Clinical characteristics and cardiac outcome of acute rheumatic fever in Italy in the last 15 years.

OBJECTIVE: To analyze clinical characteristics, cardiac outcome and response to therapy of an Italian pediatric population affected with acute rheumatic fever (ARF) in the last 15 years. METHODS: 135 patients with ARF (aged 2-14.9 years, mean 8.4+/-2.5 years) diagnosed from 1992 to 2006 at the Pediatric Rheumatology Centre of the University of Milan (Italy) were retrospectively reviewed. All patients underwent physical examination, laboratory evaluation, electrocardiogram and echocardiography. Patients were divided into 2 groups: group 1 - patients with complete adherence to updated Jones criteria (107 patients), and group 2 - exceptions (28 patients). Echocardiographic criteria were used to confirm the presence of carditis and to evaluate severity of mitral (MR) and aortic regurgitation (AR) at diagnosis and after treatment with steroids or acetylsalicylic acid (ASA)/non-steroidal anti-inflammatory drugs (NSAIDs). RESULTS: We observed a persistence of ARF in the last 15 years (mean 9 new cases/year with a peak of 19 cases in 2000). Carditis and arthritis were the main major criteria observed (102/135 and 71/135 patients respectively), then chorea (29/135), erythema marginatum (8/135) and subcutaneous nodules (1/135). Arthritis and chorea resolved completely with various therapies. At the last follow-up (> or =5 years) in group 1, loss of MR was observed in 46% steroid-treated (26/56 cases) and in 39% ASA/NSAID-treated (7/18 cases) patients and loss of AR in 59% steroid-treated (22/38) and 2/7 ASA/NSAID-treated patients (p>0.05). CONCLUSION: Incidence of ARF is clinically important currently in the area of northern Italy. Non-suppurative complications of streptococcal pharyngitis should be considered when deciding therapy in a pediatric patient that presents with sore throat.

Thymopentin in the treatment of juvenile chronic arthritis.

An immunological imbalance is probably one of the major pathogenetic causes of rheumatoid arthritis in adults as well as in children. This aspect is the rationale for the use of immuno-modulating drugs. In our study we evaluated the effects of intravenously-administered thymopentin on systemic and local features in 10 children affected with systemic onset juvenile chronic arthritis (JCA). We also considered the effects of intra-articular thymopentin in 3 children affected with pauciarticular onset JCA.

Bone mineral metabolism in juvenile chronic arthritis: the influence of steroids.

Calciotropic hormone assays and bone mineral density (BMD) evaluations were carried out on a group of 36 children affected with juvenile chronic arthritis (JCA) (13 with pauciarticular, 8 with polyarticular and 15 with systemic onset subtype) and in a matched control group. The plasma levels of calcium, phosphate and alkaline phosphatase were normal in all the groups. Basal 25-OH D plasma levels were significantly decreased both in the polyarticular and in the systemic groups; the latter showed a further decrease after 1 year. There was a significant decrease in both the basal and the 1-year plasma levels of 1-25-OH D only in the systemic group. The BMD was decreased in the systemic group alone and the percentage increase after 1 year was significantly inferior to that in the other groups and in the controls. There was a clear relationship between the decrease in hormones and the cumulative dose of steroids administered, as well as between the BMD decrease and the physical activity of the patients (according to Steinbrocker's classification).

A multicenter study on insulin-like growth factor-I serum levels in children with chronic inflammatory diseases.

OBJECTIVE: To study insulin-like factor-I (IGF-I) levels in children and adolescents with connective tissue diseases (CTDs), compare them with values obtained in normal controls, and correlate them with age, sex, steroid treatment, and inflammatory parameters. METHODS: A multicenter, cross-sectional study was performed in 3 Italian pediatric rheumatology centers. The subjects studied comprised 117 patients with juvenile arthritis (53 systemic, 25 pauciarticular and 17 polyarticular) and other CTDs (22), and 78 children without inflammatory conditions. IGF-I levels were measured by radioimmunoassay after acid-ethanol extraction. RESULTS: Mean IGF-I serum levels were 167.6 ng/ml (+/- 132.5) in patients and 214.4 (+/- 142.8) in controls. A significant correlation was found between IGF-I levels and age in the controls (P = 0.001), but not in the patients. Covariance analysis with age as the covariate showed significantly lower IGF-I levels in the patient group (P = 0.001). No significant correlation was found between IGF-I levels and the total quantity of steroid taken. Multiple regression analysis showed that IGF-I levels were inversely correlated with the ESR (P = 0.0001) and positively correlated with age (P = 0.0002) and sex (P = 0.021) in the patient group. CONCLUSION: IGF-I serum levels are decreased in patients with CTDs; inflammation could play a major role.

