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ID PMID Title PublicationDate abstract
10613744 Gastric mucosa as an additional extrahepatic localization of hepatitis C virus: viral dete 2000 Jan The hepatitis C virus (HCV) has been linked to B-cell lymphoproliferation and autoimmunity, and has been localized in several tissues. The clinical observation of an HCV-infected patient with Sjögren's syndrome (SS) and Helicobacter pylori (HP) positive gastric low-grade B-cell non-Hodgkin's lymphoma (NHL), which did not regress after HP eradication, led us to investigate the possible localization of HVC in the gastric microenvironment. HCV genome and antigens were searched in gastric biopsy specimens from the previously mentioned case, as well as from 9 additional HCV-infected patients (8 with chronic gastritis and 1 with gastric low-grade B-cell NHL). HCV-specific polymerase chain reaction (PCR) and immunohistochemistry procedures were used. The gastric B-cell NHL from the patient with SS was characterized by molecular analyses of B-cell clonality. HCV RNA was detected in both the gastric low-grade B-cell NHL and in 3 out of 6 gastric samples from the remaining cases. HCV antigens were detected in the residual glandular cells within the gastric B-cell NHL lesions, in glandular cells from 2 of the 3 additional gastric lesions that were HCV positive by PCR, and in 1 additional chronic gastritis sample in which HCV-RNA studies could not be performed. By molecular analyses, of immunoglobulin genes, the B-cell NHL from the patient with SS was confirmed to be a primary gastric lymphoma, subjected to ongoing antigenic stimulation and showing a significant similarity with rheumatoid factor (RF) and anti-HCV- antibody sequences. Our results show that HCV can localize in the gastric mucosa.
11713380 Monocytoid B cell lymphoma associated with antibodies to myelin-associated glycoprotein an 2001 Monocytoid B cell lymphoma (MBCL) is an immunologically and morphologically well-defined low-grade lymphoma with a predilection for lymph nodes of the parotid region. We describe an association of MBCL with anti-myelin-associated glycoprotein (MAG) polyneuropathy in a 53-year-old male. The diagnosis of stage IV MBCL with nodular bone marrow infiltration, Sjögren's syndrome and sensorimotor polyneuropathy was made in October 1996. Serum immunoelectrophoresis demonstrated IgMkappa paraprotein. This was then cross-reacted with epitopes of MAG and sulphated glucuronyl paragloboside (SGPG) on myelin sheaths, and detected by thin layer chromatography and Western blot. Direct immunofluorescence of a sural nerve biopsy showed loss of myelin fibres, segmental demyelinization and IgM deposits on the myelin sheaths. The cerebrospinal fluid was normal. After six cycles of chemotherapy (ChlVPP protocol), all the patient's haematological parameters normalized accompanied by an improvement in neurological signs. The improvement of the polyneuropathy after chemotherapy indicates that the autoimmune anti-MAG and anti-SGPG antibodies resulted from the neoplastic lymphoid proliferation.
11417482 Role of splenectomy in the treatment of myelodysplastic syndromes with peripheral thromboc 2001 Jun Thrombocytopenia is generally of central origin in MDS, but can be due to peripheral platelet destruction in some cases. We studied platelet lifespan in 61 MDS cases with platelets < 70,000/mm3 and marrow blasts < 10%. Nine of them (15%) had a major platelet lifespan reduction (< 3.5 days), and were considered for splenectomy. Three of them were not splenectomized due to rapid death, patient refusal and older age plus liver predominance of platelet sequestration, respectively. The remaining six patients (two females and four males, median age 50 years, range 32 to 65) were splenectomized 3 to 21 months after diagnosis. Before splenectomy, five of them had RA and one had CMML. Platelets counts ranged from 5000 to 30,000/mm3 and did not durably respond to other treatments. Three of the patients has a relapse of platelet counts, concomitantly required platelet transfusion due to recurrent blending, whereas three had anemia (two required erythrocyte transfusion) and four had neutropenia. Three months after surgery, platelet counts ranged from 55,000 to 160,000/mm3 (> 100,000/mm3 in four cases), no patient required platelet or erythrocyte transfusion, but there was no effect on neutrophil counts. Three patients had a relapse of platelet counts, concomitant with progression to AML in two of them, whereas the third relapsing case achieved normal platelet counts with further danazol. One patient died with normal platelet counts 12 months after splenectomy (from sepsis, probably related to neutropenia rather than splenectomy). Two patients remained with normal platelet counts 10 and 52 months after surgery. Our findings suggest that the mechanism of thrombocytopenia should be studied more often in 'low risk' MDS (i.e. with low bone marrow blast counts) with thrombocytopenia, as about 15% of them appear to have peripheral platelet destruction. Some of those patients may benefit from splenectomy.
