Search

Background: Risk scores are important tools for the prognostic stratification of pulmonary arterial hypertension (PAH). Their performance and the additional impact of comorbidities across age groups is unknown., Methods: Patients with PAH enrolled from 2001 to 2021 were divided in ≥65 years old vs <65 years old patients. Study outcome was 5-year all-cause mortality. French Pulmonary Hypertension Network (FPHN), FPHN noninvasive, Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) and Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL 2.0) risk scores were calculated and patients categorized at low, intermediate and high risk. Number of comorbidities was calculated., Results: Among 383 patients, 152 (40%) were ≥65 years old. They had more comorbidities (number of comorbidities 2, IQR 1-3, vs 1, IQR 0-2 in <65 years patients). Five-year survival was 63% in ≥65 vs 90% in <65 years. Risk scores correctly discriminated the different classes of risk in the overall cohort and in the older and younger groups. REVEAL 2.0 showed the best accuracy in the total cohort (C-index 0.74, standard error-SE- 0.03) and older (C-index 0.69, SE 0.03) patients, whereas COMPERA 2.0 performed better in younger patients (C-index 0.75, SE 0.08). Number of comorbidities was associated with higher 5-year mortality, and consistently increased the accuracy of risk scores, in younger but not in older patients., Conclusions: Risk scores have similar accuracy in the prognostic stratification of older vs younger PAH patients. REVEAL 2.0 had the best performance in older patients and COMPERA 2.0 had it in younger patients. Comorbidities increased the accuracy of risk scores only in younger patients., (Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Introduction: If properly evaluated, chronic kidney disease can be found in up to 50% of patients with systemic sclerosis (SSc). The renal resistive index (RRI) is a marker of intrarenal vascular resistance and can predict SSc-associated vasculopathy. This study aimed to determine the impact of bosentan, a nonselective endothelin-1 receptor antagonist, on RRI and kidney function in SSc patients with recurrent digital ulcers., Methods: Twenty-one patients (age 57 ± 9 years, 19 females) were recruited in a 16-week prospective open-label uncontrolled study. Standardized procedures were used to measure general clinical and laboratory characteristics, systolic, diastolic, and mean arterial pressure (MAP), pulse pressure (PP), diastolic to systolic blood pressure (D/S) ratio, and urinary endothelin-1 levels. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to calculate kidney function as an estimated glomerular filtration rate (eGFR). RRI was measured by Doppler ultrasound as the average of three samplings of intrarenal blood flow in different kidney regions of both kidneys. Patients with secondary causes of kidney disease or kidney diseases associated with albuminuria were excluded., Results: Bosentan treatment for 16 weeks did not change RRI (0.731 ± 0.049-0.730 ± 0.054, p = 0.925), but increased urine endothelin-1 to creatinine ratio (0.27 ± 0.15-0.49 ± 0.57 pg/mg, p = 0.032) and reduced MAP (123 ± 10-101 ± 11 mm Hg, p &lt; 0.001), PP (76 ± 11-68 ± 10 mm Hg, p = 0.003), D/S ratio (0.563 ± 0.044-0.538 ± 0.031, p = 0.006), and eGFR (92 ± 20-84 ± 24 mL/min/1.73 m2, p = 0.003)., Discussion/conclusion: In conclusion, in patients with SSc complicated by digital ulcers and normal to mildly diminished kidney function, bosentan had no effect on intrarenal hemodynamics, but reduced blood pressure levels and kidney function., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

