Methylprednisolone-induced anaphylaxis diagnosed by intradermal skin test: a case report.

BACKGROUND: Glucocorticoids rarely cause anaphylaxis. Common methods for the determination of allergens include in vivo skin prick test (SPT) and intradermal skin test (IDST) and the in vitro basophil activation test (BAT). However, to our knowledge, the best strategy for diagnosing glucocorticoid-induced anaphylaxis has not been elucidated. CASE PRESENTATION: A 10-year-old boy was admitted to our hospital because of 2 weeks of fever and arthralgia. He had not been treated with glucocorticoids before, including methylprednisolone (mPSL). He was suspected to have bacterial myositis and was treated with ceftriaxone. However, his symptoms persisted for > 2 weeks. Autoinflammatory arthritis was suspected, and he was treated with mPSL sodium succinate (MPS) pulse therapy (30 mg/kg). After 15 min of mPSL injection, he had wheezing and generalized wheal formation with decreased oxygen saturation. As anaphylaxis was suspected, mPSL was discontinued, and olopatadine and oxygen were administered. The symptoms improved considerably without the use of epinephrine and disappeared in 30 min. One month after discharge, SPT, IDST, and BAT were performed without discontinuing his prescribed oral prednisolone. SPTs for MPS, hydrocortisone sodium succinate (HCS), prednisolone sodium succinate (PSS), dexamethasone sodium phosphate (DSP), and betamethasone sodium phosphate (BSP) were negative. IDSTs for MPS, HCS, and PSS were positive, whereas those for DSP and BSP were negative. By contrast, BATs for MPS, HCS, and PSS were negative. Although glucocorticoid-induced hypersensitivity caused by nonmedicinal ingredients such as lactose, carboxymethylcellulose, polyethylene glycol, and hexylene glycol has been reported; the glucocorticoids tested in this patient did not contain any of these nonmedicinal ingredients. As the glucocorticoids that were positive on IDST share a succinate ester, this might have caused MPS-induced anaphylaxis. CONCLUSIONS: We report the case of MPS-induced anaphylaxis diagnosed by IDST but not BAT. In case reports of glucocorticoid-induced anaphylaxis in the literature, most patients were diagnosed with SPT or IDST. These results suggest that BAT should be considered when IDST and SPT are negative. Further studies are necessary to clarify the best strategy for diagnosing glucocorticoid-induced anaphylaxis.

White Blood Cell and Neutrophil Counts and Response to Intravenous Immunoglobulin in Kawasaki Disease.

We explored parameters to predicting the efficacy of intravenous immunoglobulin (IVIG) therapy for patients with Kawasaki disease (KD). We retrospectively analyzed the laboratory data of 77 children with KD treated with IVIG. Data obtained before and within 24 hours after IVIG therapy were compared between responders and nonresponders. The white blood cell (WBC) and neutrophil counts were significantly lower in responders than nonresponders within 24 hours after IVIG. The areas under the receiver operating characteristics curves of the WBC and neutrophil counts were 0.846 and 0.754, respectively. The WBC and neutrophil counts differed significantly between responders and nonresponders (the latter developed recurrent pyrexia after transient fever resolution). In conclusion, WBC and neutrophil counts within 24 hours after IVIG usefully predict the efficacy of IVIG therapy for those with KD, and identify nonresponders to such therapy.

Survey of rotavirus-associated severe complications in Aichi Prefecture.

