Biomedical subjects
Publications and source records attributed to Paola Caramaschi.
The authors describe a young patient affected by long-standing polymyositis refractory to conventional treatment who showed a rapid and striking response to mycophenolate mofetil treatment.
To evaluate ANA specificity using the fully automated multiplexed fluorescent microsphere immunoassay in patients affected either by rheumatoid arthritis or ankylosing spondylitis who developed strong positivity for ANA as assessed by indirect immunofluorescent method on HEp-2 cells during infliximab treatment. Three men affected by ankylosing spondylitis and 12 women affected by rheumatoid arthritis who developed ANA positivity at high titres during infliximab treatment underwent the identification of ANA specificity by multiplexed fluorescent microsphere immunoassay; moreover anti-DNA and anti-ENA antibodies were tested by indirect immunofluorescence and ELISA method, respectively. In 4 out of 15 cases, the determination of ANA reactivity by multiplexed fluorescent microsphere immunoassay was also performed on the serum collected before infliximab administration. One patient affected by rheumatoid arthritis showed multiple ANA reactivities against SS-A, SS-B, RNP, Sm, Jo-1 and histones; one patient affected by ankylosing spondylitis resulted positive for the same autoantibodies, except for anti-Sm antibody. Moreover, two patients, one with rheumatoid arthritis and one with ankylosing spondylitis, showed single antibody specificity to SS-B and RNP, respectively. The remaining 11 cases did not show any positivity. Instead, all the patients resulted negative for anti-ENA antibodies by the ELISA method. In the four cases tested for ANA specificity by multiplexed fluorescent microsphere immunoassay before and after infliximab administration no difference was found. The search for anti-DNA antibody always resulted negative by both the traditional immunofluorescent assay and the novel technique. The use of multiplexed fluorescent microsphere immunoassay in patients treated with infliximab with ANA positivity at high titres allowed to find some ANA specificities which were not revealed by ELISA method. Nevertheless, the majority of patients resulted negative in spite of ANA positivity at high titres; the molecular target of ANA which develop after infliximab administration still remains to be identified.
The aim of the study is to investigate the relationship between microangiopathy as assessed by nailfold videocapillaroscopy (NVC) and plasma level of homocysteine (Hcy) in systemic sclerosis (SSc). As known, Hcy is a nonessential amino acid that interferes with normal properties of a vascular tree. Sixty patients affected by SSc (4 men and 56 women, mean age 54.6) underwent the determination of plasma Hcy level; at the same time, NVC was performed. Hcy level was also determined in 30 sex- and age-matched controls. In patients affected by SSc the plasma Hcy level was significantly higher than in healthy controls (11.8 and 6.5 micromol/l, respectively; p < 0.001). A significant correlation was found between plasma Hcy concentration and the pattern of NVC with a progressive increase from early to active and above all to late pattern (10.7, 11.8, and 17.4 micromol/l, respectively; p < 0.001). Subjects with high Hcy level (i.e., >75th percentile of Hcy level in controls and in patients considered altogether) were mostly represented in the scleroderma patients with late nailfold videocapillaroscopic pattern; the crude odds ratio was 9.0 (significant; 95% CI from 2.1 to 38.8). In conclusion, Hcy plasma level is related to microvascular involvement in patients affected by SSc; the concentration increases with the progression of the nailfold videocapillaroscopic pattern. Hyperhomocysteinemia may represent an aggravating factor among the complex mechanisms involved in scleroderma damage contributing to the injury of endothelium.