PURPOSE To evaluate the performance of radiology residents (RRs) when using a dedicated structured report (SR) template for chest HRCT in patients with suspected connective tissue disease-interstitial lung disease (CTD-ILD), compared to the traditional narrative report (NR). METHODS We retrospectively evaluated 50 HRCT exams in patients with suspected CTD-ILD. A chest-devoted radiologist reported all the HRCT exams as the reference standard, pointing out pulmonary fibrosis findings (i.e., honeycombing, traction bronchiectasis, reticulation, and volume loss), presence and pattern of ILD, and possible other diagnoses. We divided four RRs into two groups according to their expertise level. In each group, RRs reported all HRCT examinations alternatively with NR or SR, noting each report's reporting time. The Cohen's Kappa, Wilcoxon, and McNemar tests were used for statistical analysis. RESULTS Regarding the pulmonary fibrosis findings, we found higher agreement between RRs and the reference standard reader when using SR than NR, regardless of their expertise level, except for volume loss.RRs' accuracy for "other diagnosis" was higher when using SR than NR, moving from 0.48 to 0.66 in the novel group (p = 0.035) and from 0.44 to 0.80 in the expertise group (p < 0.001). No differences in accuracy were found between ILD presence and ILD pattern. The reporting time was significantly lower (p = 0.001) when using SR than NR. CONCLUSION SR is of value in increasing the reporting of critical chest HRCT findings in the complex CTD-ILD scenario and should be used early and systematically during the residency.

Leflunomide, an isoxazole derivative, is a disease-modifying antirheumatic drug, that has successfully been used for the treatment of rheumatoid arthritis and psoriatic arthritis as a feasible alternative to methotrexate. Among side effects, pulmonary arterial hypertension (PAH) has been described in a few case reports.We present a 55-year-old woman treated with leflunomide for psoriatic spondyloarthritis who consulted our hospital because of progressive exertional dyspnea. Clinical examination found signs of right heart failure and severe pre-capillary pulmonary hypertension (PH) was diagnosed by right heart catheterization. All investigations for pre-capillary PH were negative and a diagnosis of severe PAH was thus established. Due to previous evidence of the association of leflunomide with PAH, the drug was stopped and upfront dual combination therapy with pulmonary vasodilators was initiated. The patient's condition rapidly improved with significant improvement in exercise tolerance and normalization of echocardiographic right ventricular systolic pressure within three months of treatment., Learning Objective: Pulmonary arterial hypertension (PAH) is a rare disease and drug-induced causes account for only a small percentage of these patients. In recent years, new drugs have been identified or suspected as potential risk factors for PAH. Among these, leflunomide, a disease-modifying antirheumatic drug, has been associated with PAH only in a few case reports. An accurate drug history is strongly recommended for all patients in which a PAH is newly diagnosed., Competing Interests: The authors declare that there are no conflicts of interest and there were no funding sources., (© 2022 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved. All rights reserved.)

