Section of Rheumatology department of Clinical and Experimental Medicine - University of Ferrara - ITALY S. Anna Hospital - Ferrara
gvl@unife.it
1982: Degree in Medicine cum laude, University of Ferrara Medical School 1985: Certified specialist in Rheumatology, University of Ferrara Medical School 1989: Certified specialist in Immuno-haematology, University of Ferrara Medical School Since 2006 Associate professor of Rheumatology - Section of Rheumatology – Department of Clinical and Experimental Medicine, University of Ferrara Teaching activities: 1988-2007 : Post-graduate School of Rheumatology University of Ferrara, Medical School Teaching Professor of Rheumatology since 2006 - University of Ferrara Research field: Systemic connective tissue disease, SLE, Neuro-psychiatric SLE (imaging, clinical features) Imaging in rheumatic diseases, Rheumatoid arthritis, Sjogren’s syndrome, Clinical trials Referee of international journals Clinical and Experimental Rheumatology, Lupus, On line archives in Rheumatology Reumatismo, Editorial Board : Reumatismo, Progressi in Reumatologia Giornale Italiano di Reumatologia Invited speaker or chairmen in more than 50 medical congress. Publications Author or co-author of more than 120 papers on national and international journals, 4 books, and more than 250 communications in national and international medical congresses.
Abstract: PURPOSE OF REVIEW: To evaluate the recent published data on the safety of biological agents, mainly anti-TNFalpha and rituximab, and diagnostic difficulties in the setting of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and inflammatory arthritides. RECENT FINDINGS: There are important differences between HBV and HCV carriers; however, clinical observations suggest that hepatotropic virus infection should not preclude the treatment with biologic agents in rheumatic diseases. Retrospective reports on limited series of HBV-infected patients with concomitant chronic arthritis convey that careful patients' clinico-virological assessment, in collaboration with the hepatologist, is necessary before starting immunosuppressive treatments, especially biological agents. Preemptive or combined antiviral treatment is mandatory, mainly in active and inactive HBV carriers. Occult HBV infection should be also carefully evaluated due to potential virus reactivation. In HCV-infected patients without chronic active hepatitis the treatment with biological agents, anti-TNFalpha or rituximab, is generally useful and well tolerated. Preliminary data suggest the possible synergic effects of combined antivirals (alpha-interferon and ribavirin) and anti-TNFalpha (or rituximab) in patients with chronic arthritis and active hepatitis C. SUMMARY: In all patients with chronic arthritis requiring immunomodulating treatments both HBV and HCV infection along with liver conditions should be evaluated before any therapeutic decisions, including differential diagnosis among virus-related autoimmune disease and simple comorbidity. Patients with HBV infection should be referred to the hepatologist and correctly classified into active, inactive, and occult carriers. Similarly, rheumatic patients with active chronic hepatitis C must be treated with sequential or combined treatment with antiviral and biological agents.
Abstract: Objectives. To perform an observational retrospective cross-sectional case-control study to evaluate prevalence, clinical patterns and outcomes of CNS involvement in a large cohort of primary SS (pSS) patients. Methods. A total of 424 pSS patients, diagnosed according to the 2002 criteria proposed by the American-European Consensus Group, were checked for CNS involvement after exclusion of secondary causes. Demographic, clinical, seroimmunological data were compared between patients with and without CNS involvement. Neuroimaging data were also analysed. Results. CNS involvement was detected in 25 (5.8%) patients (24 females and 1 male) both at disease onset (52%) and later (48%) with a mean latency after diagnosis of 7 years. Diffuse (40%), focal/multifocal (36%), multiple sclerosis (MS)-like disease (20%) and isolated optic neuritis (4%) were the most common CNS clinical pictures. Disease duration, lung involvement and decreased C(4) were associated with CNS involvement, while articular manifestations were more frequently observed in patients without neurological complications. Most cases had an acute, often recurrent course with spontaneous remission or only mild neurological impairment. Conclusions. CNS involvement represents a rare but not negligible complication of pSS, which may occur with a bimodal temporal pattern, both at onset and later, prompting attention in the differential diagnosis of apparently isolated neurological syndromes. Lung involvement emerged as the strongest risk factor for CNS involvement with a relative risk of 7.9, along with disease duration and decreased C(4).
Abstract: OBJECTIVE: We report the use of nicotine-patch therapy on active mucocutaneous lesions of Behçet's disease (BD). METHODS: Five BD ex-smoker patients with refractory active mucocutaneous manifestations were treated with nicotine patches for 6 months. RESULTS: Four out of five patients quickly responded to nicotine-patch therapy and experienced a complete regression of mucocutaneous lesions. Other manifestations of BD did not respond and new manifestations appeared during this treatment. One patient had no benefit from therapy but on restarting smoking it was promptly effective. CONCLUSIONS: Mucocutaneous lesions associated with BD may be modulated by smoking. Both smoking and nicotine-replacement therapy may be efficacious not only on oral aphthae, but also on other mucocutaneous manifestations, whereas the efficacy in the treatment and prevention of other systemic manifestations of BD is not proven. At least in ex-smokers, nicotine in its pure form is well tolerated and its use could be justified in selected cases of BD with predominant and recurrent refractory mucocutaneous manifestations.
Abstract: The aim of this study was to assess the potential clinical implications of Chlamydophila pneumoniae in patients with acute and chronic arthritic diseases and to investigate whether blood monocytes might reflect a concomitant synovial or persistent systemic infection. C. pneumoniae was investigated with advanced PCR and reverse transcriptase (RT) PCR techniques targeting different genes and combined with cell line cultures, in synovial fluid (SF) and peripheral blood mononuclear cell (PBMC) specimens collected from 28 patients with arthritis. Five out of twenty-eight patients (17.8%) were found to have C. pneumoniae DNA in either SF or PBMC specimens. Their diagnosis was reactive arthritis (ReA), S.A.P.H.O syndrome, psoriatic arthritis, undifferentiated oligoarthritis (UOA) and ankylosing spondylitis (AS). Specimens from patients with UOA and AS had also mRNA transcripts but those from AS yielded C. pneumoniae growth after co-culture. Moreover, C. pneumoniae DNA levels measured by Real-Time PCR (LightCycler) were higher in PBMC specimens compared to those found in SF at the end of antibiotic treatment. C. pneumoniae may have a role as triggering factor also in chronic arthritides including AS. The combined use of culture and molecular tools increases detection rates and improves the overall sensitivity, suggesting their potential use to detect C. pneumoniae. The different kinetics of bacterial DNA at both peripheral and synovial levels should be taken into consideration when monitoring and evaluating the effectiveness of antibiotic treatment.
Abstract: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder characterised by high spiking fever, an evanescent salmon pink rash and arthritis, frequently accompanied by sore throat, myalgias, lymphadenopathies, splenomegaly and neutrophilic leukocytosis. Aetiology is still unknown, however, it seems that an important role is played by various infectious agents, which would act as triggers in genetically predisposed hosts. Diagnosis is a clinical one and may be lengthy because it requires exclusion of infectious neoplasms, including malignant lymphomas and leukaemias, and other autoimmune diseases. Different diagnostic or classification criteria have been proposed, but not definitely accepted. There are no specific laboratory tests for AOSD, but they reflect the systemic inflammation: the ESR is consistently high, while the rheumatoid factors and antinuclear antibodies are negative. High serum ferritin levels associated with a low fraction of its glycosylated component are assessed as useful diagnostic and disease activity markers. The clinical course can be divided into three main patterns with different prognoses: self-limited or monophasic, intermittent or polycyclic systemic and chronic articular pattern. Therapy includes non-steroidal anti-inflammatory drugs, corticosteroids and disease modifying anti-rheumatic drugs: biological agents have recently been introduced and they seem to be very promising not only for the treatment but also for understanding the pathogenic mechanisms underlying the disease.
Abstract: OBJECTIVES: Visceral leishmaniasis (VL) is an extremely rare example of opportunistic infection in patients treated with TNF-alpha antagonists and only a few cases have been described. In this paper risk factors, clinical features, diagnostic work-up and outcome of patients developing VL under biologic therapy are described. METHODS: Case report and review of the published cases of VL in patients under biologic treatment. RESULTS: We retrieved six patients, including ours, all of whom presented anarchic fever and pancytopenia. In 5 cases, splenomegaly was detected. The same number of patients came from endemic areas for VL. In the majority of the cases a bone marrow examination was not diagnostic, requiring the performance of a second one and/or the execution of other diagnostic tests. One fatal outcome was observed. CONCLUSION: Even if VL represents a sporadic complication of biologic treatments, its presence should always be suspected in patients developing a triad of signs and symptoms constituted by fluctuant fever, pancytopenia and splenomegaly, especially if coming from endemic areas. In these cases an extensive diagnostic work-up must be warranted. Atypical and confusing features may resemble autoimmune diseases at presentation and during the course of the illness.
