Rheumatoid Arthritis: Fietta P

Fietta P, Delsante G, Quaini F. · Dipartimento Medico Polispecialistico, S.D. di Medicina Interna e Reumatologia, Azienda Ospedaliero-Universitaria di Parma, Italy. · Clin Exp Rheumatol. · Pubmed #19327244 No free full text.

Abstract: Autoimmune connective tissue diseases (ACTDs) constitute a heterogeneous group of chronic immune-mediated inflammatory disorders, primarily affecting connective tissues and usually characterized by multisystem involvement with variable and frequently overlapping clinical manifestations. Abnormal immune regulation patterns and persistent inflammation are ACTD hallmarks. In such a context, autoimmunity/inflammation-associated cellular and molecular networks drive a complex of reactions that may involve hemopoietic tissue and peripheral blood cells. Hematologic abnormalities affecting one or more cellular lineages are frequent manifestations of ACTDs, and may represent an important prognostic factor, reflecting the rate of activation of autoimmune/inflammatory processes. Moreover, an increased frequency of hematologic malignancies, mainly lymphoproliferative disorders, has been observed in ACTDs, such as Sjögren's syndrome, systemic lupus erythematosus, rheumatoid arthritis, and polymyositis/dermatomyositis. A proliferative drive likely constitutes the link between chronic immune activation/dysregulation and malignant transformation, creating an increased risk for genetic aberrations that may lead to uncontrolled clonal proliferation. Revealing the nature of lymphomagenesis in relation to autoimmunity/inflammation will allow the identification of subjects at risk in order to select the appropriate diagnostic and therapeutic options. In this paper, the main hematologic manifestations of adulthood ACTDs are reviewed and discussed.

Manganelli P, Fietta P, Quaini F. · Unità Operativa di Reumatologia e Medicina Interna, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. · Clin Exp Rheumatol. · Pubmed #16956437 No free full text.

Abstract: Sjögren's syndrome (SS) is a chronic autoimmune disorder, primarily characterized by the mononuclear cell infiltration of exocrine glands exiting in parenchymal damage and secretory impairment. The spectrum of the disease extends from an autoimmune exocrinopathy to a systemic process with extraglandular manifestations. SS is defined as primary (pSS) when isolated, or secondary when associated with another autoimmune disease. Patients with pSS may present hematologic abnormalities, such as anemia, hemocytopenias, monoclonal gammopathies and lymphoprolipherative disorders, predominantly non-Hodgkin's lymphoma of B-cell origin. The increased prevalence of B-cell malignancies suggests that SS may be a boundary disease between autoimmunity and lymphoproliferation. In this paper, the hematologic manifestations of pSS are reviewed.

Manganelli P, Fietta P. · Osteo-Articular Department, Rheumatic Disease and Internal Medicine Unit, Hospital of Parma, Italy. · Semin Arthritis Rheum. · Pubmed #12920696 No free full text.

Abstract: OBJECTIVE: To examine the role of apoptosis in the pathogenesis of Sjögren syndrome (SS), a chronic autoimmune disease characterized by the infiltration of mononuclear cells in the salivary and lacrimal glands, leading to the destruction of the parenchymal tissue. METHODS: A detailed search via MEDLINE (PubMed) and Biosis, covering the period from January 1994 to July 2002, was accomplished, combining the key terms SS and apoptosis. A qualitative review of the articles was undertaken and the obtained information was summarized. RESULTS: Apoptosis of the acinar and ductal epithelial cells of the salivary and lacrimal glands has been proposed as a possible mechanism responsible for the impairment of secretory function. Apoptotic cell death may be induced by either cytotoxic T cells through the release of proteases, such as perforin and granzyme B, or the interaction of Fas ligand (FasL/CD95L), expressed by T lymphocytes, with Fas (Apo-1/CD95) on epithelial cells. The increased rate of apoptosis of epithelial cells in SS may result from either the imbalance between the down-regulated apoptosis-inhibitor Bcl-2 and the up-regulated apoptosis-inducer Bax, or the autocrine and/or paracrine Fas/FasL interaction. Lymphocytes infiltrating the salivary glands are blocked in their ability to commit to apoptosis, despite the expression of the apoptosis-inducer Fas. The expression of Bcl-2 in these cells may explain their resistance to apoptosis, resulting in a prolonged production of proinflammatory cytokines and autoantibodies, as well as in their longer survival that may result in the late development of lymphoma in some SS patients. Studies of the SS-like sialoadenitis of nonobese diabetic (NOD) mice with severe combined immunodeficiency (NOD.scid) suggest that the primary defect responsible for the initiation of SS resides in the epithelial cells that undergo apoptosis mediated by the autocrine Fas/FasL interaction. This first not-immune-mediated phase of target cell destruction is followed by a lymphocyte-dependent autoimmune aggression, which leads to extensive tissue damage and subsequent loss of secretory function. Apoptosis of the salivary epithelial cells has been shown in other animal models of SS and in cell lines in vitro. Apoptosis may also play a role in the pathogenesis of some extraglandular manifestations of SS, such as interstitial nephritis and peripheral CD4(+) lymphocytopenia. CONCLUSIONS: The possible role of apoptosis in SS is suggested from the literature review. A better understanding of the mechanisms responsible for the epithelial cell apoptosis may allow the discovery of new therapeutic strategies. By inhibiting programmed cell death, the glandular damage and the subsequent impairment of the secretory function should be reduced.