9434797 Gender and androgen treatment influence the expression of proto-oncogenes and apoptotic fa 1998 Jan The objectives of this study were to (1) determine whether Fas antigen, Fas ligand, p53, and proto-oncogene mRNAs may be detected in lacrimal and submandibular glands of the MRL/lpr mouse model of Sjögren's syndrome, and (2) examine whether gender and androgen or cyclophosphamide therapy influence the mRNA expression of these apoptotic factors. Tissues were obtained from treated or untreated MRL/lpr mice after the onset of disease and processed for the analysis of mRNAs by RT-PCR and Southern blot hybridization. Our results demonstrated that (1) Fas antigen (exons 1-->2 or 3-->7+), Fas ligand, c-myb, c-myc, bcl-2, Bax, p53, and androgen receptor (AR) mRNAs are present in exocrine tissues of MRL/lpr mice; (2) the amounts of c-myb, c-myc, bcl-2, p53, and AR mRNA are higher (P < 0.05) and the level of Fas antigen (exons 1-->2) mRNA is lower (P < 0.05) in lacrimal glands of female compared to male mice. In contrast, the content of c-myb and p53 mRNA is greater (P < 0.05) in submandibular tissues of female relative to those of male mice; and (3) testosterone or cyclophosphamide treatment led to a significant (P < 0.05) decline in the mRNA levels of c-myb, bcl-2, and/or AR, but an increase (P < 0.05) in the mRNA amount of Bax, in lacrimal, but not in salivary, glands of female mice. These findings demonstrate that gender-associated differences exist in the expression of apoptotic factor mRNAs in exocrine tissues of autoimmune mice and that some of these differences appear to be due to the influence of androgens.
25905357 The Epidemiology and Pathogenesis of Osteoporosis. 2000 Osteoporosis is a multifactorial disorder associated with low bone mass and enhanced skeletal fragility. Although most prevalent in older females, some men are also at high risk. Risk factors in men and women include smoking, family history of fracture, age greater than 65 years, and low but also high BMI particularly in men. Secondary causes of osteoporosis include chronic treatment with glucocorticoids, gastrointestinal disorders, diabetes mellitus (T1D, T2D), rheumatoid arthritis, liver disease, gluten enteropathy, multiple myeloma and other hematologic disorders. However, primary osteoporosis is most often related to either postmenopausal estrogen loss or age-related deterioration of skeletal microarchitecture; both are due to uncoupling in the bone remodeling unit. Reduced bone formation with age is almost certainly a function of impaired stem cell differentiation into the osteoblast lineage with a resultant increase in marrow adipogenesis. Increased bone resorption also characterizes most forms of osteoporosis but the etiology is multifactorial. Changes in local and systemic growth factors are often responsible for uncoupling between resorption and formation. However, alterations in peak bone acquisition contribute years later to low bone mass and enhanced skeletal fragility. Fracture risk assessment tools (e.g. FRAX) in handheld apps and computers which combine bone density score and risk factors, have provided rapid assessments of future osteoporotic fractures and can be performed at the bedside. Newer methods of measuring bone quality have led to insights into micro-architectural deterioration that contributes to skeletal fragility. Notwithstanding, low areal bone mineral density by DEXA remains the strongest predictor of subsequent fracture beyond age, and this is potentially measurable in everyone after age 65. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.