Abstract: OBJECTIVE: To assess the basic features and outcomes of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. METHODS: We identified all patients seen in our unit between 1990 and 2008 diagnosed according to the proposed inclusion criteria with SAPHO syndrome, who had a followup of at least 2 years. RESULTS: Seventy-one patients (48 women, 23 men) with SAPHO syndrome were identified. The median disease duration at the end of followup was 10 years (interquartile range [IQR] 7-15 years), and the median followup duration was 11 years (IQR 6-11.5 years). Six patients were diagnosed with Crohn's disease. Fourteen patients had never had cutaneous involvement, but 8 patients presented >1 skin manifestation. Nine patients (13%) presented a limited (<6 months) monophasic disease course, 25 cases (35%) had a relapsing-remitting course, and 37 patients (52%) had an acute painful phase with a prolonged course lasting >6 months. A total of 4% of the patients were HLA-B27 positive. Female sex (odds ratio [OR] 7.2, 95% confidence interval [95% CI] 2.2-22.9) and the presence at onset of anterior chest wall (ACW) involvement (OR 5.7, 95% CI 1.8-18.1), peripheral synovitis (P = 0.0036), skin involvement (OR 10.3, 95% CI 3.4-31.1), and high values of acute-phase reactants (OR 7.7, 95% CI 2.7-22) were correlated with a chronic disease course and involvement of new osteoarticular sites. CONCLUSION: A chronic course is the more common evolution of SAPHO syndrome. Female sex, elevated erythrocyte sedimentation rate and C-reactive protein values, ACW involvement, peripheral synovitis, and skin involvement at the onset seem to be associated with a chronic course.
Abstract: To describe three cases of meningioma observed in a large cohort of 546 patients with systemic lupus erythematosus (SLE) followed at our Department in the last 15 years. We identified three cases of meningioma among 181 patients with SLE who underwent a brain magnetic resonance imaging (MRI) during their disease course (prevalence 1.65%). All three SLE cases were women with a disease onset at 47-, 18- and 42 -years-old, respectively. All patients presented neuropsychiatric (NP) symptoms and had an incidental finding of a meningioma at brain MRI. One patient presented simultaneously a breast cancer. Only one patient had the surgical removal of the mass without improvement of her symptoms while in the other two patients, the removal was not indicated. The association between meningioma and SLE may be a pure coincidence. However, it draws our attention because its detection may represent a confounding factor in the setting of a NPSLE patient.
Abstract: Adult-onset Still disease (AOSD) is a rare condition disease of unknown etiology, characterized by quotidian or double quotidian spiking fever, with an evanescent pink-salmon rash, arthritis and multi-organ involvement. Diagnosis is usually clinical and made after other diseases in the differential diagnosis are excluded. We herein report the case of a patient with a remarkable familial autoimmune background in whom adult Still disease started off with a diffuse intravascular coagulation, probably triggered by a macrophage activation syndrome, followed by an acute interstitial myocarditis, leading to a fatal complete atrioventricular block. This case highlights that AOSD represents a troubling condition and that it may suddenly get worse with life-threatening events.
Abstract: The aim of this study is to determine the effects of a combination treatment with etanercept and spa rehabilitation versus etanercept alone on function, disability and quality of life in a group of patients with active ankylosing spondylitis (AS). Sixty patients with AS underwent etanercept as suggested by ASAS/EULAR recommendations. As the clinical and laboratory conditions improved, 30 patients accepted the proposal of coupling the medical therapy with a 7-day rehabilitation program in a thermal baths centre; the remaining 30 subjects continued to take the biologic agent alone. The comparisons between the 2 groups were made after 3 and 6 months. The primary outcome was an improvement in BASFI. The secondary outcome was an improvement in the visual analogic scale of EuroQol (EQ-5Dvas). After 6 months a statistically significant improvement in BASFI (p < 0.05) and EQ-5DVAS (p < 0.05) scores was observed in both groups. The mean change in EQ-5DVAS value showed a statistically significant difference in favour of the combination therapy group versus the monotherapy group (22 vs 32, p < 0.05). A therapeutic regimen combining etanercept with an intensive rehabilitation program contributes to disability reduction and ameliorates quality of life for AS patients.
Abstract: OBJECTIVE: To evaluate the prevalence of headache and its different patterns in patients with Behçet's disease (BD) with and without neurological involvement and to investigate clinical correlations. METHODS: Patients fulfilling the International Study Group criteria for Behçet disease (ISGc) were studied. Patients were invited to fill a "headache questionnaire", which consisted of two sections: the first one included demographic and anamnestic data, family history for both headache and BD, disease duration and clinical manifestations of BD; the second section included items about headache, investigated accordingly to International Headache Society diagnostic criteria (IHS, 2004). Clinical history and current comorbidities-medications were collected. Each patient underwent a neurological examination to assess neurological involvement (Neuro-BD) and, if necessary, instrumental investigations. One hundred-fifty healthy subjects matched for age and gender were used as control group for comparison. RESULTS: Of the 55 patients diagnosed as BD (ISG criteria) 41 patients adhered and were enrolled into the study. Headache occurred in 29 of BD patients (70,7%) and in 13 of Neuro-BD patients (92,8%). Migraine without aura did prove the most frequent type of headache in BD patients (with and without neurological involvement) and there were no differences in the frequency of the different pattern of headache between BD patients and controls. CONCLUSIONS: Headache is a frequent manifestation in BD and primary headache like migraine emerged as the most frequent type of headache. A careful search for headache should be included in the diagnostic work-up of BD since this manifestation may be related to the underlying disease.
Abstract: OBJECTIVE: IL-1beta plays a key role in the pathogenesis of Schnitzler's syndrome (SS). We have investigated inflammasome activity in peripheral blood mononuclear cells (PBMCs) from a patient affected by a variant type of SS. METHODS: PBMCs were purified by Ficoll and examined for ability to secrete IL-1beta and -18, expression and function of the P2X(7) receptor and expression of apoptosis-associated speck-like protein containing a caspase recruitment domaine (ASC) and NOD-like receptor protein 3 (NLRP3) before and after the therapy with steroid. Furthermore, extracellular adenosine 5'-triphosphate (ATP) blood levels were determined by luciferase assay. Expression of inflammasome components was measured by real time PCR and western blotting. RESULTS: PBMCs of patient with SS showed a high, spontaneous and lipopolysaccharide-stimulated, IL-1beta release but low response to stimulation with the P2X(7) agonist benzoyl ATP. P2X(7) expression was several fold increased, whereas ASC expression was dramatically decreased compared with PBMCs from healthy controls. NLRP3 expression was unchanged. Prednisone treatment induced remission of clinical symptoms and normalized IL-1beta secretion and P2X(7) and ASC expression. CONCLUSION: These findings reveal the presence of an overall derangement of the inflammasome and IL-1beta processing and release in SS.
Abstract: OBJECTIVE: To assess the relationship between clinical picture and neuroimaging in patients affected by SLE with and without neuropsychiatric (NP) involvement. METHODS: One hundred and seven SLE patients including 66 with NP involvement (NPSLE) with focal or diffuse presentation and 41 without underwent single photon emission computed tomography (SPECT) and MRI. RESULTS: After stratification for diffuse or focal NP involvement, in the 52 patients with diffuse presentation, abnormalities detected with MRI or SPECT did not differ from patients without NP; however, after combining the two techniques, a normal result was more frequently observed in patients without NP involvement (P = 0.010). In the 14 patients with focal presentation, MRI alone and concordant abnormal MRI plus SPECT were more frequently detected in the NPSLE group; again normal findings by both techniques simultaneously applied were more frequently found in SLE patients without NP involvement. White matter hyperintense T2-weighted lesions were the most frequent MRI abnormal findings in both groups, but the presence of multiple lesions (>5) involving both the hemispheres at subtentorial level was limited to NPSLE patients. Multifocal hypoperfused SPECT areas were more frequently observed in frontal and parietal lobes of NPSLE. CONCLUSIONS: Combining SPECT and MRI appears more useful than the two techniques alone and may help the clinician in the assessment of patients with NP involvement since normal findings contemporarily detected by these two techniques have been rarely observed in patients with NP involvement especially in those with focal manifestations where MRI and SPECT were never simultaneously normal.