Oral versus intramuscular methotrexate in juvenile chronic arthritis. Italian Pediatric Rheumatology Study Group.

OBJECTIVE: To compare the efficacy and safety of methotrexate (MTX) after oral and intramuscular administration in children with juvenile chronic arthritis (JCA). METHODS: Pediatric rheumatology centers in Italy participated in this short-term, prospective, open trial. Each investigator was allowed to choose the oral or intramuscular route of administration according to his personal preference in everyday clinical practice. Patients enrolled by each center were given MTX through the same method of administration. All patients received 10 mg/m2 of MTX each week for six months. RESULTS: A total of 257 patients with JCA (127 treated orally and 130 intramuscularly) were enrolled in the trial by 11 Italian centers. The response rate after 6 months of MTX therapy was 58% in the oral and 61% in the intramuscular cohort. The frequency of adverse side effects did not differ significantly between the two treatment groups. CONCLUSION: The results of this study suggest that MTX at the conventional dose regimen is equally effective and has a similar safety profile in children with JCA when administered orally or by intramuscular injections.

Ex novo episodes of acute glomerulonephritis and Guillain-Barré syndrome: a case report.

A nine-year-old girl had several ex novo episodes of acute glomerulonephritis with clinical evidence of rapid progression in two of them. Guillain-Barré syndrome was diagnosed 10 days after the second episode of acute glomerulonephritis. Two renal biopsies (performed at about a four-year interval) gave morphological evidence of new episodes of acute glomerulonephritis. To our knowledge this is the first report of an association between ex novo episodes of acute glomerulonephritis and Guillain-Barré syndrome.

Local nasal immunotherapy with a powder extract for grass pollen induced rhinitis in pediatric ages: a controlled study.

Forty pediatric patients, ranging from 5-13 years of age and suffering from grass pollen rhinoconjunctivitis, were submitted to local nasal preseasonal (12 weeks) immunotherapy, either with a grass pollen extract or with placebo. After 1 year, 15 of these patients (5 previously treated with active product and 10 with placebo) were treated with the grass pollen extract preseasonally for 2 consecutive years. Before and after treatment, serum total IgA and IgE, and specific IgG and IgE were assayed as well as carrying out nasal provocation tests (NPT) with extracts at different concentrations, endpoint evaluations by rhinomanometry and prick tests with different concentrations of extract. After only 1 year, the actively treated patients showed a significant decrease of daily nasal and conjunctival signs and symptoms-as judged by a 1 to 3 score-in comparison with the control group. The placebo group showed the same results after the 3rd year. The improvement was confirmed by a significant increase of the dose threshold in NPT. No immunological alterations were evident.

Skin tests in childhood lymphoma and neuroblastoma.

Intradermal skin test antigen (Varidase, Mumps, Candidine) and contact sensitization with 2,4-dinitrochlorobenzene (DNCB) were employed in 35 previously untreated children with neuroblastoma and malignant lymphoma, to evaluate delayed cutaneous hypersensitivity. Cutaneous responses were correlated to stage of disease and survival. The limited number of patients prevents any definitive conclusion. It is apparent, however, that in childhood non-Hodgkin's lymphoma anergy to DNCB is correlated to advanced stages with rapid progressive disease. In neuroblastoma and Hodgkin's disease patients skin test sensitization seems to be of questionable clinical value.

Soy sensitivity: personal observation on 71 children with food intolerance.

The controversies on the use of soy milk as a substitute in cow's milk intolerance prompted us to study: the incidence of soy sensitivity in a pediatric population (71 children, mean age 5.9 years, 45 boys and 26 girls) with food intolerance: the influence of a prior soy milk feeding on soy sensitivity: the relationship between soy, cow's milk and seed allergy. The patients were subdivided in two groups, one of atopic patients (50 subjects, 28 of which previously fed soy) and the other of non atopic patients (21 subjects, 12 of which previously fed soy). In the atopic group prick and RAST gave positive results to soy in 46% of case, with no difference between subjects fed soy and not. There was a relationship between any and peanut RAST in 82%; between soy and pea in 70%; between soy and cow's milk in 27% of cases. Soy milk challenge was positive in 10 out of 58 children (6 atopic and 4 non atopic); 4 our of 21 atopic patients with a cow's milk intolerance had a positive soy milk challenge: 3 of 10 non atopic patients with cow's milk intolerance were reactive to soy too. 77% of atopic and 90% of non atopic children were responsive both to seeds and soy. It can be concluded that soy sensitivity is rather rare in patients with food intolerance (17.2% of cases) and is not correlated with cow's milk intolerance while is significantly correlated with seeds allergy; there is no difference between atopic and non atopic subjects and between patients previously fed soy and never fed soy.

