Rheumatoid Arthritis: Pipitone N

Pipitone N, Pitzalis C. · Weston Education Center, King's College Hospital and Rheumatology Unit, Guy's Campus, GKT School of Medicine, London. · Recenti Prog Med. · Pubmed #15473382 No free full text.

Abstract: The arthritides of the elderly comprise a fairly heterogeneous group of diseases. They include conditions that affect exclusively or predominantly the elderly (such as, for instance, remitting seronegative symmetric synovitis with pitting edema) and conditions affecting any age group, but which can present with peculiar features in the elderly, like rheumatoid arthritis and the seronegative arthropathies. Therefore, in order to arrive at a correct diagnosis, a knowledge of the specific features of these disorders is required. In addition, the treatment of elderly patients differs from that of other age groups in that elderly subjects appear to have an increased susceptibility to adverse reactions. This susceptibility is related both to the different metabolism of aged subjects, including the impairment of the renal function, and to the multiple therapies that such subjects often receive. In view of the ever increasing elderly population in the western world, all physicians, over and beyond the limited circle of rheumatologists, should be knowlegeable about the principles of diagnosing and treating senile arthritis.

Pitzalis C, Pipitone N, Pipitone V, Fioravanti A, Marcolongo R. · Rheumatology Unit, Guy's, King's and St Thomas Hospitals School of Medicine and Dentistry, London. · Recenti Prog Med. · Pubmed #11320856 No free full text.

Abstract: The etiology of rheumatoid arthritis (RA) is still unknown, and many uncertainties regarding its pathogenetic mechanisms persist. During the past decade, various hypotheses have been advanced, yet none of these has been able to explain the complexity of the disease. In light of the most recent research, a sub-division of the pathogenesis of RA, in four phases, has been proposed. The first phase is that of tissue damage, induced by unknown infective or traumatic factors with the liberation of possible arthrogenic antigens that are presented to the immune system. In the second phase the immune and inflammatory mechanisms should begin to function and, if they are effective, they should determine the resolution of the process; the failure of these mechanisms would create a further amplification of the immuno-inflammation response (the third phase). The fourth phase would then be a chronic inflammatory with progressive articular destruction, as well as anatomical and functional damage. This evolution, in response to common pathogenic agents, is dependent upon a particular hereditary genetic asset (not only the HLA system) that is able to control the production of citokines and also upon the neuroendocrine system. The final outcome of the process is, therefore, determinated by multiple interference between the inflammatory/immune system and other systems that also interact with it (the integrated pathogenetic hypothesis). This hypothesis reflects the complexity of the immune/inflammatory system that must be considered to be an acting part of an integrated network of diverse systems. A better knowledge of these interactions needed for the discovery of potential new therapies for RA.

Pipitone N, Fioravanti A, Marcolongo R, Pitzalis C. · Istituto di Reumatologia, Università, Siena. · Recenti Prog Med. · Pubmed #11260975 No free full text.

Abstract: The Authors describe the main features of the most common forms of primary hypogammaglobulinaemia (PH) focusing on the articular involvement. Patients with Bruton's agammaglobulinemia (BA) and common variable immune deficiency (CVID) are predisposed to develop septic arthritis (including arthritis due to atypical microorganisms such as mycoplasma), arthralgia and symmetrical (usually non-erosive) polyarthritis. In BA and CVID complicated by recurrent infections, amyloidosis, which may be itself a cause of arthropathy, can occur. In addition, patients with CVID and selective IgA deficiency show an increased prevalence of juvenile rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome and primary biliary cirrhosis, while patients with selective IgA deficiency are prone to developing seronegative spondylarthropathies, including ankylosing spondylitis. The mainstay of treatment for BA and CVID is replacement therapy with human immunoglobulins. Septic arthritis should be promptly treated with antibiotics, whereas other types of arthritis usually respond well to non-steroidal antiinflammatory medications. In contrast, the second line agents commonly used to treat rheumatoid arthritis do not appear to be beneficial in patients with PH-associated arthritis.

Choy EH, Kingsley GH, Khoshaba B, Pipitone N, Scott DL, Anonymous00228. · Department of Rheumatology, GKT School of Medicine, Weston Education Centre, Kings College, 10 Cutcombe Road, London SE5 9RS, UK. · Ann Rheum Dis. · Pubmed #15760929 links to  free full text

Abstract: BACKGROUND: In rheumatoid arthritis (RA), intramuscular (IM) pulsed depomedrone expedites an immediate response to disease modifying antirheumatic drugs (DMARDs). Although IM depomedrone is also widely used to treat disease flares in patients treated with DMARDs, its effect on radiological progression has not been assessed. OBJECTIVE: To evaluate the benefits of 120 mg IM depomedrone versus placebo in patients with established RA whose disease was inadequately controlled by existing DMARDs. METHODS: In a 2 year prospective randomised controlled trial patients were assessed using the ILAR/WHO core dataset, disease activity score (DAS28), x ray examination of hands and feet scored by Larsen's method, and bone densitometry. RESULTS: 291 patients with RA were screened, 166 were eligible, and 91 consented and were randomised. Disease activity improved more rapidly in the steroid treated patients than with placebo, but after 6 months no difference remained. A small but significant reduction in erosive damage in the steroid group compared with placebo was also found. More adverse reactions occurred in the steroid treated group than in the placebo patients (55 v 42), especially those reactions traditionally related to steroids (16 v 2), including vertebral fracture, diabetes, and myocardial infarction. Hip bone density fell significantly in steroid treated but not placebo patients. CONCLUSIONS: IM depomedrone improved disease activity in the short term and produced a small reduction in bone erosion at the cost of a significant increase in adverse events. Despite the initial benefit of IM depomedrone, when patients respond suboptimally to a DMARD they should not be given long term additional steroids but should be treated with alternative or additional DMARDs.