26561701 The Effect of Inflammation and Infection on Lipids and Lipoproteins. 2000 Chronic inflammatory diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis and infections, such as periodontal disease and HIV, are associated with an increased risk of cardiovascular disease. Patients with these disorders also have an increase in coronary artery calcium measured by CT and carotid intima media thickness measured by ultrasound. Inflammation and infections induce a variety of alterations in lipid metabolism that may initially dampen inflammation or fight infection, but if chronic could contribute to the increased risk of atherosclerosis. The most common changes are decreases in serum HDL and increases in triglycerides. The increase in serum triglycerides is due to both an increase in hepatic VLDL production and secretion and a decrease in the clearance of triglyceride rich lipoproteins. The mechanisms by which inflammation and infection decrease HDL levels are uncertain. With inflammation there is also a consistent increase in lipoprotein (a) levels due to increased apolipoprotein (a) synthesis. LDL levels are frequently decreased but the prevalence of small dense LDL is increased due to exchange of triglycerides from triglyceride rich lipoproteins to LDL followed by triglyceride hydrolysis. In addition to affecting serum lipid levels, inflammation also adversely effects lipoprotein function. LDL is more easily oxidized as the ability of HDL to prevent the oxidation of LDL is diminished. Moreover, there are a number of steps in the reverse cholesterol transport pathway that are adversely affected during inflammation. The greater the severity of the underlying inflammatory disease, the more consistently these abnormalities in lipids and lipoproteins are observed. Treatment of the underlying disease leading to a reduction in inflammation results in the return of the lipid profile towards normal. The changes in lipids and lipoproteins that occur during inflammation and infection are part of the innate immune response and therefore are likely to play an important role in protecting the host. The standard risk calculators for predicting cardiovascular disease (ACC/AHA, Framingham, SCORE, etc.) underestimate the risk in patients with inflammation. It has been recommended to increase the calculated risk by approximately 50% in patients with severe inflammatory disorders. The treatment of lipid disorders in patients with inflammatory disorders is similar to patients without inflammatory disorders. Of note statins, fibrates, and fish oil have anti-inflammatory properties and have been reported to have beneficial effects on some of these inflammatory disorders. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.
12587019 NTP Toxicology and Carcinogenesis Studies of Salicylazosulfapyridine (CAS No. 599-79-1) in 1997 May Salicylazosulfapyridine is widely used for the treatment of ulcerative colitis and Crohn's disease. It has been beneficial in the treatment of psoriasis and rheumatoid arthritis, and it has been used in veterinary medicine for the treatment of granulomatous colitis. Salicylazosulfapyridine was nominated for toxicity and carcinogenicity testing by the National Cancer Institute on the basis of its widespread use in humans and because it is a representative chemical from a class of aryl sulfonamides. Salicylazosulfapyridine is a suspect carcinogen because reductive cleavage of the azo linkage yields a p-amino aryl sulfonamide (sulfapyridine), and a related p-amino aryl sulfonamide (sulfamethoxazole) has been shown to produce thyroid neoplasms in rats. Toxicology and carcinogenicity studies were conducted in F344/N rats and B6C3F1 mice. Rats and mice were administered salicylazosulfapyridine (96% to 98% pure) in corn oil by gavage for 16 days, 13 weeks, or 2 years. The gavage route of administration was selected for these studies because it approximates the typical route of human exposure to the chemical. Genetic toxicology studies were conducted in vitro in Salmonella typhimurium and cultured Chinese hamster ovary cells and in vivo in rat and mouse bone marrow and mouse peripheral blood cells. 