Ruud Verstegen

A preliminary study searching for the right dose of tacrolimus in very young (</=4 years) renal transplant patients

The Radboudumc Amalia Childrens hospital in the Netherlands has a programme for renal transplantation in children aged ≤4 years. Children receive chronic corticosteroid sparing immunosuppressive therapy that consists of tacrolimus and mycophenolate mofetil. This work aimed to describe the PK of tacrolimus in children ≤4 years with renal transplants.

4. A challenging case of refractory BehÇet's disease in an adolescent with sight threatening uveitis

patient.Asignificantlyelevatedtroponinhowever,couldnotbeexplained bya tachyarrhythmiaalone.One hypothesis fordevelopinganacutecoronary syndrome, is the vasodilatation role of TNF in the maintenance of myocardial vascular perfusion through the induction of nitric oxide. It is also capable of inhibiting apoptosis of myocardiocytes and attenuation of cardiac stimulation by the sympathetic nervous system through breceptors. The administration of Infliximab, which is a potent anti-TNF antibody can neutralise both soluble and membrane-bound TNF which can suspend these homeostatic mechanisms, resulting in deprivation of first linedefencesandleadingtocoronaryvasoconstrictionandhypoperfusion. Why patients without prior cardiovascular disease develop such symptomsisstillunclearandmaybeafurtherscopeforresearch. KeyLearning Points:Potentanti-TNFagents have the theoretical ability of causing coronary vasoconstriction and hypoperfusion. Albeit rare, patients presenting with chest pain, during or after the infusion should have the appropriate coronary biochemistry and investigations performed.Youngpeoplewithnoriskofcardiovasculardiseasecandevelop transient acute coronary syndrome in response to potent anti-TNF agents. Doubling the frequency of infusion in attempt to regain control of disease after secondary failure should be done with caution and may increasetherisk. Disclosure: K.M. Achilleos: None. P. Bale: None. A. Shastri: None. N. Puvanachandra:None.K.Armon:None.

P45 What does a tertiary paediatric and adolescent service look like today

Anne-Marie McMahon, Daniel Hawley, Ruud Verstegen, Rachel Tattersall, Helen Lee, Clare Nash, Jenny Edgerton, Francesca Peech, Samantha Bull, Elizabeth Deugo, Gisella Cooper, Shirley Armstrong, Kathryn Smith, Nicola Webb, Samantha Leach, Oliver Ward, Catherine Dunbar, Jeanette Hall, Maxine Mutten, Caroline Curran, Shirley Rhodes, Tracy Rew, Barbara Smith and Anne-Marie McMahon Paediatric Rheumatology, Sheffield Children’s Hospitals, Sheffield, UNITED KINGDOM

Autoinflammation due to homozygous S208 MEFV mutation

Heterozygous mutations in the MEFV gene disrupting the Serine-242 residue in the 14-3-3 binding motif of pyrin cause Pyrin-AssociatedAutoinflammation with Neutrophilic Dermatosis (PAAND).1–5 We now describe familial autoinflammation associated with homozygous Serine-208 mutations in MEFV , the second crucial phosphorylation site of the pyrin 14-3-3 binding domain. Two Pakistani boys (IV-1 and IV-2; figure 1A) born of consanguineous parents presented aged 12 and 9 years old, respectively, with a systemic autoinflammatory disease characterised by a remitting relapsing course over time. Both had recurrent fevers with elevated acute phase responses: C-reactive protein >100 mg/L (reference range (RR) 200 mg/L (RR <10); leucocytosis 92×109/L (RR 4–11; eosinophils 82.4×109/L) and normalisation of these parameters in between fever attacks. Both had recurrent oral ulceration, intestinal inflammation, transient purpuric rashes (leucocytoclastic vasculitis on biopsy), lymphadenopathy (biopsy showed mixed lymphocytic, eosinophil infiltrate), hepatosplemonegaly, arthralgia and failure to thrive. Patient IV-2 developed pulmonary nodular changes and had a history of sterile cutaneous neck abscess at age 5. They had normal complement function studies, immunoglobulin levels and negative autoantibodies. Bone marrow aspirate for IV-2 showed marked eosinophilia (81%) with normal morphology and no malignancy; lymphocyte clonality studies were normal. Digital subtraction angiography and echocardiography were normal. Routine genetic screening for TNFRSF1A , MVK, NLRP3 , MEFV exon 10 was wild type. Both patients partially responded to corticosteroids, but subsequently received treatment with cyclophosphamide, mycophenolate mofetil, methotrexate, azathioprine and antitumour necrosis factor alpha therapy. Inflammatory attacks persisted despite these therapies. Figure 1 Family tree, genetic sequencing results, proinflammatory cytokines and pyrin inflammasome activation in patients with homozygous p.S208T MEFV mutation. (A) The family tree shows the two affected male siblings and their unaffected sibling from the consanguineous marriage of first cousins; segregation of the p.S208T MEFV variant is also shown. (B) Sanger sequencing chromatogram of …