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Immunosuppressive drugs given during pregnancy to mothers suffering from a systemic autoimmune disease (AID) can cross the placenta, thus being potentially able to affect the offspring immune system. Aim of our study was to evaluate the in vivo immune function of a series of these newborns. Twenty-two babies born from mothers suffering from autoimmune diseases (AID) who had been taking immunosuppressive drugs during pregnancy were evaluated for their response to vaccination with C. Tetani toxoid. Six babies born from mothers receiving low-dose aspirin only were used as controls. The immune response to C. Tetani vaccination was evaluated with an ELISA to detect circulating antibodies. Five children out of 28 (17%) did not achieve a protective titer of anti C. Tetanitoxoid IgG. No clear relationship was found between specific drug exposure and antibody response. Our findings suggest that maternal immunosuppressive treatment given for a systemic AID can affect the response to an active immunization, without specificities for drug types used.

The number of patients affected by systemic lupus erythematosus (SLE) that decide to have children has greatly increased probably because of recent improvements in the diagnosis and management of the disease. This has stimulated our interest in defining the outcome of children, focusing both on neonatal problems and long term development. SLE patients still carry a risk of pregnancy loss. However, due to careful monitoring and treatment by a multidisciplinary team, the number of losses has dramatically decreased, but an increased number of preterm deliveries is still a problem. Neonatal lupus is linked to the presence of anti-Ro/SS-A and anti-La/SS-B antibodies in the mother, although other factors probably of fetal origin are important. Neonatal lupus is a complex condition whose most serious manifestation is the congenital heart block (CHB). Usually, children with complete CHB need permanent pacing, but apparently do not have neuropsychological problems. Studies focusing on the neuropsychological development of SLE offspring show an increased number of learning disabilities in children with normal intelligence levels. Fetal consequence of maternal treatment need to be considered choosing non teratogenic drugs, but the withdrawal of medications just because the patient is pregnant should be avoided to avoid SLE flares.

Few data are available to assess the efficacy of rehabilitative interventions in systemic sclerosis (SSc). We refer here the results of an individualized rehabilitation program in 16 patients with SSc. In particular, when possible, the number of patients who achieved a minimal clinically important difference (MCID) was determined. Results were evaluated taking advantage of the development of validated questionnaires and tests to assess quality of life (QOL) and disability in SSc. At the end of a period of 4 months of observation, 69% and 62% of patients reported an improvement of the physical and mental components of the SF-36 higher than the MCID (as established in other rheumatic conditions). Analogously, an improvement of the impact of respiratory disease on patients’ QOL, as assessed by the Saint George’s Respiratory Questionnaire, was perceived by 67% of them. These results might be explained by better exercise tolerance, which was suggested by the significant reduction of the heart rate and of a visual analogue scale for dyspnoea at the end of the 6-min walking test. Finally, a statistically significant improvement of hand mobility, as assessed by the hand mobility in scleroderma test was obtained. This study suggests that a significant proportion of patients with SSc experience an improvement in their perception of QOL, a better exercise tolerance, and a better hand mobility after a rehabilitation program consisting by a 2-week period of daily individual 30-min sessions as outpatient, followed by at-home exercise program.

To evaluate the prevalence of patients with Systemic Sclerosis (SSc) in Valtrompia in northern Italy.Patients were recruited from the records of 28 general practitioners (GPs) whose practices covered 38,348 individuals aged over 14 years, and from a public Hospital database covering all patients evaluated in community clinics, day-hospitals and inpatient units of the area. Crossing data from the two sources revealed a 100% concordance. Rheumatological re-evaluation confirmed a diagnosis of SSc in 13 patients (11 female, 2 male; 2 diffuse SSc, 11 limited SSc), fulfilling ACR criteria in 10 cases and Le-Roy-Medsger 2001 criteria in 3 further cases.Prevalence of SSc was estimated at 33.9 cases among 100,000 adults aged over 14 years (95% confidence intervals: 15.5-52.3).This rather high prevalence reflects both changes in the diagnostic criteria for SSc including milder forms of disease, and recruitment of these mild cases due to active collaboration between GPs and specialists.

