Rheumatoid Arthritis: Italy

Palazzi C, D'Angelo S, Olivieri I. · Rheumatology Department of Lucania, San Carlo Hospital of Potenza, Potenza, Italy. · Autoimmun Rev. · Pubmed #18707027 No free full text.

Abstract: Although asymptomatic joint involvement and arthralgias are frequent in patients with hepatitis C virus chronic infection (HCV), a true arthritis affects only up to 4% of the subjects. HCV-related arthritis (HCVrA) is usually distinguished in two clinical subsets: a more frequent symmetrical polyarthritis (SP), similar to rheumatoid arthritis but much less serious, and an intermittent mono-oligoarthritis (IMO) that involves medium and large sized joints, mainly the ankle. This latter subset is strictly related to the presence of HCV-induced mixed cryoglobulinemia and its cutaneous manifestations, in particular purpura. According to recent reports, anti-CCP antibodies are considered very useful in differentiating the SP subset from rheumatoid arthritis. The treatment of HCVrA is still largely empirical because few studies have analyzed this topic. However, COXIBs, NSAIDs, low doses of corticosteroids, hydroxychloroquine and less frequently methotrexate and penicillamine have been used with partial or complete control of symptoms. On the basis of recent studies, the administration of cyclosporine also seems to be sufficiently safe. The scarcely aggressive nature of HCVrA does not favour the use of anti-TNF agents. Specific anti-viral therapy (interferon-alpha+ribavirin) must be accurately evaluated because interferon-alpha can induce the development or the worsening of several autoimmune HCV-related disorders including arthritis.

Franciotta D, Salvetti M, Lolli F, Serafini B, Aloisi F. · Laboratory of Neuroimmunology, IRCCS Neurological Institute C Mondino, via Mondino 2, 27100, Pavia, Italy. · Lancet Neurol. · Pubmed #18703007 No free full text.

Abstract: Clonal expansion of B cells and the production of oligoclonal IgG in the brain and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) have long been interpreted as circumstantial evidence of the immune-mediated pathogenesis of the disease and suggest a possible infectious cause. Extensive work on intrathecally produced antibodies has not yet clarified whether they are pathogenetically relevant. Irrespective of antibody specificity, however, the processes of antibody synthesis in the CNS of patients with MS are becoming increasingly clear. Likewise, targeting B cells might be therapeutically relevant in MS and other autoimmune diseases that are deemed to be driven predominantly by T cells. Accumulating evidence indicates that in MS, similar to rheumatoid arthritis, B cells aggregate into lymphoid-like structures in the target organ. The process of aggregation is mediated through the expression of lymphoid-homing chemokines. In the brain of a patient with MS, ectopic B-cell follicles preferentially adjoin the pial membrane within the subarachnoid space. Recent findings indicate that substantial numbers of B cells that are infected with Epstein-Barr virus (EBV) accumulate in these intrameningeal follicles and in white matter lesions and are probably the target of a cytotoxic immune response. These findings, which await confirmation, could be an explanation for the continuous B-cell and T-cell activation in MS, but leave open concerns about the possible pathogenicity of autoantibodies. Going beyond the antimyelin-antibody dogma, the above data warrant further work on various B-cell-related mechanisms, including investigation of B-cell effector and regulatory functions, definition of the consistency of CNS colonisation by Epstein-Barr virus-infected B cells, and understanding of the mechanisms that underlie the formation and persistence of tertiary lymphoid tissues in patients with MS and other chronic autoimmune diseases (ectopic follicle syndromes). This work will stimulate new and unconventional ways of reasoning about MS pathogenesis.

Conti F, Rezai S, Valesini G. · Dipartimento di Clinica e Terapia Medica Applicata, Sezione di Reumatologia, Sapienza Università di Roma, Rome, Italy. · Autoimmun Rev. · Pubmed #18700175 No free full text.

Abstract: Patients with autoimmune rheumatic diseases are at increased risk of developing infections. However, concerns about the safety and the immunogenicity of vaccines in these patients limited their use. Most of the data against the use of vaccines come from the reported cases of previously healthy individuals who presented the onset of rheumatic diseases after immunization, nevertheless a causal relationship has not been established. During the past few decades influenza and pneumococcal vaccines, administered to patients with systemic lupus erythematosus, were found to be safe and, generally, serologically effective, even though there is the possibility of inadequate response, especially in patients receiving immunosuppressive agents. In patients with rheumatoid arthritis influenza and pneumococcal vaccines can be considered safe and immunogenic in most cases. Treatment with TNFalpha blocking agents did not appear to impair the immune response.

