I. Lemelle

Abdominal manifestations in childhood-onset systemic lupus erythematosus

Background: Childhood-onset lupus erythematosus is a rare disorder of unknown origin. Objectives: To describe the frequency of gastrointestinal manifestations at presentation of systemic lupus erythematosus SLE and at follow-up, and discuss the specific causes of these manifestations. Methods: Medical records of 201 patients with childhood-onset SLE followed up in French paediatric nephrological, haematological and rheumatological centres were reviewed and abstracted for gastrointestinal manifestations. Results: Gastrointestinal involvement was recorded in 39 (19%) children. The median (range) age at the time of initial gastrointestinal manifestations was 11.3 (4.5–16) years. Gastrointestinal symptoms were present at or occurred within 1 month after diagnosis in 32% patients. Abdominal pain was the most frequent symptom, present in 34 (87%) patients. It was mostly related to lupus involvement, especially ascites (n = 14) and pancreatitis (n = 12), more rarely to treatment-induced events (n = 1) or infection (n = 1) and never to events unrelated to SLE. Three children with surgical abdomen underwent a laparotomy before SLE was diagnosed, with a final diagnosis of lupus peritonitis and lupus acalculous cholecystitis. C reactive protein values were <40 mg/l in all but two patients who had surgical abdomen. Abdominal ultrasonography and computed tomography scans were abnormal in 58% and 83% of the evaluated patients, respectively. Corticosteroids, associated with intravenous cyclophospamide in eight patients, led to complete remission of gastrointestinal involvement in 30 of 31 treated patients. Conclusion: Gastrointestinal involvement is common in children with SLE, and is mainly due to primary lupus involvement. Corticoidsteroid treatment should be promptly considered in children with lupus presenting with abdominal pain after infectious disease; side effects of treatment and intestinal perforation have been excluded.

Prevalence and incidence of juvenile idiopathic arthritis: a systematic review.

OBJECTIVES To conduct a systematic literature review on incidence and prevalence of juvenile idiopathic arthritis and to estimate these figures in Europe for 2010. METHODS Articles on incidence or prevalence of juvenile idiopathic arthritis were searched in Medline. Pooled incidence and prevalence were calculated overall, by gender, age, classification and arthritis categories. We used the available age and gender pooled rates to standardize the incidence and prevalence on the 2010 European population and estimate the number of cases in Europe in 2010. RESULTS Forty-three articles (33 on incidence, 29 on prevalence) were included. Incidence rates varied from 1.6 to 23 and prevalence from 3.8 to 400/100,000. Pooled incidence and prevalence were higher for girls (10.0 [9.4-10.7] and 19.4 [18.3-20.6]/100,000) than boys (5.7 [5.3-6.2] and 11.0 [10.2-11.9]/100,000). Oligoarthritis was the most frequent form (pooled incidence rate 3.7 [3.5-3.9] and prevalence 16.8 [15.9-17.7]/100,000). The direct standardized incidence rate was 8.2 [7.5-9.0] and prevalence 70.2 [62.9-78.1]/100,000. In Europe in 2010, the estimated number of incident cases was 6896 [5481-8578] and 59,175 [44,256-76,983] prevalent cases. CONCLUSIONS Incidence and prevalence varied greatly among published reports of juvenile idiopathic arthritis, which may be explained by methodological issues, classification used, and time. Estimating the number of affected children can be useful, especially with the new treatment possibilities.

Abatacept improves health‐related quality of life, pain, sleep quality, and daily participation in subjects with juvenile idiopathic arthritis

To assess health‐related quality of life (HRQOL) in abatacept‐treated children/adolescents with juvenile idiopathic arthritis (JIA).

A Large National Cohort of French Patients With Chronic Recurrent Multifocal Osteitis

To document more fully the characteristics of chronic recurrent multifocal osteomyelitis (CRMO) in pediatric patients, to collect data on the outcomes and management of the disease, and to define prognostic factors.

Unusual cutaneous features associated with a heterozygous gain-of-function mutation in IFIH1: overlap between Aicardi-Goutières and Singleton-Merten syndromes

Cutaneous lesions described as chilblain lupus occur in the context of familial chilblain lupus or Aicardi–Goutières syndrome. To date, seven genes related to Aicardi–Goutières syndrome have been described. The most recently described encodes the cytosolic double‐stranded RNA receptor IFIH1 (also known as MDA5), a key component of the antiviral type I interferon‐mediated innate immune response. Enhanced type I interferon signalling secondary to gain‐of‐function mutations in IFIH1 can result in a range of neuroinflammatory phenotypes including classical Aicardi–Goutières syndrome. It is of note that none of the patients with a neurological phenotype so far described with mutations in this gene was reported to demonstrate cutaneous involvement. We present a family segregating a heterozygous pathogenic mutation in IFIH1 showing dermatological involvement as a prominent feature, variably associated with neurological disturbance and premature tooth loss. All three affected individuals exhibited increased expression of interferon‐stimulated genes in whole blood, and the mutant protein resulted in enhanced interferon signalling in vitro, both in the basal state and following ligand stimulation. Our results further extend the phenotypic spectrum associated with mutations in IFIH1, indicating that the disease can be confined predominantly to the skin, while also highlighting phenotypic overlap with both Aicardi–Goutières syndrome and Singleton–Merten syndrome.

