EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides.

BACKGROUND: There has been a lack of appropriate classification criteria for vasculitis in children. OBJECTIVE: To develop a widely accepted general classification for the vasculitides observed in children and specific and realistic classification criteria for common childhood vasculitides (Henoch-Schönlein purpura (HSP), Kawasaki disease (KD), childhood polyarteritis nodosa (PAN), Wegener's granulomatosis (WG), and Takayasu arteritis (TA)). METHODS: The project was divided into two phases: (1) the Delphi technique was used to gather opinions from a wide spectrum of paediatric rheumatologists and nephrologists; (2) a consensus conference using nominal group technique was held. Ten international experts, all paediatricians, met for the consensus conference. Agreement of at least 80% of the participants was defined as consensus. RESULTS: Consensus was reached to base the general working classification for childhood vasculitides on vessel size. The small vessel disease was further subcategorised into "granulomatous" and "non-granulomatous." Final criteria were developed to classify a child as HSP, KD, childhood PAN, WG, or TA, with changes introduced based on paediatric experience. Mandatory criteria were suggested for all diseases except WG. CONCLUSIONS: It is hoped that the suggested criteria will be widely accepted around the world because of the reliable techniques used and the international and multispecialist composition of the expert group involved.

Initial presentation of childhood-onset systemic lupus erythematosus: a French multicenter study.

OBJECTIVE: To describe the clinical and laboratory manifestations of childhood-onset systemic lupus erythematosus (SLE) at presentation. STUDY DESIGN: This retrospective French multicenter study involved 155 patients in whom SLE developed before the age of 16 years. Mean patient age at onset was 11.5 +/- 2.5 years (range, 1.5-16 years). The female to male ratio was 4.5. RESULTS: The most common initial manifestations were hematologic (72%), cutaneous (70%), musculoskeletal (64%), renal (50%), and fever (58%). Thirty-two percent of children had atypical symptoms, mainly including abdominal involvement in 26 patients, which lead to negative laparotomy results for presumed appendicitis. Severe renal, neurologic, hematologic, abdominal, cardiac, pulmonary, thrombotic, and/or cutaneous manifestations occurred within the first month after the diagnosis in 40% of patients. The mean erythrocyte sedimentation rate was 72 +/- 29 mm/h, and the mean C-reactive protein value 22 +/- 21 mg/L. Antinuclear antibodies an, anti-double stranded DNA antibodies, and low C3 or C4 level were retrieved in 97%, 93%, and 78 % of patients, respectively. CONCLUSION: Initial manifestations of childhood-onset SLE are diverse and often severe. The diagnosis of SLE should be promptly considered in any febrile adolescent with unexplained organ involvement, especially when associated with an increased erythrocyte sedimentation rate.

PRINTO/PRES international website for families of children with rheumatic diseases: www.pediatric-rheumatology.printo.it.

OBJECTIVE: To prepare a website for families and health professionals containing up to date information about paediatric rheumatic diseases (PRD). METHODS: Firstly, paediatric rheumatology centres and family self help associations were surveyed to characterise current clinical practice of physicians providing care for children with PRD, research activities, and training facilities of each centre. Secondly, international consensus was reached on the content of the website. Finally, the website was developed and the texts translated. RESULTS: The web page contains three main sections: (a) description for families of the characteristics of 15 PRD; (b) list of paediatric rheumatology centres; (c) contact information for family self help associations. A version for 45 countries in 52 languages (with another three in progress) is now available on the web. 291 surveys from 171 centres and 102 family associations were received from 42 countries. The median proportion of time spent in paediatric practice in the centres examined was 100%, with 70% of this time dedicated to paediatric rheumatology. 90% of the centres were willing to perform clinical trials in the future. CONCLUSIONS: The PRINTO/PRES website provides a well defined and competent set of information about PRD, with appropriate multiple translated versions and easy web navigational direction.

[The presentation of childhood systemic lupus erythematosus with neurological symptoms: three-case reports]. / Modes de révélation neurologiques du lupus érythémateux disséminé de l'enfant: trois observations.

INTRODUCTION: neurological symptoms occurring during childhood, especially if unusual or recurrent, should attract attention. METHODS: We report three cases of childhood lupus revealed by neurological symptoms. RESULTS: Misdiagnosis was frequent and time from symptom onset to diagnosis of lupus reached up to six months. CONCLUSION: After careful history taking and physical examination, complementary tests should include erythrocyte sedimentation rate, blood count, platelets, and in some cases an immunological study with antinuclear antibodies.

