The schedule of administration of canakinumab in cryopyrin associated periodic syndrome is driven by the phenotype severity rather than the age.

INTRODUCTION: Interleukin-1 (IL-1) blockade is the treatment of choice of cryopyrin associated periodic syndromes (CAPS). Anti-IL-1 monoclonal antibody (canakinumab) was recently registered. However no clear data are available on the optimal schedule of administration of this drug. The aim of the present study was to analyse the impact of canakinumab on CAPS patients in daily clinical practice and to identify the best schedule of administration according to age and phenotype. METHODS: 13 CAPS patients (10 children and 3 young adults) treated with canakinumab were followed for 12 months. Clinical and laboratory parameters were collected at each visit. Health-related quality of life (HRQoL) was recorded at month 12. Complete response was defined as absence of clinical manifestations and normal examinations. Clinical and laboratory variables at last follow-up were compared with those registered at the moment of anakinra discontinuation. RESULTS: seven patients with chronic infantile neurological cutaneous articular (CINCA) syndrome, four patients with Muckle-Wells syndrome (MWS) and two patients with an overlapping MWS/CINCA phenotype were analysed. CINCA patients experienced a higher number of modifications of the treatment (increased dosage or decreased dosing interval) in respect to MWS patients. At the end of the follow-up CINCA patients displayed a higher frequency of administration with a median dose of 3.7 mg/kg (2.1 mg/kg for MWS patients). Canakinumab was withdrawn in a patient with CINCA for incomplete response and poor compliance. The effect of canakinumab on HRQoL was similar to that observed during treatment with anakinra, with the exception of an improvement of the psychosocial concepts after the introduction of canakinumab. CONCLUSIONS: The use of canakinumab in daily practice is associated with persistent satisfactory control of disease activity but needs progressive dose adjustments in more severe patients. The clinical phenotype, rather than the age, represents the main variable able to determine the need of more frequent administrations of the drug at higher dosage.

Antinuclear antibody-positive patients should be grouped as a separate category in the classification of juvenile idiopathic arthritis.

OBJECTIVE: We undertook this study to test the hypothesis that in the International League of Associations for Rheumatology (ILAR) classification of juvenile idiopathic arthritis (JIA), patients with similar characteristics can be classified into different categories. We sought to investigate whether antinuclear antibody (ANA)-positive patients having disease in the ILAR categories of oligoarthritis, rheumatoid factor-negative polyarthritis, psoriatic arthritis, and undifferentiated arthritis share homogeneous features and to compare these features with those of ANA-negative patients having the same categories of disease. METHODS: We identified JIA patients who had been followed up during a 22-year period. ANA positivity was defined as ≥2 positive results at a titer of ≥1:160. Demographic and clinical features were recorded retrospectively and compared between ANA-positive and ANA-negative patients. RESULTS: Of a total of 971 patients, 711 were ANA positive, 149 were ANA negative, and 111 had an indeterminate ANA status. Patients with indeterminate ANA status were excluded. ANA-positive patients in the different ILAR categories were similar in terms of age at disease presentation, female-to-male ratio, and frequency of asymmetric arthritis and iridocyclitis. Compared with ANA-positive patients, the ANA-negative group was older at disease presentation and had a lower prevalence of females, a lower frequency of iridocyclitis and asymmetric arthritis, a greater number of affected joints over time, and a different pattern of arthritis. The close relationship between the presence of ANAs and younger age at disease presentation, female predominance, asymmetric arthritis, development of iridocyclitis, lower number of affected joints over time, and lack of hip involvement was also confirmed by multivariate and multiple correspondence analysis. CONCLUSION: Our findings substantiate the hypothesis that ANA-positive patients classified into different JIA categories by current ILAR criteria constitute a homogeneous patient population.

A new familial case of spondylo-epi-metaphyseal dysplasia with multiple dislocations Hall type (leptodactylic form).

We report a father and son affected by spondylo-epi-metaphyseal dysplasia with multiple dislocations (Hall type), also called leptodactylic form. This family contributes to the delineation of the clinical and radiological phenotype of this rare condition.

Characterization of liver involvement in defects of cholesterol biosynthesis: long-term follow-up and review.

Inborn defects of cholesterol biosynthesis are a group of metabolic disorders presenting with mental retardation and multiple congenital anomalies (MCA/MR syndromes). Functional and structural liver involvement has been reported as a rare (2.5-6%) complication of the Smith-Lemli-Opitz syndrome (SLOS) and it has not been fully characterized. Here, we report on a long-term follow-up study of four patients with SLOS, and one case with lathosterolosis who presented with liver disease and underwent an extensive diagnostic work-up. Reports of liver involvement in cholesterol biosynthesis defects are reviewed. Two main different patterns of liver involvement emerged: progressive cholestasis, and stable isolated hypertransaminasemia. In our series, the first pattern was found in two patients with SLOS and one with lathosterolosis, and the second in two SLOS cases. Cholestasis was associated with early lethality and normal serum gamma-glutamyl-transferase (GGT) levels in SLOS, while possible prolonged survival and high GGT levels were seen in lathosterolosis. Hepatic fibrosis was present in both conditions. Liver biopsy performed in one of our SLOS patients with isolated hypertransaminasemia, showed only mild hydropic degeneration of the hepatocytes. The presence of liver involvement in 16% of the SLOS patients diagnosed at our Center suggests that this complication might have been underestimated in previously reported cases, possibly overshadowed by the severity of multiple malformations. Fetal hepatopathy, cholestasis, and isolated hypertransaminasemia can occur also in other disorders of cholesterol biosynthesis, such as mevalonic aciduria, desmosterolosis, Conradi-Hunermann syndrome, Greenberg dysplasia, and Pelger-Huet homozygosity syndrome. This group of inherited disorders should be considered in the differential diagnosis of patients presenting with liver disease associated with developmental delay and/or multiple malformations. Periodic liver function evaluations are recommended in these patients.