The ability of microalgae to preserve viable in coastal sediments as resting forms provides a reservoir of biodiversity and a useful tool to determine species spreadings. This study represents the first port baseline survey on dinoflagellate cysts, investigated in nine Adriatic ports during a cross border project. 40 dinoflagellate taxa were detected. The assemblages resulted in all ports dominated by Lingulodinium polyedra and Alexandrium minutum/affine/tamutum group. General separation to the western and eastern side of the Adriatic regarding cysts assemblage composition, partially abundance, was observed. Six taxa were detected as non-indigenous species for the Adriatic. Two taxa are included in the list of harmful aquatic organisms, indicating the potential threat of ballast waters in the Adriatic. Potential spreading of taxa by general circulation and ballast waters, intra- and extra-Adriatic was investigated. The entering in to force of the ballast waters management regulations should enhance prospects to minimize future harmful impacts., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Neonatal Lupus (NL) is a rare syndrome caused by placental transfer of maternal anti-SSA/Ro and anti-La/SSB autoantibodies to the fetus. The rarity of this condition requires the establishment of multidisciplinary registries in order to improve our knowledge. Method: Inclusion criteria in this retrospective study were the maternal confirmed positivity for anti-SSA/Ro and/or anti-SSB/La antibodies, and the presence of II or III degree congenital heart block (CHB) in utero or neonatal period (up to 27 days after birth). Result: Eighty-nine cases of CHB were observed in 85 women with 88 pregnancies that occurred between 1969 and 2017. CHB was mostly detected in utero (84 cases, 94.2%), while five cases were observed in the neonatal period. A permanent pacemaker was implanted in 51 of 73 children born alive (69.8), whereas global mortality rate was 25.8% (23 cases): 16 in utero , five perinatal, and two during childhood. By univariate analysis, factors associated with fetal death were pleural effusion ( p = 0.005, OR > 100; CI 95% 2.88->100 and hydrops ( p = 0.003, OR = 14.09; CI 95% 2.01-122). Fluorinated steroids (FS) were administered in 71.4% pregnancies, and its use was not associated with better survival. Some centers treated all cases with fluorinated steroids and some centers did not treat any case. CHB was initially incomplete in 24 fetuses, and of them five cases of II degree block reverted to a lower degree block after treatments. Recurrence rate in subsequent pregnancies was 17.6% (3 out of 17). A prophylactic treatment was introduced in 10 of these 16 subsequent (58.8%) pregnancies, mostly with FS or high dose intravenous immunoglobulins. Conclusion: This is the first report from the Italian Registry of neonatal lupus/CHB. The live birth rate was nearly 80%, with nearly two thirds of the children requiring the implantation of a pacemaker. The management of fetuses diagnosed with CHB was heterogeneous across Italian Centers. The registry at present is mainly rheumatological, but involvement of pediatric cardiologists and gynecologists is planned.

Objective: As many inflammatory rheumatic diseases affect patients in childbearing age, some concern has been expressed about the safety of biologic drugs during pregnancy. This study evaluated the effects of anti-tumor necrosis factor alpha (TNFα) agents on pregnancy/foetal outcomes., Methods: Thirty-eight pregnancies were followed prospectively from November 2008 to February 2015. Information about the patients' exposure to anti-TNFα, disease activity, DMARD therapy, pregnancy/foetal outcomes were registered., Results: Twenty-four/38 (71.1%) pregnancies were exposed to anti-TNFα at conception/I trimester, 11/38 (28.9%) prior to conception and 3 (11.1%) following paternal exposure. There were two congenital malformations: one infant (4.2%) was diagnosed with congenital diaphragmatic hernia and obstructive megaureter; the mother was exposed to adalimumab at conception/I trimester. While one foetus (9.1%) showed a trisomy 16, the mother 38 year-old had suspended etanercept 4 weeks before conception. There was no significant difference in pregnancy/foetal outcome between the two groups. Nor were there any significant differences in pregnancy/foetal outcomes in the various groups being treated with different anti-TNFα antagonists. No congenital malformations were found in connection to paternal exposure., Conclusion: Study results suggest that anti-TNFα drugs could be safe when administered during conception/I trimester and following paternal exposure., (Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

The Mar Piccolo is a semi-enclosed basin subject to different natural and anthropogenic stressors. In order to better understand plankton dynamics and preferential carbon pathways within the planktonic trophic web, an integrated approach was adopted for the first time by examining all trophic levels (virioplankton, the heterotrophic and phototrophic fractions of pico-, nano- and microplankton, as well as mesozooplankton). Plankton abundance and biomass were investigated during four surveys in the period 2013-2014. Beside unveiling the dynamics of different plankton groups in the Mar Piccolo, the study revealed that high portion of the plankton carbon (C) pool was constituted by small-sized (<2 μm) planktonic fractions. The prevalence of small-sized species within micro- and mesozooplankton communities was observed as well. The succession of planktonic communities was clearly driven by the seasonality, i.e. by the nutrient availability and physical features of the water column. Our hypothesis is that beside the 'bottom-up' control and the grazing pressure, inferred from the C pools of different plankton groups, the presence of mussel farms in the Mar Piccolo exerts a profound impact on plankton communities, not only due to the important sequestration of the plankton biomass but also by strongly influencing its structure.