Autologous stem cell transplantation for refractory juvenile idiopathic arthritis: analysis of clinical effects, mortality, and transplant related morbidity.

OBJECTIVE: To evaluate the safety and efficacy of autologous stem cell transplantation (ASCT) for refractory juvenile idiopathic arthritis (JIA). DESIGN: Retrospective analysis of follow up data on 34 children with JIA who were treated with ASCT in nine different European transplant centres. Rheumatological evaluation employed a modified set of core criteria. Immunological reconstitution and infectious complications were monitored at three month intervals after transplantation. RESULTS: Clinical follow up ranged from 12 to 60 months. Eighteen of the 34 patients (53%) with a follow up of 12 to 60 months achieved complete drug-free remission. Seven of these patients had previously failed treatment with anti-TNF. Six of the 34 patients (18%) showed a partial response (ranging from 30% to 70% improvement) and seven (21%) were resistant to ASCT. Infectious complications were common. There were three cases of transplant related mortality (9%) and two of disease related mortality (6%). CONCLUSIONS: ASCT in severely ill patients with JIA induces a drug-free remission of the disease and a profound increase in general wellbeing in a substantial proportion of patients, but the procedure carries a significant mortality risk. The following adjustments are proposed for future protocols: (1) elimination of total body irradiation from the conditioning regimen; (2) prophylactic administration of antiviral drugs and intravenous immunoglobulins until there is a normal CD4+ T cell count.

[Disseminated lupus erythematosus in children: guidelines about investigations during the initial evaluation and follow-up]. / Lupus érythémateux disséminé chez l'enfant: recommandations concernant les examens à effectuer lors de l'évaluation initiale et du suivi.

Childhood-onset systemic lupus erythematosus (SLE) is often severe and has a serious long-term morbidity. Pediatric guidelines about its management do not exist. The French study group of childhood-onset SLE proposes recommendations about the investigation which are needed at diagnosis and during follow-up of SLE, in order to adjust the treatment according to the severity of the disease and to avoid unnecessary investigations.

Long-term follow-up of autologous stem cell transplantation for refractory juvenile idiopathic arthritis.

Since 1997, autologous stem cell transplantation (ASCT) had been applied to more than 40 children with polyarticular or systemic juvenile idiopathic arthritis (JIA). For this review, results of the follow-up are available from 25 children with systemic JIA and six with polyarticular JIA that were reported in detail from eight different pediatric European transplant centers. Before ASCT all children had progressive disease despite the use of corticosteroids, methotrexate (MTX) up to 1 mg/kg/week, cyclosporin (2.5 mg/kg/day) and/or anti-TNFalpha therapy. The clinical follow-up of these children ranges from 8 to 60 months (median 33 months).

[Contribution of recent physiopathogenic progresses to the diagnosis of recurrent fevers]. / Apport des données physiopathogéniques au diagnostic des fièvres récurrentes.

Recurrent fevers are characterized by fever lasting for a few days or few weeks and followed by a fever-free interval and state of well-being. It is first necessary to eliminate infections, which are the most common causes of fever. Several recurrent fevers belong to inflammatory diseases of unclear physiopathogeny. Recent advances are now available permitting to immunogenetically identify some of them. It also opens a better understanding and consequently the possibility of specific therapeutic approach.

[Childhood-onset systemic lupus erythematosus]. / Le lupus érythémateux disséminé de l'enfant.

Systemic Lupus Erythematosus (SLE) remains a challenging autoimmune disease in term of etiology, pathogenesis and treatment. It is estimated that 10-17% of lupus patients present before the age of 16. SLE in children appears to have more severe organ involvement than in adults. The outcome of childhood SLE has improved during the last decade, but the morbidity remains high.

Reactive haemophagocytic syndrome in children with inflammatory disorders. A retrospective study of 24 patients.

