Objective
Mevalonate kinase deficiency (MKD) is a rare metabolic disease characterized by recurrent inflammatory episodes. This study was undertaken to describe the genotype, phenotype, and response ...to treatment in an international cohort of MKD patients.
Methods
All MKD cases were extracted from the Eurofever registry (Executive Agency for Health and Consumers project no. 2007332), an international, multicenter registry that retrospectively collects data on children and adults with autoinflammatory diseases.
Results
The study included 114 MKD patients. The median age at onset was 0.5 years. Patients had on average 12 episodes per year. Most patients had gastrointestinal symptoms (n = 112), mucocutaneous involvement (n = 99), lymphadenopathy (n = 102), or musculoskeletal symptoms (n = 89). Neurologic symptoms included headache (n = 43), cerebellar syndrome (n = 2), and mental retardation (n = 4). AA amyloidosis was noted in 5 patients, almost twice as many as expected from findings in previous cohorts. Macrophage activation syndrome occurred in 1 patient. Patients were generally well between attacks, but 10–20% of the patients had constitutional symptoms, such as fatigue, between fever episodes. Patients with p.V377I/p.I268T compound heterozygosity had AA amyloidosis significantly more often. Patients without a p.V377I mutation more often had severe musculoskeletal involvement. Treatment with nonsteroidal antiinflammatory drugs relieved symptoms. Steroids given during attacks, anakinra, and etanercept appeared to improve symptoms and could induce complete remission in patients with MKD.
Conclusion
We describe the clinical and genetic characteristics of 114 MKD patients, which is the largest cohort studied so far. The clinical manifestations confirm earlier reports. However, the prevalence of AA amyloidosis is far higher than expected.
Objective
To compare the efficacy and safety of adalimumab versus infliximab in an open‐label prospective, comparative, multicenter cohort study of childhood noninfectious chronic uveitis.
Methods
...Thirty‐three patients (22 females, 11 males, median age 9.17 years) with refractory, vision‐threatening, noninfectious active uveitis were enrolled, and received for at least 1 year infliximab (5 mg/kg at weeks 0, 2, and 6, and then every 6–8 weeks) or adalimumab (24 mg/m2 every 2 weeks). The primary outcome was to assess, once remission was achieved, the time of a first relapse. Time to remission, time to steroid discontinuation, and the number of relapses were also considered.
Results
Sixteen children (12 with juvenile idiopathic arthritis JIA, 3 with idiopathic uveitis, and 1 with Behçet's disease) were recruited in the adalimumab cohort and 17 children (10 with JIA, 5 with idiopathic uveitis, 1 with early‐onset sarcoidosis, and 1 with Behçet's disease) were recruited in the infliximab group. Cox regression analysis did not show statistically significant differences between the two groups with regard to time to achieve remission and time to steroid discontinuation, whereas a higher probability of uveitis remission on adalimumab during the time of treatment was shown (Mantel‐Cox χ2 = 6.83, P < 0.001). At 40 months of followup, 9 (60%) of 15 children receiving adalimumab compared to 3 (18.8%) of 16 children receiving infliximab were still in remission on therapy (P < 0.02).
Conclusion
Even if limited to a relatively small group, our study suggests that over 3 years of treatment, adalimumab is more efficacious than infliximab in maintaining remission of chronic childhood uveitis.
Objective
To compare the capacity of the 2004 diagnostic guidelines for hemophagocytic lymphohistiocytosis (HLH‐2004) with the capacity of the preliminary diagnostic guidelines for systemic juvenile ...idiopathic arthritis (JIA)–associated macrophage activation syndrome (MAS) to discriminate MAS complicating systemic JIA from 2 potentially confusable conditions, represented by active systemic JIA without MAS and systemic infection.
Methods
International pediatric rheumatologists and hemato‐oncologists were asked to retrospectively collect clinical information from patients with systemic JIA–associated MAS and confusable conditions. The ability of the guidelines to differentiate MAS from the control diseases was evaluated by calculating the sensitivity and specificity of each set of guidelines and the kappa statistics for concordance with the physician's diagnosis. Owing to the fact that not all patients were assessed for hemophagocytosis on bone marrow aspirates and given the lack of data on natural killer cell activity and soluble CD25 levels, the HLH‐2004 guidelines were adapted to enable the diagnosis of MAS when 3 of 5 of the remaining items (3/5‐adapted) or 4 of 5 of the remaining items (4/5‐adapted) were present.
Results
The study sample included 362 patients with systemic JIA and MAS, 404 patients with active systemic JIA without MAS, and 345 patients with systemic infection. The best capacity to differentiate MAS from systemic JIA without MAS was found when the preliminary MAS guidelines were applied. The 3/5‐adapted HLH‐2004 guidelines performed better than the 4/5‐adapted guidelines in distinguishing MAS from active systemic JIA without MAS. The 3/5‐adapted HLH‐2004 guidelines and the preliminary MAS guidelines with the addition of ferritin levels ≥500 ng/ml discriminated best between MAS and systemic infections.
Conclusion
The preliminary MAS guidelines showed the strongest ability to identify MAS in systemic JIA. The addition of hyperferritinemia enhanced their capacity to differentiate MAS from systemic infections. The HLH‐2004 guidelines are likely not appropriate for identification of MAS in children with systemic JIA.
