Minimum effective betamethasone dosage on the neurological phenotype in patients with ataxia-telangiectasia: a multicenter observer-blind study.

BACKGROUND AND PURPOSE: Ataxia-telangiectasia (A-T) is a rare neurodegenerative disease, due to A-T mutated (ATM) gene mutations, which typically presents with signs of progressive neurological dysfunction, cerebellar ataxia and uncoordinated movements. A-T severely affects patients' quality of life. Successful treatment options are still not available. The aim of this multicenter study, performed with a blind evaluation procedure, was to define the minimal effective dosage of oral betamethasone, thus preventing the occurrence of side effects. METHODS: Nine A-T patients were enrolled to receive betamethasone at increasing dosages of 0.001, 0.005 and 0.01 mg/kg/day. Neurological assessment and the evaluation of quality of life were performed through the Scale for the Assessment and Rating of Ataxia and the Italian version of the Childhood Health Assessment Questionnaire (CHAQ) at each time-point. The drug safety profile was evaluated. Patients were categorized as responders, partial responders and non-responders. RESULTS: Four of nine patients had a benefit at a dose of 0.005 mg/kg/day of oral betamethasone. Using the higher dosage, only one additional patient had a positive response. Conversely, a daily dose of 0.001 mg/kg was ineffective. A correlation between the serum adrenocorticotropic hormone levels and the clinical response was observed. Five of 30 CHAQ items improved in four patients. CONCLUSIONS: These data suggest that a short-term betamethasone oral treatment, at a daily dosage of 0.005 mg/kg, is effective in some patients. Pre-existing risk factors for side effects should be taken into account before therapy.

Wilson's disease treated with penicillamine and lupus erythematosus: related or distinct entities?

Systemic lupus erythematosus (SLE) has been reported to be associated to Wilson's disease, as a complication of treatment with penicillamine. Even though drug-induced lupus erythematosus (DILE) has some features in common with SLE, they are distinct entities. We report the case of a young girl who at the age of five had a diagnosis of Wilson's disease and she started therapy with penicillamine. Eight years after the beginning of therapy, she developed proteinuria, which was considered to be related to penicillamine. Two years later, she developed arthritis, malar rash and laboratory findings suggestive for lupus erythematosus. At the beginning her symptoms, due to the known association between penicillamine and DILE, were thought to be related to this treatment. In this hypothesis, she was referred to the Rheumatology Centre; zinc acetate was substituted for penicillamine and she started naproxen for the treatment of arthritis. Anyway, the subsequent clinical course and laboratory findings led us to a diagnosis of idiopathic SLE. A renal biopsy detected massive mesangiocapillary proliferation with subendothelial deposits (wire loops) and duplication of glomerular basement membrane (active diffuse global proliferative lupus nephritis, class IV G A). To our knowledge, this is the first report of an association between Wilson's disease and SLE.

Systemic lupus erythematosus presenting with pulmonary thromboembolism in a 15-year-old girl.

Pulmonary embolism is rare in children aged less than 15 years in whom its estimated annual incidence is 0.2 cases per 100,000, against the approximately 700 cases per 100,000 in patients aged more than 85 years. We describe the case of a 15-year-old girl who had a history of thrombocytopenia with anti-platelet and anti-nuclear antibodies. Misdiagnosed chest pain and dyspnea were treated for 6 weeks as community-acquired pneumonia, but proved to be the onset of pulmonary thromboembolism. Although this life-threatening event is rare in paediatrics, the presence of lupus anticoagulant combined with previously asymptomatic thrombocytopenia allowed a diagnosis of systemic lupus erythematosus (SLE). The combination of a history of thrombocytopenia and the presence of antinuclear antibodies, even in the absence of any other diagnostic criteria, should always suggest considering SLE as a differential diagnosis, particularly when the course of a clinical manifestation is atypical.

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.

Synovial cyst in juvenile idiopathic arthritis.

Small synovial cysts are a common manifestation of juvenile idiopathic arthritis; large brachial cysts, however, are a rare sign of the disease and they must be differentiated from other soft tissue swelling which are not related to articular involvement. We describe the case of three children with juvenile idiopathic arthritis who came to our attention with large synovial cysts. Ultrasonographic examination and MRI were performed in all cases, showing the real nature of the swelling and the connection to the joint. In all cases, swelling reduced and then disappeared with control of disease activity; in two cases, they reappeared in coincidence with a severe relapse of juvenile idiopathic arthritis. Brachial swellings represent a diagnostic challenge because they can be the clinical expression of a variety of diseases. In children with juvenile idiopathic arthritis who present with a sudden swelling of the upper arm, synovial cysts must be considered in the diagnostic workout, because they are a possible rare manifestation of juvenile idiopathic arthritis.

Breast cancer prevalence measured by the Lombardy Cancer Registry.

AIMS AND BACKGROUND: Breast cancer is the most important malignant neoplasm affecting women in Western countries. An increasing number of women undergo regular medical checkups, especially during the first years following the diagnosis. Therefore, from the health planning point of view, it is essential to have prevalence measures to furnish estimates for the demands that the health care system could possibly undergo. METHODS: By means of PREVAL, a computerized program, breast cancer prevalence has been measured in the Varese province using incidence and follow-up data from the Lombardy Cancer Registry (LCR). RESULTS: During the 1986-1988 period, breast cancer prevalence for patients alive within 10 years from diagnosis was about 625 per 100,000 resident women. Of these, 54% were over 60 years and 9% were under 45 years of age. Patients alive within 2 years from diagnosis were about 200 per 100,000 residents; considering the 1978-1980 period, patients alive within 2 years from diagnosis were just 140 per 100,000 residents. This dramatic increase in breast cancer prevalence is present also for long-term survivors (i.e. patients alive at 10-13 years from the diagnosis). Extrapolating breast cancer prevalence measured in the Varese province to the whole Lombardy region, the expected number of prevalent cases alive within 10 years of the diagnosis, presently living in Lombardy, would be 27,500. LCR's breast cancer prevalence figures were compatible with available data provided by the Finnish Cancer Registry. CONCLUSION: Owing to aging of the population, the improvement in survival and the increasing incidence, the number of prevalent cases will increase. This phenomenon has and will have great importance for the health planning.