BACKGROUND: The reactive haemophagocytic syndrome (RHS) is a little-known life-threatening complication of rheumatic diseases in children. It reflects the extreme vulnerability of these patients, especially those with systemic-onset juvenile chronic arthritis (JCA). This immunohaematological process may be triggered by events such as herpes virus infection and non-steroidal anti-inflammatory drug therapy. Treatment has not been standardized. METHODS: We characterized this unusual disorder and determined its incidence by carrying out a retrospective study of patients identified over a 10-yr period in French paediatric units. RESULTS: Twenty-four cases (nine males, 15 females) were studied. Eighteen had typical systemic-onset JCA, two had polyarthritis, two had lupus and two had unclassifiable disorders. Clinical features at diagnosis included high spiking fever (24 patients), enlargement of the liver and spleen (14), haemorrhagic diathesis (six), pulmonary involvement (12) and neurological abnormalities (coma or seizures) (12). RHS was the first manifestation of systemic disease in three cases. Admission to intensive care was required in ten cases. Hypofibrinogenaemia, elevated liver enzymes and hypertriglyceridaemia were found consistently. Phagocytic histiocytes were found in 14 of 17 bone marrow smears. RHS was presumed to have been precipitated by infection in 11 cases (four Epstein-Barr virus, three varicella-zoster virus, one parvovirus B19, one Coxsackie virus, one Salmonella, one Pneumocystis carinii) and by the introduction of medication in three cases (Salazopyrin plus methotrexate; morniflumate; aspirin). Macrophage activation was indicated by high levels of monokines in the serum of two patients. Twenty patients had only one episode, three had an early relapse and one patient had two relapses. The treatment regimen was tailored to each child as the clinical course was variable. There was no response to intravenous immunoglobulins, which were used in four cases. Intravenous steroids at doses ranging from conventional to pulse methylprednisolone induced remission in 15 of 21 episodes when used alone as the first-line treatment. Cyclosporin A was consistently and rapidly effective, both when used as second-line therapy in all seven of the episodes in which steroids failed and in all five patients who received it as their first-line treatment. This supports a central role of T lymphocytes in the haemophagocytic syndrome. Two patients died. One patient with lupus died of congestive fulminant heart failure after 4 days, despite treatment with intravenous steroids and immunoglobulins, and one patient with systemic-onset JCA died from multiorgan failure despite aggressive therapy with pulsed steroids and etoposide. CONCLUSIONS: RHS may be a more common complication of systemic disease in childhood than previously thought. This life-threatening complication should be diagnosed promptly, as it calls for the immediate withdrawal of potentially triggering medications, anti-infective therapy when relevant, and urgent immunosuppressive treatment, measures that are very often effective. Cyclosporin A may be the drug of choice.

Prognostic factors in juvenile idiopathic arthritis.

Prognostic factors in juvenile arthritis are related to many variables that must be evaluated according to the different subtypes. The International League of Associations of Rheumatologists (ILAR) recently proposed six different categories referred to as the Durban criteria, under the eponym of juvenile idiopathic arthritis (JIA). The aim of this classification was to define homogeneous groups according to their clinical and biologic features. The prognostic factors were classified into the different categories of JIA. A poor outcome in the systemic form correlated with markers of disease activity, such as fever and polyarticular involvement, within the first 6 months. The risk of joint destruction in oligoarthritis correlated with the severity of arthritis within the first 2 years. Polyarthritis with positive rheumatoid factor is associated with marked disability in adulthood. In a group of psoriatic patients, the risk of developing sacroiliitis is higher in male and HLA-B27-positive patients. Patients with enthesitis-related arthritis with lower limb, knee, and tarsal involvement also are at greater risk of developing sacroiliitis. Chronic uveitis is a complication of JIA observed mainly in patients with oligoarthritis associated with positive antinuclear antibodies in serum. Secondary amyloidosis is observed mainly in children with systemic JIA. The long-term outcome must be discussed according to the various therapies. Corticosteroids contribute to growth retardation and osteoporosis, for which the use of human recombinant growth hormone and biphosphonates may be an option. Newer encouraging therapies such as anticytokines have been proposed for children with active disease. Autologous stem cell transplantation is being evaluated in some centers with promising results; however, it has a high rate of mortality. Further discussion regarding which patients should undergo autologous stem cell transplantation is needed, as is further discussion regarding the technical adaptations necessary.

The Swiss German and Swiss French versions of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Swiss German and Swiss French languages of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Swiss German and Swiss French CHAQ-CHQ were adapted from the German and French versions of the CHAQ-CHQ, and revalidated in this study. A total of 147 subjects were enrolled: 85 patients with JIA (22% systemic onset, 31% polyarticular onset, 32% extended oligoarticular subtype, and 15% persistent oligoarticular subtype) and 62 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Swiss German and Swiss French versions of the CHAQ-CHQ are reliable, and valid tools for the functional, physical and psychosocial assessment of children with JIA.

CARD15 mutations in Blau syndrome.

We have identified three missense mutations in the nucleotide-binding domain (NBD) of CARD15/NOD2 in four French and German families with Blau syndrome. Our findings indicate that, in addition to Crohn disease, CARD15 is involved in the susceptibility to a second granulomatous disorder.