BACKGROUND: Rotavirus can, rarely, cause severe complications such as encephalopathy/encephalitis, myocarditis, sudden death, urinary stone, and gastrointestinal (GI) bleeding; and the incidence of these severe complications remains unclear. Additionally, it has not been determined whether rotavirus (RV) vaccine could reduce cases of severe complications or not. METHODS: A two-part questionnaire was designed to determine the number and clinical features of severe complications between 1 September 2008 and 31 August 2015, including the observation periods before and after RV vaccine introduction in Aichi Prefecture. RESULTS: Twenty-four cases of encephalitis/encephalopathy, eight cases of sudden death, three cases of urinary tract stone, and three cases of GI bleeding were reported during the 2008/2009 season and the 2012/2013 seasons. Although five cases of encephalitis/encephalopathy were reported, no other cases of severe complications were reported during the 2013/2014 and 2014/2015 seasons. No age difference was noted according to type of complication. Although onset of encephalitis/encephalopathy and of sudden death was around day 2 of illness, that of urinary tract stone and GI bleeding was slightly later (day 6 and day 4). In addition to the eight sudden deaths, fatal outcome was also noted in four cases (13.8%) of encephalitis/encephalopathy, and in one case of GI bleeding. CONCLUSION: According to the questionnaire survey in Aichi Prefecture, the incidence of the four severe RV-associated complications appears to have declined as the vaccination rate has increased.

Fournier's gangrene during ACTH therapy.

Fournier's gangrene is an infectious necrotizing fasciitis of the perineal, genital, or perianal regions and is uncommon in children. Adrenocorticotropic hormone (ACTH) is effective for the treatment of infantile spasms; however, suppression of immune function is one of the major adverse effects of this approach. We encountered a 2-month-old boy with infantile spasms that had been treated with ACTH and had developed complicating Fournier's gangrene. Strangulation of a right inguinal hernia was observed after ACTH treatment. Although surgical repair was successful and no intestinal injuries were detected, swelling and discoloration of the right scrotum developed in association with pyrexia and a severe inflammatory response. A scrotal incision revealed pus with a putrid smell. The patient was subsequently diagnosed with Fournier's gangrene complicated by septic shock and disseminated intravascular coagulation. Extensive debridement and intensive care was performed. Enterobactor aerogenes, methicillin-resistant Staphylococcus aureus, and Enterococcus faecalis were isolated from the pus. Meropenem, teicoplanin, and clindamycin were administered to control the bacterial infection. The patient was discharged from the intensive care unit without any obvious neurological sequelae. Suppression of immune function associated with ACTH therapy may have been related to the development of Fournier's gangrene in this case.

Clinical characteristics of influenza virus infection in juvenile idiopathic arthritis patients treated with tocilizumab.

BACKGROUND: Inhibition of interleukin-6 (IL-6) signaling by tocilizumab is highly effective for treatment of refractory juvenile idiopathic arthritis (JIA). It appears that IL-6 plays an important role in the immune response to the influenza virus, but it is not clear whether treatment with tocilizumab affects the severity of influenza. METHODS: We retrospectively collected clinical and laboratory data from JIA patients (n = 33) treated with tocilizumab. Ten patients who developed influenza (tocilizumab group; 10.1 %, 10/99 patient-years) were analyzed. Eleven JIA patients who experienced influenza during conventional treatments, without tocilizumab (control group), were compared with the tocilizumab group. RESULTS: Of the 10 patients in the tocilizumab group, 6 patients did not have high fever (>38 °C), and the other 4 febrile patients recovered from fever in 1 day. White blood cell counts and lymphocyte counts were significantly lower at the acute phase of infection compared with data from before influenza infection. The degree of fever and level of C-reactive protein in the tocilizumab group were significantly reduced compared with the control group. CONCLUSIONS: IL-6 inhibition by tocilizumab reduced inflammation associated with infection and resulted in mild symptoms during influenza. Leukopenia might be a useful indicator of viral infection, including influenza, during tocilizumab treatment.

Prospective monitoring of Epstein-Barr virus and other herpesviruses in patients with juvenile idiopathic arthritis treated with methotrexate and tocilizumab.

