Food-dependent exercise-induced anaphylaxis in Japanese elementary school children.

BACKGROUND: In 2012, we clarified that the prevalence of food-dependent exercise-induced anaphylaxis (FDEIA) was 0.018% in junior-high students in Yokohama, Japan. Furthermore, although different from FDEIA, one student who had completed oral immunotherapy developed anaphylaxis during exercise after eating causative food. There have been few large-scale epidemiological studies of FDEIA, however, in elementary school children, therefore we conducted an epidemiological study in elementary school children in Yokohama to clarify the frequency and characteristic of FDEIA. METHODS: We sent a questionnaire regarding the occurrence of FDEIA to all 348 public elementary school nurses in Yokohama. We also compared the results with those for junior-high school that we previously reported. We excluded those children with a past history of immediate food allergy who had achieved desensitization status after oral immunotherapy, from FDEIA, and instead defined them as having desensitization status and exercise-induced anaphylaxis (DEIA). RESULTS: Of 348 school nurses, 317 responded (91.1%). Overall, eight of 170 146 children were diagnosed with FDEIA, which was significantly lower than the prevalence in junior-high school students (0.0047% vs 0.018%, P = 0.0009). The causative foods were wheat (n = 4), and soy, fruit, crustaceans, and squid (n = 1 each). Four children had DEIA and the causative foods were wheat and milk (n = 2 each). Multiple episodes occurred in five children with FDEIA and in three children with DEIA. CONCLUSIONS: FDEIA was far less common in elementary school than in junior-high school, and wheat was the major causative food. The new appearance of DEIA was notable. Decreasing episode recurrence remains an issue that needs to be resolved.

Predictive Factors Associated With Acute Ocular Involvement in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

PURPOSE: To suggest an objective score for grading the acute ocular severity of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), and to determine predictive factors for severe acute ocular involvement such as ocular surface epithelial defect and/or pseudomembrane formation. DESIGN: Retrospective cohort study. METHODS: The medical records of SJS (n = 87) and TEN (n = 48) patients between 2005 and 2007 were reviewed. An acute ocular severity score was determined on a scale from 0 to 3 (none, mild, severe, and very severe) according to the existence of hyperemia, corneal or conjunctival epithelial defect, and pseudomembrane formation. The associations between the severe acute ocular involvement and factors such as patient age, exposed drugs, systemic severity, and the prevalence of ocular sequelae were examined. RESULTS: The number of cases with score grade 0, 1, 2, and 3 was 19 (21.8%), 31 (35.6%), 22 (25.3%), and 15 (17.2%) in 87 SJS cases and 12 (25.0%), 11 (22.9%), 17 (35.4%), and 8 (16.7%) in 48 TEN cases. Multivariate logistic regression analysis revealed that patient age (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.96-0.99; P = .007) and nonsteroidal anti-inflammatory drugs NSAIDs or cold remedies (OR, 2.58; 95% CI, 1.26-5.29; P = .010) were predictive factors for severe acute ocular involvement. The prevalence of visual disturbance and eye dryness increased according to the increase of acute ocular severity (P = .001 and P = .007 in SJS; P = .007 and P = .014 in TEN, respectively). CONCLUSIONS: At the onset of SJS/TEN, strict attention should be paid to ocular involvement in young patients and in patients exposed to NSAIDs or cold remedies.

Japanese Guideline for Food Allergy 2014.

A food allergy is defined as "a phenomenon in which adverse reactions are caused through antigen-specific immunological mechanisms after exposure to given food." Various symptoms of food allergy occur in many organs. Food allergies are classified roughly into 4 clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type food allergy (urticaria, anaphylaxis, etc.), and (4) food dependent exercise-induced anaphylaxis and oral allergy syndrome (i.e., specific forms of immediate food allergy). The therapy for food allergies includes treatment of and prophylactic measures against hypersensitivity such as anaphylaxis. A fundamental prophylactic measure is the elimination diet. However, elimination diets should be used only if necessary because of the patient-related burden. For this purpose, it is very important that causative foods be accurately identified. There are a number of means available to identify causative foods, including the history taking, a skin prick test, detection of antigen-specific IgE antibodies in the blood, the basophil histamine release test, the elimination diet test, and the oral challenge test, etc. Of these, the oral challenge test is the most reliable. However, it should be conducted under the supervision of experienced physicians because it may cause adverse reactions, such as anaphylaxis.