To evaluate the role of iloprost, a derivative of prostacyclin, as a possible disease-modifying agent for systemic sclerosis (SSc).Fifty-six consecutive SSc patients treated for a median period of 4 years with cyclic infusions of iloprost for severe Raynaud's phenomenon and ischemic ulcers were compared with 56 control patients matched for age, sex, disease subset and duration. Control patients were also similar to the iloprost group with regard to autoantibody status, the presence of major disease-related organ manifestations at baseline, and the use of other treatments. The evolution of lung function test results, the frequency of major disease-specific complications and the survival of the cohorts were the objects of this analysis.No significant difference was observed between the two groups with regard to changes in lung function tests over time, or the number of patients who presented with the onset of active interstitial lung disease, pulmonary arterial hypertension or scleroderma renal crisis. Survival did not differ between the two groups.The evolution of lung function test results, the frequency of major disease-specific complications, and survival did not differ significantly between SSc patients treated with cyclic iloprost and a group of patients matched for sex, age, and disease subset and duration. However, no cases of severe pulmonary arterial hypertension were observed in the patients treated with iloprost, suggesting that studies focusing on the possible preventive action of iloprost on the progression of SSc- associated mild pulmonary arterial hypertension would be warranted.

Autoimmune diseases (AD) occur frequently in women during their childbearing years and may influence pregnancy outcome and neonatal health. Patients with systemic lupus erythematosus (SLE) can experience a disease flare-up during pregnancy with potential negative effects on the product of conceptus, especially if the disease is active. Recurrent pregnancy loss is now considered as a treatable clinical condition associated with the presence of circulating antiphospholipid antibodies (aPL). The neonatal lupus syndromes (NLS), caused by the transplacental passage of maternal IgG anti-Ro/SS-A and anti-La/SS-B antibodies to the fetus, carry significant morbidity and mortality in case of cardiac manifestations. Immunosuppressive agents are often administered during pregnancy in order to control maternal disease and to ensure a better pregnancy outcome. Nowadays, owing to our increasing knowledge of the disease pathophysiological mechanisms and the development of combined medical-obstetric clinics, pregnancy outcome in patients with AD has notably improved.

The objectives of the study were to characterize the production, function and survival of T lymphocytes of children with prolonged fetal exposure to dexamethasone for anti-Ro/SS-A antibodies associated congenital complete heart block. The analysis of thymic function, studied by measuring the level of T-cell receptor excision circles, was performed by real time PCR, the composition of T-cell subpopulation was evaluated by flow cytometry and the T-cell diversity was assayed by heteroduplex analysis. T-cell competence was gauged at two functional levels by determining the proliferation and the number of T-cell divisions and by measuring γ-interferon production after mitogenic stimulation. We observed that the thymic output, distribution of T-cell subsets, thymidine incorporation, number of T-cell divisions, and γ-interferon production were comparable to those of age-matched control. On the contrary, heteroduplex analysis demonstrated the presence of both polyclonal and oligoclonal peripheral T-cell repertoires.In conclusion, the analysis of the T-cell compartment in children with prolonged intrauterine exposure to high dose dexamethasone did not disclose any relevant abnormality, except a restriction of T-cell receptor diversity in some patients.