16-DAY STUDY IN RATS: Groups of five male and five female rats were administered 0, 675, 1,350, or 2,700 mg salicylazosulfapyridine/kg body weight in corn oil by gavage for 16 days excluding weekends. All rats survived to the end of the study. With the exception of the 675 mg/kg male group, the final mean body weights of all dosed groups of males and females were significantly lower than those of controls. Mean body weight gains of all dosed groups were less than those of controls. Clinical findings included ruffled fur and distended abdomens in male and female rats receiving 2,700 mg/kg. Hypothyroidism, evidenced by decreased serum triiodothyronine and thyroxine concentrations and increased thyroid-stimulating hormone concentrations, occurred in 2,700 mg/kg male and female rats. The absolute and relative thymus weights of male rats receiving,350 or 2,700 mg/kg and female rats receiving 2,700 mg/kg were significantly lower than those of controls. At necropsy, all dosed rats had enlarged cecae/large intestines. Male rats receiving 1,350 mg/kg and male and female rats receiving 2,700 mg/kg had red, enlarged thyroid glands. Chemical-related microscopic lesions were present in the forestomach, thymus, thyroid gland, and pituitary gland. Minimal to mild hyperplasia of the forestomach mucosa was present in the 1,350 and 2,700 mg/kg male and female groups. Lymphoid depletion was observed in the thymus of three male and three female rats in the 2,700 mg/kg groups. Male and female rats receiving 1,350 and 2,700 mg/kg had thyroid gland follicular cell hyperplasia and an increase in thyroid-stimulating hormone producing cells in the pars distalis of the pituitary gland. 16-DAY STUDY IN MICE: Groups of five male and five female mice were administered 0, 675, 1,350, or 2,700 mg salicylazosulfapyridine/kg body weight in corn oil by gavage for 16 days excluding weekends. There were no chemical-related deaths, and final mean body weights of dosed mice were similar to those of controls. No chemical-related clinical findings were noted for male or female mice. There were no differences in triiodothyronine, thyroxine, or thyroid-stimulating hormone concentrations between dosed and control mice. There were no biologically significant differences in absolute or relative organ weights between dosed and control male and female mice. At necropsy, male mice receiving 2,700 mg/kg had enlarged cecae/large intestines. There were no biologically significant histopathologic lesions attributed to salicylazosulfapyridine administration. 13-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were administered 0, 84, 168.8, or 337.5 mg salicylazosulfapyridine/kg body weight in corn oil by gavage for 13 weeks. All rats survived to the end of the study. The finaludy. The final mean body weights of dosed male rats were similar to those of controls; the final mean body weights and body weight gains of dosed females were significantly lower than those of controls. No chemical-related clinical findings were noted in dosed male or female rats during the 13-week study. No significant differences in hematology or urinalysis parameters between control and dosed rats were observed. The absolute and relative right kidney weights of 337.5 mg/kg females were significantly greater than those of controls. At necropsy, some 337.5 mg/kg male rats had red, enlarged thyroid glands. Histopathologic changes were noted primarily in the thyroid gland and pituitary gland of males and females in the 337.5 mg/kg groups. The thyroid gland lesions observed were similar to those present in the 16-day study. Nine male rats receiving 168.8 mg/kg and ten male and seven female rats receiving.5 mg/kg had minimal but consistent changes in thyroid gland follicular cells. In the pituitary gland of 337.5 mg/kg males and females, the thyroid-stimulating hormone producing cells were enlarged and contained pale-staining cytoplasm and prominent Golgi complexes. Decreased serum triiodothyronine and thyroxine concentrations and increased thyroid-stimulating hormone concentration, similar to differences observed in the 16-day study, occurred in 337.5 mg/kg male rats; thyroid hormone concentrations were not affected in female rats. Sperm motility of all dosed groups of males was significantly lower than that of controls. Vaginal cytology parameters of dosed groups of females were similar to those of controls. 13-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were administered 0, 675, 1,350, or 2,700 mg salicylazosulfapyridine/kg body weight in corn oil by gavage for 13 weeks. All mice survived to the end of the study. The final mean body weights of dosed male and female mice were similar to those of controls. The mean body weight gains of 1,350 and 2,700 mg/kg male mice were less than that of controls. No chemical-related clinical findings were noted in dosed male or female mice during the 13-week study. There was minimal evidence of a responsive anemia in mice in the 13-week study. The anemia was probably related to a methemoglobinemia. There were minimal decreases in thyroxine concentration in all dosed groups of male and female mice in the -week study. There were, however, no differences in triiodothyronine and thyroid-stimulating hormone concentrations between dosed and control animals. Absolute and relative liver weights of all groups of dosed male and female mice were significantly greater than those of controls. There were no chemical-related gross lesions. Microscopic evaluation of the liver revealed centrilobular hypertrophy in five 1,350 mg/kg and all 2,700 mg/kg male mice. The right cauda weight of the 