Lunardi C, Tinazzi E, Bason C, Dolcino M, Corrocher R, Puccetti A. · Department of Clinical and Experimental Medicine, Section of Internal Medicine, University of Verona, Verona, Italy. · Autoimmun Rev. · Pubmed #18700174 No free full text.

Abstract: Human parvovirus B19 infection is responsible for a wide range of human diseases ranging from mild erythema infectiosum in immunocompetent children to fetal loss in primary infected pregnant women and aplastic anemia or lethal cytopenias in adult immunocompromised patients. Since persistent viral infection is responsible for an autoimmune response and clinical symptoms can mimic autoimmune inflammatory disorders, parvovirus B19 is the object of intense efforts to clarify whether it is also able to trigger autoimmune diseases. Indeed the virus has been implicated as the causative or the precipitating agent of several autoimmune disorders including rheumatoid arthritis, systemic lupus, antiphospholipid syndrome, systemic sclerosis and vasculitides. Molecular mimicry between host and viral proteins seems to be the main mechanism involved in the induction of autoimmunity. By means of a random peptide library approach, we have identified a peptide that shares homology with parvovirus VP1 protein and with human cytokeratin. Moreover the VP peptide shares similarity with the transcription factor GATA1 that plays an essential role in megakaryopoiesis and in erythropoiesis. These new data sustain the role played by molecular mimicry in the induction of cross-reactive (auto)antibodies by parvovirus B19 infection.

Galeazzi M, Giannitti C, Manganelli S, Benucci M, Scarpato S, Bazzani C, Caporali R, Sebastiani GD. · Sezione di Reumatologia, Dipartimento di Medicina Clinica e Scienze Imunologiche, Università di Siena, Italy. · Autoimmun Rev. · Pubmed #18694850 No free full text.

Abstract: A wide variety of rheumatic diseases has been documented in the presence of hepatitis C virus (HCV) infection and in human immunodeficiency virus (HIV) infection. In this conditions, physicians are refrained from using corticosteroids and/or immunosuppressants agents because of the risk of favouring viral replication and the progression of the underlying viral disease. In the present review we have focused our attention on the possible role of cyclosporine A (CsA), anti-Tumour Necrosis Factor (TNF) alpha agents in the treatment of HIV or HCV infected autoimmune patients. The results drown from the literature and from our personal experience confirm the safety of CsA and anti-TNF alpha agents, in terms of viral load and liver toxicity. A limited experience also suggest that both therapies can be given in combination in rheumatoid arthritis patients without increasing the risk of adverse events.

Baricordi OR, Stignani M, Melchiorri L, Rizzo R. · Laboratory of Immunogenetics, Section of Medical Genetics, Department of Experimental and Diagnostic Medicine, University of Ferrara, Via Luigi Borsari 46, Ferrara, Italy. · Inflamm Allergy Drug Targets. · Pubmed #18691135 No free full text.

Abstract: HLA-G antigens are non classical HLA-class I molecules characterized by a low allelic polymorphism, a limited tissue distribution and the presence of membrane bound and soluble isoforms. The HLA-G antigens were firstly detected in cytotrophoblast cells at the feto-maternal interface where they maintain a tolerogenic status between the mother and the semiallogenic fetus. Recently a variable expression of HLA-G molecules has been documented in several autoimmune diseases, viral infections, cancer diseases and transplantation. Overall the presence of HLA-G molecules in both membranes bound and soluble isoforms was associated with tolerogenic functions against innate and adaptative cellular responses. HLA-G antigens are able to affect the cytotoxicity of natural killer and CD8+ T cells, CD4+ T lymphocyte functions and dendritic cell maturation. In addition to the allelic polymorphism the HLA-G gene shows a deletion/insertion polymorphism of a 14 base pairs sequence (14bp) in the exon 8 at the 3' untranslated region. Several reports have associated the presence of the 14bp insertion allele (+14bp) to an unstable mRNA and a lower sHLA-G protein production, suggesting a different ability to counteract inflammation between genotypes. We reviewed the literature on the expression of HLA-G antigens in autoimmune and allergic diseases and the possible functional role of these molecules in counteracting inflammation.