Abstract: OBJECTIVE: To evaluate the predictive value of clinical and biochemical features when compared to 18FDG-PET in the diagnostic work-up of large vessel vasculitis (LVV). METHODS: Twenty-five patients underwent 18FDG-PET for the clinical suspect of LVV. All of them presented history of systemic symptoms lasting >or=6 months and laboratoristic evidence of persistently high markers of inflammation. The patients were stratified according with: i) clinical manifestations, defined as presence of one or more ACR criteria for the classification of LVV; ii) laboratory investigations: Erythrocyte Sedimentation Rate (ESR) higher or lower than 50 mm/h, C-Reactive Protein (CRP) higher or lower than 2 mg/dl; iii) prednisone dose in the 4 weeks preceding PET examination. RESULTS: The total number of positive PET was higher in the group without clinical ACR criteria and in the group with inflammation markers under the established cut-off. The number of scans consistent with LVV was higher in the groups presenting one or more clinical criteria for LVV but in those with very high ESR and CRP. In all the cases differences between groups were not statistically significative. A clear cut negative correlation between steroid dose and number of scans suggestive for LVV has been observed. CONCLUSIONS: Diagnosis of LVV remains challenging, especially in patients presenting with a constellation of non-specific symptoms and laboratory findings. In this study, both clinical and biochemical features show low correlation with a vasculitic pattern of FDG uptake. In our experience 18FDG-PET represents an useful diagnostic tool in early stages of LVV and a powerful instrument to follow the treatment responses.
Abstract: The relationship between infection and autoimmunity has been increasingly defined over the last twenty years or so. It is now quite clear that, in genetically susceptible individuals, environmental factors (mainly infections) play a critical role in the pathogenesis of autoimmune diseases. It is believed that infections contribute to the maturation of the immune system from the innate to adoptive phases, and that bacterial and viral infections are arthritogenic stimulants leading to various rheumatic conditions. A failure to isolate these microorganisms is probably due to the action of the immune system, but often casts doubt on their role in the pathogenesis of autoimmune diseases. Among bacteria, Helicobacter pylori has been associated with diseases such as autoimmune gastritis, Sjögren's syndrome, atherosclerosis, immune thrombocytopenia purpura, inflammatory bowel diseases and autoimmune pancreatitis, in each of which it seems to play a pathogenatic, but it has also been suggested that it may help to protect against the development of autoimmune gastritis, multiple sclerosis, systemic lupus erythemathosus and inflammatory bowel diseases. Infectious agents may play a dual role in the etiopathogenesis of antiphospholipid syndrome (APS): they may be the initial trigger of the production of antibodies cross-reacting with beta 2 glycoprotein I (Beta2GPI) and infectious peptides, and also induce an inflammatory response. According to the two-hit theory, pathogenetic anti-Beta2GPI antibodies act as the first hit whereas inflammatory responses may represent the second hit The slowly growing Propionibacterium acnes may be involved in the etiopathogenesis of SAPHO syndrome non-specific activation of cell-mediated immunity. Its ability to persist in bone lesions in a form that is incompatible with culturing suggests the possibility an arthritis that is secondary to a "persistent" infection.
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease mainly mediated by the deposit of immune complexes and defects in T lymphocytes and antigen-presenting cells along with a high production of T-helper 2 cytokines. A tolerance-inducible function of nonclassical class Ib human leukocyte antigen (HLA)-G molecule in innate and adaptive cellular responses has been reported, suggesting a role in inflammatory diseases. A 14 bp sequence insertion/deletion polymorphism (rs16375) in the 3'-untranslated region of the HLA-G gene has been associated to the stability of HLA-G messenger RNA. The insertion of the 14 bp sequence seems to be associated with lower levels of soluble HLA-G (sHLA-G). The aim of this study was to evaluate the possible association of the presence of the 14 bp sequence (+14 bp) with SLE. We have HLA-G genotyped 200 SLE patients and 451 healthy control subjects (HS; Italian) and analyzed the plasma levels of sHLA-G and interleukin-10 (IL-10) in a subset of SLE patients and healthy subjects (Italian and Danish). A significant increase of the +14 bp HLA-G allele was detected in the Italian SLE patients compared with HS [P = 0.003, OR 1.44 (95% CI 1.13-1.82)]. A significant increased frequency of HLA-G +14/+14 bp and a decreased frequency of HLA-G -14/-14 bp were observed in SLE patients. There median concentration of sHLA-G was significantly lower in the plasma of SLE patients compared with that in the plasma of healthy controls (P < 0.0001). Furthermore, the results confirmed higher concentrations of IL-10-positive plasma in SLE patients. These results support a potential role for HLA-G in the susceptibility of SLE.
Abstract: OBJECTIVES: To describe an unusual case of Whipple disease (WD) with confusing clinical features at onset and to discuss the diagnostic challenges for the clinician. METHODS: Description of a new case of this rare disease and thorough discussion of the atypical clinical manifestations at onset. A literature review, concerning the unusual onset, by means of a MEDLINE search from 1966 to 2007 was done. RESULTS: A 39-year-old man with sudden bilateral blurred vision due to retinal vasculitis and concomitant rapidly evolving symmetrical neurosensory bilateral hearing loss as initial features of WD is described. Due to the clinical manifestations resembling systemic vasculitis, high-dose corticosteroid and pulse cyclophosphamide therapy were started with subsequent appearance of gastrointestinal symptoms (diarrhea and weight loss) and spiking fever, suggesting superimposed infection. After a complete evaluation, including gastroscopy, extensive duodenal-jejunal mucosal involvement was seen, while diffuse infiltration of the duodenal lamina propria with periodic acid-Schiff-positive foamy macrophages was observed on the histological sample. The diagnosis was confirmed by reverse transcriptase-polymerase chain reaction for the DNA of Tropheryma whippelii. To our knowledge, no previous similar clinical onset of WD has been described. CONCLUSIONS: To avoid misdiagnosis and therapeutic mistakes, clinicians should be aware of unusual presentations of WD. Because this etiological agent is a difficult to isolate bacterium, diagnosis may be especially problematic in cases without intestinal involvement at onset.
Abstract: Central Nervous System (CNS) involvement is a frequent SLE manifestation occurring in 15-75% of patients. However, diagnosis of CNS involvement is a difficult task and requires a careful clinical and laboratory assessment along with instrumental evaluation. In recent years major advances in neuroimaging techniques allowed a great improvement in our understanding of SLE pathogenesis. Anyway, since no single imaging technique covers all brain pathology and both inflammation and neurodegeneration contribute to SLE pathogenesis, it is very important to use a multimodality approach coupling a morphological with a functional imaging modality. In this setting, to date, conventional magnetic resonance imaging and single photon emission computed tomography are the most largely available and accessible techniques. Modern techniques such as perfusion weighted imaging, diffusion weighted imaging, magnetization transfer imaging and magnetic resonance spectroscopy provide useful information to assess brain tissue damage however, their clinical relevance in individual patients needs further evidence. In this review we would like to summarize what have we learned in the last few years about neuroimaging in NPSLE, what have been major advances in neuroimaging techniques and, finally, we would like to give some suggestions about what should be done in daily clinical practice to approach SLE patients with NP symptoms.
Abstract: OBJECTIVE: In 1999, the Italian Society of Rheumatology started a project to determine the prevalence and clinical characteristics of aggressive rheumatoid arthritis (ARA). METHODS: For 1 year, all patients with RA for > 5 years and referred to participating centers were entered in a registry and classified as having ARA if they fulfilled the following criteria: 10 swollen joints for at least 6 weeks, positive rheumatoid factor (RF), and at least one bone erosion (if disease duration of 2 years); (a) RF-positive and having 10 swollen joints or at least one newly eroded joint, or (b) if RF-negative, having 10 swollen joints and at least one newly eroded joint (if disease duration > 2 to < 5 years). RESULTS: The 94 participating centers enrolled 1218 patients with RA, 1130 of whom had enough data to be classified as ARA (29.0%) or non-ARA (71.0%). The frequency of ARA was 15% in the 2-year group and 63% in the > 2 to < 5-year group, but 35% of the patients in the 2-year group had erosions. Bone erosions were associated with disease duration, a Health Assessment Questionnaire value > 1.5, female sex, and RF positivity. Conditions other than RA were recorded in about 50% of the patients, and only 30% 40% were taking disease modifying antirheumatic drugs. CONCLUSION: In an Italian RA population, the GIARA (Gruppo Italiano Artrite Reumatoide Aggressiva) criteria for ARA were met by 15% of the patients with disease duration of 2 years, but erosions were seen in 35%. Upon referral, most of the RA patients were inadequately treated and had other conditions.
