[Cushing's syndrome with subsequent tertiary adrenocortical insufficiency after simultaneous multiple intra-articular local glucocorticoid treatment : Keep an eye on hormone deficiency conditions requiring treatment after multiple administrations of local steroids]. / Cushing-Syndrom mit konsekutiver tertiärer Nebennierenrindeninsuffizienz nach simultaner multipler intraartikulärer Lokaltherapie mit Glukokortikoiden : Bei Mehrfachgabe von lokalen Steroiden behandlungsbedürftige Hormonmangelzustände im Blick behalten.

After simultaneous multiple local treatment with glucocorticoids at 46 sites a 4­year-old female patient with newly diagnosed polyarticular juvenile idiopathic arthritis (JIA) initially developed Cushing's syndrome followed by a gradual worsening of her condition and finally an acute high fever urinary tract infection. Iatrogenic adrenocortical insufficiency after multiple intra-articular glucocorticoid administration was diagnosed. The possibility of severe systemic glucocorticoid side effects after extensive local treatment should be included in the regular management of JIA patients.

Amendment of the OMERACT ultrasound definitions of joints' features in healthy children when using the DOPPLER technique.

BACKGROUND: Recently preliminary ultrasonography (US) definitions, in B mode, for normal components of pediatric joints have been developed by the OMERACT US group. The aim of the current study was to include Doppler findings in the evaluation and definition of normal joint features that can be visualized in healthy children at different age groups. METHODS: A multistep approach was used. Firstly, new additional definitions of joint components were proposed during an expert meeting. In the second step, these definitions, along with the preliminary B-mode-US definitions, were tested for feasibility in an exercise in healthy children at different age groups. In the last step, a larger panel of US experts were invited to join a web-based consensus process in order to approve the developed definitions using the Delphi methodology. A Likert scale of 1-5 was used to assess agreement. RESULTS: Physiological vascularity and fat pad tissue were identified and tested as two additional joint components in healthy children. Since physiological vascularity changes over the time in the growing skeleton, the final definition of Doppler findings comprised separate statements instead of a single full definition. A total of seven statements was developed and included in a written Delphi questionnaire to define and validate the new components. The final definitions for fat pad and physiological vascularity agreed by the group of experts reached 92.9% and 100% agreement respectively in a web survey. CONCLUSION: The inclusion of these two additional joints components which are linked to detection of Doppler signal in pediatric healthy joints will improve the identification of abnormalities in children with joint pathologies.

[Imaging options in pediatric rheumatology]. / Möglichkeiten der Bildgebung in der Kinder- und Jugendrheumatologie.

There has been growing interest in the use of imaging modalities in pediatric rheumatology for the past 15 years. Nowadays, highly sensitive imaging techniques can be used to detect early stages of pediatric rheumatic diseases in addition to the physical examination. Magnetic resonance imaging and musculoskeletal ultrasound play the most important role. Moreover, these two techniques are of great value in differential diagnostics and therapy monitoring. The use of imaging methods with a high radiation exposure could therefore be greatly reduced over the last decade.

Safety and efficacy of etanercept and adalimumab in children aged 2 to 4 years with juvenile idiopathic arthritis.

The TNF inhibitors etanercept (ETA) and adalimumab (ADA) are approved for treating patients older than 2 years with polyarticular juvenile idiopathic arthritis (JIA). Because long-term experience of treating children younger than 4 years is limited, we evaluated the efficacy and safety of ETA or ADA in patients aged 2-4 years. This prospective, long-term, observational registry study documented baseline demographics, clinical characteristics, disease activity parameters, and safety of patients treated with ETA or ADA. Efficacy was determined using the JADAS-10, the JADAS criteria for minimal disease activity (MDA) and remission, and the PedACR response criteria after 3, 6, 12, 18, and 24 months. Between January 2001 and March 2015, 85 patients with polyarticular JIA aged 2-4 years started anti-TNF-α treatment. Seventy-four (54 girls) patients were treated with ETA and 11 (7 girls) with ADA. After 6/12/24 months of treatment, JADAS-MDA was reached by 55/58/58 % of ETA patients and 50/71/66 % of ADA patients. Furthermore, JADAS-Remission was achieved by 35/44/50 % of ETA patients and 16/28/66 % of ADA patients. PedACR 50/70/90 response was achieved by 64/54/41 % of ETA patients and 56/33/22 % of ADA patients at the last treatment observation. Discontinuation because of remission or inefficacy was recorded in 24 (29 %) and 28 (33 %) patients, respectively. Seventy-nine adverse events and four serious adverse events were reported. Administration of ETA and ADA in JIA patients younger than 4 years was efficacious, well tolerated, and safe. Patients younger than 4 years may show marked improvement following anti-TNF-alpha therapy.