1,350 mg/kg group and the right epididymis weights of all dose groups were significantly lower than those of controls. There was no evidence of chemical-related alteration in the vaginal cytology parameters of female mice. 2-YEAR STUDY IN RATS: Groups of 60 male and 60 female rats were administered 84, 168, or 337.5 mg salicylazosulfapyridine/kg body weight in corn oil by gavage for up to 105 weeks. Groups of 70 male and 60 female rats were administered the corn oil vehicle by gavage for up to 105 weeks. A stop-exposure group of 70 male rats was administered 337.5 mg/kg salicylazosulfapyridine in corn oil by gavage for 6 months, after which animals received the corn oil vehicle by gavage for the remainder of the 2-year study. Ten animals from the vehicle control male group and 10 animals from the 337.5 mg/kg stop-exposure group were evaluated at 6 months; animals from each core-study group were evaluated at 15 months. Survival, Body Weights, and Clinical Chemistry: Survival of 337.5 mg/kg male core-study rats was significantly lower than that of controls; survival of 84 and 168 mg/kg core-study males, all groups of dosed females, and the stop-exposure male group was similar to controls. Mean body weights of core-study males and stop-exposure males were similar to controls throughout the study. From week 45 to the end of the study, females in the 337.5 mg/kg group had mean body weights that were lower than those of controls. The serum thyroxine concentration in 337.5 mg/kg core-study males at study termination was minimally lower than that of controls; the serum thyroid-stimulating hormone, triiodothyronine, and reverse triiodothyronine concentrations of dosed males and females were similar to those of controls. Pathology Findings: Administration of salicylazosulfapyridine for 2 years was associated with transitional epithelial papilloma in the urinary bladder of male rats and may have been associated with transitional epithelial papilloma of the kidney and of the urinary bladder of female rats. Nonneoplastic effects in the urinary bladder and kidney of male and female rats and in the spleen of male rats were also observed. Dosed male and female rats had increased incidences of grossly and microscopically observed urinary bladder concretions (diagnosed grossly as calculi at necropsy); male and female rats that developed transitional epithelial papillomas of the urinary bladder had grossly observed concretions (calculi) in the urinary bladder at necropsy. The microscopic neoplastic and nonneoplastic urinary bladder and kidney effects observed in dosed male rats during the 2-year continuous study did not occur in dosed rats during the 2-year stop-exposure study, nor were there gross observations of concretions (calculi) at necropsy. The incidences of mononuclear cell leukemia in male and female rats were decreased. The thyroid gland hyperplasia seen in the -week study was not observed in the 2-year study, and there was no evidence of chemical-related thyroid gland follicular cell adenomas or carcinomas. 2-YEAR STUDY IN MICE: Groups of 60 male and 60 female mice were administered 0, 675, 1,350, or 2,700 mg salicylazosulfapyridine/kg body weight in corn oil by gavage for up to 104 weeks. Ten animals from each group were evaluated at 15 months. Survival, Body Weights,and Clinical Chemistry: Survival of all the dosed groups of male and female mice was similar to that of controls. Mean body weights of 675 and 1,350 mg/kg male and female mice were similar to controls throughout the study. From week 12 to the end of the study, 2,700 mg/kg male mice had mean body weights that were lower than those of controls. From week 14 to the end of the study, the 2,700 mg/kg female mice had mean body weights that were lower than those of controls. There were no chemical-related differences in triiodothyronine, reverse triiodothyronine, thyroxine, or thyroid-stimulating hormone concentrations between dosed and control mice at the 15-month evaluation. Pathology Findings: Exposure of mice to salicylazosulfapyridine in corn oil by gavage for 2 years was associated with increased incidences of hepatocellular neoplasms in males and females. Nonneoplastic effects in the liver and spleen were also observed in male and female mice. The incidences of forestomach squamous cell papilloma in females and forestomach hyperplasia in males and females were decreased. GENETIC TOXICOLOGY: Salicylazosulfapyridine was not mutagenic in Salmonella typhimurium strains TA97, TA98, TA100, or TA1535, and it did not induce sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells. These in vitro assays were performed with and without S9 metabolic activation enzymes. Results from in vivo mouse bone marrow chromo somal aberration tests were uniformly negative, while results of micronucleus assays performed on male or female mice exposed to salicylazosulfapyridine for periods