Abstract: The notion of autoinflammatory diseases delineates a heterogenous group of genetic pathologies characterized by spontaneous periodic systemic inflammation in the absence of infectious or autoimmune causes. The general hypothesis is that the innate immune response in these patients is wrongly tuned, being either too sensitive to minor stimuli or turned off too late. Clinical pictures of these disorders are characterized by high spiking fever associated with involvement of musculo-skeletal system, tegumentary apparatus and serosas. Although inflammatory syndromes are considered rare, they may represent a model in order to unravel some aspects of the innate immune system and of the inflammatory cascade.
Abstract: Elderly-onset gout (EOG), defined as a disease with onset at age 65 years or over, shows relevant epidemiological, clinical and therapeutic differences from the typical middle-age form. The main differences are the more frequent subacute/chronic polyarticular onset with hand involvement, the unusual localization of tophi on ostheoarthritis (OA) nodes, the increased female/male ratio and the frequent association with drugs that decrease renal urate excretion (diuretics and low-dose aspirin) and/or with primitive renal impairment. EOG has recently been confirmed as the most common inflammatory arthropathy in older people, with important demographic implications and substantial impact on daily clinical practice. Despite the high prevalence, gout, in the elderly, often remains misdiagnosed or diagnosed late in its clinical course. Even when correctly recognized, its treatment is often difficult or unsatisfactory.
Abstract: OBJECTIVE: To develop valid instruments for the assessment of disease-related damage and disease activity in Sjögren's syndrome (SS). METHODS: Data on 206 patients with primary SS were collected in 12 Italian centers. Each patient was scored by 1 investigator, on the basis of a global assessment of the degree of disease damage and disease activity. Patients judged to have active disease at the time of enrollment underwent a second evaluation after 3 months. Univariate and multivariate analyses were performed to select the clinical and serologic variables that were the best predictors of damage and of disease activity, and these variables were used to construct the Sjögren's Syndrome Disease Damage Index (SSDDI) and the Sjögren's Syndrome Disease Activity Index (SSDAI). The weight of each variable in the index was determined by the beta coefficients in multivariate regression models. Scores obtained using the SSDDI and the SSDAI were compared with scores initially given by the investigators. Finally, a receiver operating characteristic (ROC) curve was used to determine the cutoff value in the SSDAI with the highest level of accuracy in identifying patients with a significant level of disease activity. RESULTS: A multivariate model with 9 variables was the best predictor of investigator scores of damage. The scores obtained using the SSDDI were closely correlated with investigator ratings (R = 0.760, P < 0.0001). A model composed of 11 variables was the best predictor of investigator scores of disease activity. The scores obtained using the SSDAI were strongly correlated with the investigator ratings both at the time of enrollment and 3 months after enrollment (R = 0.872, P < 0.0001, and R = 0.817, P < 0.0001, respectively). The differences between scores given by investigators at study enrollment and after 3 months, a measure of variation of disease activity over time, were also closely correlated with the differences calculated using the SSDAI (R = 0.683, P < 0.0001). The ROC curve analysis showed that patients with the highest level of disease activity could be identified on the basis of an SSDAI score of >or=5. CONCLUSION: Our findings indicate that the SSDDI is an adequate instrument to objectively measure damage in patients with SS, and that the SSDAI is a valid tool to measure disease activity when used either as a single-state index or as a transition index.
Abstract: To compare the clinical, laboratory and immunological features of a group of Caucasian systemic lupus erythematosus (SLE) patients in relation to age at disease onset. Three groups of patients with different ages at disease onset were analysed and compared: group A (30 patients, >or=65 years); group B (62 patients, 50-64 years) and group C (163 patients, <50 years). All patients were regularly followed-up for a mean period of 6.5 years. Female predominance was reduced in groups A and B. Time-lapse between disease onset and diagnosis was longer in group A and B. There were no statistically significant differences in clinical features. The only relevant difference was observed in peripheral nervous system (PNS) involvement, more frequent in group A. Anti-dsDNA and RF were more frequent in group A. Complement levels were reduced more frequently in group C. No differences were observed in disease activity scores, while SLICC/ACR score was higher in group A. In Caucasian SLE patients, age at disease onset is not associated with differences in clinical features apart from a more frequent PNS involvement in elderly patients. In the same group, the organ damage seems to develop more rapidly mostly due to higher susceptibility to jatrogenic side effects.
Abstract: OBJECTIVE: Thrombocytosis can be due to a myeloproliferative disorder or to a reactive or secondary process; among these are connective tissue disorders, in particular systemic lupus erythematosus (SLE). Besides being an expression of active disease, this unusual finding has also been described in SLE complicated by autosplenectomy. We evaluated the prevalence of thrombocytosis in a series of SLE patients and its relationship to functional asplenia. METHODS: Platelet count was evaluated in 465 consecutive Caucasian patients with SLE (387 women, 78 men, median age 54 yrs). Thrombocytosis was defined as platelet count > 400 x 10(9)/l in at least 3 blood samples. All patients with thrombocytosis underwent peripheral blood smears for erythrocyte abnormalities and instrumental spleen evaluation. RESULTS: Seventeen patients (3.7%) with thrombocytosis were observed. Peripheral blood smear showed Howell-Jolly bodies, spherocytes, and target cells in 3/17 patients (17.6%). In the same 3 patients, ultrasound and computed tomography failed to evidence the spleen, and liver-spleen scans showed absence of splenic uptake (a finding indicative of functional autosplenectomy). One satisfied criteria for antiphospholipid syndrome (APS), and the other 2 patients had positive IgG antiphospholipid antibodies (aPL) at medium titer. CONCLUSION: The sudden appearance and persistence of thrombocytosis or even the apparent reversal of thrombocytopenia in patients with SLE should raise suspicion of autosplenectomy, in particular if secondary APS or aPL is present.
Abstract: The strong link between the bowel and the osteo-articular system is suggested by many clinical and experimental observations. However, the therapeutic approach is still empirical. For symptomatic therapy it is better to favour the use of steroids and avoid non-steroidal anti-inflammatory drugs because they may induce intestinal ulcerations and can activate inflammatory bowel disease. Second line drugs (sulfasalazine, methotrexate, azathioprine, cyclosporine and leflunomide) should be used for selected indications. In some cases (severe spondylitis, severe and persistent enthesopathy) anti-TNF-alpha agents (infliximab) should be considered as first line therapy. In all cases it is mandatory to select the best therapeutic option for each individual patient, considering that the optimal treatment of bowel inflammation may induce "per se" a remission of the musculo-skeletal manifestations.
Abstract: Diffuse idiopathic skeletal hyperostosis (D.I.S.H.) is a common disorder of unknown aetiology characterized by exuberant hyperostosis of the antero-lateral aspect of the spinal column, that sometimes leads to bone ankilosis, and by ossification of extra-spinal entheses. This condition is often associated with the metabolic derangement of type 2 diabetes. Primary hypertension, its cardiovascular aftereffects and lithiasis are also often present in these patients. D.I.S.H. has to be distinguished from osteoarthritis, although they often coexist in the same patient. The mean difference lies in the anatomical target of the pathological process, that is represented by articular cartilage in osteoarthritis and by entheses in diffuse idiopathic skeletal hyperostosis. The enthesopathy leads to the ossification of the anterior longitudinal ligament of the spine and causes the formation of flowing osteophytes, while intervertebral disc space is quite preserved in early phases of the disease. Symptoms of spine involvement are not typical of the disease and consist of pain and stiffness, usually worsened by inaction and damp. It has also been described the ossification of posterior longitudinal ligament which can lead to medullary canal stenosis. Appendicular skeleton is symmetrically involved in early phases of the disease, the most distinctive affected sites being feet, olecranus and patella. Hip involvement is also frequent and may lead to severe disability and represents an important cause of invalidity. The purpose of the present review is to remark on aetiopathogenetic and clinical aspects of diffuse idiopathic skeletal hyperostosis.
