Rituximab treatment for 'rhupus syndrome': clinical and power-Doppler ultrasonographic monitoring of response. A longitudinal pilot study.

OBJECTIVE: To evaluate the safety and efficacy of rituximab in patients suffering from rhupus unresponsive to therapy with non-biological disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Six patients fulfilling criteria for both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and with a DAS28 score >5.1 were enrolled to receive two fortnightly 1000 mg rituximab doses at baseline and after 28 weeks. All patients underwent clinical, laboratory, and power- Doppler (PD) ultrasonographic (US) assessment at baseline and after 14, 28 and 56 weeks. RESULTS: A sustained improvement in DAS28, SLEDAI, HAQ, laboratory markers and ultrasound indices together with a significant reduction in the daily dose of prednisone were observed throughout follow-up. CONCLUSION: Rituximab may be a safe and effective therapeutic option in refractory rhupus patients.

Detection of early impairment of coronary flow reserve in patients with systemic sclerosis.

OBJECTIVE: To investigate whether coronary flow reserve (CFR), measured by a new non-invasive method, is impaired early in patients with systemic sclerosis (SSc) and whether CFR impairment correlates with clinical or functional measures, or both. METHODS: 27 patients with SSc without clinical evidence of ischaemic heart disease and 23 control group subjects matched for age and sex were studied. CFR was evaluated in the left anterior descending coronary artery (LAD) with a new non-invasive method: contrast (Levovist) enhanced transthoracic Doppler during adenosine infusion. The pulsed wave Doppler examination of blood flow velocity was recorded in the LAD at rest and after maximum vasodilatation by adenosine infusion. RESULTS: In patients with SSc, without clinical evidence of ischaemic heart disease, CFR was impaired (p=0.0001). 14/27 patients with SSc had severe reduction of the CFR (< or =2.5) compared with controls (p=0.002). A non-significant trend between mean CFR and the severity and duration of the disease was also seen. CONCLUSIONS: CFR is often reduced in patients with SSc, suggesting early preclinical cardiac involvement in SSc. This impairment in coronary microvasculature is detectable by a non-invasive echocardiographic method and in this study was more common in the diffuse form of SSc.

Unrelated bone marrow transplantation in thalassemia. The experience of the Italian Bone Marrow Transplant Group (GITMO).

BACKGROUND AND OBJECTIVES: Allogeneic bone marrow transplantation (BMT) is a widely accepted therapeutic approach in homozygous beta-thalassemia. However, the majority of patients do not have a genotypically identical donor within the family. This prompted us to conduct a pilot study to investigate the feasibility of matched unrelated bone marrow transplantation in thalassemia. The major drawback was the high risk of immunologic and transplant-related complications, mainly graft-versus-host disease (GvHD) and graft failure. DESIGN AND METHODS: Our aim was to reduce this risk through careful selection of donor/recipient pairs. HLA haplotypes that show a high linkage disequilibrium among their class I, class II and class III alleles are considered extended or ancestral haplotypes. RESULTS: These haplotypes are conserved and can be shared by apparently unrelated individuals. Our study shows that matching for these haplotypes significantly improves the outcome of unrelated bone marrow transplantation in thalassemia. In fact, results were comparable to those obtained in transplants using HLA-identifical family donors. INTERPRETATION AND CONCLUSIONS: Better results were obtained in patients with lesser iron overload and when the donor shared an identity for the DPB1 alleles.

[The role of HLA-B27 molecules in the pathogenesis of ankylosing spondylitis]. / Il ruolo delle molecole HLA-B27 nella patogenesi della spondilite anchilosante.

Ankylosing Spondylitis (AS) is characterised by the strongest association with an HLA antigen ever described for any disease. It represents therefore the ideal model for the understanding of the link between immune-mediated diseases and the HLA system. The role of HLA-B27 in the pathogenesis of AS will be discussed focusing on the recently described higher expression of these molecules in patients with AS compared with healthy controls.

Bleomycin-induced scleroderma: report of a case with a chronic course rather than the typical acute/subacute self-limiting form.

We report a case of bleomycin-induced scleroderma in a 35-year-old woman treated with chemotherapy for Hodgkin's disease. Approximately 6 months after the first chemotherapy cycle, the patient developed skin sclerosis in both arms. The lesion showed no signs of spontaneous clinical amelioration and treatment with steroids was unsuccessful. A partial remission of the skin sclerosis was instead obtained by the administration of D-penicillamine. A family history revealed other cases of autoimmune diseases and HLA typing showed the presence of antigens associated with scleroderma. The association between bleomycin therapy and scleroderma is discussed.

Takayasu's arteritis overlapping with systemic sclerosis.