ranging from 3 days to weeks were positive. Micronucleus tests in male mice for shorter exposure times (1 to 2 days) yielded negative or very weakly positive results. A three-treatment (72-hour exposure time) micronucleus test performed in male rats yielded equivocal results. Overall, results of these in vivo assays indicate that salicylazosulfa pyridine is capable of inducing chromosomal damage, possibly in the form of aneuploidy, in mouse bone marrow cells after multiple administrations. CONCLUSIONS: Under the conditions of these 2-year gavage studies, there was some evidence of carcinogenic activity of salicylazosulfapyridine in male and female F344/N rats based on increased incidences of neoplasms in the urinary tract. There was an increased incidence of transitional epithelial papilloma of the urinary bladder in males and a low incidence of rare transitional epithelial papillomas of the kidney and of the urinary bladder in females. There was clear evidence of carcinogenic activity of salicylazosulfapyridine in male and female B6C3F1 mice based on increased incidences of hepatocellular neoplasms. Increased incidences of nonneoplastic lesions of the urinary bladder and kidney in male and female rats and of the spleen in male rats were observed. Increased incidences of nonneoplastic lesions of the liver and spleen in male and female mice were observed. Decreased incidences of mononuclear cell leukemia in male and female rats were related to salicylazosulfapyridine administration. Decreased incidences of forestomach squamous cell papilloma in female mice and forestomach hyperplasia in male and female mice were related to salicylazosulfapyridine administration. Synonyms: 2-Hydroxy-5-[[4-[2-(pyridinylamino)sulfonyl]phenyl]azo]benzoic acid; 5-[p- (2-pyridylsulfamoyl)phenylazo]salicylic acid; sulfasalazine; salazosulfapyridine; 5-[4-(2-pyridylsulfamoyl)phenylazo]-2-hydroxybenzoic acid; 4-(pyridyl-2-amidosulfonyl)-3'-carboxy-4'-hydroxyazobenzene; sulphasalazine Trade names: Azopyrin, Azulfidine, Benzosulfa, Colo-Pleon, Reupirin, Salazopyrin
12422843 Rheumatoid arthritis. 2002 Oct Rheumatoid arthritis (RA) is a systemic, debilitating disease characterized by chronic polyarticular inflammation that leads to erosion of joint and bones and to significant extra-articular, systemic, and cardiopulmonary manifestations. RA affects the patient's psychologic and social well-being as well as physical activity. The economical burden is high. Patients with RA may be admitted to the ICU for a variety of problems and present unique challenges to all physicians, including intensivists. This article discusses the basic pathophysiology and clinical manifestations of RA and the extra-articular disorders that bring these patients to an ICU. The management of these patients in ICU is discussed, with emphasis on airway management and outcome.
12069565 Rheumatoid arthritis--a molecular understanding. 2002 Jun 18 The application of molecular immunology techniques in the study of rheumatoid arthritis has resulted in an explosion of knowledge on the risk factors for the disease, predictors of disease severity, the molecular mechanisms of inflammatory responses, and mechanisms of tissue destruction. We know, for example, that inheriting certain genes in the major histocompatibility complex partly dictates susceptibility and severity of rheumatoid arthritis. These genes and others in the major histocompatibility complex are critical for the occurrence of immune responses both constructive (prevention of infection, surveillance for malignant cells) and destructive (development of autoimmune diseases). We also now understand mechanisms of cell communication, regulation of immune responses, how the cells that mediate immune responses and tissue injury accumulate in tissues, and how the injury occurs. The knowledge itself is satisfying, but more important, based on this knowledge, effective and reasonably safe treatments that address basic mechanisms of the disease process have been developed and are now widely used. In fact, the newer treatments represent the "tip of the iceberg," and as our basic knowledge increases, so too will the armamentarium with which we can fight rheumatoid arthritis and other similar autoimmune diseases.
15286008 Is rheumatoid arthritis disappearing? 2005 Jan During the past decades a number of studies have examined the incidence of rheumatoid arthritis (RA) in different geographical settings and at different times. Some studies from the 1970s and 1980s reported a higher incidence of RA than seen during recent years, where reported incidence numbers seems to have flattened out at a lower level. Besides a real time dependent decline of RA incidence, changing methodology in classification may be an equally important explanation. Today we may assume that annually 25-50 people from a population of 100,000 will develop typical RA.