Abstract: The objective of this study was to investigate the incidence and the prevalence of systemic lupus erythematosus (SLE) in an area of northeast Italy. We retrospectively examined all patients of 16 years and older of native Italian origin and resident in Ferrara district either admitted to hospital or referred to our outpatient clinic with a diagnosis of SLE determined between 1 January 1996 and 31 December 2002. SLE subjects were identified both by a search of hospital discharge code 710.0 according to the international classification of diseases-9 codes, and using a computerized search for this pathology code in the national health care system. Incidence and prevalence rates were calculated as number of cases per 100 000 inhabitants. Population data were based on the 2002 National Census. A total of 299 cases of SLE were identified. After a review of all cases by one experienced investigator, 98 were excluded because did not satisfied the 1982 revised criteria of the American College Rheumatology. Therefore, 201 patients had a definite diagnosis of SLE. The prevalence of SLE in the district was 57.9/100 000. The mean age at diagnosis was 41 years, the average duration of the disease from symptoms onset to diagnosis was 4.8 years and the female/male ratio 9:1. Annual incidence in 2000 was 2.01/100000, in 2001 1.15/100000 and in 2002 2.6/100000. This is the first study dealing with prevalence and incidence of SLE in an Italian district. Data obtained concerning prevalence, incidence, age at diagnoses and female predominance are in agreement with those published in literature.
Abstract: OBJECTIVE: Methotrexate (MTX) represents the antirheumatic drug mainly used in rheumatoid arthritis (RA). HLA-G antigens are inducible nonclassical major histocompatibility complex class Ib molecules important for maintaining anti-inflammatory conditions. The HLA-G gene is characterized by a deletion/insertion polymorphism of 14 bp that controls specific mRNA stability and protein levels. It has been reported that MTX therapy mediates an increase of interleukin-10-producing cells. This cytokine up-regulates HLA-G expression. For this, we tested the hypothesis of an MTX-mediated HLA-G production and the possible relationship with the HLA-G 14-bp polymorphism. METHODS: Peripheral blood mononuclear cells from healthy individuals and non-MTX-treated RA patients were activated with different MTX concentrations, and soluble HLA-G (sHLA-G) and interleukin-10 production was investigated by specific immunoenzymatic assay. HLA-G 14-bp polymorphism genotyping was performed in healthy individuals and RA patients, defined as 'responders' and 'nonresponders' to the MTX therapy. RESULTS: MTX activation induces the production of sHLA-G molecules. A significant association was observed between the highest sHLA-G1 concentrations and the -14/-14 bp genotype. The analysis of the HLA-G 14-bp polymorphism in MTX-treated RA patients has confirmed an increase of the -14/-14 bp genotype in the responder group (chi=6.12, P=0.02; chi test) (odds ratio=2.46 (95% confidence interval, 1.26-4.84) P=0.009; logistic regression model). CONCLUSION: Our results propose that the MTX induces the production of the anti-inflammatory sHLA-G molecules that concur with the therapy response. Furthermore, the association between -14/-14 bp genotype and MTX clinical outcome proposes this polymorphism as a therapy marker in the early phases of the disease.
Abstract: When dealing with Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) there are still many controversial topics. In 1999 the American College of Rheumatology gave classification criteria for 19 clinical syndromes. However major problems are still related to low specificity of some of them such as headache, cognitive impairment or mood disorders. Even though a frequency of CNS involvement from 14 to 75% has been described, depending on both the population studied and the methodology of assessment, a lower frequency ranging from 21 to 28 % derived by larger case series seems more realistic. The introduction of the concept of "borderline cases", proposed by Italian Study Group for NP-SLE, is based both on clinical and instrumental evaluation and could represent a useful tool when dealing with conditions which do not fulfil ACR classification. Also the relationship between SLE activity and NP involvement is a debated issue. Concerning pathogenesis, it seems reasonable to consider multifactorial mechanisms related to antibody-mediated damage, antiphospholipid pro-thrombotic effect, non-inflammatory vasculopathy and cytokines mediated cytotoxycity. However, direct and unequivocal evidence for the implication of any of the above-mentioned mechanisms is still lacking. Although a wide range of neuroimaging tools have been used to evaluate CNS involvement, no single technique has proven to be definitive and, when dealing with a patient with suspected NPSLE, it is important to combine different diagnostic techniques. Due to the lack of effective imaging along with limitation in knowledge of underlying pathogenetic mechanisms and paucity of histopathologic findings, therapeutic approach in NPSLE remains a difficult issue and is currently based on personal experience. Italian Study Group for NP-SLE proposes the creation of a national registry on NPSLE to validate ACR classification criteria. Furthermore, the possibility to collect large series and stratifying them for each of the included neuro-psychiatric syndromes seems a good strategy for planning multicentric controlled therapeutic trials in the near future.
Abstract: OBJECTIVE: To determine whether single photon emission tomography (SPECT) and magnetic resonance spectroscopy (1H-MRS) can predict the appearance of new lesions in systemic lupus erythematosus (SLE), detectable by magnetic resonance imaging (MRI). METHODS: (99)Tc(m)-HMPAO-SPECT, brain MRI, and (1)H-MRS were done in eight women with SLE (mean age 31.8 years; disease duration 5.5 years). NAA/Cho, NAA/Cre, and Cho/Cre ratios were assessed in hypoperfused and normoperfused areas detected by SPECT that were normal on MRI examination. Reference values were obtained in 20 normal healthy controls. In five patients, MRI was repeated four to six years after the first evaluation. RESULTS: Mean NAA/Cho and Cho/Cre ratios in hypoperfused and normoperfused frontal areas were, respectively, lower and higher than control. There were no differences in NAA/Cre ratios. Mean Cho/Cre ratios were increased in hypoperfused v normoperfused brain areas (mean (SD): 1.43 (0.27) v 1.00 (0.07); p<0.023). NAA/Cre ratios were not altered (2.18 (0.30) v 1.99 (0.28); p = 0.381). Three of five patients who had a second MRI had new lesions in areas previously abnormal on MRS and SPECT but normal on first MRI. One patient with positive MRI, SPECT, and MRS showed an increase in the number of MRI lesions; one patient with negative MRI, SPECT, and MRS did not show any new lesions. CONCLUSIONS: Abnormalities reflecting altered perfusion or neuronal-chemical changes can be demonstrated by functional imaging techniques even in the absence of morphological lesions detectable by MRI. The abnormal areas identified by SPECT and MRS may predict future parenchymal damage.
Abstract: OBJECTIVE: The aim of this study was to investigate the performance of functional neuro-imaging for describe neurological involvement in Lupus Erithematosus Systemicus. METHODS: 20 SLE patients were included into this study (18 females / 2 males). Median age was 40.5 years (range 16 -66 ys), 9 patients with a clear neurological involvement, 7 with aspecific neurological symptoms and 4 were asymptomatics, according to 1999 ACR Classification. All patients were underwent to conventional resonance imaging (RM-FLAIR), RM perfusion ( RM-PWI), RM diffusion (RM-DWI) and cerebral SPECT. The RM techniques was performed using a 1 Tesla "Signa-Horizon" Tomograph by General Electric: The data analysis was performed from two independent neuroradiologist and than trough coordinated evaluation after coregistration of acquired volumes. RESULTS: In 11/20 patients (55%) lesions were demonstrated in RM-FLAIR evaluation, more frequent in cases with focal symptoms than in diffuse. RM-PWI was positive in 50% of cases. SPECT analysis was altered in 85 % of patients. In all patients RM-DWI evaluation was negative. 5 of 29 lesional areas (3 patients) showed by SPECT analysis were positive in RM-PWI. None of them was positive in RM-FLAIR study. After coordinated evaluation of RM-FLAIR, SPECT and RM-PWI, 7 findings were considered false positive. 6 Of patients with negative RM-FLAIR were positive in SPECT and 3 in RM-PWI. Only 1 patient was positive in SPECT and RM-PWI. CONCLUSIONS: According to the literature, the RM-FLAIR is a very sensitive procedure to describe the lesional charge, especially in patients with focal symptoms. All lesions was considered as stable outcomes due to negativity of RM-DWI analysis. The SPECT is a sensitive technique to individuate cerebral areas of altered perfusion. The coregistration seems to be an helpful method to improve the explanation of uncertain cases. e the sections are prepared for the microscopic analysis of the various histomorphometric parameters.
Abstract: We report the occurrence of visceral leishmaniasis in three patients coming from the northern part of Italy treated with immunosuppressive drugs for different rheumatic conditions. This paper highlights the importance of adequate work-up in those patients presenting with serious clinical manifestations that can complicate, exacerbate or mimic a systemic connective tissue disorder. A prompt diagnosis is very important because visceral leishmaniasis has a high mortality and, if untreated, can be fatal.