The future growing demand of fossil fuels likely will lead to an increased deployment of liquefied natural gas terminals. However, some concerns exist about their possible effects on the marine environment and biota. Such plants showed to cause the production of foam, as occurred at the still operative terminal of Porto Viro (northern Adriatic Sea). Here, we present results from two microcosm experiments focused on the effects of such foam on microbially mediated degradation processes and its consequent incorporation within the pelagic food web. Such material could be considered as a heterogeneous matrix of both living and non-living organic matter, which constitutes an important substrate for exoenzymes as suggested by the faster hydrolytic rates measured in the treatment microcosms. In the second experiment, a quite immediate and efficient carbon transfer to planktonic biomass through prokaryotic incorporation and consequent predation by heterotrophic flagellates was highlighted. Although no negative effect was evidenced on the overall microbes' growth and foam-derived C seemed to be easily reworked and transferred to higher trophic levels, an important reduction in biodiversity was evidenced for microalgae. Among them, mixotrophic organisms seemed to be favoured suggesting that the addition of foam could cause a modification of the microbial community structure.

Previous thrombosis, diagnosis of systemic lupus erythematosus (SLE) and triple antiphospholipid (aPL) antibody positivity have recently been found to be independent factors associated to pregnancy failure during conventional therapy in women with antiphospholipid syndrome (APS). This study aimed to assess the effect of various treatment strategies on pregnancy outcomes in women with APS and the risk factors for pregnancy failure. One hundred ninety-six pregnancies of 156 patients diagnosed with APS were analysed: 118 (60.2%) of these had previous thrombosis, 81 (41.3%) were diagnosed with SLE, and 107 (54.6%) had triple aPL positivity. One hundred seventy-five (89.3%) were treated with conventional therapies (low-dose aspirin [LDA] or prophylactic doses of heparin + LDA or therapeutic doses of heparin + LDA), while 21 (10.7%) were prescribed other treatments in addition to conventional therapy. The pregnancies were classified into seven risk profiles depending on the patients' risk factors - thrombosis, SLE, and triple aPL positivity - and their single, double or triple combinations. It was possible to find significant difference in outcomes correlated to treatments only in the thrombosis plus triple aPL positivity subset, and logistic regression analysis showed that additional treatments were the only independent factor associated to a favourable pregnancy outcome (odds ratio=9.7, 95% confidence interval=1.1-88.9, p-value<0.05). On the basis of this retrospective study, we found that APS pregnant patients with thrombosis and triple aPL positivity treated with additional therapy had a significant higher live-birth rate with respect to those receiving conventional therapy alone.

Objective: To assess fetal and maternal outcomes in women with systemic sclerosis (SSc)., Methods: Prospectively collected data on 99 women with SSc from 25 Italian centers were analyzed retrospectively. Women with SSc were observed during 109 pregnancies (from 2000 to 2011), and outcomes were compared to those in the general obstetric population (total of 3,939 deliveries). The maternal age at conception was a mean ± SD 31.8 ± 5.3 years, and the median disease duration at conception was 60 months (range 2-193 months)., Results: SSc patients, compared to the general obstetric population, had a significantly increased frequency of preterm deliveries (25% versus 12%) and severe preterm deliveries (<34 weeks of gestation) (10% versus 5%), intrauterine growth restriction (6% versus 1%), and babies with very-low birth weight (5% versus 1%). Results of multivariable analysis showed that corticosteroid use was associated with preterm deliveries (odds ratio [OR] 3.63, 95% confidence interval [95% CI] 1.12-11.78), whereas the use of folic acid (OR 0.30, 95% CI 0.10-0.91) and presence of anti-Scl-70 antibodies (OR 0.26, 95% CI 0.08-0.85) were protective. The disease remained stable in most SSc patients, but there were 4 cases of progression of disease within 1 year from delivery, all in anti-Scl-70 antibody-positive women, 3 of whom had a disease duration of <3 years., Conclusion: Women with SSc can have successful pregnancies, but they have a higher-than-normal risk of preterm delivery, intrauterine growth restriction, and babies with very-low birth weight. Progression of the disease during or after pregnancy is rare, but possible. High-risk multidisciplinary management should be standard for these patients, and pregnancy should be avoided in women with severe organ damage and postponed in women with SSc of recent onset, particularly if the patient is positive for anti-Scl-70 antibodies., (Copyright © 2012 by the American College of Rheumatology.)