The objective of this study was to present our clinical experience about scleroderma-related pulmonary hypertension in the patients treated with intermittent iloprost infusions. Eighty-one patients affected by systemic sclerosis (12 men, 69 women; 30 with diffuse pattern and 51 with limited pattern; mean age 55.1 years; mean duration of disease 105.3 months) have been treated with cyclic iloprost infusions for at least 15 months (range 15-126 months). During the last 4 months all patients underwent Doppler echocardiography in order to estimate the value of systolic pulmonary artery pressure. In 14 subjects (17.2%) systolic pulmonary artery pressure was = or > 35 mmHg. Four patients presented high systolic pulmonary artery pressure associated with pulmonary fibrosis (mean value 40.5 +/- 4.5 mmHg). Ten women (one with diffuse pattern of disease and nine with limited form) showed isolated high systolic pulmonary artery pressure; one of these patients underwent right heart catheterization which resulted normal. The remaining nine patients (mean age of 67.1 years; age at the onset of scleroderma 52.2 years) showed estimated systolic pulmonary artery pressure values between 35 and 50 mmHg. Among these patients affected by isolated pulmonary hypertension only one has been receiving bosentan in association with iloprost infusions. None of our scleroderma patients treated with cyclic iloprost infusions developed severe isolated pulmonary hypertension. In systemic sclerosis the multiple effects of iloprost on endothelium, platelets and cytokine network may counteract the vasospastic profile of lung microvasculature in pulmonary arterial hypertension and the consequent vascular wall remodelling, thus preventing the development of severe illness.
To evaluate the coexistence of additional autoimmune disease in a population of patients suffering from systemic sclerosis. The record-charts of 118 Italian patients affected by systemic sclerosis (12 men, 106 women, mean age of 57.2 years, mean duration of disease 8.7 years) followed by a single centre were reviewed; any other diagnose of autoimmune disease the patient was given was recorded. Thirty-eight scleroderma patients (32.2%) were affected by one or two concomitant autoimmune diseases, for a total of 42 diagnoses. The most represented associated autoimmune diseases were autoimmune thyroiditis (17 cases) and primary Sjögren's syndrome (10 cases). Both pulmonary fibrosis as diagnosed by chest X-ray and the extension of skin involvement evaluated by Rodnan total skin score were not correlated with an increased incidence of an additional autoimmune disorder. Our study shows that approximately one third of patients affected by systemic sclerosis developed one or more additional autoimmune diseases. Therefore patients with systemic sclerosis should be carefully evaluated both at onset and during the follow-up for the possible coexistence of other autoimmune disorders.
OBJECTIVES: Myocardial involvement is frequent in systemic sclerosis, but symptoms are usually delayed and non-specific, thus often misrecognized. The aim of this study was the evaluation of the early subclinical cardiac involvement in patients with systemic sclerosis by means of non-invasive laboratory cardiac markers. DESIGN AND METHODS: Cardiac troponin T (cTnT), ischemia modified albumin (IMA) and NT-prohormone-brain natriuretic peptide (NT-proBNP) were measured in 40 female patients with systemic sclerosis and in 40 matched healthy controls. RESULTS: Patients with systemic sclerosis displayed significantly increased concentrations of serum IMA (106 versus 93.5 kunits/l, P < 0.0001) and NT-proBNP (89 versus 37 pg/ml, P < 0.0001), whereas no significant differences could be observed in both IMA and NT-proBNP values in limited versus diffuse pattern of disease. CONCLUSIONS: The increased levels of NT-proBNP and IMA could be considered a sign of early myocardial involvement, warranting further heart examination and a regular follow-up.
BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disorder of the connective tissue characterized by widespread vascular lesions and fibrosis. Little is known so far on the activation of the hemostatic and fibrinolytic systems in SSc, and most preliminary evidences are discordant. METHODS: To verify whether SSc patients might display a prothrombotic condition, plasma D-dimer was assessed in 28 consecutive SSc patients and in 33 control subjects, matched for age, sex and environmental habit. RESULTS AND DISCUSSION: When compared to healthy controls, geometric mean and 95% confidence interval (IC95%) of plasma D-dimer were significantly increased in SSc patients (362 ng/mL, IC 95%: 361-363 ng/mL vs 229 ng/mL, IC95%: 228-231 ng/mL, p = 0.005). After stratifying SSc patients according to disease subset, no significant differences were observed between those with limited cutaneous pattern and controls, whereas patients with diffuse cutaneous pattern displayed substantially increased values. No correlation was found between plasma D-dimer concentration and age, sex, autoantibody pattern, serum creatinine, erythrosedimentation rate, nailfold videocapillaroscopic pattern and pulmonary involvement. CONCLUSION: We demonstrated that SSc patients with diffuse subset are characterized by increased plasma D-dimer values, reflecting a potential activation of both the hemostatic and fibrinolytic cascades, which might finally predispose these patients to thrombotic complications.