Abstract: Involvement of the central nervous system (CNS) is one of the most important complications of systemic lupus erythematosus (SLE), occurring in 14-75% of SLE patients. Neurological and psychiatric involvement is mainly manifested as cerebrovascular disease, seizures, cognitive impairment, headaches and psychosis. However, diagnosis of brain involvement in SLE (i.e., neuropsychiatric lupus: NPSLE) as well as understanding of pathogenetic mechanisms still remains a difficult challenge. Although a wide range of neurodiagnostic tools have been used in the last decade to assess CNS involvement, no single technique has proven to be definitive or reliable. Since neurometabolic impairment, neurochemistry and perfusion abnormalities in NPSLE may precede anatomic lesions, new functional techniques such as magnetic resonance spectroscopy, diffusion and perfusion weighted imaging, and magnetization transfer imaging may be useful in order to indentify pathologic changes unrevealed by conventional imaging. So these new diagnostic tools could modify diagnostic and therapeutic approaches to this major unsolved problem, also shedding some light on the physiopathology of CNS disease in SLE.
Abstract: PURPOSE: To compare the performance of MR, cerebral flow SPECT and perfusion MRI (PWI) in NPSLE patients by using image co-registration. MATERIALS AND METHODS: 20 SLE patients underwent MR (T2-weighted FLAIR), perfusion and diffusion MR, and SPECT (after ( 99m)Tc-HMPAO intravenous injection). Two experienced operators analysed the images both independently and jointly after multi-modal volumetric co-registration ("Statistical Parametric Mapping" software, based on the Maximization of mutual information method). RESULTS: The FLAIR examination depicted 82 small lesions in 11/20 patients. Perfusion SPECT showed 43 hypoperfused areas in 17/20 patients. PWI showed 13 hypoperfused areas in 10/20 patients. After co-registration of images, anatomical agreement between SPECT and PWI was found in 10 hypoperfused areas (8 patients). Co-registration with FLAIR showed some false positives, more frequent in SPECT (9/43 areas) than in PWI (2/13 areas). DISCUSSION AND CONCLUSIONS: The FLAIR examination confirmed its high sensitivity in detecting lesions. Perfusion SPECT confirmed high sensitivity for the detection of hypoperfused cerebral areas. PWI showed fewer areas of cerebral hypoperfusion than did SPECT. The disagreement between SPECT and PWI may be related to the different modalities for disease detection. The anatomical agreement of hypoperfused areas between SPECT and PWI, assessed after co-registration, can suggest the prognostic hypothesis of delayed appearance of permanent parenchymal lesions. Co-registration modality, being able to show some false positives, seems to be a valid support for the interpretation of SPECT and PWI findings; the joint analysis of SPECT and PWI highlighted the capability of PWI for the interpretation of uncertain cases.
Abstract: OBJECTIVES: To describe a systemic lupus erythematosus (SLE) patient with functional asplenia and antiphospholipid syndrome (APS) and to review the literature to better define its pathogenesis and diagnosis, emphasizing a possible relationship with antiphospholipid antibodies (aPL). METHODS: Descriptive report of 1 case and review of the literature by means of a MEDLINE search from 1966 to 2002. RESULTS: A SLE patient presented with cutaneous vasculitis and an unexpected thrombocytosis which resulted from autosplenectomy. Subsequently, she developed full-blown APS. In the literature, autosplenectomy has been described only in 1 other case of APS secondary to SLE. However, clinical or laboratory features linked to aPL occurred in several other cases among the 17 cases reported with functional asplenia. CONCLUSIONS: Autosplenectomy in SLE may be pathogenetically related to aPL. Thrombocytosis, unusual in SLE, may be a diagnostic clue of this condition. Pneumococcal vaccination is warranted to prevent life-threatening infections that frequently complicate this asplenia.
Abstract: The main problems related to "early arthritis" are making an accurate diagnosis and predicting the outcome. Clinical evidence strongly suggest that structural damage occur early and that early DMARD treatment improves the long term outcome of disease. Clinical criteria would facilitate early referral of the patients to establish the risk of persistent disease. From the "early arthritis clinics" (E.A.C.) experience has been developed a set of diagnostic criteria characterized by an excellent ability to discriminate, at the first visit, between self-limiting, persistent non-erosive and persistent erosive arthritis. The proposed set consists of 7 criteria: symptom duration (6 weeks - 6 months), morning stiffness of at least 1 hour, arthritis in >/= 3 joints, bilateral compression pain in the metatarsophalangeal joints, IgM-rheumatoid factor positivity, anti-cyclic-citrullinated-peptide antibody positivity and erosions on radiographs of the hands or feet. This approach requests an easy organization to simplify the access to sanitary services and represents an hard challenge both for rheumatologist and health administration.
Abstract: Sjögren's syndrome (SS) is a cell-mediated immune disorder primarily affecting the exocrine glands and hearing loss may be the first otological manifestation of this autoimmune disease. In order to assess the degree of sensorineural hearing loss in SS, 22 female patients were examined by means of standard audiometric tests (pure-tone audiometry, acoustic reflexes and impedance testing) and using distortion product otoacoustic emissions (DPOAEs). The results indicated that only 36.3% of the patients had mild sensorineural hearing loss. Hearing level and distortion product threshold estimates were found to be significantly correlated. No relationship was found between the duration of the disease and the DPOAE and hearing threshold variables. The data suggest that SS may not directly cause sensorineural hearing loss.
Abstract: Rheumatoid arthritis is a chronic inflammatory disease characterised by diarthrodial joint involvement, where bone erosions are the first signs. Early diagnosis, polyarticular exacerbation, treatment unefficacy, concomitant disease or intollerance to therapy represent the reasons that often require hospital admission. The discharges's report is divided into sections. The reason of admission, clinical and laboratory findings, result of aimed tests performed, the treatment administrated, the conclusions in diagnosis favour and the suggested therapy are precised. The discharge's report represents an health iter conclusion, in which the medical services and certificative functions of charitable institutions are combined.
Abstract: Among the systemic manifestations of primary Sjögren's syndrome, neurological involvement is still an intriguing and debated issue. Although peripheral nervous system abnormalities are a well documented occurrence with a reported prevalence ranging from 10 to 20%, opinions differ as to the prevalence of CNS disease, with suggestions from 'nonexistent' to 'very common'. The lack of agreement probably reflects the different populations selected, different inclusion criteria and lack of rigorous epidemiological studies. In our experience, CNS involvement was detected in 7 of 87 (8%) unselected consecutive patients observed over a period of 5 years. The spectrum of CNS involvement is wide, including focal, diffuse, neuropsychiatric and spinal cord symptoms, frequently characterised by insidious onset, remitting course and, sometimes, progressive evolution. The diagnostic approach enabling early recognition of this complication relies on careful clinical assessment using history and physical examination combined with neuropsychological testing and instrumental, laboratory and imaging investigations such as magnetic resonance imaging, single photon emission computed tomography, electrophysiological testing and CSF analysis. The clinical picture often shows spontaneous remission, but when overt neurological symptoms occur or become progressive, therapeutic interventions with high dose corticosteroids and cytotoxic agents, such as intravenous cyclophosphamide pulse therapy, may be indicated.
Abstract: OBJECTIVE: Intercellular adhesion molecule 1 (ICAM-1) is strongly expressed in vascular endothelial cells and perivascular inflammatory infiltrates in immunopathologic studies of Behçet's disease (BD) lesions. ICAM-1 genes may contribute to the inflammatory events responsible for the vessel damage in BD. We examined potential associations of ICAM-1 gene polymorphisms with BD susceptibility. METHODS: Case patients were 74 consecutive Italian patients with BD who were followed at the Bologna, Ferrara, Milano, Potenza, Prato, Reggio Emilia, and Trento rheumatology, ophthalmology, and neurology units over a 3 year period (1997-99) who satisfied the International Study Group criteria for BD; 228 healthy Italian blood donors from the same geographic areas were selected as control groups. All BD patients and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for ICAM-1 polymorphisms at codon 241 (exon 4) and codon 469 (exon 6). RESULTS: The frequency of R241 was significantly higher in BD patients than in controls (20.3% vs 5.7%; p = 0.001, pcorr = 0.002, OR 4.2, 95% CI 1.9-9.3). The distribution of E/K 469 genotype was similar in patients and controls. Comparing patients with different clinical features, we found only a trend to higher frequency of R241 in patients with articular manifestations (21.4% vs 12.5%; p = 0.08). CONCLUSION: Our findings show that G/R 241 polymorphism of ICAM-1 is associated with BD susceptibility.
