Anne-Marie McMahon

Takayasu arteritis in childhood: retrospective experience from a tertiary referral centre in the United Kingdom

IntroductionTakayasu arteritis (TA) is an idiopathic large-vessel vasculitis affecting the aorta and its major branches. Although the disease rarely affects children, it does occur, even in infants. The objective of this study was to evaluate the clinical features, disease activity, treatment and outcome of childhood TA in a tertiary UK centre.MethodsWe analysed a retrospective case series of children fulfilling the TA classification criteria of the European League against Rheumatism, the Paediatric Rheumatology European Society and the Paediatric Rheumatology International Trials Organisation. Data regarding demographics, clinical features, treatments and outcomes were recorded. Descriptive statistics are expressed as median and range. Fisher’s exact test was used for group comparisons. The Paediatric Vasculitis Activity Score (PVAS), Paediatric Vasculitis Damage Index (PVDI), Disease Extent Index-Takayasu (DEI.Tak) and Indian Takayasu Arteritis Activity Score (ITAS2010) were calculated retrospectively.ResultsA total of 11 children (64% female) with age at diagnosis of 11.8 (1.3 to 17) years were identified over a 23-year period. The median time to diagnosis was 17 (0 to 132) months. The most common clinical features at presentation were arterial hypertension (72.7%), systemic features (36%) and cardiovascular (45%), neurological (36%), pulmonary (27%), skin (9%), renal (9%) and gastrointestinal (9%) involvement. At presentation, PVAS was 5/63 (1 to 13); DEI.Tak was 7/81 (2 to 12) and ITAS2010 was 9/57 (6 to 20). Treatment included corticosteroids (81.8%), combined with methotrexate in most cases (72.7%). Cyclophosphamide (36.4%) and biologic agents (45.5%) were reserved for severe and/or refractory cases. PVDI at latest follow-up was 5.5/72 (3 to 15). Mortality was 27%. Young age at disease onset (<5 years old) and permanent PVDI scores ≥3 were significantly associated with mortality risk (P = 0.024).ConclusionTA is a rare and potentially life-threatening large-vessel vasculitis. Improved awareness of TA is essential to secure a timely diagnosis. Although the evidence base for the treatment of TA in children is weak, we found that it is essential to treat it aggressively because our data emphasise that the mortality and morbidity in the paediatric population remains high.

Diagnosing juvenile idiopathic arthritis

Juvenile Idiopathic Arthritis (JIA), is the commonest cause of chronic arthritis in childhood worldwide, has considerable morbidity and is a common cause of acquired visual loss in children due to the strong association with chronic anterior uveitis. The diagnosis is clinical and confidence in examination of the musculoskeletal system for synovitis is essential. Management of JIA is based on a combination of pharmacological interventions, physical and occupational therapy, and psychosocial support, managed by an experienced multidisciplinary team. The aim of therapy is to reach complete control of the disease, preserve the physical and psychological integrity of the child and to prevent any long-term consequence related to the disease or treatment. There is overwhelming research evidence to support early treatment and aggressive intervention in juvenile idiopathic arthritis. This has developed with the growing awareness that there is a “window of opportunity” to alter the natural history of the disease and the process of inflammation. Early recognition of, and skill in, diagnosis of JIA is therefore essential and reviewed here.

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

Inter- and intra-observer reliability of contrast-enhanced magnetic resonance imaging parameters in children with suspected juvenile idiopathic arthritis of the hip

BackgroundPrevious work at our institution demonstrated discrepancies between radiologists in interpretation of contrast-enhanced magnetic resonance imaging (MRI) in suspected hip arthritis.ObjectiveTo assess inter- and intra-observer reliability of selected MRI parameters (effusion, marrow oedema and synovial thickness and enhancement) used in the diagnosis of juvenile idiopathic arthritis.Materials and methodsA retrospective cohort study was conducted of patients with confirmed or suspected juvenile idiopathic arthritis who underwent hip contrast-enhanced MRI between January 2011 and September 2014. Three pediatric musculoskeletal radiologists independently assessed all scans for effusion, marrow oedema, measurement of synovial thickness, synovial enhancement and subjective assessment of synovium. Categorical variables were analysed using the Cohen κ, and measurement using Bland-Altman plots.ResultsEighty patients were included. Interobserver reliability was moderate for effusion (κ=0.5–0.7), marrow oedema (κ=0.6), subjective synovial assessment (κ=0.4–0.5) and synovial enhancement (κ=0.1–0.5). Intra-observer reliability was highest for marrow oedema (κ=0.6–0.8) and lowest for effusion (κ=0.4–0.7). Intra-observer reliability for synovial enhancement (κ= −0.7-0.8) and subjective synovial assessment (κ=0.4–1.0) ranged from poor to excellent. For synovial thickness, intra- and interobserver Bland-Altman plots were well clustered around the mean suggesting good agreement.ConclusionThere were large differences across variables and only moderate agreement between observers. The most reliable parameters were presence of joint effusion and bone marrow oedema and subjective assessment of synovium.

