Systemic sclerosis in children: A national retrospective survey in Japan

A retrospective questionnaire survey of pediatric departments, for childhood collagen disease from 1985 to 1994 was used to clarify the clinical features of scleroderma in Japan. In the primary survey, 0.9% of the children with a rheumatic condition had scleroderma. Answers to this questionnaire were received on 18 (localized 9; systemic 9) patients from 15 institutions. In order to examine systemic sclerosis (SSc), seven cases of SSc in Japanese articles during the same period as the questionnaire were added to these answers and compared to the Japanese epidemic study investigated by Fukuyama in 1974. There were 16 children, seven boys and nine girls, with SSc during the 10-year period in Japan. The mean age of onset of symptoms was 8.0 ± 2.8 years and the age at diagnosis was 10.1 ± 3.0 years. Eighty percent of children had Raynaud's phenomenon at the onset of SSc, and skin and musculoskeletal involvement was highly recognized during the course of the disease. Atrophy of the frenulum linguae and lung fibrosis were commonly seen in SSc. In serological studies, 80% of children have antinuclear antibodies and approximately 50% of patients have anti-Scl-70 (topoisomelase I) antibodies at the onset and during the course of childhood SSc. The prognosis is poor, as remission occurred in only one child. The clinical symptoms and examination of serological autoimmune antibodies were supportive of an early diagnosis of SSc. When compared to the previous national survey of children with SSc, the present results showed that the male-to-female ratio was reduced, the age at onset was low, the positive incidence of serological autoimmune antibodies elevated, and the usage of vasodilators and nonsteroid anti-inflammatory drugs (NSAID) increased, with corticosteroids decreased. But, the positive percentage of clinical symptoms were not changed in both studies. For a complete retrospective nationwide epidemic survey carried out on children with scleroderma, especially SSc, it is important to include dermatology departments.     

Dramatic response to nivolumab in xeroderma pigmentosum skin tumor

We report the case of a 6‐year‐old female with xeroderma pigmentosum (XP) who developed a nonoperable scalp tumor, treated with anti‐programmed cell death protein 1 (anti‐PD‐1) therapy (nivolumab). She presented with a sarcomatoid carcinoma of the scalp with bone lysis as well as vascular and meningeal contact. Nivolumab was initiated because it has emerged as a promising immunotherapy. We observed a dramatic tumor response with excellent tolerance. However, while on nivolumab therapy she developed two large skin melanomas and several squamous cell carcinomas, which have been resected. These results demonstrate that cancer immunotherapy in patients with XP can be impressive but complex and warrants further investigation.     

Relationship between height and blood pressure in Japanese schoolchildren

Background: Blood pressure examinations for health education use have been conducted at several schools in Japan. It has been reported that blood pressure is closely associated with bodyweight and height in US children. The aim of the present paper was to evaluate the association between height and blood pressure in Japanese schoolchildren. Methods: In Iwata city in Japan, blood pressure screening was conducted by the school administration. A total of 98.9% (10 152/10 270 children) of all fifth (10‐year‐olds) and ninth graders (14‐year‐olds) residing in the Old Iwata area from 2002 to 2007 were analyzed. Results: In 10‐year‐old and 14‐year‐old boys, regression analysis indicated that a positive correlation between weight and blood pressure was the strongest among the three body size indices (height, weight, and body mass index), but the association between height and blood pressure was also significant. For girls from both the 10 and 14 year age groups, the correlation of weight and blood pressure was stronger than those for the other body size indices, but there were also significant associations between height and blood pressure, except for height and diastolic blood pressure in the 14‐year‐olds. Conclusions: There is a significant positive relationship between height and blood pressure. Further study is necessary to provide a blood pressure reference based on height in the Japanese program to prevent children from developing lifestyle‐related risk factors.     

Severe cytokine release syndrome in a patient receiving PD‐1‐directed therapy

Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of cellular and bispecific T‐cell engaging immunotherapy. Checkpoint blockade using anti‐programmed cell death 1 (anti‐PD‐1) inhibitors is an approach to antitumor immune system stimulation. A 29‐year‐old female with alveolar soft part sarcoma developed severe CRS after treatment with anti‐PD‐1 therapy. CRS was characterized by high fevers, encephalopathy, hypotension, hypoxia, hepatic dysfunction, and evidence of coagulopathy, and resolved after infusion of the interleukin‐6 inhibitor tocilizumab and corticosteroids.     

