Hypothermia, bradycardia and hypotension during glucocorticoid or cyclosporine A therapy in a boy with Kikuchi-Fujimoto disease.

Kikuchi-Fujimoto disease (KFD) is an inflammatory disease of unknown etiology characterized by fever and cervical lymphadenopathy. Although KFD is a self-limiting disease, patients with severe or long-lasting course require glucocorticoid (GC) therapy. We report a presently 17-year-old boy with KFD who had 7 relapses since the onset at 4-year-old. He suffered from hypothermia, bradycardia, and hypotension during the treatment with prednisolone or methylprednisolone. All of his vital signs recovered after cessation of the drug in addition to fluid replacement and warming. Thus, GC was effective but could not be continued because of the adverse event. Although hypothermia developed during the treatment with 5 mg/kg/day of cyclosporine A (CsA) at his second relapse, he was successfully treated with lower-dose CsA (3 mg/kg/day). Thereafter, he had five relapses of KFD until the age of 12 and was treated by 1.3-2.5 mg/kg/day of CsA. Hypothermia accompanied by bradycardia and hypotension developed soon after concomitant administration of ibuprofen at his 5th and 6th relapses even during low-dose CsA therapy. Conclusively, GC, standard dose of CsA or concomitant use of NSAIDs may cause hypothermia, bradycardia and hypotension and needs special attention. Low-dose CsA could be a choice for such cases with KFD.

Successful treatment of IgA vasculitis with prolonged cutaneous manifestation with colchicine in a 10-year-old boy.

We report a 10-year-old boy with immunoglobulin (Ig)A vasculitis (IgAV) with prolonged cutaneous manifestations who was successfully treated with colchicine. At the age of 9 years, he was diagnosed as having IgAV by typical purpura, abdominal pain, and haematochezia. Initially, his severe gastrointestinal manifestation subsided by prednisolone 60 mg/day and intravenous methylprednisolone pulse therapy. However, his gastrointestinal manifestation was glucocorticoid-dependent and refractory to factor XIII concentrate, intravenous IgG, and mycophenolate mofetil. His abdominal pain and haematochezia responded to the combination therapy with dapsone and low dose of prednisolone 5 mg/day and did not relapse even after discontinuation of dapsone. On the other hand, the effect of dapsone on his cutaneous manifestation was dose-dependent as well as dapsone had no glucocorticoid-sparing effect. Approximately 12 months after onset, colchicine treatment was started, which resulted in remission of his chronic cutaneous manifestation. After prednisolone was tapered off, his cutaneous manifestation is currently well-controlled on colchicine 0.5 mg/day without adverse events. He had never complicated kidney involvements. In conclusion, it is observed that colchicine treatment exerts a beneficial effect in IgAV patients with prolonged cutaneous manifestation refractory to multiple drugs.

Development of Graves' disease during drug-free remission of juvenile dermatomyositis.

We report a Japanese boy with Graves' disease (GD) which developed during drug-free remission of juvenile dermatomyositis (JDM). He had been diagnosed with JDM at the age of 6 years by typical skin rashes, muscle weakness, elevated serum transaminase levels, and typical findings of both magnetic resonance imaging and muscle biopsy. Although anti-melanoma differentiation antigen 5 autoantibody was positive, there was no complication of interstitial lung disease. He showed good response to methylprednisolone pulse therapy followed by oral prednisolone in combination with weekly methotrexate (MTX) and achieved drug-free remission after 3.5 years of treatment. Nevertheless, serum levels of soluble interleukin-2 receptor (sIL-2R) gradually elevated to 3185 U/ml despite no signs of relapse or malignancy. Hyperactivity and attention deficit was also noted. One year and 3 months after the cessation of MTX, he presented with abdominal pain, tachycardia, and apparent goitre. Laboratory tests showed elevated free triiodothyronine, undetectable thyroid stimulating hormone (TSH), and positive anti-TSH receptor antibodies. 99mTc scintigraphy showed high levels of thyroid uptake. He was diagnosed with GD and treated with 15 mg/day of thiamazole. Although transient drug eruption was observed, his thyroid functions are currently well-controlled on 5 mg/day of thiamazole. In conclusion, to our knowledge, this is the first report in English literature describing complication of GD with JDM. Unexpected elevation of sIL-2R could be a clue to the diagnosis of GD during the follow-up of JDM.

[Evaluation of Improvement of Tissue Contrast and Reduction of Imaging Time by Shortening TR in Brain T2 FLAIR Using MTC Pulse].