TNF-alpha is thought to play a pivotal role in the initiation and perpetuation of the chronic inflammatory process in rheumatoid arthritis. TNF-alpha blockers such as infliximab and etanercept are currently used in the treatment of active rheumatoid arthritis (RA) when traditional DMARDs have failed and are effective in a significant proportion of patients. However, about one third are non-responders to anti-TNF-alpha. The aim of this study was to verify whether rheumatoid patients, after failing infliximab, can benefit from etanercept. We analysed 18 patients with active RA with no response to at least 3 DMARDs and where infliximab therapy had failed. The patients had received infliximab associated with methotrexate: eleven of them did not show any significant response, while seven patients, after a good response, relapsed. Etanercept was then started. EULAR criteria of response were used with calculation of activity index DAS28 at baseline, after 2 weeks, 3 months and every third month until last follow-up. A moderate or good response was achieved with etanercept in 13 out of 18 patients. From our experience, etanercept can be considered as a good alternative choice when infliximab has failed.

Objective: To analyze tumor necrosis factor-alpha (TNF-alpha) synthesis by mononuclear cells stimulated with lipopolysaccharide (LPS) in patients with rheumatoid arthritis (RA)., Methods: TNF-alpha molecular expression and extracellular release were assessed in the peripheral blood mononuclear cells (PBMC) of 27 RA patients and 16 healthy blood donor controls during 8 hours of LPS stimulation. We also analyzed the mRNA expression of tristetraprolin (TTP), the major TNF-alpha mRNA destabilizing factor. TNF receptor p75 (TNFR 2) plasma concentrations were also tested in all patients., Results: Controls and patients demonstrated a comparable wide range of TNF-alpha release capability, but patients achieved the peak value of protein release more quickly. Defining the median TNF-alpha release in controls as the cutoff value to distinguish high and low LPS-induced TNF-alpha-releasing phenotypes, patients with early RA (disease duration < 1 yr) belonged mainly to the low TNF-alpha producer subgroup, whereas patients with long-standing RA (> 1 yr) were prevalently high TNF-alpha producers. TTP molecular expression was higher in patients with shorter, than in patients with longer, disease duration. The profile of TNF-alpha release in patients with early RA changed significantly when retested after 6 months of therapy, while patients with long-standing disease maintained the same behavior as at baseline. Finally, a baseline low TNF-alpha-producer phenotype predisposed to a better responsiveness to disease modifying antirheumatic drugs., Conclusion: The LPS-induced TNF-alpha-releasing phenotype differs between cells obtained from RA patients with different disease durations and seems to influence the therapeutic outcome.

Objective: To assess the agreement between presence and location of central nervous system (CNS) structural damage and neuropsychological performance., Methods: 21 unselected SLE patients underwent a 3 hours-long battery of neuropsychological tests sampling 15 cognitive functions. A neuropsychologist hypothesized for each SLE patient the most likely site of possible involvement, according to the neuropsychological performance. Patients underwent MRI scans within 6 months (3 months before or after) from neuropsychological tests and SPECT., Results: 14 of the 21 SLE patients (66.6%) were impaired in at least 1 function; among these, 7 patients (33.3%) were mildly impaired and 7 (33.3%) had more than 3 functions impaired. 10 patients (48%) had abnormal MRI scan. Negative and positive agreements between neuropsychological performance and MRI scan were detected in 15 patients (71%; ?2 with Yates' correction 6.09, p 0.007, measure K for concordance 0.44, p 0.03). All the 6 negative agreements had no records of major neurologic or psychiatric events; among the 9 positive agreements, 6 presented previous major neurologic events and 2 minor neuropsychiatric symptoms. Among the subjects with disagreement, 1 was unimpaired with positive MRI and without neuropsychiatric symptoms, 5 were mildly impaired with negative MRI., Conclusions: A detailed neuropsychological evaluation along with MRI arose as a valid method to exclude or to identify, localize and clinically interpret CNS involvement in SLE. Disagreement between MRI and neuropsychological tests was detected mainly for mild cognitive impairment that might be the expression of functional (inflammatory or ischemic) processes.