Alteraciones tiroideas y enfermedades reumáticas infantiles

IntroductionThe relationship between thyroid dysfunction and autoimmune diseases has mainly been described in adults. The aim of this study was to analyse the prevalence and characteristics of thyroid abnormalities in children with rheumatic diseases.Patients and methodOne hundred and forty-five patients (109 girls and 36 boys) from a rheumatology paediatric unit were studied for two years. The diagnoses were: juvenile idiopathic arthritis (JIA) (n=115), lupus (n=17), juvenile dermatomyositis (n=5), scleroderma (n=4), and one case each of the following: mixed connective mixed disease, CINCA syndrome (chronic infantile neurological, cutaneous and articular), TRAPS (tumour necrosis factor receptor-associated periodic syndrome), and familial mediterranean fever. T4 and TSH levels were carried out, and if these showed abnormalities, antithyroid antibodies (ATA) were determined.ResultsSix girls aged between 2 and 17 years old had thyroid abnormalities. Three had JIA and three had lupus. Five were diagnosed with autoimmune hypothyroidism, with high ATA levels, and there was one case of hyperthyroidism. All of the patients with thyroid dysfunction had positive antinuclear antibodies (ANA), compared to 34.5% of the rest of the patients (p=0.003).ConclusionsThe prevalence of thyroid abnormalities in children with rheumatic disease was 4.14% to 7.9% in JIA patients with positive ANA, and up to 17.6% with lupus. The majority of patients were asymptomatic. Thyroid hormones should be determined when rheumatic disease is diagnosed and periodically afterwards.     

Collagenous sprue in a 3‐month‐old infant

Collagenous sprue (CS) is a severe malabsorption disorder, the etiology of which has not been well defined. Herein, we report the case of a 3‐month‐old infant with CS who responded to steroid and immunomodulator treatment and presented a thick subepithelial collagen band. A 3‐month‐old Japanese girl presented with severe watery diarrhea that lasted for 2 weeks. She was admitted to the referring hospital, but symptomatic improvement was not achieved with fasting and rehydration. Gastroduodenal endoscopy showed an edematous duodenal mucosal surface. Duodenal biopsy indicated severe villous atrophy with infiltration of mostly CD8‐positive T cells; and deposition of subepithelial collagen was confirmed. The subepithelial collagen deposits, however, had disappeared after treatment. Historically, child‐onset CS is extremely rare and this case is likely to be the youngest case of infantile CS. The present case suggests that CS should be considered as a differential diagnosis for intractable diarrhea, even in infants.     

Pediatric Hashimoto's encephalopathy with peripheral nervous system involvement

Hashimoto encephalopathy is a syndrome of encephalopathy associated with elevated concentration of circulating serum anti‐thyroid antibodies usually responsive to steroid therapy. We report a 13‐year‐old girl with Hashimoto encephalopathy and peripheral nervous system involvement. The child had experienced high‐grade pyrexia, global headache and sleeplessness. After admission she had an ileus with a distended urinary bladder, hallucinations and cognitive impairment. She had reduced deep tendon reflexes and distal sensory deficiency. Anti‐thyroglobulin antibodies were raised at 2121 IU/mL (normal, 0–40) and the anti‐thyroperoxidase was high at 886 IU/mL (normal, 0–50). Progressive neurological and psychiatric remission was noted after i.v. methylprednisolone. Follow‐up magnetic resonance imaging showed complete resolution of the foci of signal abnormality previously yielded. This case report is the first, to the best of our knowledge, to describe peripheral nervous system involvement in a child with a diagnosis of Hashimoto's encephalopathy.     

A case study of a child with chronic hemolytic anemia due to a Donath-Landsteiner positive, IgM anti-I autoantibody

In children, paroxysmal cold hemoglobinuria (PCH) is generally considered an acute self‐limited autoimmune hemolytic anemia caused by an IgG biphasic auto‐anti‐P antibody identified by the Donath–Landsteiner (D‐L) test. We report a case of a 5‐year‐old female with a chronic hemolytic anemia. The etiology of the hemolysis appears to be an unusual D‐L positive, IgM antibody with specificity for the I antigen. The clinical course is described and a discussion of PCH and the D‐L antibody is presented. We also discuss intravenous immunoglobulin infusions as a therapy for children with this form of severe chronic autoimmune hemolytic anemia. Pediatr Blood Cancer 2012; 59: 953–955. © 2012 Wiley Periodicals, Inc.     

CD5 positive B‐ALL,a uniquely aggressive subcategory of B‐ALL? A case report and brief review of the literature

CD5 antigen expression in B‐cell acute lymphoblastic leukemia (B‐ALL) is exceptionally rare. There are six detailed case reports in the literature, with only 16 cases described. Case series analyzing the frequency of aberrant B‐ALL immunophenotypes suggest that this variant may occur in as little as 2‐4.5% of all B‐ALL cases, with one series having no CD5⁺ positive cases. Herein we report a case of CD5⁺ B‐ALL in a 15‐year‐old female, and review the previously reported cases. As limited information is available, more data from prospective clinical trials are required to determine whether CD5 positivity portends a poorer prognosis.     