Abstract: OBJECTIVE: To evaluate the distribution of the MHC class I chain related gene A transmembrane (MICA-TM) alleles in Italian patients with Behçet's disease (BD), and to investigate the relative contribution of MICA alleles and HLA-B51 in the susceptibility and specific clinical features of BD. METHODS: A total of 69 consecutive Italian patients who satisfied the International Study Group criteria for BD were followed at rheumatology, ophthalmology, and neurology units during a 3 year period (1997-99). We selected 130 healthy subjects from the same geographic areas as controls. All patients and controls were examined for MICA microsatellite polymorphisms using polymerase chain reaction. Serological HLA class B51 typing was performed by a standard microlymphocytotoxicity technique. RESULTS: A strong association with HLA-B51 was observed in patients with BD (OR 5.7, 95% CI 2.8-11.3). The MICA-TM allele A6, in linkage disequilibrium with HLA-B51, was only slightly increased in patients compared to controls (60.9% vs 50.8%; p = NS). No significant associations between HLA-B51 or MICA-TM alleles and clinical subgroups, particularly central nervous system or eye involvement, were found. CONCLUSION: HLA-B51 is the most important susceptibility gene in BD. Association with MICA-A6, when it exists, is secondary to the strong linkage disequilibrium with HLA-B51.
Abstract: The presentation, severity and prognosis of rheumatoid arthritis (RA) differ depending on the age of disease onset. Elderly onset RA (EORA: age of onset > 60 years) has been reported to differ from younger-onset RA (YORA) by a more balanced gender distribution, a higher frequency of acute onset often associated with systemic features, more frequent involvement of the shoulder girdle and higher disease activity. To add to our knowledge of this disease, 101 EORA and 88 YORA patients, not previously treated with DMDARs or steroids, were studied and compared, paying particular attention to the onset. The female to male ratio was higher in the YORA group (4.4:1 vs 1.6:1; p < 0.05). The disease duration was similar: 5.6 +/- 3.3 months in EORA and 7.9 +/- 3.8 months in YORA. EORA presented a more frequent acute onset (33.6% vs 13.6%; p < 0.05) especially if rheumatoid factor was absent. This subset also showed more frequent polymyalgic onset. Constitutional symptoms (fever, weight loss, fatigue) were more frequent in EORA patients without differences between seropositive and seronegative patients. The distribution of involved joints showed a significantly higher frequency of shoulder involvement in EORA (64% vs 38%; p < 0.05) and of feet involvement in YORA (25% vs 52%; p < 0.05). Hands and wrists were the most frequently involved joints in all patients.
Abstract: We report a 38-year-old patient affected by refractory adult onset Still's disease who achieved a prolonged remission following CD34-selected ABMT. The conditioning regimen was based on the use of CY and anti-thymocyte globulin. A 3.0 and 2.0 log reduction of T (CD3+) and B (CD19+) lymphocytes, respectively, was obtained using a Ceprate device to select CD34+ cells from PBSC. In the pre-transplant period (1994-1998) the patient had a chronic persistent disease course with frequent and recurrent systemic articular flares and loss of some functional abilities, despite daily prednisone, pulses of CY and immunosuppressive therapy (CYA or MTX). At the time of ABMT the patient had become non-ambulatory. Within 3 weeks of ABMT the patient showed a marked decrease in joint swelling, and morning stiffness. Joint pain and systemic symptoms disappeared, the patient was able to walk and run and gained general well being. ESR, C-reactive protein and WBC count were significantly decreased, while Hb level increased. This partial remission persisted for at least 1 year after ABMT, although at 15 months of follow-up a reappearance of moderate synovitis in the knees and wrists was noted. Our data further showed that both patient BM microenvironment and stem-progenitor cell function (as assessed by LTC-IC assay) were damaged even 1 year after CD34-selected ABMT, suggesting that the persistence of these alterations could have facilitated the favorable outcome of the disease following ABMT. Bone Marrow Transplantation (2000) 25, 1307-1310.
Abstract: To evaluate nervous system involvement in a cohort of Italian patients with primary Sjögren's syndrome (pSS), 87 unselected patients (83 female, and four male) observed consecutively at our institution over a period of 5 years were screened by clinical and instrumental (MRI, SPECT, electrophysiological testing, CSF analysis) investigations for peripheral and central neurological abnormalities. Seroimmunological parameters and extraglandular features other than neurological manifestations were also evaluated. Seven patients had central nervous system (CNS) disease (8%), mostly non-focal dysfunction, and 12 had peripheral nervous system (PNS) disease (13.8%), mostly mild or severe sensory or sensory-motor polyneuropathies. One patient had concomitant CNS and PNS involvement. Compared with CNS disease, PNS involvement occurred in older patients (> 50 years), independent of the disease duration. Patients with and without neurological abnormalities did not differ for seroimmunological parameters (including antiphospholipid antibodies) or extraglandular manifestations. From a statistical point of view, the only relevant finding was the detection of a slight increase in serum IgA and IgM levels (p < 0.05) in patients with an intact nervous system. Neurological involvement in pSS, be it central or peripheral, is not a rare finding. A careful clinical neurological evaluation, combined with a multiplicity of instrumental investigations, is recommended in the global assessment of pSS patients.
Abstract: OBJECTIVE: To determine whether acute attacks of uric acid and calcium pyrophosphate microcrystalline arthritis show a seasonal variation and, if so, to verify whether the distribution of single episodes shows a rhythmic circannual pattern. METHOD: All suspected cases of microcrystalline acute arthritis observed at the General Hospital of Ferrara during an 8 yr period (January 1990-December 1997) were considered. Diagnosis was made on the basis of history, physical examination and analysis of synovial fluid by means of polarized light microscopy. Month and day of each event were categorized both into four 3-month periods (by seasons) and 12 monthly intervals. Two different statistical methods have been utilized: chi(2) test for goodness of fit and partial Fourier series. RESULTS: During the period considered, 210 episodes of acute gout were observed [196 in males (93.3%) and 14 in females (6.7%)] in 179 different subjects, and 179 episodes of acute pseudogout [58 in males (32.4%) and 121 in females (67.6%)] in 165 different subjects. Gout attacks showed a higher frequency peak in spring [76 cases (36. 2%), P<0.001]. Analysis of distribution of events by gender confirmed the clear spring pattern in males (36.2%), whereas the paucity of cases in females did not allow any valid statistical analysis. Pseudogout attacks showed a higher frequency peak in autumn [52 cases (29.1%)], without reaching a statistically significant level either for the total sample or for subgroups divided by gender. Analysis of the seasonal distribution of gout or pseudogout events was significantly different (chi(2) 15.7, P=0.001). Chronobiological evaluation by means of Fourier analysis showed a circannual pattern for gout attacks, both for the total sample (P=0.006) and the male subgroup (P=0.003), characterized by a peak in April and a trough in October. Again, as for pseudogout events, no seasonal variation was found, either for the total sample or subgroups by gender. CONCLUSIONS: The present study gives further confirmation that acute gout attacks exhibit a circannual distribution in their occurrence, being more frequent in April, whereas pseudogout attacks do not. Moreover, the seasonal distribution of gout and pseudogout acute events is significantly different.
Abstract: Our objective was to identify nuclear calreticulin-binding protein(s) and investigate whether there is a correlation between presence of autoantibodies against calreticulin and calreticulin-binding protein(s) in the sera of patients suffering from systemic lupus erythematosus (SLE). The ligand overlay procedure using digoxigenin-labelled calreticulin was used to identify a calreticulin-binding protein in the nuclear fraction of bovine brain. Fractionation of the nuclear components was used to localize the major positive calreticulin-binding protein. The protein was partially purified using hydroxylapatitie chromatography and subjected to NH2-amino acid sequence analysis. Immunoblots using the sera of SLE patients were then carried out on calreticulin and the calreticulin-binding protein. The calreticulin-binding protein present in the nucleoplasm was identified as histone H1. Approximately 62% (26/42) patients with SLE had IgG antibodies directed against H1 whereas the sera of healthy individuals did not react with the antigen; 36% of patients with SLE had both anti-calreticulin and anti-histone H1 antibodies. Phosphorylation of the latter protein did not alter its immunoreactivity. These findings demonstrate that the concomitant presence of autoantibodies directed against both calreticulin and histone H1 occurs frequently in patients with SLE and may help shed some light on the mechanisms which bring about the autoimmune response.
