allergic disorders did not show any significant association. To our knowledge, this is the first cross-sectional study to demonstrate the frequency and the factors affecting supplement use in pediatric patients with allergic disorders.

Sporadic hemiplegic migraine presenting as acute encephalopathy.

A 10-year-old boy with psychomotor developmental delay and cerebellar vermis atrophy developed right hemiplegia with vomiting, unconsciousness, convulsions, and late-onset fever. Slow delta activity was noted over the left hemisphere on electroencephalography, and neuroimaging revealed swelling of the left temporo-occipital cerebral cortex with restricted diffusivity, successive transient cortical atrophy, and hyperperfusion over the left cerebral hemisphere. Interleukin-6 was elevated in the cerebrospinal fluid. The acute symptoms resolved completely within 3 weeks after onset, but hypoperfusion persisted in the left posterior cortex thereafter. Another episode with transient left hemiplegia appeared 7 months later, followed by recurrence of migraine attacks. Analysis of the CACNA1A gene revealed a mutation of c.1997 C>T (p.T666M). None of his family members had migraine. This case represents an unusual evolution of sporadic hemiplegic migraine with manifestations of acute encephalopathy, for which the role of migraine-related inflammatory process is assumed.

Neurodegenerative central nervous system disease as late sequelae of Langerhans cell histiocytosis. Report from the Japan LCH Study Group.

Clinical features, brain magnetic resonance imaging findings and EDSS scores of 11 patients with neurodegenerative central nervous system Langerhans cell histiocytosis were analyzed in Japan. All patients initially had multi-system-type Langerhans cell histiocytosis; 8 at 1-2 years of age and 3 at a later age. Neurodegenerative central nervous system Langerhans cell histiocytosis disease developed after a median time interval of 3.9 years from initial diagnosis. With a median follow-up of 4.5 years, 6 patients showed progression of disease with an EDSS score >3. This study demonstrates the importance of early detection of neurodegenerative central nervous system Langerhans cell histiocytosis by brain magnetic resonance imaging, particularly in the follow-up of patients who developed multi-system-type Langerhans cell histiocytosis in early infancy.

A case of splenosis after laparoscopic splenectomy.

Splenosis is the heterotopic autotransplantation of splenic tissue usually following traumatic rupture of the spleen or surgical manipulation of splenic tissue. Although it is generally asymptomatic, it may present with abdominal pain or mass. Furthermore, there may be recurrence of the hematological disorders for which the patient underwent splenectomy. We report a rare case of splenosis in a 9-year-old girl after laparoscopic splenectomy for hereditary spherocytosis, which required laparotomy due to bowel obstruction.

Nephrotic syndrome and aberrant expression of laminin isoforms in glomerular basement membranes for an infant with Herlitz junctional epidermolysis bullosa.

Herlitz junctional epidermolysis bullosa (H-JEB) is a hereditary bullous disease caused by absent expression of laminin-5, a component of anchoring filaments within the dermal-epidermal basement membrane zone. Affected individuals usually die during the first 1 year of life. We studied an infant with H-JEB who presented with nephrotic syndrome, a previously unreported complication that may contribute to early death in this disease. DNA analysis revealed a compound heterozygote for mutations 2379delG and Q995X in the LAMB3 gene. The patient had massive albuminuria, attributable to failure of the glomerular filtration barrier, and high urinary N-acetylglucosaminidase levels, indicating renal tubular involvement. Electron-microscopic examination of the renal tissue revealed diffuse fusion of the foot processes, irregular swelling of the lamina rara interna, and disappearance of endothelial cell fenestrations. Immunohistopathologic analysis of the patient's renal tissue revealed compositional changes in laminin isoforms of the glomerular basement membrane and no detectable laminin-5 in the renal tubular basement membrane, which suggests that laminin-5 may play an important role in renal function. Our findings strongly suggest that H-JEB should be considered in the spectrum of congenital nephrotic syndromes. Combination therapy with meticulous skin care and treatment strategies established for congenital nephrotic syndromes may rescue patients with this disease.