Validation of the French version of the Childhood Health Assessment Questionnaire (CHAQ) in juvenile idiopathic arthritis

OBJECTIVES To translate, cross-culturally adapt, and validate the functional disability tool Childhood Health Assessment Questionnaire (CHAQ), a variant of the Health Assessment Questionnaire (HAQ), in children with juvenile idiopathic arthritis (JIA). CHILDREN AND METHODS The disability index is the mean of the scores on the eight domains of the CHAQ and can range from 0 (no disability) to 3 (maximum disability). The CHAQ was first translated into French and adapted, then validated in a multicenter cross-sectional study in 306 children with JIA (systemic onset, 23%; polyarticular onset, 22%; extended oligoarticular subtype, 25%; and persistent oligoarticular subtype, 30%). RESULTS Overall CHAQ scores discriminated between the four JIA subtypes (systemic: 1.1 +/- 0.9; polyarticular: 0.8 +/- 0.7, extended oligoarticular 0.8 +/- 0.7, and persistent oligoarticular: 0.4 +/- 0.5 [P < 0.0001]). Reproducibility evaluated by test-retest at a 7-day interval was excellent (intraclass coefficient, 0.91), as was agreement between the Parents and Childrens versions of the questionnaire (intraclass coefficient, 0.89). Significant correlations were found between the overall CHAO score and variables reflecting disease severity (joint counts, physicians and parents global assessments, and erythrocyte sedimentation rate), indicating excellent convergent validity of the tool. CONCLUSION The French version of the CHAQ displays good psychometric characteristics, although its sensitivity to change remains to be established. The French version of the CHAO should prove useful in international studies and can be expected to be helpful for monitoring individual patients with JIA.

Musculoskeletal Symptoms in Patients With Cryopyrin-Associated Periodic Syndromes: A Large Database Study

To determine the type and frequency of musculoskeletal symptoms at onset and during followup of cryopyrin‐associated periodic syndromes (CAPS).

Familial and syndromic lupus share the same phenotype as other early-onset forms of lupus

OBJECTIVE Studies of early-onset systemic lupus erythematosus (SLE) have identified monogenic forms of the disease. The primary objective of this study was to compare the clinical and laboratory features of the first patients included in the GENIAL/LUMUGENE cohort to those reported in previous publications. The secondary objective was to determine whether subgroups with a distinctive pattern of clinical and biological features are seen in predominantly genetic forms of SLE. METHODS GENIAL/LUMUGENE is a French nationwide study of the clinical, immunological, and genetic features of juvenile-onset SLE (clinicaltrials.gov #NCT01992666). Clinical and laboratory data from the first 64 patients younger than 18 years who were included in the first part of the study were collected retrospectively. Predefined criteria were used to divide the patients into three subgroups: syndromic SLE (n=10) and familial SLE (n=12) - both presumed to have a strong genetic component - and other forms of early-onset SLE (n=42). RESULTS The predefined criteria for identifying subgroups based on knowledge of the clinical and epidemiological features of monogenic SLE showed a significantly younger age at onset in syndromic SLE (P<0.05) and a lower frequency of joint manifestations in familial SLE. CONCLUSIONS In this study, clinical and epidemiological data alone failed to identify a specific patient subgroup characterized by the same disease presentation or progression. This result may be related to the small sample size or indicate marked heterogeneity of juvenile-onset SLE. Genetic studies using new sequencing techniques in these patients might identify genetic factors responsible for marked phenotypic variability.

Creation of a cohort of French patients with chronic recurrent multifocal osteitis : preliminary results

Chronic recurrent multifocal osteomyelitis (CRMO), also known as chronic nonbacterial osteomyelitis, is an orphan disease that manifests as recurrent flares of inflammatory bone pain with or without a fever. Its frequency seems to be underestimated and it often leads to consequential residual impairments.

Conventional radiography in juvenile idiopathic arthritis: Joint recommendations from the French societies for rheumatology, radiology and paediatric rheumatology

BackgroundJuvenile idiopathic arthritis (JIA) can cause structural damage. However, data on conventional radiography (CR) in JIA are scant.ObjectiveTo provide pragmatic guidelines on CR in each non-systemic JIA subtype.MethodsA multidisciplinary task force of 16 French experts (rheumatologists, paediatricians, radiologists and one patient representative) formulated research questions on CR assessments in each non-systemic JIA subtype. A systematic literature review was conducted to identify studies providing detailed information on structural joint damage. Recommendations, based on the evidence found, were evaluated using two Delphi rounds and a review by an independent committee.Results74 original articles were included. The task force developed four principles and 31 recommendations with grades ranging from B to D. The experts felt strongly that patients should be selected for CR based on the risk of structural damage, with routine CR of the hands and feet in rheumatoid factor-positive polyarticular JIA but not in oligoarticular non-extensive JIA.ConclusionThese first pragmatic recommendations on CR in JIA rely chiefly on expert opinion, given the dearth of scientific evidence. CR deserves to be viewed as a valuable tool in many situations in patients with JIA.Key Points• CR is a valuable imaging technique in selected indications.• CR is routinely recommended for peripheral joints, when damage risk is high.• CR is recommended according to the damage risk, depending on JIA subtype.• CR is not the first-line technique for imaging of the axial skeleton.