Japanese pediatric guideline for the treatment and management of bronchial asthma 2012.

A new version of the Japanese pediatric guideline for the treatment and management of bronchial asthma was published in Japanese at the end of 2011. The guideline sets the pragmatic goal for clinicians treating childhood asthma as maintaining a "well-controlled level" for an extended period in which the child patient can lead a trouble-free daily life, not forgetting the ultimate goal of obtaining remission and/or cure. Important factors in the attainment of the pragmatic goal are: (i) appropriate use of anti-inflammatory drugs; (ii) elimination of environmental risk factors; and (iii) educational and enlightening activities for the patient and caregivers regarding adequate asthma management in daily life. The well-controlled level refers to a symptom-free state in which no transient coughs, wheezing, dyspnea or other symptoms associated with bronchial asthma are present, even for a short period of time. As was the case in the previous versions of the guideline, asthmatic children younger than 2 years of age are defined as infantile asthma patients. Special attention is paid to these patients in the new guideline: they often have rapid exacerbation and easily present chronic asthmatic conditions after the disease is established.

Japanese Guideline for Food Allergy 2014.

A food allergy is defined as "a phenomenon in which adverse reactions are caused through antigen-specific immunological mechanisms after exposure to given food." Various symptoms of food allergy occur in many organs. Food allergies are classified roughly into 4 clinical types: (1) neonatal and infantile gastrointestinal allergy, (2) infantile atopic dermatitis associated with food allergy, (3) immediate-type food allergy (urticaria, anaphylaxis, etc.), and (4) food dependent exercise-induced anaphylaxis and oral allergy syndrome (i.e., specific forms of immediate food allergy). The therapy for food allergies includes treatment of and prophylactic measures against hypersensitivity such as anaphylaxis. A fundamental prophylactic measure is the elimination diet. However, elimination diets should be used only if necessary because of the patient-related burden. For this purpose, it is very important that causative foods be accurately identified. There are a number of means available to identify causative foods, including the history taking, a skin prick test, detection of antigen-specific IgE antibodies in the blood, the basophil histamine release test, the elimination diet test, and the oral challenge test, etc. Of these, the oral challenge test is the most reliable. However, it should be conducted under the supervision of experienced physicians because it may cause adverse reactions, such as anaphylaxis.

Japanese pediatric guidelines for the treatment and management of bronchial asthma 2008.

Abstract The fourth version of the Japanese Pediatric Guidelines for the Treatment and Management of Bronchial Asthma 2008 (JPGL 2008) was published by the Japanese Society of Pediatric Allergy and Clinical Immunology in December 2008. In JPGL 2008, the recommendations were revised on the basis of the JPGL 2005. The JPGL 2008 is different to the Global Initiative for Asthma guideline in that it contains the following items: a classification system of asthma severity; recommendations for long-term management organized by age; a special mention of infantile asthma; and an emphasis on prevention and early intervention. Here we show a summary of the JPGL 2008 revising our previous report concerning JPGL 2005.

Whole blood interferon-gamma assay for tuberculosis in children in Japan.

BACKGROUND: Whole blood interferon-gamma assay QuantiFERON-TB2G (QFT-2G), which is a new specific method for diagnosing tuberculosis (TB), has been developed and used in the clinical field. The aim of the present study was to assess the usefulness of QFT-2G as an indicator, both for diagnosing childhood TB and for assessing therapeutic effectiveness. METHODS: The subjects were 61 children introduced to the TB outpatient department for the first time between June 2004 and March 2006. QFT-2G, the tuberculin test and chest computed tomography (CT) were performed for all patients. RESULTS: Ten patients having typical characteristics of primary tuberculosis (PTB) on chest CT, and diagnosed as having tubercle bacillus infections, all had positive reaction on QFT-2G. Of seven patients who had no abnormalities on diagnostic imaging but who reacted positively on QFT-2G, one developed TB later, and no TB was detected over the period of observation in 44 patients with negative QFT-2G at their first consultation. Moreover, four patients with non-tuberculous acid-fast bacilli in which Mycobacterium avium or Mycobacterium gordonae was detected had negative reaction on QFT-2G. In addition, all 10 patients with positive reactions on QFT-2G in whom the subsequent course of the disease was observed had decrease on QFT after treatment. CONCLUSIONS: QFT-2G is a powerful tool with a wide application both in diagnosis and in assessment of treatment effectiveness in PTB.

