Characteristics of joint involvement and relationships with systemic inflammation in systemic sclerosis: results from the EULAR Scleroderma Trial and Research Group (EUSTAR) database.

OBJECTIVE: To determine the prevalence of and independent factors associated with joint involvement in a large population of patients with systemic sclerosis (SSc). METHODS: This study was cross-sectional, based on data collected on patients included in the European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) registry. We queried this database to extract data regarding global evaluation of patients with SSc and the presence of any clinical articular involvement: synovitis (tender and swollen joints), tendon friction rubs (rubbing sensation detected as the tendon was moved), and joint contracture (stiffness of the joints that decreased their range of motion). Overall joint involvement was defined by the occurrence of synovitis and/or joint contracture and/or tendon friction rubs. RESULTS: We recruited 7286 patients with SSc; their mean age was 56 +/- 14 years, disease duration 10 +/- 9 years, and 4210 (58%) had a limited cutaneous disease subset. Frequencies of synovitis, tendon friction rubs, and joint contractures were 16%, 11%, and 31%, respectively. Synovitis, tendon friction rubs, and joint contracture were more prevalent in patients with the diffuse cutaneous subset and were associated together and with severe vascular, muscular, renal, and interstitial lung involvement. Moreover, synovitis had the highest strength of association with elevated acute-phase reactants taken as the dependent variable. CONCLUSION: Our results highlight the striking level of articular involvement in SSc, as evaluated by systematic examination in a large cohort of patients with SSc. Our data also show that synovitis, joint contracture, and tendon friction rubs are associated with a more severe disease and with systemic inflammation.

Clinical, serologic and instrumental data of ten patients affected by sclerodermatous chronic graft versus host disease: similarities and differences in respect to systemic sclerosis.

Chronic graft versus host disease (cGVHD), the most common late complication of allogeneic haematopoietic stem cell transplantation (HSCT), may present with sclerodermatous lesions resembling in some cases the cutaneous involvement of systemic sclerosis (SSc). Certain pathogenetic findings connect the two diseases. In this report we describe ten subjects affected by cGVHD who underwent the examinations routinely carried out to stage SSc patients. Demographic, clinical, serologic and instrumental data were recorded. These patients showed differences in appearance, extent and progression of the sclerodermatous lesions with greater involvement of the trunk and proximal part of the limbs than the extremities. In seven subjects ANA test was positive; scleroderma-associated autoantibodies were not detected in any of the cases. Moreover, typical organ involvement of SSc was not found. Only one patient developed Raynauds phenomenon after HSCT and only one patient demonstrated a nailfold videocapillaroscopic scleroderma pattern. Except for cutaneous involvement of cGVHD, that may resemble SSc, the clinical features of the two diseases are quite different, suggesting that the fibrotic process characterizing cGVHD and SSc has different etiologies and different initial pathobiologic events.

Study on the possible role of the -174G>C IL-6 promoter polymorphism in predicting response to rituximab in rheumatoid arthritis.

OBJECTIVE: Identification of genetic biomarkers of response to biologics in rheumatoid arthritis (RA) is a relevant issue. The -174G>C interleukin-6 (IL-6) promoter polymorphism was investigated in RA patients treated with rituximab (RTX), being IL-6 a key cytokine for B cell survival and proliferation, thus possibly implicated in rituximab efficacy. METHODS: The study was conducted in a real-life retrospective cohort of 142 unselected RA patients (120F/22M) treated with RTX and referred to 7 rheumatologic centres in the north of Italy. One hundred and thirteen (79.6%) patients were rheumatoid factor (RF)-positive and 112 (78.9%) were anti-CCP antibodies positive. The response to therapy was evaluated at the end of the sixth month after the first RTX infusion, by using both the EULAR criteria (DAS28) and the ACR criteria. The IL-6 -174G>C promoter polymorphism was analyzed by RFLP following previously reported methods. RESULTS: Lack of response to RTX at month +6 by EULAR criteria was more prevalent in RA patients with the IL-6 -174 CC genotypes (9/21, 42.8%), than in the GC/GG patients (23/121, 19.0%) (OR 3.196, 95% CI=1.204-8.485; p=0.0234). Similar results were found when evaluating the response by ACR criteria. No differences were found in RA duration, baseline DAS28, baseline HAQ, RF status, anti-CCP status according to the different IL-6 -174 genotypes. CONCLUSION: IL-6 promoter genotyping may be useful to better plan treatment with RTX in RA. Larger replication studies are in course to confirm these preliminary results.

[Sustained response to infliximab treatment in two cases of early rheumatoid arthritis that has been maintained after drug withdrawal]. / Due casi di artrite reumatoide trattati in fase precoce con infliximab con mantenimento dell'effetto dopo la sospensione del farmaco.