Objective: To analyse clinical efficacy, onset of new autoantibodies or symptoms of autoimmune disease in patients affected by rheumatoid arthritis with anti-Ro/SSA treated with anti-TNFa agents. Methods: Six anti-Ro/SSA positive subjects with RA were studied every six months until 24th month of treatment in order to detect ANA titer (IFI), anti-dsDNA (Farr), anti-cardiolipin and anti-beta2glycoprotein I (ELISA), anti-ENA (CIE). The titre of anti-Ro/SSA were analysed by ELISA. Four patients were diagnosed as overlap RA/SS. Results: Six female patients (mean age 58ys, SD 9.8ys), with long-standing RA (mean 7ys, range 5-22 ys) were treated with anti-TNFa agents for a mean of 31 months (SD: 20.4 m): 4 with Infliximab and 2 with Etanercept. All the patients showed a significant reduction of DAS until 24th month (p

The objective of this study was to analyse clinical and serological associations of anti-Ki antibodies. Thirty-five patients with anti-Ki antibodies, detected by CIE, selected from laboratory routine, were studied. All patients were affected by autoimmune diseases: SLE and pSS were the most frequent diagnoses. The cohort was constituted by 27 female and eight males. Main clinical features were skin involvement (60%), xerophtalmia (48.6%), Raynaud’s phenomenon (43%), photosensitivity (34%), xerostomia (31.4%). CNS involvement was present in four (11.4%) and renal disease in seven cases (20%). ANA, anti-dsDNA and RF were detected in 100%, 60% and 34.5%. In SLE, anti-Ki was detected in 6% of cases, more frequently in males compared to other SLE patients without anti-Ki ( P < 0.004). Nineteen anti-Ki positive patients affected by SLE showed more frequently malar rash and multiple autoantibody specificities compared to 16 anti-Ki positive patients with other diseases ( P = 0.044 and P = 0.0003, respectively). Our study confirms a preferential occurrence of anti-Ki antibodies in patients with sicca and skin involvement. Malar rash and multiple ANA specificities were significantly associated with SLE compared to other diseases in our study. Anti-Ki were detected in 6% of patients with SLE with a significant prevalence in males.

The aim of this study was to evaluate health-related quality of life (HR-QOL) in patients with systemic sclerosis (SSc), to compare it with that of patients with rheumatoid arthritis (RA), and to correlate it with other parameters. HR-QOL was evaluated by the Short Form 36 (SF-36), SSc disease activity and severity by preliminary indexes recently proposed, disability by the Health Assessment Questionnaire (HAQ), and depressive symptoms by the Beck Depression Inventory. HR-QOL perception was not statistically different in patients with SSc and RA, except that patients with diffuse cutaneous involvement had worse scores in the general health and mental health dimensions than patients with RA (p=0.03). Compared with RA, patients with SSc tended to perceive less bodily pain (p=0.06) and have less disability (p=0.04) but to report higher depressive symptom scores (p=0.05). SSc patients' HR-QOL was associated with some disease severity scales (general, kidney and, less significantly, heart), but it was poorly correlated with the other evaluated disease activity and severity indexes. A strong correlation with disability and with depressive symptoms was observed. In conclusion, patients with SSc perceived a reduced HR-QOL similar to that of patients with RA. SF-36 may provide useful information in their evaluation.

The objective of this study was to evaluate the oesophageal dysfunction in patients with "early" systemic sclerosis (SSc), as defined by LeRoy and Medsger, to compare it with that of patients with definite SSc, and to correlate it with other features of the disease. Oesophageal manometry results were retrospectively evaluated in 181 patients classified by the 2001 LeRoy and Medsger criteria and the 1980 American College of Rheumatology (ACR) criteria: group 1: limited SSc: Raynaud's phenomenon plus specific nailfold capillaroscopy abnormalities and/or autoantibodies; group 2: limited cutaneous SSc not satisfying the ACR criteria (lcSSc ACR-); group 3: lcSSc ACR+; group 4: diffuse cutaneous SSc. Peristaltic abnormalities in the oesophageal body were present in 73 of 125 patients with SSc ACR+ (groups 3 and 4) compared with 13 of 56 with SSc ACR- (groups 1 and 2) (p0.0001). They were more severe in patients with more advanced disease (1 vs 2; 1 vs 3; 1 vs 4; 2 vs 4; p0.05) and in patients anti-Scl-70+ than in patients anticentromere positive (p = 0.02). Abnormalities of the lower oesophageal sphincter (LES) were present in 35 of 125 patients with SSc ACR+ and 11 of 56 with SSc ACR- (not statistically different). They were correlated with forced vital capacity (FVC) (LES pressure: p = 0.0005; LES length: p = 0.0004). Abnormalities of the oesophageal body and of the LES were found in 21 and 16% of 46 patients without oesophageal symptoms. Oesophageal manometry can detect abnormalities in a sizeable proportion of patients with "early SSc" not fulfilling the ACR criteria, including asymptomatic patients. The correlation between LES abnormalities and FVC suggests a possible causal relationship between these disease manifestations.