We describe an unusual case of overlap between Takayasu's arteritis (TA) and systemic sclerosis (SSc). TA has been found in association with several diseases, but not with SSc. To our knowledge this is the first case report of TA associated with SSc in the literature. It is possible that the expression of the two diseases in our patient was influenced by the presence of genetic factors predisposing to both TA and SSc.

Calcitonin decreases lithium plasma levels in man. Preliminary report.

Lithium kinetics were studied in four manic-depressive women treated with calcitonin for post-menopausal osteoporosis. During calcitonin therapy all patients showed a significant decrease of lithium blood levels, and an increase in lithium renal clearance was observed in two out of two patients. According to these data, lithium therapy needs to be adjusted in patients undergoing concomitant treatment with calcitonin.

Tracheo-bronchial mucociliary clearance in patients with primary and secondary Sjögren's syndrome.

We determined the tracheo-bronchial mucociliary clearance (MCC) in order to evaluate a possible impairment of this function in patients affected by Sjögren's syndrome (SS) with or without overt clinical symptoms of xerotrachea. The MCC was expressed as flow rate (mm/min) and studied in 22 non-smoking SS patients (10 pSS and 12 sSS) and in 8 control subjects by specifically adapted ventilation lung scintigraphy (VLS). The MCC in the control group was 5.9 +/- 1.1 mm/min. No values were produced for MCC in 16 SS patients (8 pSS and 8 sSS) in the time interval considered and were reduced in the remaining 6 SS patients (3.3 +/- 1.2 mm/min). In all nine cases with clinical evidence of xerotrachea no values for MCC were obtained. A significant correlation was found between the MCC values and the rate of stimulated salivary excretion determined by dynamic scialoscintigraphy in the same patients (p < 0.001). These preliminary data show that the majority of SS patients studied presented with MCC impairment, always found when clinical symptoms of xerotrachea were present.

Abnormalities of magnetic resonance imaging of the central nervous system in patients with systemic lupus erythematosus correlate with disease severity.

Forty randomly selected patients with systemic lupus erythematosus (SLE) were studied by clinical and serologic parameters and magnetic resonance imaging (MRI). Abnormal MRI was found in 15/40 patients (37.5%): all 15 cases showed multiple widespread small-sized areas of increased signal in T2 in the white matter; in one of these patients MRI also displayed a large area with a reduced signal in T1 and an increased signal in T2 involving both the white and the gray matter. Among the 15 patients with abnormal MRI, only 7 had neuropsychiatric symptoms. The presence of MRI changes was highest in patients with organic type symptoms and was associated to the highest disease severity scores. A long-term follow up of asymptomatic patients would be useful to establish whether the application of MRI is appropriate for the assessment of CNS involvement in SLE.

Prevalence of peripheral arterial occlusive disease and associated risk factors in a sample of southern Sardinian population.

We studied a sample of adult population over 20 years old of Donori (totally 2049 inhabitants), a small town near Cagliari, South Sardinia, to: (1) Evaluate the prevalence of peripheral arterial occlusive disease of lower limbs (PAOD) diagnosed by standard questionnaire and US CW Doppler examination and associated risk factors in South Sardinia. (2) Compare the reliability of these two diagnostic methods. Our study included the answers to a standard anamnestic questionnaire (according to the WHO recommendations), physical examination and CW Doppler study of the lower limb arteries, the determination of the arterial systolic and diastolic pressure, ankle/arm pressure ratio, Body Mass Index, blood glucose, total and HDL-cholesterol, triglycerides and fibrinogen (the hematochemical examination only on 50% of the sample). The surveyed sample was of 577 subjects (37.96% of 1520, the eligible subjects over 20 years old), 237 males and 340 females. An arteriopathy was diagnosed by means of CW Doppler in 27 subjects, 20 M and 7 F. The overall prevalence of PAOD was 4.67% of the sample (2.06% of females, 8.43% of males). Prevalence steadily increased with age, and, surprisingly, the disease was not absent in young people (2 cases within males with age < or = 40 years). Conversely only 18.5% of PAOD patients were symptomatic. The overall prevalence of associated risk factors was: diabetes 3.6%, hypercholesterolaemia 59.1%, smoking 21.3%, arterial hypertension 21.6%, obesity 17.9%, hypertriglyceridaemia 9.3%, hyperfibrinogenaemia 4.67%. Among the males a significant correlation has been found, among the values of BMI vs age and total cholesterol, age vs total cholesterol, systolic blood pressure, diastolic pressure, fibrinogenaemia. Among the females, the systolic and diastolic pressure, BMI, total cholesterol, LDL-cholesterol, triglycerides and fibrinogen are significantly correlated with age; BMI correlates with systolic and diastolic blood pressure, fibrinogen; a nearly significant correlation has been found between BMI and triglycerides.