Monika Moll

Are Recommended Phototherapy Thresholds Safe Enough for Extremely Low Birth Weight (ELBW) Infants? A Report on 2 ELBW Infants with Kernicterus despite Only Moderate Hyperbilirubinemia

Two extremely low birth weight (ELBW) infants developed characteristic signs of kernicterus at 4 and 8 months corrected age despite only moderate neonatal hyperbilirubinemia (peak serum bilirubin <10 g/dl) and phototherapy being applied according to current guidelines. Both girls were from twin pregnancies and had fetal complications (donor in a twin-twin transfusion syndrome and acardius-acranius malformation in the second twin, respectively), connatal anemia (initial hematocrit 30%), and mild acidosis after birth. They had been neurologically normal at discharge except for abnormal otoacustic emissions (OAE). At the time kernicterus was diagnosed, both infants were nearly deaf, showed severe psychomotor retardation with dystonic features and had marked bilateral hyperintensities in the globus pallidum on MRI. Based on these and similar cases from the literature, we question whether current phototherapy guidelines are appropriate for high-risk ELBW infants. Lower thresholds may be preferable, at least if additional risk factors, such as anemia, are present.

The 'Effects of Transfusion Thresholds on Neurocognitive Outcome of Extremely Low Birth-Weight Infants (ETTNO)' Study: Background Aims, and Study Protocol

Background: Infants with extremely low birth weight uniformly develop anemia of prematurity and frequently require red blood cell transfusions (RBCTs). Although RBCT is widely practiced, the indications remain controversial in the absence of conclusive data on the long-term effects of RBCT. Objectives: To summarize the current equipoise and to outline the study protocol of the ‘Effects of Transfusion Thresholds on Neurocognitive Outcome of extremely low birth-weight infants (ETTNO)’ study. Methods: Review of the literature and design of a large pragmatic randomized controlled trial of restrictive versus liberal RBCT guidelines enrolling 920 infants with birth weights of 400–999 g with long-term neurodevelopmental follow-up. Results and Conclusions: The results of ETTNO will provide definite data about the efficacy and safety of restrictive versus liberal RBCT guidelines in very preterm infants.

Surgical management of extremely low birth weight infants with neonatal bowel perforation: a single-center experience and a review of the literature.

Background: Necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) are major causes of morbidity in infants with extremely low birth weight (ELBW). Objective: To evaluate the surgical procedures applied, and the survival and long-term outcome of ELBW infants with NEC and FIP in a single-center study. Methods: Inborn and outborn ELBW infants (<1000 g) with NEC and FIP were analyzed retrospectively from 2002 to 2007. Data collected include surgical procedures, survival as well as complications, length of partial parenteral nutrition and hospital stay. The short-term and long-term outcomes after 2–7 years were assessed and compared with a matched control group. Results: Out of 280 ELBW infants, 28 underwent surgery, 19 because of FIP and 9 for NEC. Fourteen infants in the FIP group were treated with primary laparotomy and 5 with peritoneal drainage (PD). In the NEC group, only 1 infant was treated with PD. PD was used for unstable patients and was always followed by secondary laparotomy after stabilization. Five of 28 (18%) surgically treated ELBW infants and 4 (14%) matched controls died. The following complications occurred in the surgical group: complete (n = 1) or minor wound dehiscence (n = 4), stoma prolapse (n = 5), parastomal hernia (n = 2), stoma fistula (n = 1), and wound infection (n = 2). Dependency on parenteral nutrition was significantly shorter in infants with FIP, while there were no differences in time to stoma closure and length of hospital stay between those with FIP and those with NEC. Eleven of 23 (47.8%) surviving patients with FIP or NEC showed developmental delay, compared with 9 of 24 (37.5%) in the controls. Conclusions: The management of EBLW infants with NEC and FIP remains challenging. Our treatment approach was associated with low mortality. Developmental delay seems to be caused by extreme prematurity rather than NEC- or FIP-related bowel perforation.

Prospective controlled study to evaluate cryocontact therapy for infantile haemangioma in preterm infants

Despite the high prevalence of infantile haemangioma (IH) of preterm infants, methods for treating it have not yet been evaluated in controlled trials.1 Therefore, we conducted a prospective controlled study, comparing nitrogen-cooled cryocontact therapy (NCCT,−196°C) for early treatment of IH in preterm infants with no treatment. From 1 August 2004 to 31 December 2008, we allocated IH of infants ≤34 weeks gestational age with at least two IH into either a cryocontact or a control group, thus using intraindividual controls to exclude interpersonal differences potentially affecting growth. If IH appeared simultaneously, they were numbered from head to foot; even numbers were treated, odd numbers served as controls. In sequentially erupting IH, always the second one …

Are diffuse and limited juvenile systemic sclerosis different in clinical presentation? Clinical characteristics of a juvenile systemic sclerosis cohort