G262 Can early aggressive treatment of Kawasaki disease with coronary artery involvement aid in resolution in coronary artery aneurysms/dilation? A case series of three children

Methods Here were present a case series of three children with Kawasaki disease or atypical Kawasaki disease (KD) who were seen in a tertiary hospital in 2015 and received early aggressive treatment. Results Case one: A three month old girl with atypical KD. Treated with IVIG and high dose aspirin on day six, resulting in resolution of pyrexias until day thirteen. Echocardiogram on day sixteen showed: right coronary artery (RCA) 2.4mm and left coronary artery (LCA) 2.8mm. Treated on day sixteen with second dose of intravenous immunoglobulins (IVIG) and seven days IV methylprednisolone (IVMP) then oral prednisolone and infliximab on day 31 (received a total of three doses). Maximal dilatations were of RCA2.7 and LCA 3.1. Repeat echocardiogram on day 89 showed RCA 1.8mm and LCA 1.3mm. Case two: A two year ten month old girl with typical KD. Treated with IVIG on day six with good response but return of pyrexia, conjunctivitis and irritability on day fourteen. Day fifteen echocardiogram showed LCA 4.6mm, RCA 6.2mm and aortic root inflammation. Treated with a second dose of IVIG, high dose aspirin and four days high dose IVMP followed by oral prednisolone. Day fifty-one repeat echo showed LCA normal (no measurement given) and RCA 4mm with resolution of the aortic root inflammation. Case three: A seven week old girl with atypical KD diagnosed at day 13 following an echocardiogram showing dilated coronary arteries. Treated with two doses of IVIG, aspirin and three days of IVMP followed by oral prednisolone. Initial echocardiogram showed LCA 4.8mm, RCA 2.5mm, LAD 3.0mm. Infliximab was given on day eighteen. Day twenty echocardiogram showed LCA 4.8mm, RCA 4mm and LAD 5.6mm. A repeat echo on day forty-eight showed LCA 4.4mm, RCA 2.4mm and LAD now normal. Conclusions These cases suggest a role for early aggressive treatment in KD with known coronary artery involvement.

G258 Diagnosing childhood arthritis: What does it take?

Many young people have an unacceptably long delay in referral to tertiary services often undergoing unnecessary invasive investigations. A validated examination screening tool, pGALS (paediatric gait, arms, legs, spine)1 has been developed but trainees have low confidence examining paediatric joints.2 Local audit data highlights the lack of musculoskeletal examinations in paediatric clerking compared to examinations of other body systems in response to clinical red flags.3 Aims To review the impact of educational clinics on trainees performing pGALS screening examinations and how successful they are at identifying active arthritis (swollen joints) or restricted movement of joints compared to the examination findings of a paediatric rheumatologist performing a pGALS in the same patient. Identify the trend in personal confidence of junior doctors in diagnosing childhood arthritis using the pGALS screening tool with increased exposure to patients with clinical signs of arthritis. A prospective service review of teaching clinics within a tertiary paediatric rheumatology department was performed. Medical students, adult rheumatology trainees and paediatric trainees were invited to attend. Confidence questionnaires were completed before and after clinic attendance. A pGALS proforma was completed by the trainee per patient and sealed in an envelope. A second proforma was completed on the same patient by the consultant before teaching commenced. Data was analysed using sensitivities, specificities and Cohen’s Kappa inter-observer agreement. Adult rheumatology trainees had a higher overall sensitivity for detecting active arthritis (42%) and detecting restriction in movement (45%) compared to other trainee groups (paediatric trainee 34% and 40% respectively, medical student 35% and 33% respectively). Overall specificity was good for active arthritis (90–100%) and restrictive movement (90–100%). Inter-observer agreement was ‘moderate’ for detection of active arthritis and detection of restricted movement ( Table 1 ). A statistically significant (p < 0.05) increase in confidence was seen for the trainee cohort examining the joints of those under 16 years of age, even after only one clinic attendance.Abstract G258 Table 1 The significant improvement in confidence in joint examination is a very positive finding. Performing increased numbers of pGALS examinations increased the sensitivity of picking up abnormal joints. This study has demonstrated the benefit of the pGALS tool as an educational intervention in clinical practice. References Foster, HE, Kay, LJ, Friswell, M, Coady, D and Myers, A. Musculoskeletal Screening Examination (pGALS) for School-Age Children Based on the Adult GALS Screen. Arthritis & Rheumatism (Arthritis Care & Research). 2006;55(5):709–716 Jandial, S, Myers, A, Wise, E and Foster, H Doctors likely to encounter children with musculoskeletal complaints have low confidence in their clinical skills. The Journal of Pediatrics. 2009;154:267–71 Abusrewil, W, Whiteley, A, McMahon, A and Al-Obaidi, M. A, B, C, don’t ever forget the joints. Oral presentation at the Royal College of Paediatrics and Child Health meeting 2013. (Personal communication with Dr W. Abusrewil)