Kawasaki shock syndrome (KSS) is a rare manifestation of Kawasaki disease (KD) characterized by systolic hypotension or clinical signs of poor perfusion. The objectives of the study are to describe ...the main clinical presentation, echocardiographic, and laboratory findings, as well as the treatment options and clinical outcomes of KSS patients when compared with KD patients. This is a retrospective study. All children referred to two pediatric rheumatology units from January 1, 2012, to December 31, 2014, were enrolled. Patients were divided into patients with or without KSS. We compared the two groups according to the following variables: sex, age, type of KD (classic, with less frequent manifestations, or incomplete), clinical manifestations, cardiac involvement, laboratory findings, therapy administered, response to treatment, and outcome. Eighty-four patients with KD were enrolled. Of these, five (6 %) met the criteria for KSS. Patients with KSS had higher values of C-reactive protein (
p
= 0.005), lower hemoglobin levels (
p
= 0.003); more frequent hyponatremia (
p
= 0.004), hypoalbuminemia (
p
= 0.004), and coagulopathy (
p
= 0.003); and increase in cardiac troponins (
p
= 0.000). Among the KSS patients, three had a coronary artery involvement, but none developed a permanent aneurysm. Intravenous immunoglobulin resistance was more frequent in the KSS group, although not significantly so (3/5, 60 % vs. 23/79, 30 %, P = NS). None of the five cases was fatal, and all recovered without sequelae. KSS patients are more likely to have higher rates of cardiac involvement. However, most cardiovascular abnormalities resolved promptly with therapy.
Summary Background Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis ...factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments. Methods We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6–17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. Of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. Of the patients who did respond to abatacept, 60 were randomly assigned to receive 10 mg/kg of abatacept at 28-day intervals for 6 months, or until a flare of the arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173. Findings Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0·0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0·0002). The risk of flare in patients who continued abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0·31, 95% CI 0·16–0·95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups. Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0·47); only two serious adverse events were reported, both in controls (p=0·50). Interpretation Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis. Funding Bristol-Myers Squibb.
Objective To evaluate the quality of life and long-term follow-up of patients enrolled in the Italian registry of cryopyrin-associated periodic syndromes (CAPS). Study design Since 2004, 20 patients ...with CAPS were enrolled in a common registry from different Italian Centers of Pediatric Rheumatology; 14 patients were treated with Anakinra in an open fashion. Both treated and untreated patients were routinely followed according to standard of care. The Child Health Questionnaire (CHQ-PF 50) was used to assess the health-related quality of life. Results The mean duration of follow-up was 37.5 months. In all treated patients, a complete and persistent control of the inflammatory manifestations was observed with no further progression of the disease. At enrollment in the registry, patients showed a poorer health-related quality of life than healthy children in both physical and the psychosocial summary scores. Treatment was associated with a dramatic and sustained amelioration of a variety of measures of poor quality of life, particularly in those concerning the global health perception, bodily pain-discomfort, and other physical domains. Conclusions Long-term IL-1 blockade produces a significant and persistent improvement in the clinical manifestations associated with the disease and on the overall quality of life.
Objectives The aim of the study is to assess the rate of atypical manifestations at onset in pediatric systemic lupus erythematosus (SLE) and to evaluate their effect on disease outcome. Study design ...This is a multicenter retrospective cohort study. A manifestation was considered atypical if it was not included in the American College Rheumatology classification criteria for SLE but was reported in literature as associated with SLE. Unfavorable outcome was considered presence of organ damage in the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index at the last available evaluation. Results One hundred patients were enrolled in the study; 24% presented atypical clinical features at onset. Univariate analysis showed a significant association of worse outcome variables with the presence of atypical manifestations at onset ( P = .004), as well as renal involvement ( P = .027). A multivariate logistic regression analysis showed that atypical manifestations at onset ( P = .018), renal involvement at onset or during follow up ( P = .024), and central nervous system disease involvement during follow up ( P = .021) were independent predictors of poor prognosis. Conclusions Our data support a relatively high rate of atypical onset in pediatric SLE. Presence of atypical manifestations at presentation and early kidney disease correlate with poor outcome. Similarly, during follow-up, kidney and central nervous system diseases are associated with worse outcome.
Behçet's disease is a chronic multisystem vasculitis characterized by mucocutaneous, articular, neurological, gastrointestinal and ophthalmological lesions. Ocular involvement is mainly represented ...by recurrent uveitis, especially posterior uveitis; however, iridocyclitis, retinal and choroidal vasculitis, optic neuritis and retinal vascular occlusion can also occur.
A 12-year-old Caucasian boy with a history of recurrent buccal aphthosis and nonspecific gastrointestinal symptoms was admitted to our hospital with blurred vision associated with acute episcleritis and papillitis. The patient's pathergy test was positive, suggesting a diagnosis of Behçet's disease. Corticosteroid and cyclosporine therapy was started, but further episodes were noted in both eyes. The patient was then switched to intravenous infliximab, with complete resolution of the inflammation after the second infusion.
Episcleritis and papillitis should be added to the list of uncommon manifestations of pediatric Behçet's disease. Infliximab is an effective, new therapeutic approach for Behçet's disease that is refractory to the conventional corticosteroid and immunosuppressive therapy.
PDF