Introduction: Juvenile systemic sclerosis is an orphan disease. Currently, the majority of juvenile systemic sclerosis cohort studies are retrospective in design without standardized assessment. This study was conducted prospectively to investigate the difference in manifestations of limited cutaneous juvenile systemic sclerosis and diffuse cutaneous juvenile systemic sclerosis subtypes. An additional aim was to compare these data to other juvenile systemic sclerosis cohorts and a large adult systemic sclerosis cohort. Methods: Patients fulfilling the Paediatric Rheumatology European Society juvenile systemic sclerosis classification criteria were included. Clinical characteristics and patient-related outcomes were assessed. Results: In all, 88 patients with a mean disease duration of 3.5 years were enrolled, 72.5% with diffuse cutaneous juvenile systemic sclerosis with a mean modified Rodnan Skin score of 18 and 27.5% with limited cutaneous juvenile systemic sclerosis with mean modified Rodnan Skin score of 9. The mean age at the onset of Raynaud’s and first non-Raynaud’s symptoms was similar in both groups, approximately 9 and 10.5 years. Active digital tip ulcerations were present in 29% diffuse cutaneous juvenile systemic sclerosis and none in the limited cutaneous juvenile systemic sclerosis subjects (p = 0.005). Of those with cardiopulmonary testing, 3% of diffuse cutaneous juvenile systemic sclerosis and 23% of limited cutaneous juvenile systemic sclerosis group had cardiac involvement (p = 0.015), and 41% diffuse cutaneous juvenile systemic sclerosis and 22% of the limited cutaneous juvenile systemic sclerosis group had pulmonary involvement (p = 0.009). Physician global disease damage assessment was higher in the diffuse cutaneous juvenile systemic sclerosis group compared to the limited cutaneous juvenile systemic sclerosis group: 35 and 15 (p = 0.021). Discussion: The majority of this international juvenile systemic sclerosis cohort had diffuse cutaneous juvenile systemic sclerosis (72.5%) with more frequent vascular and pulmonary involvement compared to the limited cutaneous group, who had increased cardiac involvement. Our cohort reflects prior findings of published juvenile systemic sclerosis cohorts and emphasizes a difference in the presentation compared to adult-onset systemic sclerosis.

SAT0257 Update on The Juvenile Systemic Sclerosis Inception Cohort Project. Characteristics of The First 74 Patients at First Assessment

Background Juvenile systemic sclerosis (jSSc) is an orphan autoimmune disease. Currently just retrospective data exist regarding evolvement of organ involvement. In the retrospective studies assessment of the organ involvement is not standardized. Our project is the first one, where prospectively and with a standardized assessment data of jSSc patients are collected. Objectives to learn about the characteristics and evolvement of jSSc Methods Patients with jSSc were recruited worldwide and were prospectively assessed, using the proposed standardized patient assessment protocol. Results 26 centers from 17 countries applied to participate on the project. The assent and consent forms were translated into the local native languages. Up till now 74 patients were enrolled. Sixty (81%) of the 74 patients were female. The mean age of the onset of Raynaud symptomatic was 9.2 years (0.2 – 15.9). The mean age at the onset of the non-Raynaud symptomatic were 9,7 years (0.3 -15.9). 56 (76%) of the 74 have diffuse subtype, 10 (14%) of them have an overlap symptomatic. At the time of the inclusion the mean modified Rodnan Skin Score was 16.0. ANA positive were 55/71 (77%), 24/70 (34%) of them were anti-Scl 70 positive and 3/42 (7%) was anticentromere positive. 43/74 (58%) had already capillary changes and 36/72 (50%) inactive ulcerations, 13/72 (18%) had active ulceration at the time of the inclusion. 38/74 (51%) had cardiopulmonary involvement, 19/38 (50%) of had signs of interstitial lung disease on imaging, 18/42 (43%) had FVC <80% and 12/21 (57%) had DLCO <80%. 6/38 (16%) patients had pulmonary hypertension. 5/74 (7%) had renal involvement. 26/74 (35%) had gastrointestinal involvement, and 23/26 (88%) of them esophageal involvement. 46/73 (63%) had musculoskeletal involvement. 2/74 (3%) showed neurologic involvement. The mean CHAQ score was 0.4 (0–2.5). Patient global disease activity on VAS (0–100) was 44.9 and disease damage 41.6. Physician global of disease activity on VAS (0–100) was 39.7 and physician global of disease damage was 34.6. Conclusions The current recruitment data confirms that pediatric patients are different from the adult patients, there is a significantly higher proportion of diffuse subset patients with 81%. 14% of the patients have overlap features. Disclosure of Interest None declared

Update on the juvenile systemic sclerosis inception cohort http://www.juvenile-scleroderma.com