Pattacini L, Casali B, Boiardi L, Pipitone N, Albertazzi L, Salvarani C. · Laboratorio di Biologia Molecolare, Arcispedale S. Maria Nuova, Viale Risorgimento, 80, 42100 Reggio Emilia, Italy. · Rheumatology (Oxford). · Pubmed #17526929 links to  free full text

Abstract: OBJECTIVE: To evaluate the effects of angiotensin II (Ang II) treatment on apoptosis of fibroblast-like synoviocytes (FLS) from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: AT1 receptor expression was detected by western blotting and flow cytometry. Apoptosis induction was quantified by nucleosome ELISA and by TUNEL; cell proliferation was determined by a bromodeoxyuridine (BrdU) incorporation assay. Silencing of p65 NF-kappaB was obtained by using a specific siRNA. Caspase 3 activation was evaluated by a colorimetric assay and its cleavage by western blotting. RESULTS: AT1 expression resulted comparable in FLS from OA and RA patients. Ang II pre-treatment reduced FLS apoptotic response to serum starvation and nitric oxide (NO) exposure. This protective effect was reverted in the presence of the AT1 receptor antagonist losartan as well as after silencing the expression of NF-kappaB. Moreover, FLS treatment with the caspase inhibitor z-VAD-fmk cancelled this Ang II effect on apoptosis. Caspase 3 activation was reduced in presence of Ang II. CONCLUSIONS: Ang II could represent an important mediator involved in FLS expansion, reducing their capacity to undergo apoptosis, through the activation of NF-kappaB and the blockage of caspase cascade.

Ingegnoli F, Manzo A, Fantini F, Caporali R, Montecucco C, Pipitone N, Pitzalis C. · Rheumatology Unit, Thomas Guy House, GKT School of Medicine, Guy's Campus, London SE1 9RT, UK. · Reumatismo. · Pubmed #12089609 links to  free full text

Abstract: Chemokines play a central role in the pathogenesis of rheumatoid arthritis (RA) synovitis which is characterised by new blood vessel formation, thickening of the lining layer and infiltration of immune cells. The inflammatory infiltrate is generated by a series of events which include the recruitment of leukocytes from the blood stream into the tissue, their local retention and activation to effector cells. All these processes are finely regulated by the interplay of different cell adhesion molecules (CAMs) and chemoattractant factors called chemokines (CK). CK are a superfamily of small proteins that play a crucial role in immune and inflammatory reactions. These chemoattractant cytokines share structural similarities including four conserved cysteine residues which form disulphide bonds in the tertiary structure of the proteins. CK mediate their effects by binding specific receptors (CK-R) characterised by a domain structure which spans the cell membrane seven times and signal through heterotrimeric GPT-binding proteins. Activation of the CK network results in an amplification of the inflammatory cascade and consequently in the progressive destruction of RA joints. The recognition of the central role of CK in inflammation has paved the way to the development of new agents capable of interfering with CK and CK-R. This review will focus in particular on the role of CK in regulating leukocyte trafficking in RA joints.

Pipitone N, Jolliffe VA, Cauli A, Scott DG, Pitzalis C. · Rheumatology Unit, GKT, Guys, Kings and St Thomas Hospitals, School of Medicine and Dentistry, London and. Rheumatology Unit, Norfolk & Norwich Hospital, Norwich, Norfolk, UK. · Rheumatology (Oxford). · Pubmed #11085811 links to  free full text

Abstract: We describe a 62-yr-old male patient with primary hypogammaglobulinaemia (PH) who fulfilled the 1987 American Rheumatism Association/American College of Rheumatology revised diagnostic criteria for rheumatoid arthritis (RA) but, despite persistent symmetrical synovitis, did not develop erosions. Virology studies and blood and synovial fluid (SF) cultures were consistently negative; a search for crystals in the SF was unrevealing. Peripheral blood (PB) B cells were absent, whilst the PB CD3(+) cell count was normal. The ratio of naive (CD45RA(+)) to memory (CD45R0(+)) cells was also normal (1:1) but the CD4:CD8 ratio was reversed. To our knowledge, this is the first report which combines the immunophenotypic analysis of the PB with that of the SF and synovial membrane (SM). This confirmed the absence of B cells and the reversed CD4:CD8 ratio. However, as in other chronic arthropathies, the SF and SM cellular infiltrate consisted almost exclusively of memory T cells, consistent with the preferential localization of this subset to inflamed tissues. This case indicates that synovitis can proceed persistently in the absence of B cells and that the migratory mechanisms of T cells are not altered. However, the case suggests that the absence of B cells and negativity for rheumatoid factor, combined with an increased presence of CD8(+) (suppresser/cytotoxic) T cells in the joint, might contribute to the non-erosive nature of the synovitis.

Ghinoi A, Pipitone N, Boiardi L, Pizzini A, Salvarani C. · No affiliation provided · Rheumatology (Oxford). · Pubmed #17303582 links to  free full text

This publication has no abstract.