Wolcott-Rallison Syndrome, a Rare Cause of Permanent Diabetes Mellitus in Infants-Case Report.

Wolcott-Rallison syndrome is a rare cause of permanent neonatal diabetes mellitus caused by mutations in the eukaryotic translation initiation factor 2 alpha kinase 3 gene (EIF2AK3). Individuals affected by this disorder have severe hyperglycemia, pancreatic failure, and bone abnormalities and are prone to severe and life-threatening episodes of liver failure. This report illustrates the case of a 2-month-old infant with extreme hyperglycemia and severe diabetic ketoacidosis. Acute management was focused on correcting severe acidosis. Further management aimed to obtain stable blood glucose levels, balancing the patient's need for comfort and lack of distress with the clinicians' need for adequate information regarding the patient's glycemic control. Genetic testing of the patient and his parents confirmed the diagnosis. The follow-up for 18 months after diagnosis is detailed, illustrating both the therapeutic success of subcutaneous insulin therapy and the ongoing complications that patients with Wolcott-Rallison syndrome are subject to.

Evaluation of anti-cyclic citrullinated peptide antibodies may be beneficial in RF-negative juvenile idiopathic arthritis patients.

Despite the high diagnostic and prognostic performance in adult rheumatoid arthritis, the role of antibodies to cyclic citrullinated peptide (anti-CCP) in juvenile idiopathic arthritis (JIA) is controversial. Occurrence of anti-CCP was mainly seen in rheumatoid factor (RF)-positive polyarthritis patients. In the present study, our aim was to investigate the prevalence and significance of anti-CCP for subjects with JIA in our population. We evaluated anti-CCP reactivity in the sera of 70 patients with various subtypes of JIA in a prospective cohort study. Anti-CCP titres were correlated with the evolution of joint involvement and the presence of joint damage. Nine JIA patients were seropositive for anti-CCP with respect to the cut-off value of the test. In our cohort, 34 patients had a polyarticular joint disease, most of them being RF-negative (30/34, 88 %). All four RF-positive polyarthritis patients had high anti-CCP concentrations and an aggressive erosive disease. In the RF-negative JIA patients, anti-CCP reactivity was in lower titres but significantly associated with polyarticular joint involvement (p = 0.016) and also with the presence of joint damage (p < 0.001). Presence of anti-CCP, at both low and high concentration, was significantly associated with a more severe articular disease in our JIA patients. Investigating anti-CCP should clearly be taken into consideration even among patients with JIA subtypes other than RF-positive polyarthritis.

Primary complement and antibody deficiencies in autoimmune rheumatologic diseases with juvenile onset: a prospective study at two centers.

BACKGROUND: Our aim was to investigate the prevalence and clinical relevance of inherited complement and antibody deficiency states in a large series of patients with various autoimmune rheumatologic diseases (ARD) with juvenile onset. METHODS: A total number of 117 consecutive patients from 2 tertiary referral hospitals were included in the study. All patients underwent genetic screening for type I C2 deficiency and C4 allotyping. Serum levels of immunoglobulin classes measured systematically throughout their regular medical care were recorded retrospectively. RESULTS: Our cohort of patients included 84 with juvenile idiopathic arthritis (JIA), 21 with systemic lupus erythematosus (SLE), 6 with systemic vasculitis, 2 with juvenile scleroderma, 2 with idiopathic uveitis, 1 with mixed connective tissue disease and 1 with SLE/scleroderma overlap syndrome. We have found 16 patients with evidence of primary immunodeficiency in our series (13.7%), including 7 with C4 deficiency, 5 with selective IgA deficiency, 3 with C2 deficiency and 2 with unclassified hypogammaglobulinemia (one also presented C4D). Of the 84 patients with JIA, 4 (4.8%) had a complement deficiency, which was less prevalent than in the SLE cohort (23.8%), but all of them have exhibited an aggressive disease. Most of our patients with primary antibody deficiencies showed a more complicated and severe disease course and even the co-occurrence of two associated autoimmune diseases (SLE/scleroderma overlap syndrome and SLE/autoimmune hepatitis type 1 overlap). CONCLUSIONS: Our findings among others demonstrate that complement and immunoglobulin immunodeficiencies need careful consideration in patients with ARD, as they are common and might contribute to a more severe clinical course of the disease.

Relation of interleukin-6, TNF-alpha and interleukin-1alpha with disease activity and severity in juvenile idiopathic arthritis patients.

BACKGROUND: Evaluation of disease activity in children with Juvenile Idiopathic Arthritis (JIA) is primarily based on clinical examination and conventional parameters of inflammation. But, in daily clinical practice, these two findings often fail to be in accord, making therapeutic decisions difficult. The aim of our research was to evaluate the potential usefulness of IL-6, IL-1alpha and TNF-alpha in monitoring disease activity and severity in JIA. METHODS: In a 2-year prospective study, IL-6, IL-1alpha, and TNF-alpha levels were measured using ELISA in 63 serum samples for 40 JIA patients. The control population consisted of 18 healthy children. The data were correlated with disease activity and severity (quantified with JADAS-27 composite score). RESULTS: The patients with active disease had greater IL-6 levels than did the patients with inactive disease [47.2 pg/mL (2 to 578.7) vs. 2.6 pg/mL (2 to 8.3); p = 0.002] and controls [47.2 pg/mL (2 to 578.7) vs. 2.25 pg/mL (2 to 4); p = 0.006]. Differences between active disease and remission were also significant for every JIA subgroup. The cutoff value for IL-6 in the diagnosis of active disease obtained from the ROC curve analysis was 8.33 pg/mL. Levels of circulating IL-6 were elevated in patients with severe and moderate disease activity (JADAS-27 score > 10) compared with those of low disease activity (JADAS-27 score < or = 10) [80.1 pg/mL (2 to 578.7) vs. 7.41 (2 to 69); p = 0.010]. We found no correlation of serum TNF-alpha and IL-1alpha levels with disease activity in our patients. The most elevated levels of serum TNF-alpha were found in patients during clinical remission with Etanercept. CONCLUSIONS: Serum IL-6 concentrations may serve as a biomarker of disease activity and severity in JIA, providing additional information in certain clinical situations with great discrepancy between clinical assessment and conventional laboratory tests. Upon treatment with Etanercept, although many JIA patients reached remission on medication, they developed increased circulating TNF-alpha levels.