Methotrexate (MTX) is widely used for the treatment of articular-type juvenile idiopathic arthritis (JIA), but patients receiving MTX for rheumatoid arthritis have been reported to be at increased risk of reactivation of Epstein-Barr virus (EBV) and the development of lymphoproliferative disorder. The association between MTX and reactivation of herpesviruses in pediatric patients is not yet understood. We prospectively monitored the viral load of EBV, cytomegalovirus (CMV), and herpesvirus 6 (HHV-6) in four JIA patients treated with MTX for 12-24 months. Tocilizumab, an anti-interleukin 6 receptor monoclonal antibody, was added to the therapeutic regimen in three patients during the observation period. Prior to the administration of MTX, EBV and HHV-6 were detected by PCR in two patients. Significant increases in EBV and HHV-6 load were not observed following the administration of MTX or tocilizumab. In one patient, a relatively high EBV load remained detectable during 21 months of observation in the absence of clinical symptoms. CMV was not detected throughout the observation period in any patient. This is the first report monitoring the longitudinal DNA loads of EBV and other herpesviruses in JIA patients. EBV and HHV-6 were often detectable, but treatment with MTX and tocilizumab did not appear to influence the viral load.

Detection of submicroscopic disease in the bone marrow and unaffected testis of a child with T-cell acute lymphoblastic leukemia who experienced "isolated" testicular relapse.

Testicular relapse has an impact on the prognosis of boys with acute lymphoblastic leukemia (ALL). Because isolated testicular relapse often precedes hematological relapse, systemic therapy is required in addition to local therapy. However, a rationale for the use of a combination of systemic chemotherapy and local therapy is unclear. A 12-year-old boy with T-ALL suffered from isolated testicular relapse at 27 months after diagnosis. He was successfully treated with systemic chemotherapy with orchiectomy and prophylactic irradiation to the contralateral testis. We retrospectively estimated the minimal residual disease in the bone marrow (BM) and the testis by detection of clone-specific T-cell receptor rearrangement of leukemic cells. We detected leukemic cells in the affected testis at relapse, as well as in the BM at initial diagnosis. In addition, we confirmed submicroscopic disease in the unaffected testis and the BM at relapse. We conclude that molecular analysis could reveal the submicroscopic disease in the patient with apparently isolated testicular relapse. This finding may provide a rationale for intensified systemic treatment of patients with isolated testicular relapse.

Development of diffuse large B cell lymphoma during the maintenance therapy for B-lineage acute lymphoblastic leukemia.

Non-Hodgkin lymphoma (NHL) is a very rare complication of acute lymphoblastic leukemia (ALL). A Japanese boy presented with B-lineage ALL at the age of 2.5. He was treated with chemotherapy for standard-risk ALL. While he was receiving maintenance treatment 2 years and 9 months after the diagnosis of ALL, diffuse large B cell lymphoma (DLBL) was diagnosed from a biopsy of an abdominal mass. DLBL was treated by surgical resection followed by chemotherapy for 6 months. The patient has been free from the recurrence of ALL or DLBL for 16 months after the development of DLBL.

Antineoplastic agents for pediatric anaplastic large cell lymphoma: Vinblastine is the most effective in vitro.

Anti-neoplastic effects of a total of 11 agents (adriamycin, briplatin, cytarabine, dexamethasone, etoposide, 4-hydroperoxycyclophosphamide, 4-hydroperoxyifosphamide, methotrexate, predonisolone, vinblastine, vincristine) were tested on 4 cell lines (DEL, Ki-JK, SR-786, SU-DHL-1) established from pediatric ALCL cases. The individual cell lines were treated with those agents at different concentrations (0.01 microM/L, 0.1 microM/L, 1 microM/L, 10 microM/L, 100 microM/L) for 1 h or 24 h, and their cellular growths were measured by the microculture tetrozolium (MTT) assay. Of those anti-neoplastic agents, methotrexate, vinblastine, and vincristine were highly effective on the cell growth inhibition in all these cell lines with time- and dose-dependent manner. Among them, vinblastine was found to be the most effective in 3 cell lines (DEL, Ki-JK, SR786) with 50% effective doses (ED50, concentrations causing 50% cell survival after treatment) ranging from 0.0016 to 1.27 microM/L for the 1-h treatment and 0.0002 - 0.59 microM/L for the 24-h treatment. Further experiments demonstrated that vinblastine treatment induced cellular apoptosis and caused severe disruption in mitotic spindle formation on these cell lines. The results support the protocol of ALCL 99 study, which uses vinblastine as one of the first-line anti-neoplastic agents for the high-risk ALCL patients in the pediatric age group.