15125859 Rheumatoid arthritis of the cervical spine. 2004 May BACKGROUND CONTEXT: Rheumatoid arthritis affects over 2 million patients in the United States. It is the most common inflammatory disorder of the cervical spine. The natural history is variable. Women tend to be more commonly involved than men. Atlantoaxial instability is the most common form of cervical involvement and may occur either independently or concomitantly with cranial settling and subaxial instability. Cervical spine involvement can be seen in up to 86% of patients and neurologic involvement in up to 58%. Myelopathy is rare but when present portends a poor prognosis. What is frustrating for clinicians treating these patients is that pain cannot be equated with instability or instability with neurologic symptoms. The goal is to identify patients at risk before the development of neurologic symptoms. Both radiographic and nonradiographic risk factors play an important role in the surgical decision-making process. PURPOSE: We will describe the current concepts in rheumatoid arthritis of the cervical spine. Emphasis is placed on the natural history, anatomy, pathophysiology and decision-making process. STUDY DESIGN: A review of the current concepts of rheumatoid arthritis of the cervical spine. METHODS: MEDLINE search of all English literature published on rheumatoid arthritis of the cervical spine. RESULTS: Rheumatoid arthritis of the cervical spine was first described by Garrod in 1890. The prevalence has been estimated to be 1% to 2% of the world's adult population. Despite its prevalence, the etiology of rheumatoid arthritis remains unknown. Because of its potentially debilitating and life-threatening sequelae in advanced disease, rheumatoid arthritis in the cervical spine today remains a high priority to diagnose and treat. CONCLUSIONS: Many aspects of the natural history and pathophysiology of the rheumatoid spine remain unclear. The timing of operative intervention in patients with radiographic instability and no evidence of neurologic deficit is an area of considerable controversy. Continued surveillance into the natural history of the rheumatoid spine is required.
15253402 Management of rheumatoid arthritis. 2004 May The past few years have witnessed a major change in the approach to the treatment of rheumatoid arthritis. The present focus is on early recognition and prompt treatment with disease-modifying antirheumatic drugs of which methotrexate continues to be the drug of choice. Leflunomide is an important recent addition to the list of available drugs. The use of combinations of disease-modifying antirheumatic drugs is gaining wide acceptance. A better understanding of the pathobiology of rheumatoid arthritis has led to the development of targeted therapies such as tumour necrosis factor blockers. There are robust data to show the clinical utility of tumour necrosis factor blockers in patients with rheumatoid arthritis.
15541704 Rheumatoid arthritis: evaluation and surgical management of the cervical spine. 2004 Nov BACKGROUND CONTEXT: Rheumatoid arthritis is a debilitating polyarthropathic degenerative condition. Eighty-six percent of patients with rheumatoid arthritis have cervical spine involvement. Often these lesions are clinically asymptomatic or symptoms are erroneously attributed to peripheral manifestation of the patient's rheumatoid disease. Because these lesions are common and missed diagnosis can result in death, early recognition is vital. PURPOSE: The purpose of this literature review is to identify common lesions present in the rheumatoid neck and review diagnostic methods as well as treatment options for those requiring surgical intervention. STUDY DESIGN: A review of the English medical literature with focus on more recent studies on the presentation, diagnosis, management, surgical treatment and clinical outcomes of rheumatoid arthritis of the cervical spine. METHODS: A comprehensive literature review of the English medical literature obtained through Medline up to November 2003 was performed identifying relevant and more recent articles that addressed the presentation, evaluation, surgical management and outcomes of rheumatoid patients with cervical spine involvement. RESULTS: If left untreated, a large percentage of rheumatoid patients with cervical spine involvement progress toward complex instability patterns resulting in significant morbidity and mortality. Once myelopathy occurs, prognosis for neurologic recovery and long-term survival is poor. In properly selected patients, anterior and/or posterior cervical procedures can prevent neurologic injuries and preserve remaining function. CONCLUSION: Cervical spine involvement in the rheumatoid patient is common and progressive. Early diagnosis and treatment is imperative; however, surgical intervention should be considered carefully because associated morbidity and mortality is high.
15156823 Rheumatoid arthritis of the wrist. 2003 The wrist is the most commonly involved joint in the upper extremity of patients with rheumatoid arthritis. Up to 75% of patients will develop wrist problems during the course of the disease. Cartilage degeneration and synovitis cause the typical skeletal erosions, ligamentous laxity, deformity, and tendon problems seen in the disease. Treatment involves a multidisciplinary approach with careful coordination of the primary care physician, rheumatologist, orthopaedic surgeon, and other members of the care team. As rheumatoid arthritis is a systemic, polyarticular disease, it is critical to consider the entire patient in any management decision. Initial management is usually non-operative and involves pharmacological treatment, activity modification, and possibly bracing. Operative treatments are geared to limit the negative effects of the disease, namely pain, loss of function, and deformity. Numerous procedures have been described. Common procedures from tenosynovectomy/synovectomy, distal radio-ulnar joint arthroplasty, arthrodesis, and total wrist arthroplasty are reviewed.