Abstract: OBJECTIVES: Conflicting results on the relationship between gallstone disease and the use of nonsteroidal antiinflammatory drugs (NSAIDs) have been reported, but studies on the effect of NSAID use in populations not selected on the basis of a high risk for gallstone development are still lacking. METHODS: We conducted a case-control study involving 216 patients, regular NSAID users (43 men and 173 women) consecutively admitted to a rheumatology department, suffering from rheumatoid arthritis (n = 147), osteoarthritis (n = 49), and ankylosing spondylitis (n = 20). Two-hundred sixteen patients who were not NSAID users, matched for gender, age, and body mass index, consecutively admitted to a medical department for various medical pathologies, acted as a control group. All patients underwent upper abdomen ultrasonography. RESULTS: The overall prevalence of gallstones was similar in the two groups: 24.0% in NSAID users (15.7% actual stones and 8.3% previous cholecystectomy) and 21.3% in controls (13.9% gallstones and 7.4% cholecystectomy). The prevalence of gallstone disease was significantly higher in women than in men, and the mean age was higher in gallstone patients than in gallstone-free patients, in both groups. No significant differences in type and duration of arthritis condition, type and dose of NSAID taken, and duration of treatment between gallstone patients and gallstone-free patients were found. On logistic regression analysis only female gender, aging, and family history of gallstone disease were significantly associated with the presence of gallstones, whereas no relationship between NSAID use and gallstone disease was found. CONCLUSIONS: Chronic NSAID ingestion does not seem to prevent gallstones in arthritis patients; in these patients gallstone disease is associated with classic risk factors (female gender and age).
Abstract: The diagnosis of central nervous system (CNS) involvement appears to be a major problem in systemic lupus erythematosus (SLE), especially when the clinical signs are non-specific or neuroimaging is unremarkable. Two SLE patients with mild neuropsychiatric manifestations were studied with magnetic resonance imaging (MRI), single photon emission tomography (SPET) and localized proton magnetic resonance spectroscopy (H-1 MRS). MRI was normal in both patients. SPET revealed areas of hypoperfusion in both patients. H-1 MRS demonstrated metabolic abnormalities in the regions corresponding to the hypoperfused areas. A correlation between H-1 MRS and SPET was noted: patients with mild neuropsychiatric SLE may have disturbances evident on SPET and H-1 MRS in the presence of normal anatomy on MRI, suggesting that CNS involvement in SLE has very strong physiological and neurometabolic components in individual patients.
Abstract: About one third of all patients with systemic sclerosis (SS) presents colon abnormalities, although these may be underestimated because they frequently remain asymptomatic for a long time. Thirty-five patients (33 women and 2 men; mean age 56.5 years; mean disease duration 11.9 years) affected by SS (25 with limited and 10 with diffuse pattern of skin involvement) were investigated using barium enema to detect radiological changes in the colon, and to correlate them with other visceral involvement, autoantibody profile, abdominal symptoms and duration of the disease. Ten patients (28.6%) showed X-rays abnormalities (excluding isolated diverticula), wide-mouthed sacculations being the most frequent finding. Our data confirm that the colon is frequently involved in SS, even in the limited form of the disease. The most relevant finding was the dissociation between clinical symptoms and radiological features which proved to be more evident among the patients with limited SS. No correlations were found between the radiological picture and any other parameter, thus suggesting that careful evaluation of the colon should be performed in any patient suffering from the disease.
Abstract: Pulmonary hypertension is rarely described in association with Sjögren's syndrome. The authors report the case of a patient in which pulmonary hypertension was the inaugural clinical manifestation of primary Sjögren's syndrome. Clinical assessment, differential diagnosis, etiopathological implications, and therapeutic approach are discussed.
Abstract: OBJECTIVE--To determine the frequency and relative risk of bronchial hyperreactivity to methacholine in systemic sclerosis patients with or without associated Sjögren's syndrome. METHODS--A prospective study of 56 patients with systemic sclerosis (42 with the diffuse and 14 with the limited variant; 24 with associated Sjögren's syndrome), 57 with primary Sjögren's syndrome, and 61 healthy controls. RESULTS--Bronchial hyperreactivity (BH) was present in 6.5% of the healthy controls, 25% of the systemic sclerosis patients without associated Sjögren's syndrome, 42.2% of those with primary Sjögren's syndrome, and in 50% of those with systemic sclerosis with associated Sjögren's syndrome. The presence of BH did not correlate with age, disease duration, chest radiograph abnormalities, respiratory, and immunological data. The subgroup of subjects with the limited variant of systemic sclerosis more frequently had associated BH than did those with the diffuse variant of the disease; coexisting Sjögren's syndrome further increased this frequency. CONCLUSIONS--In agreement with previous studies, we have confirmed the high prevalence of bronchial hyperreactivity in primary Sjögren's syndrome; systemic sclerosis likewise appears to be associated with an increased frequency of bronchial hyperreactivity compared with healthy control subjects. There is evidence also that the coexistence of Sjögren's syndrome and systemic sclerosis further increases the frequency and the calculated relative risk of developing bronchial hyperreactivity.
Abstract: Previous studies with intraarticular administration of somatostatin (SST14) in rheumatoid arthritis showed an antiinflammatory and analgesic effect. The aim of the present study was to demonstrate the efficacy and tolerability of SST14 in rheumatoid arthritis (RA) patients for a longer period of treatment than previously scheduled. Forty-one patients with RA of the knee were treated with a cycle of intraarticular injection of 750 micrograms of SST14, every 15 days. The efficacy of SST14 was evaluated by determining acute phase parameters (erythrocyte sedimentation rate, C-reactive protein [CRP]) and by clinical assessment (pain at rest and on movement, joint tenderness, morning stiffness, spontaneous pain). Additionally, telethermography was performed to evaluate the intensity of the joint inflammation. The tolerability of the treatment was also assessed both by patients and physicians. SST14 produced a reduction in all parameters; this was already statistically significant after the second injection in terms of pain at rest and on movement, and after the third injection for all other symptoms. The treatment showed an excellent tolerability, both local and systemic. Our results indicate the analgesic property of SST14 and demonstrate its capacity to reduce progressively joint inflammation confirmed by thermography and by reduction of pain, after a month of therapy.
Abstract: STUDY OBJECTIVE: To determine whether there is a specific temporal risk for opioid drug overdose. DESIGN: To study patients presenting to the ED in a comatose state from accidental drug opioid overdose. PARTICIPANTS: Two hundred seventy-four patients were admitted to the ED of the Hospital of Ferrara, Italy, from 1988 to 1990, 225 men (82.1%; mean age, 25 +/- 3.4 years) and 49 women (17.9%; mean age, 23.5 +/- 2.8 years). INTERVENTIONS: Month, day, and hour and minute of admissions were recorded, and time-qualified frequency data were analyzed by the single cosinor method. RESULTS: Cosinor analysis demonstrated a significant circadian rhythm for both the total number of observations and the separate male and female subgroups with an early evening peak ("acrophase") at about 7:00 PM. No significant circannual rhythm was evident, but for the total group a significant 6-month rhythm was demonstrable with peaks in late November and late May. CONCLUSION: There is a distinct "chronorisk" of opioid drug overdose in the early evening hours.
Abstract: Various musculoskeletal abnormalities caused by electrical injury are described. Such abnormalities usually include fractures or dislocation of adjacent bones and joints. Osteonecrosis is a noteworthy, but less common, consequence of electric shock. The case is discussed of a 52-year-old woman who had received an electric shock (220-V alternating household current) to the right hand and developed osteonecrosis in the ipsilateral humeral head, most likely caused by bone "melting." An osteonecrotic lesion may therefore develop in a joint at a distance from the point of electrical contact, and this must always be kept in mind in diagnosis and treatment.
Abstract: A detailed examination of the hands and feet was performed in a group of 34 patients affected by systemic lupus erythematosus (SLE), using low-dose mammographic film and Rank Xerox selenium plate, according to current diagnostic techniques. All patients presented articular symptoms (pain and arthralgia). The high incidence (38,8%) of patients with no radiographic evidence of bone damage-even though articular symptoms are present-is emphasized. In such cases, it is very difficult to distinguish SLE from rheumatoid arthritis, especially as far as therapeutic management and prognosis are concerned. The lack of any "pathognomonic" radiological sign of the lupus arthritis, in the hands as well as in the feet, is then stressed. Nevertheless, arthropathy in SLE is defined as a deforming non-erosive arthritis, with a typical symmetric distribution, affecting most commonly-according to incidence-the proximal interphalangeal and metacarpophalangeal joints. In the hand, arthropathy is referred to as Jaccoud's type arthritis, because it is characterized by joint deformities which can be corrected. In the foot, the main abnormalities include hallux valgus, subluxation of the metatarsophalangeal joints and widening of the forefoot.