Sales C, Oliviero F, Spinella P. · Servizio di Dietetica e Nutrizione Clinica, Dipartimento di Medicina Clinica e Sperimentale, Università di Padova, Via Giustiniani 2, Padua, Italy. · Reumatismo. · Pubmed #18651052 links to  free full text

Abstract: The beneficial effects of omega-3 polyunsaturated fatty acids have been widely described in the literature in particular those on cardiovascular system. In the last decade there has been an increased interest in the role of these nutrients in the reduction of articular inflammation as well as in the improvement of clinical symptoms in subjects affected by rheumatic diseases, in particular rheumatoid arthritis (RA). Nutritional supplementation with omega-3 may represent an additional therapy to the traditional pharmacological treatment due to the anti-inflammatory properties which characterize this class of lipids: production of alternative eicosanoids, reduction of inflammatory cytokines, reduction of T-lymphocytes activation, reduction of catabolic enzymes activity. The encouraging results of dietetic therapy based on omega-3 in RA are leading researchers to test their effectiveness on patients with other rheumatic conditions such as systemic lupus erythematosus and ankylosing spondylitis. Nutritional therapy based on food rich in omega-3 or on supplementation with fish oil capsules, proved to be a valid support to he treatment of chronic inflammatory rheumatic diseases.

Alivernini S, Fedele AL, Cuoghi I, Tolusso B, Ferraccioli G. · Cattedra e Clinica di Reumatologia, Università Cattolica del Sacro Cuore, Via Moscati 31, Rome, Italy. · Reumatismo. · Pubmed #18651051 links to  free full text

Abstract: Rheumatoid arthritis is a chronic inflammatory disease characterized by synovial inflammation and pannus formation leading to destruction of cartilage and bone. Several self proteins have been suggested to be disease-driving autoantigens. Proteins are encoded by a limited number of genes in our genome. Post-translational modifications such as citrullination of the arginine residues, can increase the morphological and the functional diversity of the proteome. The positivity of anti-citrullinated peptides autoantibodies occurs then at an early stage of the disease development. Several factors, among which the synovial tissue inflammatory and the nitric oxide reaction, are involved in the regulation of the citrullination reaction. All of them have to be analysed and considered to understand the loss of tolerance and the development of autoimmunity leading to the disease.

Adorini L, Penna G. · Intercept Pharmaceuticals, Corciano (Perugia), Italy. · Nat Clin Pract Rheumatol. · Pubmed #18594491 No free full text.

Abstract: 1,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], the biologically active form of vitamin D(3), is a secosteroid hormone essential for bone and mineral homeostasis. It regulates the growth and differentiation of multiple cell types, and displays immunoregulatory and anti-inflammatory properties. Cells involved in innate and adaptive immune responses--including macrophages, dendritic cells, T cells and B cells--express the vitamin D receptor (VDR), and can both produce and respond to 1,25(OH)(2)D(3). The net effect of the vitamin D system on the immune response is an enhancement of innate immunity coupled with multifaceted regulation of adaptive immunity. Epidemiological evidence indicates a significant association between vitamin D deficiency and an increased incidence of several autoimmune diseases, and clarification of the physiological role of endogenous VDR agonists in the regulation of autoimmune responses will guide the development of pharmacological VDR agonists for use in the clinic. The antiproliferative, prodifferentiative, antibacterial, immunomodulatory and anti-inflammatory properties of synthetic VDR agonists could be exploited to treat a variety of autoimmune diseases, from rheumatoid arthritis to systemic lupus erythematosus, and possibly also multiple sclerosis, type 1 diabetes, inflammatory bowel diseases, and autoimmune prostatitis.

Atzeni F, Bendtzen K, Bobbio-Pallavicini F, Conti F, Cutolo M, Montecucco C, Sulli A, Valesini G, Sarzi-Puttini P. · Rheumatology Unit, L. Sacco Hospital, Milan, Italy. · Clin Exp Rheumatol. · Pubmed #18570757 No free full text.