Safety and efficacy of etanercept in children with juvenile idiopathic arthritis below the age of 2 years.

Etanercept is approved for the treatment of patients with juvenile idiopathic arthritis (JIA) above the age of 2 years. Experience with younger children is limited. The aim of the present study was to evaluate the efficacy and safety of treatment with etanercept in children with JIA younger than 2 years. The prospective long-term observational BIKER registry documents baseline demographics, clinical characteristics, disease activity parameters and safety issues. Efficacy was determined using the PedACR response criteria, the JADAS-10 and the proposed criteria for inactive disease and remission after 3, 6, 12, 18 and 24 months. Safety assessments were based on adverse events (AE) and serious adverse events (SAEs) reports. Between January 2001 and June 2013, a total of 13 patients including four patients with systemic JIA (sJIA), four patients with extended oligoarthritis, one patient with persistent oligoarthritis and four patients with RF negative polyarthritis were treated with etanercept. Eleven patients with follow-up assessments were analysed in our study. Prior to etanercept, all patients have been exposed to methotrexate. At last observation, 6/11 patients reached a PedACR 70 response. Two patients with sJIA and 1 with nonsystemic JIA achieved inactive disease. Tolerability was good in most of the patients. Eight AE and one SAE occurred. One patient with sJIA was affected by Hodgkin's disease 18 months after discontinuation of etanercept. New onset uveitis occurred in two patients. Reasons for discontinuation were inefficacy in three (2 sJIA), intolerance in two, remission in three (2 sJIA) and the parents' request in one patient. Etanercept seems to improve JIA patients younger than 2 years including some of the patients with sJIA. Attention should be paid to the development of malignancies and autoimmune disorders.

Safety and efficacy of etanercept in children with the JIA categories extended oligoarthritis, enthesitis-related arthritis and psoriasis arthritis.

The approval of etanercept for the treatment of the juvenile idiopathic arthritis (JIA) categories extended oligoarthritis (ExtOA), enthesitis-related arthritis (ERA) and psoriasis arthritis (PsA) was recently added to the approval for the treatment of polyarticular-course JIA (PA). This study aims to evaluate the efficacy and safety of etanercept in a large number of patients with the additional JIA categories. The Biologika in der Kinderrheumatologie (BIKER) registry documents baseline demographics, clinical characteristics and disease activity parameters. Efficacy was determined using the PedACR 30/50/70 response criteria and the Juvenile Arthritis Disease Activity Score (JADAS)-10. Safety assessments were based on adverse events' reports. Until December 2012, a total of 1,678 JIA patients, incorporating 238 ERA, 315 ExtOA and 127 PsA patients were included. JADAS-10 demonstrated marked improvement compared to baseline after 3 to 24 months in ExtOA [16.1 ± 7.6 (baseline), 5.1 ± 5.2 (3 months), 3.0 ± 3.5 (24 months)]; ERA (15.3 ± 7.2, 4.4 ± 4.7, 4.0 ± 4.9) and PsA (14.7 ± 6.4, 5.0 ± 4.6, 5.3 ± 6.4). Compared to patients with PA, the rate of serious adverse events [relative risk (RR) 1.39 (0.95-2.03, p = 0.08)] and nonserious [1.18 (1.02-1.35; p = 0.03)] adverse events were elevated. The rate of uveitis flares was significantly higher in PsA (3.3/100 patient-years), ExtOA (2.8/100 patient-years) and ERA (2.7/100 patient-years) than in rheumatoid factor (RF)-negative polyarticular JIA (1.3/100 pat.yrs) or RF-positive polyarticular JIA (0.27/100 patient-years). Reports on chronic inflammatory bowel disease were numerically more frequent in ExtOA, ERA and PsA. Administration of etanercept in patients with the JIA categories ExtOA, ERA and PsA is safe and very efficacious in children. Attention should be paid to the occurrence of extraarticular autoimmunopathies.

[Current news from the BIKER register]. / Aktuelles aus dem BIKER-Register.

Innovative developments in the pharmacotherapy of juvenile idiopathic arthritis and especially biologics allow the formulation of new therapeutic targets, such as the rapid induction of remission with shortening of the period of active disease and therefore preventing damage and disability. These new therapies also represent a challenge to the monitoring of drug safety, the pharmacovigilance. For this purpose the Society for Paediatric and Adolescent Rheumatology has set up an early register to record achievements in treatment improvement and in addition to independently assess information on drug safety, acute tolerance and long-term safety.