The authors report two cases of active seropositive rheumatoid arthritis who were treated in an early phase of the disease with infliximab plus methotrexate obtaining a clinical remission. The benefit was maintained after the discontinuation of the anti-TNF alpha inhibitor for adverse events, indicating that the early administration of the drug may be followed by a sustained remission.

[Chikungunya arthritis: report of 6 cases]. / Artropatia da Chikungunya: descrizione di 6 casi.

Chikungunya is an arboviral disease transmitted by Aedes mosquitoes. The disease typically consists of an acute illness characterised by fever, rash, and incapacitating arthralgia, that can persist for months. Chikungunya virus, a member of the genus Alphavirus, has recently caused a large outbreak on islands in the Indian Ocean and on the Indian subcontinent. The ongoing outbreak has involved more than 1.5 million patients, including travellers who have visited these areas. We describe our casistic of six travellers with Chikungunya arthropathy. All patients experienced fever and rash of short term during a travel in areas of epidemicity. All patients had peripheral poliarthralgias, which duration was >2 months in 4 cases (66%) and >6 months in 1 case (16%).

Scleroderma patients nailfold videocapillaroscopic patterns are associated with disease subset and disease severity.

OBJECTIVE: To evaluate in a large group of scleroderma patients, the association of nailfold videocapillaroscopic patterns with both demographic and clinical features. METHODS: One hundred and three Italian patients (91 women and 12 men, mean age 54.3 years, median disease duration 7 yrs, 68 with limited and 35 with diffuse subset of disease), consecutively enrolled for the study, underwent nailfold videocapillaroscopy; the microvascular alterations were classified into three different patterns, early, active and late. The nailfold videocapillaroscopic patterns were correlated with such numerous clinical features as sex, age, disease duration, disease subset, disease activity, haematochemical data, involvement of skin, heart, lung and peripheral vessels. RESULTS: Nailfold videocapillaroscopic patterns were significantly associated with disease subsets (P = 0.018). Severity of skin, lung, heart and peripheral vascular involvement progressively increased across nailfold videocapillaroscopic patterns, from early to late pattern (P < 0.001 for cutaneous and peripheral vascular involvement; P = 0.003 and 0.002 for lung and heart involvement, respectively) as well as homocysteine plasma levels (P = 0.02). Patients with late pattern showed an increased risk to have an active disease [OR (odds ratio) 3.50; 95% CI (confidence interval) 1.31-9.39], to present digital ulcers (OR 5.74; 95% CI 2.08-15.89) and moderate to severe skin (OR 5.28; 95% CI 1.93-14.19), heart (OR 5.75; 95% CI 2.04-16.21) and lung involvement (OR 4.41; 95% CI 1.63-11.92). CONCLUSIONS: Our study showed that scleroderma microangiopathy correlates with disease subset and severity of peripheral vascular, skin, heart and lung involvement; patients with late pattern showed an increased risk to have an active disease and to show a moderate/severe skin or visceral involvement compared to patients with early and active patterns. Therefore nailfold videocapillaroscopy, a simple, non-invasive and non-expensive investigation, is useful in staging scleroderma patients and also provides prognostic information.

Levels of F2-isoprostanes in systemic sclerosis: correlation with clinical features.

OBJECTIVE: Oxidative stress may be one of the important complex pathogenetic mechanisms that lead to damage in scleroderma; free radicals may provoke endothelial injury, fibroblast proliferation and fragmentation of autoantigens favouring induction of autoantibodies. The present study investigates the oxidant status in scleroderma patients by measuring the urinary concentration of 8-isoprostaglandin-F2alpha, an F2-isoprostane, and a product of free radical-mediated peroxidation of arachidonic acid. METHODS: Forty-three scleroderma patients (42 women and 1 man, mean age 54.1 yr, mean disease duration 9.0 yr) underwent clinical evaluation and instrumental investigations in order to assess skin, vascular, lung and heart involvement. Von Willebrand factor was evaluated as marker of vascular dysfunction in 36 out of the 43 cases. The urinary level of 8-isoprostaglandin-F2alpha was measured in all scleroderma patients and in the 43 age- and sex-matched healthy controls. RESULTS: Urinary levels of 8-isoprostaglandin-F2alpha were higher in scleroderma patients than in the healthy control group (341.7 vs 147.6 pg/mg creatinine; P < 0.001). Values of 8-isoprostaglandin-F2alpha were strongly correlated with the nailfold videocapillaroscopy pattern and lung involvement (P = 0.002 and 0.003, respectively), showing increasing levels with the progression of pulmonary severity. Correlation between 8-isoprostaglandin-F2alpha level and von Willebrand factor narrowly failed to reach statistical significance (P = 0.05). There was no correlation between 8-isoprostaglandin-F2alpha concentration and disease activity, vascular, skin and heart involvement, disease pattern or autoantibody profile. CONCLUSIONS: Our study further supports the role of oxidant stress in the pathogenesis of scleroderma, showing a strong correlation between a marker of free radical damage with both the severity of lung involvement and the videocapillaroscopic patterns.