Mizoribine for renal sarcoidosis: effective steroid tapering and prevention of recurrence.

Sarcoidosis is a systemic disease of unknown etiology that is characterized by chronic non-caseating granulomatous inflammation with tissue destruction. It is an uncommon disease in children, and renal sarcoidosis in particular is very rare in adults and children. A 17-year-old boy with renal sarcoidosis was referred to our hospital with an initial diagnosis of pyelonephritis. Prior treatment with various antibiotics had not been effective, but tentative oral daily prednisolone (PSL) had partially ameliorated his symptoms, although the symptoms recurred during steroid tapering. We detected non-caseating granulomatous interstitial nephritis and numerous sclerotic glomeruli in a second biopsy specimen, compatible with the diagnosis of renal sarcoidosis. The patient was treated with pulsed methyl-prednisolone and oral daily doses of PSL and mizoribine (MZR). During the treatment with MZR, the PSL was successfully tapered, and the patient has since presented no signs of recurrence. Our treatment of this patient shows that treatment with MZR can allow steroid sparing and prevent recurrence in a patient with sarcoidosis.

A report of two cases of Kawasaki disease treated with plasma exchange.

Kawasaki disease is a generalized vasculitis of unknown etiology that occurs predominantly in infants and young children. It is very important to prevent its cardiovascular manifestations, especially coronary artery lesions. Early treatment with intravenous immunoglobulin reduces cardiovascular sequelae, but some patients do not respond to this treatment, and they have a high incidence of coronary artery lesions. On the other hand, acute heart failure is rare in Kawasaki disease. We report on the cases of two patients with persistent fever and shock even after intravenous immunoglobulin therapy. In both cases, plasma exchange may have reduced the risk of coronary artery lesions and proved effective against acute heart failure with catecholamine-refractory shock; yet the mechanism of this improvement remains unclear.

Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial.

BACKGROUND: Systemic-onset juvenile idiopathic arthritis does not always respond to available treatments, including antitumour necrosis factor agents. We investigated the efficacy and safety of tocilizumab, an anti-interleukin-6-receptor monoclonal antibody, in children with this disorder. METHODS: 56 children (aged 2-19 years) with disease refractory to conventional treatment were given three doses of tocilizumab 8 mg/kg every 2 weeks during a 6-week open-label lead-in phase. Patients achieving an American College of Rheumatology Pediatric (ACR Pedi) 30 response and a C-reactive protein concentration (CRP) of less than 5 mg/L were randomly assigned to receive placebo or to continue tocilizumab treatment for 12 weeks or until withdrawal for rescue medication in a double-blind phase. The primary endpoint of the double-blind phase was an ACR Pedi 30 response and CRP concentration of less than 15 mg/L. Patients responding to tocilizumab and needing further treatment were enrolled in an open-label extension phase for at least 48 weeks. The analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, numbers NCT00144599 (for the open-label lead-in and double-blind phases) and NCT00144612 (for the open-label extension phase). FINDINGS: At the end of the open-label lead-in phase, ACR Pedi 30, 50, and 70 responses were achieved by 51 (91%), 48 (86%), and 38 (68%) patients, respectively. 43 patients continued to the double-blind phase and were included in the efficacy analysis. Four (17%) of 23 patients in the placebo group maintained an ACR Pedi 30 response and a CRP concentration of less than 15 mg/L compared with 16 (80%) of 20 in the tocilizumab group (p<0.0001). By week 48 of the open-label extension phase, ACR Pedi 30, 50, and 70 responses were achieved by 47 (98%), 45 (94%), and 43 (90%) of 48 patients, respectively. Serious adverse events were anaphylactoid reaction, gastrointestinal haemorrhage, bronchitis, and gastroenteritis. INTERPRETATION: Tocilizumab is effective in children with systemic-onset juvenile idiopathic arthritis. It might therefore be a suitable treatment in the control of this disorder, which has so far been difficult to manage.