Objective: To define the frequency of the exon 6 tumor necrosis factor-alpha (TNF-alpha) receptor II (TNFRII) gene polymorphism in severe and mild-moderate rheumatoid arthritis (RA) and its possible influence on anti-TNF-alpha treatment responsiveness., Methods: Two cohorts of patients with RA, the first (n = 97) defined as methotrexate responders (MTX-R) with mild-moderate synovitis, and the second (n = 78) defined as nonresponders to combination therapy and receiving anti-TNF-alpha treatment because of their severe and aggressive disease (TNF-T), were studied retrospectively and compared to age, sex, and ethnically matched controls (n = 84). In the prospective study, 66 patients with severe RA were followed over the first 6 months of anti-TNF-alpha therapy and their response was examined according to genotype., Results: We observed a trend towards an increased frequency of the GG genotype in patients with severe RA (6.4%) in comparison with patients with mild-moderate disease (3.1%) and controls (1.2%). When looking at the response to anti-TNF-alpha therapy, we observed that after 12 weeks of treatment, 37.8% of the TT versus 10.7% of the TG/GG patients passed from high to medium-low disease activity (p = 0.03)., Conclusion: In our cohorts of patients selected by response to the conventional therapy and by disease severity, our preliminary study results showed a trend towards a higher prevalence of the GG genotype for the exon 6 TNFRII polymorphism in the less responsive patients with more aggressive disease. We also found a lower degree of response to anti-TNF-alpha treatments in patients carrying the G allele.

Objectives: To study -238 and +489 TNF-alpha polymorphisms in severe-unresponsive (more than 6 swollen joints and still active disease despite at least 6 months of DMARDs combination therapy) and mild-responsive (less than 3 swollen joints and good response to MTX or other conventional DMARDs) rheumatoid arthritis (RA)., Methods: We investigated 100 RA patients (56 with severe and 44 with mild disease activity) and 45 healthy blood donors (HBDs). Genotyping was performed by PCR-restriction fragment length polymorphism procedure. Several clinical and serological parameters were also examined., Results: Severe RA patients disclosed the -238 GG genotype in 100% of the cases versus 95.5% in the mild-responsive patients and 91.2% in the HBDs. The +489 GG genotype disclosed only a trend towards a prevalence in severe RA patients. However the +489 A allele seems to associates with early onset, longer disease duration and longer responsiveness to conventional therapy., Conclusion: The -238 AG genotype is absent in severe-unresponsive RA, but present in mild-responsive RA subjects. Thus -238 GG homozygosity associates with severity and unresponsiveness. In contrast the +489 polymorphism does not segregate differently between responsive and unresponsive RA patients.

Objective: To examine whether severe rheumatoid arthritis (RA) carries a -238 or +489 tumor necrosis factor-alpha (TNF-alpha) genotype different from mild-moderate RA., Methods: We investigated 163 patients (66 with severe disease) and 67 healthy blood donor controls. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism., Results: Patients with severe RA (all active disease despite disease modifying antirheumatic drug combination therapy) disclosed the -238 GG genotype in 100% of cases versus 92.8% of the mild-moderates and 92.5% of controls (OR 11.7, Cl 0.6-216, p = 0.03). The +489 AA genotype was seen less often in patients than in controls (OR 4.2. CI 0.97-18.4, p = 0.045), and the contribution to this trend appeared predominant in the anti-TNF treated subgroup., Conclusion: The -238 AG genotype was absent in severe RA; in contrast, patients with mild-moderate RA disclosed the same frequency as controls. Thus -238 GG homozygosity is associated with severe RA. The +489 AA genotype might instead protect against worse outcome in RA.

