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 erythema nodosum with salazosulfapyridine in a 9-year-old patient with chronic non-bacterial osteomyelitis.

We report a 9-year-old Japanese girl with chronic non-bacterial osteomyelitis (CNO) accompanied by recurrent erythema nodosum (EN) which was successfully treated with salazosulfapyridine (SASP). She was referred to our hospital because of recurrent erythema on her lower extremities and persistent knee and ankle arthralgia, which had been present for approximately one year. Although naproxen, a nonsteroidal anti-inflammatory drug (NSAID), was initiated, her symptoms frequently recurred. Magnetic resonance imaging demonstrated multiple distinct high-intensity signals in the talus bones suggestive of multiple bone edemas. Additionally, a histological examination of erythematous lesions was consistent with the histopathological findings of EN. She was diagnosed as having CNO complicated by EN, and received 250 mg/day of SASP as a second-line treatment, which showed partial response of both skin and bone lesions. Following increase in the dose of SASP to 500 mg/day resulted in complete remission of her skin and bone lesions. In conclusion, our findings suggest that SASP is effective not only for CNO bone lesions but also for EN. SASP could serve as a second-line therapeutic option at least for some cases of CNO complicated by EN refractory to NSAIDs.

Treatment for macrophage activation syndrome associated with systemic juvenile idiopathic arthritis in Japan.

OBJECTIVES: To clarify how pediatric rheumatologists treat systemic juvenile idiopathic arthritis (s-JIA) associated macrophage activation syndrome (MAS) in the real world and to assess the efficacy and safety of dexamethasone palmitate (DEX-P) in the treatment of s-JIA-associated MAS. METHODS: This multicenter, retrospective study was conducted at 13 pediatric rheumatology institutes in Japan. This study included 28 patients with s-JIA-associated MAS. Clinical findings, such as treatment details and adverse events, were evaluated. RESULTS: Methylprednisolone (mPSL) pulse therapy was selected as the first-line treatment in more than half of the patients with MAS. Cyclosporine A (CsA) was used as first-line therapy in combination with corticosteroids in half of the patients with MAS. DEX-P and/or CsA were selected as the second-line therapy in 63% of patients with corticosteroid-resistant MAS. Plasma exchange was selected as the third-line therapy for DEX-P and CsA-resistant MAS. All patients improved and there were no characteristically severe adverse events associated with DEX-P. CONCLUSIONS: The first-line treatment for MAS in Japan is mPSL pulse therapy and/or CyA. DEX-P could be an effective and safe therapeutic option for patients with corticosteroid-resistant MAS.

Epidemiology conduction of paediatric rheumatic diseases based on the registry database of the Pediatric Rheumatology Association of Japan.

OBJECTIVES: Although epidemiological surveys of paediatric rheumatic diseases in Japan have been conducted, they were single surveys with no continuity. This is the first report of the Pediatric Rheumatology Association of Japan registry database, which was established to continuously collect data for paediatric rheumatic diseases. METHODS: Pediatric Rheumatology International Collaborate Unit Registry version 2 (PRICUREv2) is a registry database established by the Pediatric Rheumatology Association of Japan. The registry data were analysed for the age of onset, time to diagnosis, sex differences, seasonality, and other factors. RESULTS: Our data showed the same trend regarding rates of paediatric rheumatic diseases reported in Japan and other countries. The age of onset was lower in juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis and higher in systemic lupus erythematosus and Sjögren's syndrome. The time to diagnosis was relatively short in JIA and systemic lupus erythematosus but longer in juvenile dermatomyositis and Sjögren's syndrome. Rheumatoid factor-positive polyarticular JIA showed a seasonality cluster with regard to onset. CONCLUSION: PRICUREv2 aided the retrieval and evaluation of current epidemiological information on patients with paediatric rheumatic diseases. It is expected that the data collection will be continued and will be useful for expanding research in Japan.

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.

A Serum Level of Squamous Cell Carcinoma Antigen as a Real-Time Biomarker of Atopic Dermatitis.

Background: Although serum levels of squamous cell carcinoma antigen (SCCA) are elevated in atopic dermatitis (AD), their clinical utility has not been fully elucidated. Methods: Thirty-three cases of AD who admitted to our hospital were analyzed. Results: Baseline characteristics on admission were as follows: median age 19 months [interquartile range (IQR), 12-52 months], median objective severity scoring of atopic dermatitis (O-SCORAD) 19.2 (IQR, 4.2-36.0), and median serum SCCA levels 3.2 ng/mL (IQR, 2.1-6.8 ng/mL). O-SCORAD significantly correlated with serum SCCA levels (rs = 0.865, P < 0.001). In 9 cases whose information before and after treatment was available (median interval, 3 days; IQR 2-5 days), median serum SCCA levels significantly decreased from 8.0 to 2.0 ng/mL (P = 0.008) after the treatment. Conclusions: Serum levels of total SCCA rapidly declined in response to the treatment and could be used as a real-time biomarker in childhood AD.

Autoimmune haemolytic anaemia caused by anti-M antibody in a patient with Kawasaki disease.

Intravenous immunoglobulin (IVIG) is a standard therapy for Kawasaki disease (KD), because it prevents formation of coronary artery aneurysm, a major complication of KD. Herein, we report a 3-year-old boy with KD complicated by haemolytic anaemia (HA) which developed following two courses of IVIG. Although both direct and indirect antiglobulin tests and anti-M antibodies were positive in his blood obtained after the onset of HA, indirect antiglobulin tests and anti-M antibodies were negative either in the blood sample before the treatment or the same lot of IVIG products as those used for the therapy, suggesting autoimmune mechanism. This is, to our knowledge, the first report of autoimmune HA caused by anti-M autoantibodies after IVIG therapy in KD.