G263 MRCPCH Clinical Success Initiative (CSI)

Background The Membership of the Royal College of Paediatrics and Child Health (MRCPCH) clinical examination, represents the final hurdle for paediatric trainees in achieving full membership of the college and is necessary for training progression. In our locality, the MRCPCH clinical examination pass rate had raised concerns. Repeated examination attempts are stressful, financially demanding, and can affect career progression. Examination failure can impact significantly on workforce planning. Aim To introduce a revision initiative for paediatric trainees to improve the MRCPCH clinical pass rate. Method Locally, prior to October 2012, revision sessions were organised by trainees themselves, with more senior trainees and consultants supporting candidates with ad-hoc teaching sessions prior to the examination. Commencing prior to the 3rd 2012 clinical examination sitting, the local Postgraduate Medical Education (PGME) department initiated a structured revision timetable for trainees in the six weeks prior to the clinical examinations. Results MRCPCH Clinical examination pass rates were reviewed prior to, and after the introduction of the programme. Comparisons have been drawn within the deanery and nationally. Trainees have given anonymised feedback on the programme. All trainees undertaking the MRCPCH Clinical examination since the initiative was launched have engaged with the programme and trainee feedback has been unanimously positive. Table 1 illustrates the improvement in the local examination pass rate following the introduction of the CSI, from 43.3% in the preceding year to 78.5%. Abstract G263 Table 1 Pre initiative Post initiative Number of examination attempts 30 28 Number of examination passes 13 22 Pass rate 43.4% 78.5% The local pass rate is now surpassing both the deanery-wide and the national pass rates (see Graph 1). Discussion PGME organisation has facilitated targeted training, improved teaching attendance, and allowed consultant flexibility to organise opportunistic teaching in a co-ordinated manner with selected cases. Significantly, since the introduction of this initiative, no outcome 4 has been given to any trainee. Conclusion The success of this initiative highlights the benefits for trainees of a supportive revision programme at local level in improving examination success. Abstract G263 Figure 1

G360 A cytokine storm is brewing

Background Haemophagocytic lymphohistiocytosis (HLH) is a severe systemic inflammatory condition caused by dysregulation in Natural Killer T cell function. This results in excessive activation and proliferation of lymphocytes and histiocytes which results in a “cytokine storm” and uncontrolled haemophagocytosis. HLH should be considered in cases of unexplained unremitting fevers, sudden onset of cytopaenias, liver dysfunction and clotting abnormalities. It can be associated with rashes, hepatomegaly, splenomegaly and central nervous system symptoms (headache, lethargy, irritability, seizures, coma). Due to the non specific nature of presentation, HLH can often be overlooked, even when patients are extremely unwell. Traditionally, HLH is divided into primary HLH (genetic cause identified), and secondary HLH, which is associated with a variety of conditions (neoplasic, infectious and autoimmune). In autoimmune disease HLH is usually referred to as macrophage activation syndrome (MAS). HLH can be difficult to diagnose and early recognition and prompt treatment is essential to prevent the significant mortality associated with this disorder. Aims To raise awareness of HLH, to outline the complexity of this disorder and the challenges that exist in diagnosis. Methods We present three cases of HLH seen at a tertiary paediatric hospital with a tertiary paediatric rheumatology unit between January and October 2013. In two cases there was MAS associated with systemic juvenile idiopathic arthritis. In one case the diagnosis is likely to be a primary HLH. We outline the presentation and course of the illness and the results of investigations. Results (Image 1) one and two were successfully treated with methylprednisolone and Anakinra (Interleukin – 1 blocker). Patient three initially responded to methylprednisolone however, subsequently eventually required treatment with dexamethosone and cyclosporine HLH protocol. Conclusion HLH or MAS, regardless of terminology preferred, needs prompt recognition and treatment to prevent fatality. We present this series of cases to highlight the complexities and challenges of diagnosis of this condition. It is essential to raise awareness of this condition amongst paediatricians and furthermore to stimulate the development of guidelines that encompass the diagnosis and management of primary and secondary HLH.