Oral cyclophosphamide (CYC) is a promising therapy for Systemic Sclerosis (SSc)-related interstitial lung disease (ILD). The use of intravenous (i.v.) pulses has been considered as an alternative route of drug administration, possibly associated with reduced toxicity. Our objectives were to re-evaluate our experience with i.v. CYC, to review the literature, and to pool our results with those available from other groups, improving the statistical power of the analysis.1) Retrospective analysis of our center experience on 16 patients with SSc and active alveolitis, treated with i.v. CYC 750 mg + 6-methylprednisolone 125 mg every 3 weeks. 2) Pooled analysis of papers published in peer-reviewed journals reporting detailed data on each patient treated with i.v. CYC. The end-point was modification in the results of lung function tests (LFT) after 6 months. Piecewise regression analysis was performed using a linear mixed-effects model adjusted for baseline values to evaluate the changes in LFT.Retrospective analysis. In the period before therapy there was a significant deterioration in FVC (in 6 months: -4.3%; p=0.0009) and DLCO (-2.1%; p=0.018). After 6 months of treatment there was a modest improvement in the FVC (+2.7% p=0.08) and DLCO (+2.2%; p=0.08). Pooled analysis. In 53 evaluable patients, the improvement in LFT reached conventional statistical significance (FVC: +2.85%; 95% confidence intervals: +0.04, +5.66%; p=0.04. DLCO: +4.4%; 95% confidence intervals: +1.2%, +7.5%; p0.001).i.v. CYC for 6 months can achieve a small, but significant improvement of LFT in patients with SSc and active alveolitis.

To verify the neuropsychological development in the offspring of patients with systemic lupus erythematosus (SLE), 47 children (23 male and 24 female) from affected women were studied. The tests applied were related to the children’s ages: Griffiths scale up to four years, WPPSI and metaphonological tests (MP, evaluating the phonological consciousness) from four to six years of age, WISC-R test and Rey test (evaluating the visual-space abilities) from six years onwards; finally, specific tests for the diagnosis of learning disabilities (LD) between the ages of seven and 13. Intelligence levels were always normal (mean IQ score 106.32; median 104; SD 9.05). Three out of eight examined children failed MP, therefore may develop LD and will need further evaluation later. Fourteen children were specifically studied for LD and three reported scores lower than normal, but only two (who were brothers) were defined dyslexic. Antiphospholipid antibodies (aPL) were positive in the mothers of the three children with impaired LD tests. Other maternal autoantibodies or drugs administered during pregnancy did not seem to be related to LD. In conclusion, maternal SLE does not impair intelligence levels, but may increase the occurrence of LD particularly in male children (2/8 males examined, 25%). Both maternal aPL and genetic background may have pathogenetic implications. Lupus (2004) 13, 805–811.