Abstract: Glucocorticoids (GCs) have many complex quantitative and qualitative immunosuppressive effects which induce cellular immunodeficiency and increase host susceptibility to various viral, bacterial, fungal and parasitic infections. As cortisol secretion is inadequate in chronic immune/inflammatory conditions, and current therapies have the aim of providing adequate (low) compensatory doses, the timing of GC administration, such as during the nocturnal turning-on phase of tumour necrosis factor (TNF) secretion, can be extremely important. The use of the lowest possible GC dose, at night, and for the shortest possible time should therefore greatly reduce the risk of infections. Infection is a major co-morbidity in rheumatoid arthritis (RA), and conventional disease-modifying anti-rheumatic drugs (DMARDs) can increase the risk of their occurrence, including tuberculosis. TNF-alpha plays a key role in the pathogenesis of RA, and the data concerning infections in RA patients treated with anti-TNF agents are controversial. Patients and physicians should vigilantly monitor for signs of infection when using anti-TNF agents. Recombinant gene technologies now make it possible to produce protein drugs that are almost identical to naturally occurring human polypeptides, including antibody (Ab) constructs; unfortunately, all human biological agents are potentially immunogenic.An increasing number of recent studies have demonstrated the safety of influenza and pneumococcal vaccines administered to patients with systemic lupus erythematosus (SLE) or RA. These vaccinations are generally immunogenic (i.e., capable of inducing a protective level of specific antibodies) but may not induce an adequate response in a substantial proportion of patients.

Antonelli A, Ferri C, Galeazzi M, Giannitti C, Manno D, Mieli-Vergani G, Menegatti E, Olivieri I, Puoti M, Palazzi C, Roccatello D, Vergani D, Sarzi-Puttini P, Atzeni F. · University of Pisa School of Medicine, Pisa, Italy. · Clin Exp Rheumatol. · Pubmed #18570753 No free full text.

Abstract: Chronic hepatitis C virus (HCV) infection is a worldwide public health problem with a global prevalence of 2-3%. It is believed that about 170 million people are currently infected (about 3% of the world's population), and a further 3-4 million are infected each year. HCV is the main reason for liver transplantation in the developed world, and the main cause of liver-related morbidity and mortality in a number of countries, including Italy. It is not only a frequent cause of chronic liver diseases such as hepatitis, cirrhosis and hepatocellular carcinoma, but is also involved in the pathogenesis of various autoimmune and rheumatic disorders (arthritis, vasculitis, sicca syndrome, porphyria cutanea tarda, lichen planus, nephropathies, thyroid diseases, and lung fibrosis), as well as in the development of B-cell lymphoproliferative diseases. Furthermore, patients suffering from C hepatitis tend to produce rheumatoid factor, cryoglobulins and a large series of autoantibodies (ANA, anti-SSA/SSB, SAM, ATG, aCL). The use of glucocorticoids or immuno-suppressant agents in HCV infected individuals, which are needed to treat autoimmune and rheumatic disorders, leads to a risk of worsening the clinical outcome of HCV. Under these conditions, the viral infection often needs to be treated with antiviral agents, mainly pegylated interferon combined with ribavirin. However, cyclosporine A seems to be safe and effective in patients with autoimmune disease (AD) and concomitant chronic HCV infection as is documented by the reduction in viremia and transaminases, particularly in patients with high baseline levels. Finally, HCV is the main trigger of mixed cryoglobulinemia. An attempt at viral eradication is therefore indicated in most patients, and is particularly effective in the case of mild or moderate manifestations. In severe cases, rituximab is an apparently safe and effective alternative to conventional immunosuppression and, specifically, it controls B-cell proliferation.

Paradisi A, Bugatti L, Sisto T, Filosa G, Amerio PL, Capizzi R. · Department of Dermatology, Catholic University of the Sacred Heart, Rome, Italy. · Clin Ther. · Pubmed #18555940 No free full text.

Abstract: INTRODUCTION: Acute generalized exanthematous pustulosis (AGEP) is a clinical reaction pattern that is principally drug induced and is characterized by acute, extensive formation of nonfollicular sterile pustules on an erythematous and edematous substrate. Hydroxychloroquine (HHCQ), an antimalarial drug widely used to treat rheumatic and dermatologic diseases, has been described as an uncommon cause of AGEP. OBJECTIVES: This article reports 3 cases of HCQ-induced AGEP and reviews similar cases in the published literature. CASE SUMMARIES: The first case involved a 36-year-old woman with a 10-year history of rheumatoid arthritis and Sjögren's syndrome who had begun a 25-day course of HCQ 100 mg BID due to lack of response to a corticosteroid, with a skin reaction developing 21 days into the new treatment. In the second case, a 70-year-old man with poorly controlled rheumatoid arthritis had begun a course of oral HCQ 100 mg BID 20 days before development of AGEP. The final case involved a 79-year-old woman with polymyalgia rheumatica who had been receiving HCQ 100 mg BID as a steroid-sparing agent for 22 days, with rash developing 20 days after the initiation of HCQ. Sixteen cases of HCQ-induced AGEP were identified in the literature, including some that may have been reported under a different name but were consistent with a clinical diagnosis of AGEP.The US Food and Drug Administration has mandated a change to the labeling for HCQ to include AGEP among potential adverse dermatologic reactions to the drug. CONCLUSIONS: This article reports 3 cases of AGEP related to administration of HCQ. HCQ-induced AGEP is a rare but severe, extensive, and acute reaction. No specific therapy is available, and correct diagnosis generally leads to spontaneous resolution once the causative drug has been withdrawn.

