Takayasu's arteritis: A study of 104 Italian patients.

OBJECTIVE: Takayasu's arteritis (TA) is a rare vasculitis. The Italian Takayasu's Arteritis study group was established with the aim to describe a large cohort of patients. METHODS: Data were collected by means of an ad hoc form. Demographic information, clinical history, vascular findings, treatment, risk factors, and comorbidities were analyzed. RESULTS: Data of 104 patients were collected. The median delay in diagnosis was 15.5 months (range 0-325 months). Age at onset <15 years was associated with a higher probability, whereas elevated erythrocyte sedimentation rate with a lower probability, of a delay in diagnosis. The majority of patients experienced nonspecific signs and symptoms indicative of an inflammatory disease in the early phase. Among vascular involvement, stenosis was the most frequent lesion, being present in 93% of patients, followed by occlusion (57%), dilatation (16%), and aneurysm (7%). Glucocorticoids were the mainstay of treatment in our series; however, treatment with cytotoxic agents was required in about half of the patients. Fifty-two patients underwent at least 1 surgical procedure. The main indications for intervention were renal vascular hypertension, cerebral hypoperfusion, and limb claudication. CONCLUSION: As with many rare diseases, delay in diagnosis is an important issue for patients with TA. The increasing occurrence of vascular lesions along with the disease progression put to question the long-term effectiveness of contemporary treatment. These data may be helpful in increasing physicians' awareness to prevent diagnosis delay, update guidelines, and plan future research projects.

Interleukin-6 and RANTES in Takayasu arteritis: a guide for therapeutic decisions?

BACKGROUND: In patients with Takayasu arteritis, circulating lymphocytes are activated, and histological findings indicate that cell-mediated immunity plays an important role in the pathogenetic sequence leading to vascular lesions. METHODS AND RESULTS: To delineate the profile of inflammatory and chemoattractant cytokines involved in T-cell activation in Takayasu arteritis, we measured by ELISA serum levels of interleukin (IL)-6, IL-1beta, and RANTES in 18 patients. Subsequently, we wanted to establish whether any of these molecules could be used as a marker to monitor the clinical course of the disease and to predict disease exacerbations. We found that all patients with Takayasu arteritis studied during an active phase of the disease have increased serum concentration of IL-6 compared with healthy control subjects (P<0.01). Enhanced IL-6 serum levels paralleled disease activity to the extent that its serum concentrations were comparable to those of control subjects when patients were studied in remission. RANTES concentrations were also higher than normal in the serum of all patients with Takayasu arteritis (P<0.01) studied during an active phase of the disease. RANTES serum levels tended to normalize in remission, but values remained higher than those of control subjects (P<0.05). In contrast, serum concentrations of IL-1beta were below the detection limit of ELISA in both healthy subjects and all patients with Takayasu arteritis. A positive correlation was found between either IL-6 (rho=0.705, P<0.01) or RANTES (rho=0.607, P<0.05) serum level and disease activity. CONCLUSIONS: The close correlation of serum IL-6 and RANTES levels with disease activity suggests that these cytokines contribute to vasculitic lesions in Takayasu arteritis and raises the possibility that their monitoring in serum helps clinicians find adequate treatment adjustments in individual patients.

Mycophenolate mofetil for the treatment of Takayasu arteritis: report of three cases.

BACKGROUND: Takayasu arteritis is a rare form of chronic inflammatory disease of the large arterial vessels. Some patients do not respond to steroids or immunosuppressant drugs. OBJECTIVE: To evaluate the effect of mycophenolate mofetil in patients with severe Takayasu arteritis. DESIGN: Case series. SETTING: Clinical Research Center for Rare Diseases in Bergamo, Italy. PATIENTS: Three patients with Takayasu arteritis. INTERVENTION: Mycophenolate mofetil (2 g/d) given orally in two divided doses. MEASUREMENTS: Clinical evaluation and assessment of leukocyte counts were done weekly. Vascular lesions were assessed by using Doppler ultrasonography. RESULTS: All patients showed clinical benefit, and two resumed work after months of inactivity. Patients were also able to taper and discontinue steroid use. Mycophenolate mofetil was well tolerated, and no signs of toxicity were observed. CONCLUSIONS: Mycophenolate mofetil may be an alternative to steroids and cytotoxic agents in patients with Takayasu arteritis. Before results of controlled trials become available, mycophenolate mofetil should be considered only for patients who do not improve or stabilize with conventional therapy.