The authors describe two patients with no personal or family history of psoriasis who developed psoriatic lesions during infliximab treatment: a woman affected by seronegative rheumatoid arthritis and a man affected by ankylosing spondylitis.
INTRODUCTION: Recent investigations show that activated factor VII, the primary enzyme in the extrinsic pathway of blood coagulation, exerts additional extra-coagulant functions, such as apoptosis and angiogenesis. On the basis of these recent acquisitions, the present study was aimed to evaluate activated factor VII in patients with systemic sclerosis and to establish a potential association with pathogenesis and complications of this severe autoimmune disorder. MATERIALS AND METHODS: Activated factor VII level was measured in twenty-eight consecutive scleroderma patients (2 men and 26 women, mean age 49.7 +/- 14.8 years). The main clinical correlates of disease, such as disease activity, renal function, skin, vascular and lung involvement, were evaluated by clinical and instrumental investigations. Activated factor VII level was also evaluated in 28 sex and age matched controls. RESULTS: Systemic sclerosis patients exhibited plasma activated factor VII activities significantly lower than those of healthy matched controls (15.2 versus 37.7 U/l, respectively; p < 0.001). No correlation was observed between plasma activated factor VII concentration and age, disease duration, disease subset, disease activity, renal, lung, skin and microvascular involvement. CONCLUSIONS: Results of our investigation provide first evidence of low activated factor VII activity in patients with systemic sclerosis. Reduced activated factor VII activity might be involved in the pathogenesis of the ischemic complications, by modulating apoptotic and angiogenetic processes.
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OBJECTIVES: To evaluate by computerized digital thermometry (CDT) the effect of cyclic iloprost infusions on finger skin temperature (FST) in scleroderma patients. METHODS: Twenty-two scleroderma outpatients (one man, 21 women, mean age 54.2 years) underwent three computerized digital thermometries, the first one 3 days before a 5-day cycle of iloprost infusion, the second the day of the fifth infusion soon after the end of the therapy and the third 1 month after. FST was evaluated under basal conditions, immediately after a cold test and after an 18 min recovery period. For comparison CDT was performed in 10 sex and age matched control subjects. RESULTS: FST was lower in scleroderma patients before iloprost infusion than in the control group either after cold test either at the end of the recovery period while no difference was found before the cold test. Soon after iloprost infusion and 1 month later the FST at the end of the recovery period increased from the pre-treatment value of 27.8 +/- 5.3 to 30.4 +/- 3.5 degrees C and to 30.0 +/- 4.5 degrees C, respectively (P < 0.05 for both values). No substantial differences were found concerning FST before and at the end of the cold test. CONCLUSION: Iloprost administration for 5 days allows to normalize the FST value after cold exposition not only immediately after the infusions but even at 1 month distance from the therapy. Despite its short half-life the effect of the drug on endothelium is protracted.
BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disorder of the connective tissue characterized by widespread vascular lesions and fibrosis, associated with endothelial dysfunction, that might finally promote occlusive vascular complications. Little is known so far on the lipid profile of these patients. METHODS: To investigate the potential contribution of lipid abnormalities in genesis and progression of vascular occlusive complications, an extensive lipid profile, including total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, total cholesterol to HDL-C ratio, the atherogenic index of plasma, lipoprotein[a] (Lp[a]) and high-sensitive C Reactive Protein (Hs-CRP), was assessed in 31 consecutive female SSc patients and 33 matched healthy controls. RESULTS: When compared to healthy matched controls, SSc patients displayed statistically significant differences in median and 25-75th percentile distribution of Lp[a] (110 mg/l, 51-389 mg/l vs. 79 mg/l, 29-149 mg/l; P =0.005) and in the mean concentration of Hs-CRP (4.49 +/- 5.06 mg/l vs. 1.36 +/- 1.19 mg/l; P =0.001), but not in the other lipid parameters. When compared to the current NCEP or AHA/ACC goals, the values distributions and the relative percentage of patients with undesirable or abnormal vales were statistically different for Lp[a] (29% versus 3%) and Hs-CRP (42% vs. 12%) (both P <0.001). CONCLUSIONS: If further studies will strengthen these preliminary findings, owing to the growing evidence that Lp[a] might act in synergy with other defined prothrombotic conditions in the pathogenesis of a variety of vascular disorders, we hypothesize that Lp[a] measurement might be useful in SSc to identify and eventually treat subsets of patients more predisposed to develop thrombotic complications.