Palomba S, Russo T, Sacchinelli A, Oppedisano R, Falbo A, Sena T, Zullo F, Mastrantonio P. · Cattedra di Ginecologia ed Ostetricia, Università degli Studi Magna Graecia, Catanzaro, Italy. · Minerva Ginecol. · Pubmed #18487968 No free full text.

Abstract: The Sjögren's syndrome (SS) is an autoimmune disease which causes injury to lacrimal and salivar glands and is characterized by a potential systemic involvement. The present review will treat mainly of SS extraglandular expressions, focusing on scientific literature articles regarding SS implications in gynecology and obstetrics.

Racanelli V, Prete M, Minoia C, Favoino E, Perosa F. · Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Piazza G. Cesare 11, Bari, Italy. · Autoimmun Rev. · Pubmed #18486921 No free full text.

Abstract: The long-established observation that some rheumatologic disorders (RDs) are associated with--or precede--the clinical manifestations of a variety of solid and hematological tumors represents an important clue for the early diagnosis and effective treatment of the cancers. Inflammatory myopathies, seronegative rheumatoid arthritis and some atypical vasculitides are the most frequently reported paraneoplastic RDs, although paraneoplastic scleroderma- and lupus-like syndromes, erythema nodosum, and Raynaud's syndrome have also been observed. Generally, the clinical course of a paraneoplastic RD parallels that of the cancer, and surgical removal of the tumor or its medical treatment usually results in a marked regression of the clinical manifestations of the RD. Most paraneoplastic RDs are difficultly distinguishable from idiopathic RDs. Even so, some atypical features of the clinical presentation raise the suspicion of an underlying tumor. This review summarizes current hypotheses for the pathogenesis that leads a tumor to present as an RD and discusses the clinical features that help distinguish paraneoplastic from idiopathic RDs.

Rizzi R, Curci P, Delia M, Rinaldi E, Chiefa A, Specchia G, Liso V. · Hematology Section, Department of Pathology and Hematology, Bari University Medical School, Piazza Giulio Cesare-11, 70122 Bari, Italy. · Med Oncol. · Pubmed #18461290 No free full text.

Abstract: There are a number of intriguing reports of lymphoproliferative disorders (LPDs) diagnosed during immunosuppressive treatment for underlying autoimmune disease, and spontaneously abated shortly after treatment discontinuation. Such LPDs, completely or partially regressing, occur in the clinical setting of "Methotrexate (MTX)-associated LPDs", recognized by the World Health Organization (WHO) among the "Immunodeficiency-associated LPDs". We identified 26 literature patients achieving spontaneous complete remission (CR) of their LPD, and eight others showing partial remission (PR). Most of them were affected by rheumatoid arthritis, received low-dose and long-term pulsed MTX alone or combined with other immunosuppressants, and developed a lymphoma. By reviewing the patients achieving CR, the following can be drawn: the absence of a unique type of LPD, the occurrence of an increased incidence of diffuse large B cell lymphoma as well as of frequent extranodal involvement, and EBV-infection. Further, CR mostly occurred within 4 weeks after discontinuation of immunosuppressant, and appeared to be persistent overtime. Conversely in the patients experiencing PR, the interval between discontinuation of immunosuppressive treatment and clinical response was mostly reported as longer than 4 weeks; moreover, in many cases the persistence of LPD or its progression induced to start cytotoxic therapy. Increased awareness is needed on the possible occurrence of LPD spontaneous remission following immunosuppressant discontinuation, after that it is therefore advisable to have a careful monitoring of the patient for some weeks, before starting cytotoxic therapy.