Tocilizumab modifies clinical and laboratory features of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis.

BACKGROUND: This study aimed to determine the influence of tocilizumab (TCZ) in modifying the clinical and laboratory features of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA). Furthermore, we assessed the performance of the 2016 MAS classification criteria for patients with s-JIA-associated MAS while treated with TCZ. METHODS: A panel of 15 pediatric rheumatologists conducted a combination of expert consensus and analysis of real patient data. Clinical and laboratory features of s-JIA-associated MAS in 12 TCZ-treated patients and 18 untreated patients were evaluated. Possible MAS was defined as having characteristic laboratory features but lack of clinical features of MAS, or atypical MAS, or early treatment that prevented full-blown MAS. RESULTS: Clinically, the TCZ-treated patients with s-JIA-associated MAS were less likely febrile and had significantly lower ferritin, triglyceride, and CRP levels than the untreated patients with s-JIA-associated MAS. Other laboratory features of MAS including lower platelet counts and lower fibrinogen were more pronounced in TCZ-treated patients. The TCZ-treated patients with s-JIA-associated MAS were less likely to be classified as MAS based on the MAS classification criteria (25% vs 83.3%, p < 0.01). This is ascribed to the absence of fever or insufficient ferritin elevation, compared with the untreated patients. CONCLUSION: TCZ could modify the clinical and laboratory features of s-JIA-associated MAS. When evaluating the s-JIA patients while treated with TCZ, it is not applicable to use MAS classification criteria. Care must be taken to not underdiagnose MAS based on the MAS classification criteria.

Clinical features and characteristics of uveitis associated with juvenile idiopathic arthritis in Japan: first report of the pediatric rheumatology association of Japan (PRAJ).

BACKGROUND: Although there are many reports on Juvenile Idiopathic arthritis-associated uveitis (JIA-U) from various countries, especially from Europe and North America, there are few reports from Asia. Our aim was to investigate the epidemiology, characteristics and predictors of JIA-U in Japan. METHODS: Data were retrospectively collected on 726 patients with JIA from medical records as of April 2016 at 15 medical centers specialized in pediatric rheumatic diseases. Of these, patients with uveitis were further investigated for the specific characteristics of this manifestation. RESULTS: The prevalence of uveitis was 6.1% in the 726 JIA patients examined. Incidence of uveitis was significantly higher in patients with an earlier arthritis onset (2.6-vs.-5.8 years, P < 0.0001), oligoarthritis (16.1%-vs.-1.6%, P < 0.001), or anti-nuclear antibodies. On the contrary, it was significantly less common in patients with rheumatoid factor or anti-cyclic citrullinated peptide antibodies. A history of using methotrexate (MTX), infliximab or adalimumab was also associated with uveitis occurrence. The median age at uveitis diagnosis was 5 years, and the median time from arthritis onset to uveitis diagnosis was 2 years. The occurrence of anterior and bilateral uveitis was 79.3 and 53.7%, respectively. There were no symptoms at uveitis diagnosis in 58.5% of cases. Complications arising between the time of uveitis diagnosis and the last observation increased from 31.7 to 56.1%; in particular, cataract was increased 3-fold. While no patients lost their vision, 61.9% did not recover normal vision (≥ 1.0), and in many cases active uveitis persisted, especially in males. In addition to steroid eye drops (97.6%) and MTX (15.4%), biological agents were used for treating the uveitis in 41.5% of patients. CONCLUSIONS: The epidemiology, characteristics and predictors of JIA-U in Japan are described here for the first time. Although the prevalence of JIA-U in Japan is lower than in predominantly Caucasian cohorts, as reported from North America and Europe, the epidemiology, characteristics and predictors were found to be similar.

Evaluation of systemic activity of pediatric primary Sjögren's syndrome by EULAR Sjögren's syndrome disease activity index (ESSDAI).

OBJECTIVES: The purpose of this study is to evaluate systemic disease activity of pediatric Sjögren's syndrome (SS) using European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI). METHODS: We retrospectively reviewed medical records of patients with SS who have been diagnosed according to 1999 Japanese diagnostic criteria for SS before 16 years old at KKR Sapporo Medical Center, Hokkaido University Hospital, and affiliated hospitals. We analyzed clinical and laboratory data and calculated ESSDAI at both diagnosis and peak activity. RESULTS: Twenty-five patients (2 boys and 23 girls) were enrolled. Only 4 patients had sicca symptoms at diagnosis. Mean ESSDAI scores at diagnosis and peak activity were 12.68 (2-31) and 15.08 (2-38), respectively. Only 3 patients were inactive (ESSDAI score <5) at diagnosis. Frequently involved domains at diagnosis were the biological (96%) followed by the constitutional (68%), glandular (44%), articular (44%), cutaneous domains (28%), renal (16%), and central nervous system (12%). At peak activity, biological domain (96%) was followed by the constitutional (72%), glandular (60%), articular (44%), cutaneous (28%), central nervous system (20%), and renal domains (16%). CONCLUSION: Pediatric SS is suspected from active systemic manifestations. The items of ESSDAI are useful clues to the diagnosis of pediatric SS.