To evaluate antibodies against cyclic citrullinated peptides (anti-CCP) together with rheumatoid factor (RF), antinuclear antibodies (ANA) and C-reactive protein (CRP), in patients affected by rheumatoid arthritis (RA), before and after infliximab treatment. Twenty-seven patients (five men and 22 women, mean age of 51.9 years, mean duration of disease 12.6 years) affected by RA, refractory to conventional DMARDs, were treated with infliximab, at the conventional dosage. Before starting infliximab and after 22 weeks, on the occasion of the fifth infusion, anti-CCP antibodies were tested by ELISA method. At the same time IgM RF, ANA and CRP level were measured. Before infliximab therapy, anti-CCP antibodies resulted positive in 23 patients (85.1%); the serum level did not change after infliximab treatment; only one case negative at baseline became slightly positive after treatment. Before and after therapy RF resulted positive in 22 cases (81.4%) and 21 cases (77.7%) respectively; comparing values at baseline with those after 22 weeks of treatment with infliximab, RF levels significantly decreased, as well as CRP values. In contrast to both anti-CCP antibodies, which remained stable, and to RF, which fell after infliximab, ANA were positive > or = 1: 160 in four cases at baseline and in 12 after treatment. The titre of anti-CCP antibodies did not significantly change after anti-TNFalpha blocker administration; instead the positivity of RF significantly decreased. As opposed to antinuclear and anti-dsDNA antibodies, which may appear or increase in titre during infliximab treatment, the typical autoantibodies detectable in RA show a different trend; in fact, anti-CCP antibodies remained stable and RF decreased.
We studied HLA-DRB1 alleles in 101 patients with rheumatoid arthritis (RA) and 229 normal subjects by polymerase chain reaction and sequence-specific oligonuclotide hybridization. We observed a statistically significant association between HLA-DR4 and RA (p = 0,0088). This association was not observed for the DR1 status. No particular DR4 suballeles were preferentially expressed in patients. Allele *0102 was more frequent in RA patients (p = 0.0084), while *0103 in controls (p = 0.000047). No difference was observed for the presence of early erosions and extra-articular features in patients with no, one or two RA associated alleles and among share epitope positive and negative patients.
The aim of the study was to evaluate a panel of autoantibodies in patients affected by rheumatoid arthritis (RA) treated with anti-TNFalpha blockers, and to consider a different autoantibody induction effect by infliximab and etanercept; and in addition to evaluate in these cases a relationship between antinuclear antibody (ANA) titre and both C-reactive protein (CRP) and Blys levels. Fifty-four patients (8 men, 46 women, mean age 51.4 years, mean duration of disease 13.6 years) affected by refractory RA were treated with anti-TNFalpha blockers for 12 consecutive months; 43 patients were given infliximab and 11 etanercept. At baseline and every 4 months a panel of autoantibodies consisting of rheumatoid factor, antinuclear, anti-double-stranded DNA, anti-ENA, anti-mitochondrial, anti-thyroid and anti-neutrophil cytoplasmic antibodies (ANCA) was tested. At the same time CRP level was measured. Blys level was determined at baseline and after 1 year in five cases that developed a strong positivity for ANA during infliximab therapy. In 41 cases (95.3%) treated with infliximab, ANA were detected on at least one occasion, and in almost half of these cases the titre was very high, equal to or higher than 1:1.280. On the other hand, patients treated with etanercept presented ANA positivity in a lower percentage of cases and at a low titre. No correlation was found between ANA titre and CRP level; Blys level did not present a constant trend in patients who developed a very high positivity for ANA. Anti-double-stranded DNA, anti-thyroid or ANCA were found only in a few patients, in the absence of a clinical picture indicative of systemic lupus erythematosus, autoimmune thyroiditis or ANCA-associated vasculitis. A different incidence of ANA positivity was found in infliximab- and etanercept-treated RA patients; this finding might be due to the partially different method of inhibition of TNFalpha between the two drugs. Both CRP and Blys do not seem to participate in this phenomenon. Other autoantibodies were detected in a few patients, but no case of onset of new autoimmune disorders was observed.