Patients with systemic sclerosis (SSc) may have arterial and venous thrombosis and, according to the limited and controversial data available, may have an increased incidence of pregnancy losses.1 These observations preceded the definition of antiphospholipid syndrome (APS) as the association of thrombosis and pregnancy loss with antiphospholipid antibodies (aPL), and did not focus on patients with SSc. However, the association of thrombosis and aPL, detected as lupus anticoagulant (LAC) and/or anticardiolipin antibodies (aCL), although rare, was described in SSc,2 supporting the possible existence of a “secondary” APS in SSc.3 In view of the fact that most aCL are directed to β2 glycoprotein I (aβ2GPI),4 the possibility that patients with APS may be negative for aCL, but positive for aβ2GPI,5 and considering the scarcity …

Starting from their first description, antiphospholipid antibodies (aPL) were associated with repeated miscarriages and fetal losses. Other complications of pregnancy like preterm birth,with pre-eclampsia or severe placental insufficiency were also frequently reported and are included in the current classification criteria of the antiphospholipid syndrome (APS). The titre, the isotype of the antibodies or their antigen specificity may be important in the risk level determination. Some of the difference in the reported results can be explained by the poor standardization achieved in aPL testing or by the not univocal classification of pregnancy complications. The pathogenesis of pregnancy failures is linked to the thrombophilic effect of aPL but also to different mechanisms including a direct effect of antibodies on the throphoblast differentiation and invasion. The study of experimental animal models provided sound evidence of the pathogenic role of aPL both in lupus prone and naive mice. The definition of APS as a condition linked to high obstetric risk and the application of an effective therapy have completely changed the prognosis of pregnancy in these patients. In fact, despite the high number of complications and preterm delivery, today a successful outcome can be achieved in the large majority of the cases.

Iloprost is useful in the short-term treatment of severe Raynaud's phenomenon and ischaemic ulcers in patients with systemic sclerosis (SSc), but its long-term effects are largely unknown. The aim of this study was to report long-term outcome (median follow-up 36 months) in a prospective observational study of a cohort of 30 consecutive patients with SSc who received iloprost therapy with maintenance infusions every 3 weeks after an initial cycle of 5 consecutive days. At the end of the observation, compared to the pretreatment point, we observed complete healing of digital ulcers in 19/21 patients (90%), a decrease of the Raynaud's phenomenon visual analogue score from 10/10 (25th-75th percentile 7-10) to 5/10 (4-6.75) ( P0.001) and, in patients with diffuse cutaneous involvement, of the modified Rodnan skin thickness score from 25.5 (16.5-31.5) to 16 (13.5-20) ( P = 0.02), minimal improvement of the Health Assessment Questionnaire from 0.87 (0.68-1.37) to 0.75 (0.62-1.25), which was neither statistically nor clinically significant. The forced vital capacity was not significantly changed, but the diffusion capacity corrected for the alveolar volume decreased from 71% (54-76.7) of the expected value to 62% (51.5-71) ( P = 0.02). In one patient with limited SSc a positive effect on pulmonary hypertension was observed. Six patients, after a median of 25 months of treatment and healing of digital ulcers, discontinued the therapy; after a median of 10 months ulcers did not recur in five of these six. Other reasons for discontinuation were: tolerability (1), disease progression (normotensive renal crisis: 1), and death due to intracranial haemorrhage (1). This same patient had previously suffered a central retinal vein thrombosis. In conclusion, long-term therapy with iloprost in patients with SSc has a durable effectiveness on ischaemic ulcers and Raynaud's phenomenon, but it is not possible to conclude that the natural history of the disease was modified.

This paper describes a simple model of a beam charging experiment. The motivation for the model is the need to understand low voltage breakdown such as that which occurs in dielectric material exposed to the radiation environment of space [1]. Our approach to the problem is motivated by the work of O'Dwyer [2] on high voltage breakdown.

Le syndrome d'agenesie du vernis cerebelleux de Marie Joubert avec episodes d'hyperpnee, mouvements oculaires anormaux, ataxie, arrieration motrice et mentale a ete decrit en 1969. En 1980 l'association a un colobome chorio-retinien bilateral typique etait signale par Lindhout. Une nouvelle fois cette association a ete observee chez un garcon de 3 mois et la presence d'une malformation rare dans 2 cas d'une maladie genetique (vraisemblablement autosomique recessive d'apres les 15 cas familiaux publies) pourrait ne pas etre due au hasard