Expression of Epstein-Barr virus in Langerhans' cell histiocytosis.

Langerhans' cell histiocytosis (LCH) is a proliferative histiocytic disorder of unknown etiology. We previously reported that Epstein-Barr virus (EBV) infects and proliferates in macrophages, and investigated the possibility that EBV exhibits etiologic effects in LCH. To detect EBV expression, paraffin sections from 17 LCH cases were examined by mRNA in situ hybridization for EBV BamHIW, Epstein-Barr virus nuclear antigen-2 (EBNA2), and Epstein-Barr virus-encoded small nonpolyadenylated RNA (EBER1) sequences, and by indirect immunofluorescence staining for EBNA2, latent membrane protein 1 (LMP1), and BamHIZ-coding leftward-reading frame 1 (BZLF1). To detect EBV DNA, polymerase chain reaction (PCR)-Southern blotting was used. All cases showed positive hybridization signals by BamHIW mRNA in situ hybridization. Also, 13 and 14 cases showed positive signals for EBNA2 and EBER1 RNA in situ hybridization, respectively. Furthermore, almost all cases exhibited fluorescence after immunofluorescence staining with monoclonal anti-EBNA2 and anti-BZLF1 antibodies, and 15 cases were positive after treatment with monoclonal anti-LMP1 antibody. PCR-Southern blotting detected an amplified EBER1 sequence in all 9 cases examined. EBV expression was confirmed in LCH using in situ hybridization and immunofluorescence. Furthermore, EBV DNA was also detected by PCR-Southern blotting. These positive results of BZLF1 suggest that EBV replicates in LCH tissues.

Rapid improvement of paraplegia caused by epidural involvements of Burkitt's lymphoma with chemotherapy.

STUDY DESIGN: Case report. OBJECTIVE: The authors present a case of atypical Burkitt's lymphoma with multiple epidural involvements. SUMMARY OF BACKGROUND DATA: Spinal cord compression in children is an emergency that requires urgent attention to minimize neurologic dysfunction. Although it is not life-threatening in most patients, cord compression can cause severe neurologic morbidity. MATERIALS AND METHODS: Because the patient showed rapid neurologic deterioration, we started chemotherapy and high-dose steroids without laminectomy or radiotherapy immediately after a tumor biopsy from the left mandible. RESULT: The combined therapies were very effective and his neurologic symptoms improved immediately. The epidural involved masses disappeared in imaging studies after the first course of chemotherapy including methylprednisolone (20 mg/kg per day for 3 consecutive days and gradually tapered off over 2 weeks), vincristine (1.5 mg/m2 per day), cyclophosphamide (2 g/m2 per day for 2 days) and pirarubicin (40 mg/m2 per day). After completing seven courses of chemotherapy, the patient is now fully ambulant. CONCLUSION: Considering the severe late effects of laminectomy and radiotherapy, chemotherapy should be considered as a first choice of treatment for spinal cord compression caused by malignant lymphoma.

[The effectiveness of the long-term treatment with pranlukast in pediatric patients with mild to moderate asthma].

To investigate the efficacy of the long-term treatment with pranlukast, a specific cysteinyl leukotriene receptor antagonist, in pediatric patients with mild to moderate asthma, 77 pediatric asthmatic patients who received pranlukast for up to 36 months (mean duration, 13 months) were evaluated retrospectively. Treatment with pranlukast resulted in improvements from the pretreatment baseline in asthma attacks per month, episodes of hospitalization, and episodes of intravenous amynophiline treatment on emergent clinic visits. The percentage of responders who had marked or moderate improvements in the above-mentioned parameters of asthma control was 79%. In conclusion, pranlukast caused significant improvements in long-term asthma control in pediatric patients with mild to moderate asthma.