Ehlers‐Danlos syndrome,vascular type: A novel missense mutation in the COL3A1 gene

We report a 34‐year‐old Japanese female with the vascular type of Ehlers‐Danlos syndrome. She had thin translucent skin, extensive bruising, toe joint hypermobility, left lower extremity varicose veins, and chronic wrist, knee and ankle joint pain. She also had dizziness caused by autonomic dysfunction. Magnetic resonance angiography showed tortuous vertebral and basilar arteries, mild left carotid canal bulging, and right anterior tibial artery hypoplasia. Electron microscopic examinations of a skin biopsy revealed extremely dilated rough endoplasmic reticulum in dermal fibroblasts and wide variability of individual collagen fibril diameters. A molecular analysis using a conventional total RNA method and a high‐resolution melting curve analysis using genomic DNA revealed a novel missense mutation within exon 48 of the COL3A1 gene, c.3428G>A, leading to p.Gly1143Glu.     

Paroxysmal cold hemoglobinuria caused by an IgM‐class Donath–Landsteiner antibody

We report on a 4‐year‐old boy who developed paroxysmal cold hemoglobinuria (PCH) following the first dose of a seven‐valent pneumococcal conjugate vaccine. He was admitted because of dark urine after exposure to cold air. Laboratory tests indicated anemia, increased serum indirect bilirubin and lactate dehydrogenase, and decreased serum haptoglobin. Donath–Landsteiner (D‐L) test was positive. The D‐L antibody belonged to the IgM class and exhibited anti‐P specificity. Symptoms and signs subsided after supportive care without any medication. Although PCH is often associated with viral or bacterial infection and is caused by IgG‐class D‐L antibodies with anti‐P specificity, this case was unique because a D‐L antibody of the IgM class with anti‐P specificity caused PCH after immunization with a pneumococcal vaccine.     

Renal‐limited necrotizing granulomatous vasculitis in a pediatric patient

A 10‐year‐old girl presented with mild proteinuria and hypertension. Laboratory data indicated slightly elevated serum creatinine (0.67 mg/dL) and elevated serum IgG (2111 mg/dL). On renal arteriography mild stenosis over the entire length of the right renal artery and irregular stenosis of the interlobar arteries in the right kidney were seen. She was diagnosed with renovascular hypertension, and received conventional anti‐hypertensive therapy, but did not respond to them. The right kidney had atrophy and dysfunction on technetium‐99m‐labeled dimercaptosuccinic acid renal scintigraphy, and was therefore resected. Histopathology of the kidney indicated severe necrotizing granulomatous vasculitis affecting the arteries from the renal hilus to the interlobar area. After nephrectomy plus steroid pulse therapy, blood pressure and urinary protein returned to normal. To our knowledge, this is the first report of necrotizing granulomatous vasculitis limited to the medium‐sized renal arteries.     

Low cardiac output thyroid storm in a girl with Graves’ disease

A 15‐year‐old girl with Graves’ disease presented with hypotension after methimazole and propranolol were re‐started for hyperthyroidism. She was found to have pulmonary artery hypertension resulting in obstructive shock. Thyroid storm was diagnosed according to Burch and Wartofsky score. She was promptly treated with anti‐thyroid drugs, inorganic iodide, corticosteroid, and respiratory support. Pulmonary hypertension was treated with inhaled nitric oxide until the clinical status improved. Propranolol was withdrawn due to poor cardiac function. We herein present a unique case of a difficult‐to‐treat Graves’ disease presenting with severe pulmonary hypertension resulting in low cardiac output thyroid storm.     

Treatment of childhood kaposiform hemangioendothelioma with sirolimus

Sirolimus (Rapamune), a mammalian target of Rapamycin (mTOR) inhibitor, which has been used extensively in children following solid organ transplantation, has been demonstrated to have anti‐angiogenic activity in pre‐clinical models. Limited experience suggests that it may have application to the treatment of vascular lesions. We describe our experience with a 1‐year‐old female with a kaposiform hemangioendothelioma and Kasabach–Merritt phenomenon who had rapid and dramatic response to sirolimus (0.1 mg/kg/day). This case provides further rationale for clinical trials of sirolimus in the treatment of vascular lesions. Pediatr Blood Cancer. 2010;55:1396–1398. © 2010 Wiley‐Liss, Inc.     