12699368 Rheumatoid arthritis of the shoulder. 2003 Jan Rheumatoid arthritis affecting the shoulder region is a progressive disorder that results in pain, loss of range of motion, and functional disability. The inflammatory response, which is of unknown etiology, results in synovitis, pannus formation, and articular destruction. Even when patient history and physical examination suggest rheumatoid involvement of the shoulder, laboratory assessment and radiographic evaluation often are necessary to establish the diagnosis. Nonsurgical management is the primary treatment, including pharmacologic and physical therapy regimens for patients with mild symptoms and functional disability. Surgical intervention is indicated in patients with significant pain and functional limitation when nonsurgical treatment fails to provide relief. The procedure selected depends on careful assessment of the degree of articular cartilage injury and compromise of the periarticular soft tissues.
15645961 Rheumatoid arthritis and the kidney. 2004 Jun It is clear that kidney is involved in rheumatoid arthritis (RA) with both glomerular and tubular damage. Renal disease in RA however is usually asymptomatic and is detected only on laboratory investigations. It is often difficult to differentiate between damage due to disease activity and that due to drugs used to treat RA. Although there are a number of parameters to study renal function, these cannot be applied to day to day practice and still remain research tools. In such a scenario, it is important to periodically monitor serum creatinine and carry out urine examination so as to pick up the earliest signs of renal dysfunction.
12110126 Angiogenesis in rheumatoid arthritis. 2002 The expansion of the synovial lining of joints in rheumatoid arthritis (RA) and the subsequent invasion by the pannus of underlying cartilage and bone necessitate an increase in the vascular supply to the synovium, to cope with the increased requirement for oxygen and nutrients. The formation of new blood vessels - termed 'angiogenesis' - is now recognised as a key event in the formation and maintenance of the pannus in RA. This pannus is highly vascularised, suggesting that targeting blood vessels in RA may be an effective future therapeutic strategy. Disruption of the formation of new blood vessels would not only prevent delivery of nutrients to the inflammatory site, but could also lead to vessel regression and possibly reversal of disease. Although many proangiogenic factors are expressed in the synovium in RA, the potent proangiogenic cytokine vascular endothelial growth factor (VEGF) has been shown to a have a central involvement in the angiogenic process in RA. The additional activity of VEGF as a vascular permeability factor may also increase oedema and hence joint swelling in RA. Several studies have shown that targeting angiogenesis in animal models of arthritis ameliorates disease. Our own study showed that inhibition of VEGF activity in murine collagen-induced arthritis, using a soluble VEGF receptor, reduced disease severity, paw swelling, and joint destruction. Although no clinical trials of anti-angiogenic therapy in RA have been reported to date, the blockade of angiogenesis - and especially of VEGF - appears to be a promising avenue for the future treatment of RA.
11840692 Rheumatoid arthritis. The genetic components. 2002 Feb Rheumatoid arthritis is a multifactorial disease, with genetic, environmental, and stochastic components to its susceptibility. The search for susceptibility genes is still in progress. Preliminary results suggest the involvement of multiple genes, each with relatively modest effect. Genes within the major histocompatibility complex appear to have the strongest influence on disease susceptibility.
15224492 Rheumatoid arthritis: symptoms, diagnosis, and management. 2004 Jun 15 Rheumatoid arthritis is the most common inflammatory joint disease and a major cause of disability, morbidity, and mortality. It occurs worldwide, affecting approximately one per cent of adults. Inflammation of the synovial membrane surrounding a joint leads to swollen, tender, and stiff joints. This may be accompanied by fatigue, weight loss, anxiety, and depression. Nursing management goals should include the relief of symptoms, preservation of joint function, prevention of joint damage and deformity, maintenance of an acceptable lifestyle, and patient education. To achieve these aims the nurse should play a pivotal role within the multidisciplinary team, ensuring the highest quality of care.
14969065 Early rheumatoid arthritis in Finland. 2003 Sep The first Finnish early rheumatoid arthritis (RA) cohort was established in 1973-75 at the Rheumatism Foundation Hospital in Heinola, a hospital for rheumatic diseases only. Since then early RA cohorts for the purposes of longitudinal observation have been established at the Jyväskylä Central Hospital and Helsinki University Hospital. Furthermore, 199 patients with early RA were enrolled in a multicenter randomized controlled study in 1993-95. The primary observations from these cohorts are summarized in this essay.