[Diagnosis of fibromatosis colli via color-coded duplex sonography in 13 infants]. / Diagnose der Fibromatosis colli mit der farbkodierten Duplexsonografie bei 13 Säuglingen.

AIM: Fibromatosis colli is the most common cause of congenital torticollis. Patients show a solid tumor in the region of the sternocleidomastoid muscle which has to be differentiated from other congenital space-occupying lesions in the cervical region. PATIENTS AND METHOD: 13 infants (7 boys, 6 girls) with a mean age of 28 +/- 21 days with fibromatosis colli were examined with a high-resolution linear transducer via color-coded duplex sonography. The location of the tumor within the sternocleidomastoid muscle, delineation from surrounding structures, the echogenicity, and the vascularization were estimated. 3 tumors were surgically removed, and the other 10 infants were treated conservatively with physiotherapy. RESULTS: The tumors were located on the right side in 10 patients and on the left side in 3 infants. In 10 patients the tumor was located in the caudal part, in 3 in the middle part of muscle. All tumors showed a good delineation from the surrounding structures. The volume of the tumor was 5.4 +/- 2.7 ml. 8 tumors showed inhomogeneous echogenicity, and 5 showed homogenous echogenicity. 9 tumors had echopoor, 3 echogenic, 1 isoechogenic internal echoes compared to the contralateral healthy muscle. 13 tumors showed increased perfusion (10 diffusely, 3 focally) via color-coded Doppler sonography. CONCLUSION: Diagnosis of fibromatosis colli can be affirmed sonographically. The tumors are commonly located in the distal 2 / 3 of the sternocleidomastoid muscle and show good delineation from surrounding structures. Typically an inhomogeneous, echopoor tumor with increased perfusion can be shown. Additional diagnostic imaging modalities are usually not necessary. The treatment of choice is physiotherapy. In special cases with a lack of improvement, surgery is necessary.

[Ischemia of the brain stem caused by compression of the vertebral arteries by head rotation--an etiology for SIDS?]. / Minderperfusion des Hirnstammes durch Kompression der Vertebralarterien bei Kopfrotation--Eine Ursache von SIDS?

UNLABELLED: Hypoperfusion of the brainstem during head rotation may be a risk factor for the development of SIDS. On this background we established a Doppler sonographic screening programme of the basilar cerebral arteries to evaluate the dependency of blood flow on head and body position. PATIENTS AND METHOD: We investigated 3840 newborns (1872 girls and 1968 boys) with a birth weight of 3399 +/- 497 g and a gestational age of 39.2 +/- 1.4 weeks. The investigations were performed in the neonatal period with an average age of 4.7 +/- 3 days. In all infants blood flow was measured in the basilar artery (BA) in supine position with the head in the midline. From the flow profile peak systolic flow velocity Vs and time average flow velocity TAV were measured. Additionally flow measurements were performed in supine and prone position with rotation of the head to the right and left side. A decrease of blood flow velocities below 50% of the value in neutral position was considered to be abnormal. Retrograde or biophasic flow profiles during rotation were considered to be pathologic. In infants with abnormal or pathologic flow during rotation of the head flow measurements in the vertebral arteries (VA) were additionally performed. Blood flow velocities in the VA were measured in supine and prone position with the head in the midline position and after rotation to the right and to the left. In neutral position unilateral vertebral hypoplasia, aplasia and normal VA were differentiated. The judgement after rotation was performed such as in the BA. RESULTS: In 3807 infants (99.14%) blood flow velocities during head rotation did not decrease below 50% of the value measured in neutral position. In 33 infants (0.86%) a decrease of blood flow velocities below 50% could be found during rotation. In 7 infants (0.18%) a pathologic flow could be found during head rotation. 27 of the 33 infants with abnormal and pathologic blood flow in the BA during rotation showed anatomic abnormalities of the VA. 20 of these infants (61%) had unilateral vertebral hypoplasia (11 right, 9 left side), 7 (21%) had unilateral vertebral aplasia (4 right, 3 left side). 32 of the 33 infants with abnormal flow in the BA showed a decrease of blood flow in the contralateral VA during head rotation. 9 infants had an abnormal, 19 a pathologic flow within the contralateral VA. In 4 infants the corresponding VA could not be measured during head rotation. The decrease of blood flow velocities in the BA during head rotation was caused by compression of the contralateral VA at the craniocervical junction. CONCLUSION: Blood flow within the basilar artery of healthy infants is independent of body position and rotation of the head. A decrease of the flow velocities below 50% during rotation has to be considered as an abnormality. The incidence of pathologic blood flow during head rotation with 1.8@1000 approximates the incidence of SIDS. Hypoperfusion of the brainstem during head rotation may be a risk factor of SIDS.