Ruperto N, Meiorin S, Iusan SM, Ravelli A, Pistorio A, Martini A. · IRCCS G. Gaslini, Pediatria II-PRINTO, University of Genoa, Largo Gaslini, 5, 16147 Genova, Italy. · Curr Rheumatol Rep. · Pubmed #18460270 No free full text.

Abstract: The Delphi Technique and Nominal Group Technique are two well-recognized consensus-formation methodologies specifically designed to combine judgments from a group of experts. The Delphi Technique utilizes a series of well-defined questionnaire-based surveys, whereas Nominal Group Technique is a structured face-to-face meeting designed to facilitate consensus. Consensus-formation techniques require that each step build on the results of the previous steps. In this review, we describe these techniques, how they work, and their practical application in pediatric rheumatology, where they have been widely used to develop the outcome measures of several chronic rheumatic diseases, including juvenile idiopathic arthritis, rheumatoid arthritis, systemic lupus erythematosus, and idiopathic inflammatory myopathies, as well as the classification criteria for juvenile systemic sclerosis and juvenile vasculitides.

Randone SB, Guiducci S, Cerinic MM. · Department of Biomedicine DENOThe Centre, Division of Rheumatology AOUC, University of Florence, Italy. <> · Best Pract Res Clin Rheumatol. · Pubmed #18455689 No free full text.

Abstract: Musculoskeletal involvement is more frequent than expected in patients with systemic sclerosis (SSc) and is a major cause of disability, even if the prognosis of the disease largely depends on visceral involvement. The most common clinical feature of musculoskeletal involvement is arthralgia; less frequent features are arthritis, flexion contractures, stiffness (affecting predominantly fingers, wrists and ankles), proximal muscle weakness (mainly of the shoulder and hip) and tendon sheath involvement. Tendon friction rubs are predictive of poor prognosis. If musculoskeletal involvement is suspected, serum creatinine phosphokinase, aldolase, lactate dehydrogenase, alkaline phosphate, rheumatoid factor and anticyclic citrullinated peptide autoantibodies should be checked routinely. Treatment for muscle involvement has not yet been considered adequately and, in the future, it is to be hoped that clinical trials will identify new drugs to control this aspect of SSc, which seriously compromises patients' quality of life.

D'Arena G, Taylor RP, Cascavilla N, Lindorfer MA. · Hematology and Stem Cell Transplantation Unit, Scientific Institute, Casa Sollievo della Sofferenza Hospital, 71013 San Giovanni Rotondo, Italy. · Endocr Metab Immune Disord Drug Targets. · Pubmed #18393924 No free full text.

Abstract: Conventional treatment of autoimmune hemolytic anemia (AIHA) comprises corticosteroids and splenectomy and/or other immunosuppressive drugs for refractory/relapsed patients. Monoclonal antibodies (MoAbs) rituximab and alemtuzumab have gained widespread acceptance in the management of B-cell malignancies. More recently, they have been used to treat a number of autoantibody-mediated diseases, such as both idiopathic and secondary AIHA, with encouraging results. Herein we report an overview of the medical literature on the use of MoAbs to treat AIHA. The therapeutic mechanism of action of rituximab in the treatment of autoimmune diseases such as rheumatoid arthritis and lupus is currently a subject of considerable investigation. We have proposed that cell-associated IgG immune complexes, generated by the binding of rituximab to CD20 on B cells, may serve as decoys that attract FcgammaR-expressing effector cells and downregulate effector cell pathogenic action, thus reducing inflammation and tissue destruction in these diseases. We briefly review evidence that suggests that this immune complex decoy hypothesis plays a role in the therapeutic action of rituximab in AIHA, and we propose new measurements that should allow for a more complete evaluation of the importance of this mechanism in AIHA.

Aloe L, Tirassa P, Lambiase A. · Institute of Neurobiology and Molecular Medicine, NGF Section, National Research Council (CNR), 00413 Rome, Italy. · Pharmacol Res. · Pubmed #18329283 No free full text.