[Current views on the pathogenesis of vasculitis in children]. / Attuali vedute sulla patogenesi delle vasculiti nell'infanzia.

Classification criteria and pathogenetic mechanisms of vasculitis in childhood are discussed. The paper is focused on the role played by immunocomplexes, cell-mediated immunity and granulomatous reactions in vascular injury.

[Systemic lupus erythematosus in childhood: review of the literature and personal observations on 32 cases]. / Il lupus eritematoso sistemico nell'infanzia: revisione della letteratura e osservazioni personali su 32 casi.

The main clinical features as well as the most important laboratory test in systemic lupus erythematosus (SLE) are reviewed. The peculiar aspects both in clinical presentation and in natural history of this disease in childhood are stressed. Personal experience is reported: 32 cases, 8 males and 24 females, mean age of onset 10.9 + 2.1 yrs, are evaluated. The most frequent clinical symptoms at diagnosis were fever, skin involvement and joint involvement, while anemia, nephropathy and hepatosplenomegaly were frequently present at onset. ANA were detected in all the subjects, anti dsDNA in 84% of cases; in only one patient SS-A/SS-B assayed positive. C4 was decreased in 17/32 cases at onset, in the others during the course of disease. Three patients died, 2 for infections, 1 for a non-Hodgkin lymphoma. Two cases present a chronic renal failure (1 is dialyzed).

[Chronic mononucleosis: a case of difficult diagnosis]. / Mononucleosi cronica: un caso di difficile diagnosi.

Here is referred the case history of a boy - age 6 yrs - who was hospitalised for a persistent high temperature with generalised limphonodes hypertrophy. The limphonode biopsy together with decreased NK activity and increased antiEAD and antiVCA antibodies allowed the diagnosis of chronic mononucleosis.

[Ketoconazole treatment of candidiasis in children: clinico-pharmacokinetic study]. / Il trattamento delle candidosi in età pediatrica con ketoconazolo: dati clinici e farmacocinetica.

Twenty-one children, age range 5 mo - 14 yrs, affected by candidosis, were treated with ketoconazole (tablets or suspension). Patients had alimentary tract involvement (12), oesophagitis (1), urinary tract candidosis (3), vaginitis (2), septicaemia (1), endophtalmitis (1) and chronic pulmonary illness with persistence of Candida albicans in sputum (3). Daily drug doses ranged from 3 to 13 mg/Kg and treatment period from 7 days to 14 months. Pharmacokinetic study in 15 children showed large individual variability of drug serum levels. Pharmacokinetic parametres, related to different schedules of the two ketoconazole formulations (tablets and suspension) are reported; drug levels after chronic administration are also evaluated. A daily dose of 3 mg/Kg of ketoconazole suspension, given in 3 administrations, did not result in sufficiently high levels, which indeed were obtained with a daily dose of 10 mg/Kg (3.3 X 3). The effect of treatment is proven by negativization of cultures in 90% of patients, by disappearance of clinical signs in 67% by improvement in 9%. The therapeutic effect on the remaining 24% (5 patients) is not evaluable. Adverse effects were only nausea and pyrosis in four cases; no laboratory abnormalities were found. A daily dosage from 7 to 10 mg/Kg, in two or three administrations, is suggested to obtain therapeutic levels in children.

[Development of lupus nephritis in childhood]. / Evoluzione della nefrite lupica in età pediatrica.

The outcome of lupus nephritis was studied in 12 children. Their age at onset was 5-13 years (mean 9.8 +/- 2.1 years), less than that reported in recent years of children with lupus nephritis. All patients had clinical symptoms and signs and/or laboratory findings of renal involvement. Renal biopsy, performed in all patients, showed: minimal change in 3 patients, mesangial glomerulonephritis in 5, focal proliferative glomerulonephritis in 3 and membranous glomerulonephritis in one patient. There was no correlation between age at onset and histological categories, while clinical data were well correlated with the degree of histological involvement. 11 patients were followed for 5.16 +/- 3.2 years (range 1-13 years); 7 patients are in complete remission, 3 patients have only microscopic hematuria and/or mild proteinuria, one patient died because of infection complicating pulmonary involvement. Our report confirms a more favorable evolution of lupus nephritis in children than in adults. In particular none of our patients whose disease started before the age of 10 years had poor outcome, in contrast to previous report describing a higher mortality and morbidity in younger children. The more favorable prognosis of our patients could depend not only on the absence of the more severe form of lupus nephritis that is diffuse proliferative glomerulonephritis, but also on the earlier diagnosis and subsequent therapy.