T2 fluid-attenuated inversion recovery (FLAIR) using inversion recovery pulse to suppress cerebrospinal fluid signal needs adequate T1 recovery time after data acquisition, otherwise, the T2-weighted contrast in brain tissue will get lower. Over 10000 ms of repetition time (TR) is recommended for the 1.5 T MR scanner, so it is difficult to shorten the imaging time. We verified whether T2 FLAIR combined with the magnetization transfer contrast (MTC) pulse shows better gray-to-white matter (GM/WM) and lesion-to-normal tissue contrasts even when the TR is shortened compared to the conventional T2 FLAIR. Optimal parameters of the MTC pulse were determined with a self-produced phantom, which modeled on cerebral cortical gray and white matters. GM/WM contrasts of the phantom were measured in T2 FLAIR with the MTC pulse while decreasing TR gradually from 10000 ms to 6500 ms. Although GM/WM contrast of the phantom in T2 FLAIR with the MTC pulse gradually decreased as the TR got shortened, the T2 FLAIR with the MTC pulse of 6500 ms of TR still showed 27% higher contrast than the conventional T2 FLAIR (TR 10000 ms). GM/WM contrast in T2 FLAIR with the MTC pulse was improved also in healthy volunteers, but improvement in thalamo-medullary contrast was less than that of cerebral cortico-medullary and putamino-medullary contrasts. It seems to be because thalamus, which is a deep gray matter, shows a higher MTC effect than other gray matters. Thus, it is necessary to note that the tissue contrast might differ between T2 FLAIR with the MTC pulse and the conventional T2 FLAIR. Because general lesions with an elongated T2 value show lower MTC effect compared to the normal brain tissue, a clinical case with thalamic lesion showed that the lesion-to-normal tissue contrast improved in T2 FLAIR with the MTC pulse of 6500 ms of TR. Although it is necessary to note the difference in contrast between some tissues, T2 FLAIR with the MTC pulse improves GM/WM and lesion-to-normal tissue contrasts even when the TR is shortened compared to the conventional T2 FLAIR, and it enables to shorten the imaging time.

Molecular analysis of the CLCNKB gene in Japanese patients with classic Bartter syndrome.

Deletions or mutations in the gene encoding the basolateral chloride channel CLC-Kb (CLCNKB) cause classic Bartter syndrome (MIM 602023), which is characterized by hypokalemic metabolic alkalosis, hyperreninemic hyperaldosteronism and hypercalciura. These patients are usually diagnosed during infancy or childhood due to failure to thrive and growth retardation. The purpose of this study was to investigate the underlying mutations in Japanese patients with classic Bartter syndrome. Seven Japanese patients from seven different families diagnosed as having classic Bartter syndrome were studied. Analysis of CLCNKB demonstrated a large deletion in two patients, a partial deletion in one patient and two mutations (DeltaL130 in exon 4 and W610X in exon 16) in the remaining four patients. DeltaL130 is a novel mutation, but W610X was previously reported in three unrelated Japanese patients. Six out of the seven patients were diagnosed due to typical characteristics of classic Bartter syndrome such as failure to thrive and poor weight gain however, one patient was asymptomatic with mild hypokalemia. In conclusion, we identified a novel mutation of the CLCNKB gene, DeltaL130. We did not determine whether the W610X mutation in our patients was from a common ancestor or if this mutation is frequent in Japan.

[Clinical evaluation of urinary leukotriene e4 levels in children with respiratory syncytial virus infection].

The levels of leukotriene E4 (LTE4) of the urine were determined in 24 pediatric patients with infectious diseases due to respiratory syncytial virus (RSV), i.e., bronchitis, pneumonia, and bronchiolitis, and compared with those in controls without allergic disease. The level for LTE4 of the acute-phase urine was 620+/-562 pg/mg. cr in the pediatric patients infected with RSV, being significantly higher than 190+/-67 pg/mg. cr in controls (P<0.005). The levels for LTE4 of the urine in the recovery phase showed a tendency toward decrease, as compared to those in the acute phase. However, there was no significant difference in the level for LTE4 of the acute-phase urine between the presence and the absence of each of the following conditions: expiratory wheezing; the association of pneumonia; family history of allergic diseases; the association of atopic dermatitis; and a past history of expiratory wheezing. An allergological study also revealed that there was no significant difference in LTE4 level between the presence and the absence of peripheral eosinophilia or between the presence and the absence of the high total level for IgE of the serum or positivity for the specific IgE level in the serum. These results suggest that LT is involved with the pathological conditions of RSV infection, but there are no direct relation between atopic diathesis or expiratory wheezing and the amounts of LT production.