抗环瓜氨酸肽抗体在幼年特发性关节炎中的意义

目的探讨抗环瓜氨酸肽(CCP)抗体检测对幼年特发性关节炎(JIA)的诊断价值。方法用酶联免疫吸附试验(ELISA)对22例JIA患儿(男9例,女13例)、30例成人类风湿关节炎(RA)患者血清抗CCP抗体、RF进行检测,了解抗CCP抗体在JIA中的诊断价值。结果JIA患儿22例中2例抗CCP抗体阳性,阳性率为9.1%(2/22),显著低于成人RA组阳性率53.3%(16/30),P<0.01;JIA患儿与健康对照组(无CCP抗体阳性)抗CCP抗体阳性率尤差别,P>0.05。结论抗CCP抗体可在JIA中检测到,但阳性率很低,作为JIA诊断指标具有一定的局限性。     

A case of neuroblastoma in DICER1 syndrome: Chance finding or noncanonical causation?

DICER1 syndrome is an inherited disorder associated with at least a dozen rare, mainly pediatric‐onset tumors. Its characterization remains incomplete. Some studies suggested that neuroblastoma (NB) may be involved in this syndrome. Here, we describe the case of a 14‐year‐old female presenting with a multinodular goiter (MNG) and a collision tumor composed of NB and cystic nephroma (CN). She is a carrier of a deleterious germline mutation in exon 23 of DICER1 and harbored different somatic mutations in the CN and MNG. However, no second hit was found in the NB, questioning its status as a DICER1‐related tumor.     

Variance in the transaminase levels over the body mass index spectrum in 10‐ and 13‐year‐olds

Background: Transaminase levels increase with body mass index (BMI) and also with an extreme drop in the BMI, as in the case of patients with anorexia nervosa. We examined these levels over the BMI spectrum in Japanese 10‐ and 13‐year‐olds. Methods: Fifth‐ and eighth‐grade students (n= 3747) from all schools in Shunan City, Japan, between 2006 and 2008 were included in the study. BMI z‐score and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma‐glutamyltransferase (GGT) were measured. Results: The ALT and GGT levels increased with z‐BMI values in the boys and 10‐year‐old girls (P≤ 0.001). In the 13‐year‐old girls, only the ALT levels increased with the z‐BMI values (P= 0.018). Similarly, the proportion of subjects with elevated ALT and GGT levels increased with the z‐BMI values (p_trend < 0.05). The AST levels were negatively associated with BMI in the girls (P < 0.001). Among the boys, these levels were elevated at the highest z‐BMI values and slightly elevated at lower values, but not significantly. These associations did not change after adjustments for confounders. Generalized additive model analyses revealed that transaminase had non‐linear relationships with z‐BMI, except for the AST levels in the girls. Conclusion: The elevated ALT and GGT levels were associated with high BMI in both sexes. In the same study population, however, AST increased in the girls with low BMI and in the boys with high BMI.     

Chronic urticaria of neonatal onset: A potential sign of autoinflammation

We present a 6 year old boy with chronic urticaria of neonatal onset associated in childhood with features of neurological and joint inflammation. Genetic analysis confirmed the diagnosis of neonatal onset multi‐inflammatory disorder (NOMID). Daily subcutaneous anti‐IL‐1 receptor antagonist therapy resulted in a dramatic and sustained amelioration of systemic inflammation. NOMID must be considered in any child with chronic urticaria of neonatal/infantile onset, particularly if associated with joint and/or neurological inflammation.     

Neonatal pulmonary arteriovenous malformation in hereditary haemorrhagic telangiectasia

A 3 week old infant presented with persistent hypoxaemia and was diagnosed with pulmonary arteriovenous malformations. Her family history was positive for hereditary haemorrhagic telangiectasia. She was treated successfully with coil embolotherapy at the age of 4 months. Transcatheter embolisation may be considered the primary treatment for pulmonary arteriovenous malformations in infancy.     

Transmission of clear cell tumor in a graft liver from cadaveric donor: Case report

Backes AN, Tannuri ACA, de Mello ES, Gibelli NEM, de Castro Andrade W, Tannuri U. Transmission of clear cell tumor in a graft liver from cadaveric donor: Case report. Abstract: Neoplasms in children after organ transplantation are related to the type and intensity of immunosuppression and the donor–recipient serostatus, especially in relation to the Epstein–Barr virus. The patient was a two‐yr‐old female child with biliary atresia who underwent a liver transplantation from a female cadaver donor. Two adults received kidney transplants from the same donor. Nine months after transplantation, one of the adult recipients developed an urothelial tumor in the kidney graft. Imaging tests were repeated monthly in the liver‐transplanted child and revealed no abnormalities. However, one yr and two months after the transplantation, the patient developed episodes of fever. At that time, imaging and liver biopsy showed a clear cell tumor of urothelial origin in the graft and the disease was limited to the liver. The patient underwent liver retransplantation, and she is currently free of tumor recurrence. Although rare, the occurrence of tumors in the post‐transplant period from cadaver donors, without previously diagnosed tumors, is one of the many problems encountered in the complex world of organ transplantation.