Pregnancy, microchimerism and autoimmunity: an update.

The presence of a small population of cells or DNA in one individual that derives from another genetically distinct person is referred to as microchimerism; this process may occur in course of pregnancy from mother to fetus, and vice versa. The clinical similarities between some features of autoimmune diseases and the chronic graft versus host disease, the increased incidence of autoimmune diseases observed in women after childbearing age, and the long-term persistence of microchimerism have raised the hypothesis that microchimerism could be involved in the pathogenesis of autoimmune diseases. To assess the possible relationship between pregnancy and the incidence of systemic sclerosis we performed a hospital-based case-control study. Our results, indicating a reduced risk for systemic sclerosis in women who had been pregnant in comparison with women who had not, seem to indicate that pregnancy is not a risk factor for systemic sclerosis.

A case of ANCA-associated vasculitis with predominant involvement of central nervous system.

The authors present a peculiar case of a 53-year-old woman affected by ANCA-associated vasculitis with prevailing involvement of the central nervous system. Diagnosis was really difficult.

Mucosa-associated lymphoid tissue lymphoma of the salivary glands occurring in patients affected by Sjögren's syndrome: report of 6 cases.

OBJECTIVE: Mucosa-associated lymphoid tissue (MALT) lymphoma of the salivary glands occurring in 6 patients affected by primary Sjögren's syndrome is reported. METHODS: Clinical findings, histologic type, stage, treatment and outcome of the 6 patients have been revised. RESULTS: In all 6 cases the lymphoma was of the MALT type. Four patients had stage IE disease, 1 patient had stage IIE disease and 1 patient had stage IV disease. The patients received different treatments resulting in all cases in prolonged remission. After 7 years of complete remission 1 patient developed a diffuse large B-cell lymphoma. CONCLUSION: MALT lymphoma of the salivary glands is an indolent disease. Though the best therapy of this lymphoproliferative disorder remains to be established, prolonged remission has been obtained in our cases with different therapeutic approaches. We review the literature regarding the relationship between Sjögren's syndrome and MALT lymphomas and study the mechanisms which may be involved in the transformation from a lymphoepithelial lesion into a neoplastic disorder.

[Thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus. Clinical diagnosis and therapeutic strategies]. / Porpora trombotica trombocitopenica associata a lupus eritematoso sistemico. Inquadramento clinico-diagnostico e strategie terapeutiche.

The aim of our work is the focusing on some aspects about both the etiopathogenesis of thrombotic thrombocytopenic purpura and the therapeutic choices required to strongly reduce the mortality. Moreover the article reviews the association between thrombotic thrombocytopenic purpura and systemic lupus erythematosus. Thrombotic thrombocytopenic purpura is a rare and severe hematologic syndrome, first described in 1924, characterized by a clinical pentade: fever, microangiopathic anemia, thrombocytopenia, neurologic abnormalities and renal involvement. It is unknown if the endothelial damage represents the first lesion or if the platelet hyperaggregability precedes the vascular injury. Some data suggest a possible role of immune mechanisms in the development of the disease, that may be associated in some cases with autoimmune disorders. To our knowledge 31 cases of association between thrombotic thrombocytopenic purpura and systemic lupus erythematosus are reported in the English literature from 1970 today; the link between the two diseases is unclear. The authors review these cases with particular care to the diagnosis, that may be very difficult, and the therapy.

[Aspects of thrombophilia in Buerger's disease]. / Aspetti di trombofilia nel morbo di Buerger.

Buerger's disease or thromboangiitis obliterans is a disorder of unknown etiology which affects young heavy smokers, mainly of male sex; it is not clear why this disease afflicts only a little number of heavy smokers. Studies about genetic predisposition, autoimmune phenomena and platelet function have been performed in order to search additional etiologic factors without finding significant alterations. Recently some cases of Buerger's disease in association with hypercoagulable states have been described. The authors reported ten subjects affected by Buerger's disease, who have undergone to a clotting process evaluation. We have found 3 cases with fasting hyperhomocysteinemia in association with low level of plasma folate, 3 cases with high value of lipoprotein(a) (in 1 subject in association with IgG anticardiolipin antibody positivity), 1 case with IgM anticardiolipin antibody positivity. These findings, along with literature data, induce to hypothesize that hypercoagulable states may favour the clinical expression of Buerger's disease.