Fietta P, Manganelli P. · Unità Operativa di Reumatologia e Medicina Interna, Dipartimento Osteo-Articolare, Azienda Ospedaliera Universitaria, Parma, Italy. · Minerva Med. · Pubmed #11850612 No free full text.

Abstract: Adult onset Still's disease (AOSD), the adult variant of the systemic form of the juvenile rheumatoid arthritis, is an uncommon disorder of unknown origin. Although the pathogenesis has not yet been clarified, an immunologically mediated inflammation occurs in active AOSD. High spiking fever, evanescent maculo-papular skin rash, arthralgias/arthritis, neutrophilic leukocytosis, negative rheumatoid factor and antinuclear antibodies, as well as a marked hyperferritinemia are the major features of AOSD. Sore throat, lymphadenopathies, hepato-splenomegaly, abdominal pain, polyserositis, respiratory distress syndrome, multiple organ dysfunction and disseminated intravascular coagulation may also occur. The clinical course of AOSD is extremely variable and unpredictable and can be divided into three main patterns: a self-limited or monocyclic pattern, a polycyclic or intermittent course, with one or more flares of the disease and complete remission among the episodes, and a chronic course, characterized by persistently active disease, usually due to a chronic, destructive arthritis. Since there are not pathognomonic laboratory parameters or histological findings, the diagnosis of AOSD requires the exclusion of infectious, malignant and autoimmune disorders. Some sets of criteria for classification have been proposed, but so far not validated. The prognosis of AOSD is usually considered relatively benign, although a destructive arthritis may cause severe disability and the multisystemic life-threatening complications of the disease may determine a fatal outcome. Treatment usually consists in nonsteroidal anti-inflammatory drugs and corticosteroids, but a more aggressive approach with disease modifying antirheumatic or immunosuppressive drugs may be required.

Manganelli P, Fietta P, Martella EM, Quaini F. · Dipartimento Osteo-Articolare, Unità Operativa di Reumatologia e Medicina Interna, Azienda Ospedaliera di Parma, Via Gramsci 14, 43100 Parma, Italy. · Clin Rheumatol. · Pubmed #14677031 No free full text.

Abstract: Inflammatory pseudotumour (IPT) of the lymph nodes is an uncommon, self-limiting, non-neoplastic proliferation of spindle cells, associated with a polymorphous inflammatory cell infiltrate embedded in a collagen-rich stroma and a variable degree of fibrosis, arising in the nodal parenchyma. Its clinical picture is characterised by site-specific signs and the presence, in most cases, of constitutional symptoms. The pathogenesis of IPT is unknown, but it has been interpreted as an aberrant reactive condition of the nodal connective framework, possibly related to viral infections or chronic inflammatory conditions. Its prognosis is usually favourable. We here report the simultaneous onset of seronegative rheumatoid arthritis (RA) and nodal IPT in a 31-year-old woman. Notably, in the nodal biopsy the coexistence of rheumatoid nodules, as well as histological and immunohistochemical features of IPT, was observed. To our knowledge, such an association has not been previously reported and the hypothesis that IPT could represent an unusual epiphenomenon of an RA-related chronic inflammatory response is suggested.

Fietta P, Manganelli P. · No affiliation provided · J Rheumatol. · Pubmed #17086622 links to  free full text

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Fietta P, Manganelli P. · No affiliation provided · J Korean Med Sci. · Pubmed #14676458 links to  free full text

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Manganelli P, Fietta P, Zuccoli P. · No affiliation provided · Clin Exp Rheumatol. · Pubmed #12673909 No free full text.

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Fietta P, Manganelli P. · No affiliation provided · Clin Exp Rheumatol. · Pubmed #10812512 No free full text.

This publication has no abstract.