Abstract: AIM: The nerve growth factor is a soluble protein produced by and acting upon a number of different cells located in the nervous, endocrine and immune systems. Recent studies have shown that nerve growth factor (NGF) exerts a critical role on epithelial cells and fibroblasts under normal and pathological conditions. In this review, we present data prospecting the clinical potentiality of NGF in cutaneous and ocular "non-healing" chronic ulcers. DATA SYNTHESIS: A consistent number of in vitro and in vivo studies carried out on animal models and in humans indicated that fibroblasts and epithelial cells are receptive to the action of NGF and that NGF promotes skin and cornea ulcer healing. These observations lead to the hypothesis that NGF can be a potential useful pharmacological agent for clinical investigations. CONCLUSION: The available clinical evidences suggest that the topical application of NGF promotes healing action without side effects on corneal and cutaneous tissues damaged by chemical, physical and surgical insults and autoimmune disorders.

Filippucci E, Meenagh G, Epis O, Iagnocco A, Riente L, Delle Sedie A, Montecucco C, Valesini G, Bombardieri S, Grassi W. · Cattedra di Reumatologia, Università Politecnica delle Marche, Ancona, Italy. · Clin Exp Rheumatol. · Pubmed #18328139 No free full text.

Abstract: Despite its indubitable potential, ultrasonography still has limited diffusion in rheumatology related principally to the image acquisition process due to at least five main factors: the steep learning curve, lack of standardisation of the technique, intra- and inter-observer variability, time consumption and the high initial cost of top quality sonographic equipment. Of all these barriers, the first four are undoubtedly the most difficult to overcome. This review discusses the available evidence supporting the potential of three-dimensional ultrasound with high-frequency volumetric probe to overcome the first four barriers. The challenge to three-dimensional ultrasound is to prove itself to be a method that requires no particular skills that can be mastered in just a few minutes and is not operator-dependant [corrected]

Delle Sedie A, Riente L, Bombardieri S. · Rheumatology Unit, Department of Internal Medicine, University of Pisa, Pisa, Italy. · Mod Rheumatol. · Pubmed #18306005 No free full text.

Abstract: Musculoskeletal sonography (MSUS) has played a growing role in the diagnosis and management of rheumatic diseases, enabling the imaging of synovitis, bone erosion, and cartilage damage in the early phase of arthritis. "Dynamic" evaluation of tendons and help in guiding needle positioning in interventional manoeuvres are some of the other reasons for its success. MSUS, particularly when coupled with power Doppler (PD) examination, has recently been shown to be an efficient tool for monitoring disease activity and progression in rheumatoid arthritis, spondyloarthritis, crystal-related arthropathy, and osteoarthritis, with general consensus on its interesting results. More specifically, the PD signal has proved to be a simple and promising tool for short-term monitoring of synovial vascularity changes induced by steroids or biological agents in RA patients. MSUS has some limits, because of the physical properties of US and the quality of the equipment; it is, moreover, an operator-related imaging technique, with few standardized protocols. Future goals should be standardization of the examining approach in grey scale and Doppler ultrasound (US), including use of new equipment (3D US), extensive use in other fields (i.e. connective tissue diseases and vasculitis), and possible new applications (e.g. thoracic US).

Marmont AM. · II Division of Hematology and Stem Cell Transplantation Center, Azienda Ospedaliera-Universitaria S. Martino, Genova, Italy. · J Autoimmun. · Pubmed #18222646 No free full text.

Abstract: Hematopoietic stem cell transplantation is becoming an accepted therapy for severe autoimmune diseases, and over 1,000 patients have been transplanted worldwide. Diseases include neurological (multiple sclerosis, others), rheumatological (systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, vasculitis), haematological (aplastic anemia, single line immune mediated cytopenias) and others. The aim of this article is not to review the copious specific literature, but to analyze whether the up to now existing evidence satisfies the requirements of cure. Prospective randomized trials have been launched by the European Group of Blood and Marrow Transplantation (EBMT). Autologous transplantation, by far the most widely utilized because of its safety, has been shown to possess a powerful disease-arresting effect, but whether the attendant immune reconstitution ("re-education") will finally lead to cure is not demonstrated. The experience with allogeneic transplantation is too limited to draw even tentative conclusions. A Graft-versus-Autoimmunity effect has been ascertained both experimentally and clinically, but cure of autoimmunity by this procedure has not been demonstrated. Unexpected relapses in spite of full donor chimerism have been published. Further experience and studies are necessary.

Del Rosso A, Cerinic MM, De Giorgio F, Minari C, Rotella CM, Seghier G. · Department of Medicine, Division of Medicine I and Rheumatology, University of Florence, Viale G. Pieraccini, 18 - 50139 Florence, Italy. · Curr Diabetes Rev. · Pubmed #18220648 No free full text.