[Food-dependent exercise-induced anaphylaxis].

Food-dependent exercise-induced anaphylaxis (FEIAn) is a rare disease. The disease is classified into physical allergy and/or a subtype of food allergy. However, the pathophysiology and epidemiology are not well known. In this article we presented our studies of the epidemiology of FEIAn, in school students (elementary. junior-high, and high school) in Yokohama City and/or Kanagawa Prefecture, Japan. Also, we reviewed FEIAn cases in the literatures in Japan as well as in foreign countries. Six hundred and seven school nurses responded the questionnaire, 30 (Male:Female, 24:6) cases of FEIAn and 44 (M:F, 22:22) with exercise-induced anaphylaxis (EIAn) among 353977 students were reported. The frequency of FEIAn and EIAn was 0.0085% and 0.012%, respectively. Only one third of nurses had knowledge of FEIAn. We performed provocation tests in 11 of the 30 students with FEIAn and confirmed the diagnosis. We demonstrated transient increases in plasma histamine but not serum tryptase levels during the tests. The causative foods were mainly wheat and crustaceans in 170 Japanese cases and beans and wheat in foreign countries. As for exercise, ball games and running were more frequent sports in both groups. The age of first episode of FEIAn was 10 to 20 years old in most cases. Provocation test often fails to induce symptoms. In addition, we do not have the standard method. Now we are establishing the protocol. FEIAn and EIAn are relatively rare among school students in Japan. There is no evidence to prevent the onset of FEIAn with medicines. Therefore, to avoid serious outcomes and unnecessary restriction, we believe it is important to be familiar with the diseases for not only physicians, but also school nurses and teachers of physical education.

Amelioration of steroids and cyclosporine-resistant nephrotic syndrome by pravastatin.

We report the case of a girl with steroids and cyclosporine (CsA) resistant focal segmental glomerulosclerosis (FSGS) whose proteinuria and hypoproteinaemia were dramatically resolved by pravastatin. She had been in a nephrotic condition for 6 years. Prednisolone, pulse methylprednisolone therapy, low-density lipoprotein (LDL) apheresis, CsA, cyclophosphamide and mizoribine (MZR) had proved to be ineffective. She was started on pravastatin for her hyperlipidaemia 6 and a half years from onset, in addition to the baseline therapy, which included CsA; remission of the nephrotic syndrome was unexpectedly attained after 10 months of treatment. The baseline therapy has not been changed since the inclusion of pravastatin. This case suggests that, in patients with hyperlipidaemia, the response to CsA could be restored by lowering cholesterol levels with statins. The decrease of cholesterol levels might have improved the pharmacokinetics of CsA in this patient. Furthermore, the anti-inflammatory and immuno-modulatory effects, recently attributed to statins, may also have been involved in the improvement experienced by our patient.

Intravenous gamma globulin for thrombotic microangiopathy of unknown etiology.

We encountered the case of a 4-year-old boy with thrombotic microangiopathy (TMA) of unknown etiology. Verotoxin-induced hemolytic uremic syndrome (HUS), Streptococcus-pneumoniae-related HUS, factor H deficiency, drug-induced thrombotic thrombocytopenic purpura (TTP), and ADAMTS13 (von Willebrand factor-cleaving protease; a disintegrin-like and metalloprotease with thrombospondin type 1 repeats)-related TTP were excluded. His condition was refractory to anticoagulants and plasma exchange, and his clinical course was catastrophic, with central nervous system symptoms and progressive renal failure. However, factual treatment of intravenous gamma globulin (IVIG) ended the hemolysis and resulted in a rise in platelet count. He fully recovered except for end-stage renal failure, but he underwent a successful renal transplant after peritoneal dialysis. He has not suffered a relapse of TMA or an allograft rejection for 4 years. IVIG might be an option for some patients with TMA of unknown etiology refractory to conventional treatment.

Henoch-Schonlein purpura presenting duodenal involvement similar to superior mesenteric artery syndrome in a girl.

Henoch-Schonlein purpura (HSP) is an inflammatory vasculitis involving the skin, joints, gastrointestinal (GI) tract, and kidneys. This is the first case report describing a 5-year-old girl with HSP presenting duodenal involvement which might be associated with superior mesenteric artery syndrome (SMAS).