OBJECTIVE: The aim of this study was to evaluate pulmonary function in patients suffering from scleroderma treated for 3 years with cyclic iloprost infusions. METHODS: Thirty patients affected by scleroderma (five men and 25 women, mean age 49.3 years, mean disease duration 8 years, 19 with limited and 11 with diffuse disease patterns) were treated for 5 consecutive days every 4 months for 3 years with iloprost. Pulmonary function was evaluated at baseline and after 3 years. At the end of the trial, color Doppler echocardiography was performed in 26 of the patients. RESULTS: Spirometric parameters did not significantly change after 3 years of therapy when expressed as percentage of the predicted normal value. Diffusing lung capacity for carbon monoxide decreased at the limit of statistical significance. No patients developed clinical pictures suggestive of severe pulmonary arterial hypertension, which was confirmed in 26 subjects by evaluation of estimated pulmonary artery systolic pressure. CONCLUSIONS: This long-term study showed that lung function remained substantially stable after 3 years of treatment with cyclic iloprost infusions. No cases of severe pulmonary hypertension were observed.
Salivary gland mucosa-associated lymphoid tissue (MALT) lymphomas (SGML) are rare, as are data concerning their behaviour. We analysed clinical features at presentation, particularly the association with Sjoegren syndrome (SS) and hepatitis C virus (HCV) infection, and outcome in 33 cases of SGML diagnosed between March 1985 and April 2003. There were five males and 28 females, with a median age of 61 years. At presentation, 12/33 (36%) had multiple salivary glands or mucosal involvement and four had bone marrow infiltration. Ann Arbor stage was IE in 15 (46%), IIE in four (12%) and IV in 14 patients (42%). Fifteen patients had a history of SS (46%), two of other autoimmune diseases, seven of HCV infection. No case had both SS and HCV. Of the 29 treated patients, 17 received surgery or local radiotherapy; 69% achieved complete remission. Histological transformation occurred in four (12%). Five patients died (three of lymphoma, two of unrelated causes). The 5 year-overall survival (OS), cause-specific survival and progression-free survival was 85 +/- 8%, 94 +/- 6% and 65 +/- 10% respectively. Overall, the disease course was indolent, despite the advanced stage at diagnosis, and local therapy often appeared to be adequate. The only prognostic factors influencing OS were histological transformation and age. The close association of SGML with either autoimmune diseases or HCV infection in our series (73%) confirms their possible role in the pathogenesis of these lymphomas.
In this review the authors focus on Erdheim-Chester disease, a rare systemic disorder of unknown etiology, likely neoplastic, characterised by xantogranulomatous infiltrates of foamy, lipid-laden histiocytes in all involved sites, principally bone, retroperitoneum, lung, pleura, pericardium, retroorbital tissue and brain; moreover periadventitial tissue of the aorta and major arteries may be present. The clinical picture and the course are very various. Erdheim-Chester disease belongs to histiocytosis and differs from Langerhans' cell histiocytosis for clinical, histologic and immunohistochemical features. After the observation of 2 cases we have reviewed the literature; we think useful to present the principal features of the disease, which is likely more frequent than expected; Erdheim-Chester disease is rarely diagnosed because of the poor knowledge of the disease, which is not reported on the common textbooks of medicine.