The therapeutic approach to polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) remains mainly based on corticosteroids. A few studies in PMR suggest a steroid-sparing effect with methotrexate in a subset of patients. No real alternative to steroids exists in GCA. Given the high chance of long-term treatment with corticosteroids in both diseases, randomized controlled trials with new immunosuppressive steroid-sparing drugs are eagerly awaited.

Objective: To assess longitudinally over a 12 month period circulating serum levels of interleukin 10 (IL-10) and cytokines IL-3, IL-4, IL-6, and IL-12 in a cohort of patients with early onset rheumatoid arthritis (RA) treated with either cyclosporin A (CyA) or with combination therapy of CyA plus hydroxychloroquine as disease modifying antirheumatic drugs., Methods: We studied 8 patients receiving CyA and 12 patients receiving CyA plus hydroxychloroquine. IL-3, IL-4, IL-6, IL-10, and IL-12 were determined by ELISA at entry, after 2 weeks, after one month, after 6 months, and after 12 months. Rheumatoid factor levels and the possible appearance of monoclonal gammopathies over time were studied by immunofixation and immunoblotting techniques., Results: The pooled data show that at entry only the median baseline levels of IL-10 (3.9 vs 1.6 pg/ml; p < 0.01) and IL-6 (16.9 vs 1.4 pg/ml, p < 0.001) were higher in patients than in controls. IL-4 was not detectable. Some patients at entry (those with the longest disease duration) had detectable levels of IL-3. Only levels of IL-10 decreased significantly between entry and final values, in monotherapy and combination therapy as well. A single transient monoclonal band was observed after 6 months of treatment, which disappeared afterwards. No difference was seen in any of the cytokines between the CyA and the CyA plus hydroxychloroquine treated patients., Conclusion: During treatment with either CyA or CyA plus hydroxychloroquine, IL-10 levels decreased significantly. No additive effect of the 2 drugs was detected.

The actual efficacy and applicability of high dose intravenous immunoglobulin (IVIG) therapy in the rheumatic disorders is still being debated. In the last few years clinical results have become available on a large number of patients, and efforts have been devoted to experimental studies of the mechanism of action of IVIG. However, the results of controlled clinical trials will be crucial to indicate stricter guidelines and directions for future clinical and experimental research. IVIG is of major value in Kawasaki disease and in severe lupus-associated thrombocytopenia. Its possible benefits are also remarkable in refractory dermatomyositis and probably in some patients with the antiphospholipid syndrome and recurrent miscarriages despite standard treatment. At present, the role of IVIG therapy remains controversial in lupus nephritis and in systemic vasculitis, while it does not seem to be effective in rheumatoid arthritis.

Hyperadrenergic orthostatic hypotension was diagnosed in a 27-year-old man because of recurrent episodes of hypotension associated with high plasma noradrenaline levels. In this patient, laboratory tests were performed to evaluate autonomic nervous system function. Decreased response to Valsalva maneuver and carotid sinus massage indicated decreased baroreflex and vagal responsiveness, respectively. Cardiovascular response to the handgrip was reduced in comparison to controls. Passive leg raise showed normal reduction of plasma norepinephrine, indicating normal responsiveness of cardiopulmonary receptors. 'Non-dipper' profile in the ambulatory blood pressure monitoring provided further evidence for an impaired autonomic control of cardiovascular function in this patient. This report suggests the presence of autonomic dysfunction in hyperadrenergic orthostatic hypotension.