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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0545-1) contains supplementary material, which is available to authorized users.

The aim of this study was to describe the abnormalities identified with conventional MRI in children with neuropsychiatric systemic lupus erythematosus (NPSLE). This was single-centre (Great Ormond Street Hospital, London) retrospective case series of patients with juvenile NPSLE seen in 2003–2013. Brain MR images of the first episode of active NPSLE were reviewed. All patients fulfilled the 1999 ACR case definitions for NPSLE syndromes. Presenting neuropsychiatric manifestations, immunological findings and treatment are reported. Results are expressed as median and ranges or percentages. Fisher’s exact test was used to identify clinical predictors of abnormal MRI. A total of 27 patients (22 females), median age 11 years (4–15), were identified. Presenting clinical symptoms included the following: headaches (85.1 %), mood disorder/depression (62.9 %), seizures (22.2 %), acute psychosis (18.5 %), cognitive dysfunction (14.8 %), movement disorder (14.8 %), acute confusional state (14.8 %), aseptic meningitis (7.4 %), demyelinating syndrome (3.7 %), myelopathy (3.7 %), dysautonomia (3.7 %) and cranial neuropathy (3.7 %). The principal MR findings were as follows: (1) absence of MRI abnormalities despite signs and symptoms of active NPSLE (59 %); (2) basilar artery territory infarction (3 %); (3) focal white matter hyperintensities on T2-weighted imaging (33 %); (4) cortical grey matter lesions (3 %); and (5) brain atrophy (18.5 %). The presence of an anxiety disorder strongly associated with abnormal MRI findings (p = 0.008). In over half the children with NPSLE, no conventional MRI abnormalities were observed; white matter hyperintensities were the most commonly described abnormalities. Improved MR techniques coupled with other alternative diagnostic imaging modalities may improve the detection rate of brain involvement in juvenile NPSLE.Electronic supplementary materialThe online version of this article (doi:10.1007/s10067-016-3376-9) contains supplementary material, which is available to authorized users.

BackgroundWe previously described an endogamous Pakistani kindred in whom we identified a novel homozygous missense mutation in the PRKCD gene encoding for protein kinase C δ (PKCδ) as a cause of monogenic systemic lupus erythematosus (SLE). PKCδ has a role in the negative regulation of B cells. Given the nature of the disease, a logical targeted therapeutic approach in these patients is B cell depletion. Indeed, the 3 siblings all had a marked clinical response and resolution of symptoms with rituximab, although 2 of the siblings had severe reactions to rituximab thus precluding further treatment with this. We therefore describe the first successful use of ofatumumab for this rare form of monogenic SLE.Case presentationAll three affected siblings presented with SLE before the age of 3-years with lethargy, intermittent fever, thrombocytopenia, cutaneous involvement, alopecia, and hepatosplenomegaly. Tubulointerstitial nephritis was also present in 1 of the siblings. Homozygosity mapping followed by whole exome sequencing identified a homozygous missense mutation in PRKCD (p.Gly432Trp), subsequently confirmed by Sanger sequencing to be present in all 3 siblings. All 3 patients were initially treated with rituximab, however 2 of the siblings developed severe infusion-related reactions. For subsequent disease flare in these individuals we therefore used an alternative B cell depleting agent, ofatumumab (300 mg/1.73m2 on day 1; 700 mg/1.73m2 on day 15). This resulted in marked clinical improvement in both patients. To the best of our knowledge, this is the first report describing the successful use of ofatumumab for PKCδ deficiency.ConclusionsPKCδ deficiency causes a monogenic form of SLE which responds well to B cell depletion. Ofatumumab is also likely to have a therapeutic role for sporadic juvenile SLE (jSLE) patients intolerant of rituximab.

Juvenile systemic lupus erythematosus (JSLE) is characterised by onset before 18 years of age and more severe disease phenotype, increased morbidity and mortality compared to adult-onset SLE. Management strategies in JSLE rely heavily on evidence derived from adult-onset SLE studies; therefore, identifying biomarkers associated with the disease pathogenesis and reflecting particularities of JSLE clinical phenotype holds promise for better patient management and improved outcomes. This narrative review summarises the evidence related to various traditional and novel biomarkers that have shown a promising role in identifying and predicting specific organ involvement in JSLE and appraises the evidence regarding their clinical utility, focusing in particular on renal biomarkers, while also emphasising the research into cardiovascular, haematological, neurological, skin and joint disease-related JSLE biomarkers, as well as genetic biomarkers with potential clinical applications.

Objective The aim of this study was to: (a) screen a large group of unselected patients with juvenile systemic lupus erythematosus for anti-aquaporin 4 antibodies (AQP4-Ab); (b) identify clinical and laboratory predictors of the presence of AQP4-Ab positivity in juvenile systemic lupus erythematosus. Methods Sera from 90 patients with juvenile systemic lupus erythematosus were tested for the presence of AQP4-Ab using a cell-based assay. Demographics, clinical and immunological features, treatment received were summarized. Fisher’s exact test was used to identify clinical predictors of positivity for AQP4-Ab. Results Five of 90 (5.5%) patients tested positive for AQP4-Ab, all of which had neurological involvement, mainly transverse myelitis and optic neuritis. AQP4-Ab-positive patients were more likely to have neurological symptoms ( P = 0.002), less likely to experience dermatological manifestations ( P = 0.045), and less likely to have detectable anti-dsDNA antibodies ( P = 0.022). These patients were also more likely to have received anti-epileptic ( P = 0.023) and anti-coagulant ( P = 0.007) drugs. Conclusions The findings of this study indicate that some patients with juvenile systemic lupus erythematosus develop antibodies against aquaporin-4 and may be at risk of developing a neurological clinical phenotype. We suggest that all juvenile systemic lupus erythematosus patients should be systematically screened for the presence of AQP4-Ab and this may help identify a high risk for neurological involvement in juvenile systemic lupus erythematosus.