Abstract: Rheumatological manifestations of Diabetes Mellitus may be classified in: non articular, articular and bone conditions. Among non articular conditions, diabetic cheiroarthropathy, frequent in type I diabetes, the most important disorder related to limited joint mobility, results in stiff skin and joint contractures. Adhesive capsulitis of the shoulder, flexor tenosynovitis, and Duputryen's and Peyronie's diseases are also linked to limited joint mobility. Diffuse skeletal hyperostosis, due to calcification at entheses, is frequent and early, particularly in type 2 diabetes. Neuropathies cause some non articular conditions, mainly neuropathic arthritis, a destructive bone and joint condition more common in type I diabetes. Algodistrophy, shoulder-hand and entrapment syndromes are also frequent. Mononeuropathy causes diabetic amyotrophy, characterised by painless muscle weakness. Among muscle conditions, diabetic muscle infarction is a rare, sometimes severe, condition. Among articular conditions, osteoarthritis is frequent and early in diabetes, in which also chondrocalcinosis and gout occur. Rheumatoid arthritis (RA) and diabetes I have a common genetic background and the presence of diabetes gives to RA an unfavourable prognosis. Among bone conditions, osteopenia and osteoporosis may occur early in type 1 diabetes. Contrarily, in type 2 diabetes, bone mineral density is similar or, sometimes, higher than in non diabetic subjects, probably due to hyperinsulinemia.

Vaglio A, Palmisano A, Ferretti S, Alberici F, Casazza I, Salvarani C, Buzio C. · Department of Clinical Medicine, Nephrology and Health Science, University of Parma, Parma, Italy. · Rheumatology (Oxford). · Pubmed #18218649 No free full text.

Abstract: OBJECTIVES: Chronic periaortitis (CP) is a rare disease with a potentially immune-mediated pathogenesis. The study aims to report the frequency and the clinical characteristics of peripheral inflammatory arthritis in a cohort of CP patients, and to review the literature regarding the association between arthritis and CP. METHODS: Forty-nine consecutive CP patients were seen at our department between 2000 and 2006; all of them underwent imaging (abdominal computed tomography and magnetic resonance imaging) and laboratory examinations, also including erythrocyte sedimentation rate, C-reactive protein and a panel of autoantibodies. The clinical history of the patients who developed peripheral inflammatory arthritis is reported in detail. A PubMed/Medline search without any date limits was performed for English-language articles reporting the association between CP and arthritis. RESULTS: Five of the 49 enrolled patients developed an inflammatory form of peripheral arthritis: three were diagnosed as having RA, one palindromic rheumatism and one acute reactive arthritis. In all but one case, arthritis became clinically overt months to years after the onset of CP, and its outcome was good, since almost all patients were asymptomatic at the end of follow-up. No patient suffered from ankylosing spondylitis. In the literature review, 20 cases of CP-associated arthritis were found, mainly in the form of case reports: 14 of them were spondyloarthropathies, whereas the remaining ones were RA, juvenile RA or undifferentiated arthritis. CONCLUSIONS: Peripheral inflammatory arthritis, particularly RA or RA-like forms, may develop in CP patients. This overlap strengthens the hypothesis of an autoimmune origin of CP.

Cutolo M, Straub RH. · Research Laboratory and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Viale Benedetto XV, 6, IT-16132 Genova, Italy. · Autoimmun Rev. · Pubmed #18190882 No free full text.

Abstract: Biological signaling and rhythms occur in a complex network with participation and interaction of the central nervous system, the autonomic nervous system, the endocrine glands, peripheral endocrine tissues and the immune system. It is a clinical observation that patients affected by chronic immune/inflammatory conditions (i.e. rheumatoid arthritis/RA) exhibit circadian, circamensual (females) and circannual rhythms of disease-related symptoms. Proinflammatory cytokines exhibit a peculiar rhythmicity, in particular serum TNF and serum IL-6, and together with other relevant immunological parameters display an elevation in the early morning hours in patients with RA. As a matter of fact, RA patients particularly experience joint pain, morning stiffness, and functional disability in the early morning hours. Since circadian rhythmicity of neuroendocrine pathways is closely coupled to immune/inflammatory reactions, new aspects at least concerning RA management are suggested. In particular, further investigations will indicate whether timed release of immunosuppressive/antiinflammatory drugs will have increased efficacy and whether dosages can be reduced below critical levels above which adverse events appear.