Plasma clearance of nonradioactive iohexol as a measure of glomerular filtration rate.

Renal clearance of inulin is the best available indicator of GFR but cannot be used routinely for clinical purposes and is also difficult to perform for clinical investigation when repeated measurements are required. The aim of this study was to find a reliable alternative to inulin clearance that would allow one to avoid the use of radioactivity and problems related to the continuous infusion of the marker. The plasma clearance of unlabeled iohexol, a nonionic contrast agent, was used. Forty-one patients (creatinine clearance 6 to 160 mL/min per 1.73 m2) underwent simultaneous measurements of renal clearance of inulin and plasma clearance of iohexol. Iohexol was given as a single iv dose, and blood samples were drawn up to 600 min after the administration. Iohexol concentrations (by HPLC) were analyzed by a two-compartment, open-model system. A highly significant correlation between the plasma clearance of iohexol and the renal clearance of inulin over a wide range of GFR values was found. By analyzing the data with a simplified method that uses a one-compartment model corrected with the Bröchner-Mortensen formula, an excellent correlation with the inulin clearance was also observed. When only patients with moderate to severe renal failure were considered, a significant correlation between the two methods was found. A further comparison between GFR determined with iohexol and iopromide, a new low-osmolarity, low-viscosity contrast medium, was also performed in a subgroup of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Methylprednisolone dosage effects on peripheral lymphocyte subpopulations and eicosanoid synthesis.

Glucocorticoids have a major role in the treatment of glomerular diseases. Despite recent advances in understanding of their mechanism of action, very few studies have addressed the relative advantage of the wide range of different dose regimens employed in clinical practice. We studied the effects of methylprednisolone given intravenously for three consecutive days at the doses of 1 mg/kg (group 1, N = 7; group 2, N = 5), 5 mg/kg (group 3, N = 5) or 15 mg/kg (group 4, N = 6) on total blood peripheral leukocytes and on lymphocyte subsets in patients with glomerular diseases, and investigated whether such effects were a function of the drug concentration in the blood. Since glucocorticoids have an inhibitory effect on the formation of eicosanoids in different cells, we also investigated in the same patients the effect of 1 and 15 mg/kg methylprednisolone on systemic and renal eicosanoid synthesis. Results of pharmacokinetic study showed that the three different doses of methylprednisolone we used resulted in major differences in patient's exposure to the drug, and within the same dose there was a great individual variability. By contrast the three different doses of methylprednisolone induced a comparable drop in the absolute number of lymphocytes six hours after the first injection of methylprednisolone, while 24 hours later blood lymphocyte counts returned to the pre-injection values in all patients. Analysis of lymphocyte subsets showed a selective decrease in the number of circulating CD4+ and CD8+ cells six hours after methylprednisolone which was comparable in the four groups of patients studied. As for the effect of methylprednisolone on systemic and renal eicosanoid synthesis in patients with glomerular diseases, 1 and 15 mg/kg were equally unable to reduce thromboxane A2 (TxA2) and prostaglandin E2 (PGE2) release by circulating polimorphonuclear cells (PMNs). By contrast, methylprednisolone partially inhibited eicosanoid synthesis by PMNs in vitro. Consistent with the data on PMNs, urinary excretion of TxA2 and prostacyclin (PGI2) metabolites were unaltered by the different doses of methylprednisolone. By contrast urinary PGE2 was markedly and significantly reduced in patients given 15 but not 1 mg/kg. We conclude that 1 mg/kg methylprednisolone given to patients with glomerular diseases has the same effect on peripheral total blood leukocyte count and lymphocyte subsets than 5 and 15 mg/kg. The same is true for eicosanoid synthesis by PMNs. Renal synthesis of PGE2 is inhibited by 15 mg/kg but not by 1 mg/kg.(ABSTRACT TRUNCATED AT 400 WORDS)