Gitelman syndrome associated with chondrocalcinosis and severe neuropathy: a novel heterozygous mutation in SLC12A3 gene.

Gitelman syndrome (GS) is an inherited salt-wasting tubulopathy characterized by hypocalciuria, hypokalemia, hypomagnesemia and metabolic alkalosis, due to inactivating mutations in the SLC12A3 gene. Symptoms may be systemic, neurological, cardiovascular, ophthalmological or musculoskeletal. We describe a 70 year-old patient affected by recurrent arthralgias, hypoesthesia and hyposthenia in all 4 limbs and severe hypokalemia, complicated by atrial flutter. Moreover, our patient reported eating large amounts of licorice, and was treated with medium-high dosages of furosemide, thus making diagnosis very challenging. Genetic analysis demonstrated a novel heterozygous mutation in the SLC12A3 gene; therefore, we diagnosed GS and started potassium and magnesium replacement. GS combined with chondrocalcinosis and neurological involvement is quite common, but this is the first case of an EMG-proven severe neuropathy associated with GS. Herein, we underline the close correlation between hypomagnesemia, chondrocalcinosis and neurological involvement. Moreover, we report a new heterozygous mutation in exon 23 (2738G>A), supporting evidence of a large genetic heterogeneity in this late-onset congenital tubulopathy.

Prevalence and incidence of osteoporotic fractures in patients on long-term glucocorticoid treatment for rheumatic diseases: the Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) study.

Osteoporosis and fractures are common and invalidating consequences of chronic glucorticoid (GC) treatment. Reliable information regarding the epidemiology of GC induced osteoporosis (GIOP) comes exclusively from the placebo group of randomized clinical trials while observational studies are generally lacking data on the real prevalence of vertebral fractures, GC dosage and primary diagnosis. The objective of this study was to evaluate the prevalence and incidence of osteoporotic fractures and to identify their major determinants (primary disease, GC dosage, bone mineral density, risk factors, specific treatment for GIOP) in a large cohort of consecutive patients aged >21 years, on chronic treatment with GC (≥5 mg prednisone - PN - equivalent) and attending rheumatology centers located all over Italy. Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) is a national multicenter cross-sectional and longitudinal observational study. 553 patients suffering from Rheumatoid Arthritis (RA), Polymyalgia Rheumatica (PMR) and Connective Tissue Diseases (CTDs) and in chronic treatment with GCs were enrolled. Osteoporotic BMD values (T score <-2.5) were observed in 28%, 38% and 35% of patients with CTDs, PMR or RA at the lumbar spine, and in 18%, 29% and 26% at the femoral neck, respectively. Before GC treatment, prevalent clinical fractures were reported by 12%, 37% and 17% of patients with CTDs, PMR, or RA, respectively. New clinical fragility fractures during GC treatment were reported by 12%, 10% and 23% of CTDs, PMR and RA patients, respectively. Vertebral fractures were the prevailing type of fragility fracture. More than 30% of patients had recurrence of fracture. An average of 80% of patients were in supplementation with calcium and/or vitamin D during treatment with GCs. Respectively, 64%, 80%, and 72% of the CTDs, PMR and RA patients were on pharmacological treatment for GIOP, almost exclusively with bisphosphonates. The GIOTTO study might provide relevant contributions to clinical practice, in particular by highlighting and quantifying in real life the prevalence of GIOP and relative fractures, the frequency of the main risk factors, and the currently sub-optimal prevention. Moreover, these results emphasize the importance of the underlying rheumatic disease on the risk of GIOP associated fractures.

Regional differences of vitamin D deficiency in rheumatoid arthritis patients in Italy.

Vitamin D deficiency is very common in patients with rheumatoid arthritis (RA). Aim of this study was to evaluate the prevalence of vitamin D deficiency among the different Italian regions and whether these variations are associated with different severity of the disease. The study includes 581 consecutive RA patients (464 women), not taking vitamin D supplements, from 22 Italian rheumatology centres uniformly distributed across Italy. Together with parameters of disease activity (disease activity score 28), functional impairment (activities of daily living and health assessment questionnaire disability index) and mean sun exposure time, all patients had serum 25-hydroxyvitamin D (25OHD) measured in a centralized laboratory. Vitamin D deficiency (25OHD level <20 ng/mL) was very frequent among RA patients; its prevalence was 60%, 52% and 38% in southern, central and northern Italy, respectively. Mean disease activity and disability scores were worse in southern regions of Italy. These scores were inversely related to 25OHD levels and this correlation remained statistically significant after adjusting for both body mass index (BMI) and sun exposure time. However, disease severity remained significantly higher in southern regions versus central-northern Italy after adjustment also for serum 25OHD levels, age and BMI. In RA Italian patients there are significant regional differences in the prevalence of vitamin D deficiency explained by different BMI, and sun exposure time, and inversely associated with disease activity and disability scores.

Treatment of advanced colorectal cancer with high-dose intensity folinic acid and 5-fluorouracil plus supportive care.

This randomised clinical trial, involving patients with advanced colorectal cancer, was carried out to compare the effectiveness of accelerated folinic acid (FA) plus 5-fluorouracil (5-FU) with that of the conventional regimen of 5-FU alone. Both regimens were administered with simulataneous supportive care. 185 patients were eligible: 94 were randomly allocated to receive FA 200 mg/m2 i.v. plus 5-FU 400 mg/m2 i.v. on days 1-5 every 3 weeks; and 91 to receive 5-FU 400 mg/m2 i.v. on days 1-5 every 4 weeks. The response rate was 33.3% in the accelerated FA/5-FU and 18.6% in the 5-FU arm (P = 0.045). Median survival was 13.5 months in the FA/5-FU arm and 7.5 months in the 5-FU arm (P = 0.039). Toxicity was mild and slightly more pronounced in the FA/5-FU arm (P = 0.078). This study indicates that, in patients with advanced colorectal cancer, accelerated chemotherapy with FA and 5-FU and simultaneous supportive care is capable of achieving a higher response rate and longer survival than conventional 5-FU alone, without severe toxicity.