Results We report the patient characteristics at time point 0, 6 and 12 months of their follow up. We present date on 25 patients. The mean follow up of the patients in the cohort are 3.5 years. No patient died during the follow up. Eighteen of the 25 patients were female. The mean age of the onset of Raynaud symptomatic was 10.4 years, the youngest patient was 2.0 years of age. The mean age at the onset of the non-Raynaud symptomatic were 11.0 years. 19 of the 25 have diffuse subtype, 6 of them have an overlap symptomatic, two of them associated with diffuse subtype. ANA positive were 20, and 8 of them were antiScl 70 positive. None of them was anticentromere positive The mean modified Rodnan Skin Score was at timepoint 0, 6 and 12 month 18.1, 15.1 (n=21) and 15.1. (n=17). Raynaud ́s Phenomen occurred in 22/25 at time point 0 and 16 of 21 at time point 6 months and 12 of 17 at 12 months. 18 of 25 of them had capillary changes already at time point 0. 7 of them had already ulcerations at time point zero, 9 of 21 at month 6 and 4 of 17 at months 12. 15 of them had cardiopulmonary involvement, at time point zero already, 9 of them had interstitial lung disease. 6 of 21 have cardiopulmonary involvement at month 6 and 7 of 17 at month 12 of follow up. Two of them have renal involvement at time point 0 and 3 at time point 6 and 12 months. 9 of 25 had gastrointestinal involvement, and 5 of them oesophageal involvement at time point zero, 3 from 21 at month 6 and 5 of 17 at 12 months. 22 of 25 have musculoskeletal involvement 19 of 21 at month 6 and 16 of 17 at 12 months.

THU0299 IL-1 inhibition in a patient with polymorphism in the interleukin 1-receptor type 1 gene and clinical phenotype of CRMO/DIRA

Background Deficiency of the IL-1 receptor antagonist (DIRA) is an autosomal-recessive disorder caused by mutations of the IL-1 receptor antagonist (IL-1Ra) presenting with systemic inflammation, periostitis, osteolytic lesions, and a pustular rash. Mutations in the IL-1 pathway may also cause chronic recurrent multifocal osteomyelits (CRMO) with the leading symptom of sterile osteomyelits. Methods We report here a 2 year-old German girl with unremarkable family history. She was admitted to the pediatric rheumatology service due to refusal to walk, mild diarrhea, high fever and swollen right foot and left hand. Laboratory tests showed highly elevated inflammatory parameters (ESR 85 mm/h, CRP 14 mg/dl) but normal results for LDH, liver enzymes and uric acid. Whole body MRI revealed osteitis and periostitis in arms and legs. Bone biopsy showed fibrosis of the bone marrow and inflammation of the subcortical bone with signs of chronic osteomyelitis. The patient tested negative for DIRA-associated mutations in the IL-1RN gene, however she was found to carry an unreported intronic variant of unknown clinical significance in the IL-1R1 gene. This variant resides at the position c.840-6bp upstream to the exon 9 splice-acceptor site and could potentially interfere with transcript splicing. Further testing of other family members showed that this variant has been inherited through the unaffected mother and the grandmother. Initial therapy consisted of high-dose steroids with no significant improvement however in face of the novel genetic variant, an autoinflammatory disease was suspected and the patient was treated with anakinra. Inflammatory parameters normalized promptly and bone lesions decreased on MRI. After nine months, the patient was readmitted due to bad general condition, high inflammatory markers, severe oral mucosal lesions and mild pustular lesions of the perioral skin but this time without bone involvment. Endoscopy of the GI-tract showed nonspecific inflammation of the whole intestine but without granulomas. Immunosuppressive therapy (short-time steroids, azathioprine) and iv-immunoglobulines were reintroduced while anakinra was discontinued. Subsequently MRI showed typical signs of CRMO with no further systemic inflammation. Levels of IL-1 receptor antagonist, different cytokines and chemokines were analyzed prior to anakinra treatment and after withdrawal of anakinra-therapy. Results In summary, this child presents with inconsistant features of both CRMO and DIRA. In addition to the polymorphism of the IL1-R1 gene, which was also found in the female first-degree relatives, a so far uncharacterized IL-1β mediated disorder was suspected and treated empirically. Conclusions Further insight into the course of this disease and study of the novel IL1-R1 polymorphism are needed to provide an accurate diagnosis and effective treatment. References Aksentijevich I et al, An Autoinflammatory Disease with Deficiency of the Interleukin-1–Receptor Antagonist, N Engl J Med 2009; 360:2426-2437 Disclosure of Interest None Declared

A refractory heterogeneous Cryopyrin-Associated Periodic Syndrome (CAPS) phenotype related to V198M mutation responds to canakinumab - a case report

Methods A 9-year old boy, diagnosed with symptomatic MWS and evidence of a V198M mutation (father also V198M), only partially responsive to anakinra, participated in a phase III study of canakinumab in CAPS patients (N=166). Study treatment was 8-weekly administration of canakinumab by s.c. injection, 150 mg to adults and 2 mg/kg to patients ≤40 kg for up to 2 years. Administration frequency and dose (maximum 600 mg or 8 mg/kg [≤40 kg]) were increased in case of residual symptoms.

Autologous stem cell transplantation in two children with disabling pansclerotic morphea

Background Disabling pansclerotic morphea is an extremely rare and severe disorder in children, systemic treatment with corticosteroids and methotrexate (MTX) or mycophenolate mofetil (MMF) are the most common therapies. However, patients can develop severe disabilities. Autologous stem cell transplantion (ASCT) is a successful treatment option for systemic scleroderma and might also be beneficial for severe therapy resistant disabling pansclerotic morphea.