RESUMEN

The remarkable similarity in inflammatory response and pathology of periodontal disease and rheumatoid arthritis has been recognized for several decades. However, how these two disease may be interrelated has been less clear. During the pathogenesis of rheumatoid arthritis there is a preclinical immunological phase which precedes the clinical manifestation of rheumatoid arthritis. During this phase serum autoantibodies appear many years before the clinical signs and symptoms of rheumatoid arthritis become apparent. To date, the two best studied autoantibodies have been rheumatoid factor and anti-citrullinated protein antibodies (ACPA). Of these the production of ACPA has been considered very important due to their high predictive value in future manifestation of rheumatoid arthritis. Citrullination is a common post-translational modification of proteins based on the enzymatic conversion of arginine into citrulline. Extra-articular citrullination and production of ACPA, as a priming immunological experience, is well documented in many tissues including the inflamed gingival tissues associated with periodontal disease. More recently, carbamylation of proteins has also been implicated in the pathogenesis of rheumatoid arthritis in a manner similar to citrullination. Carbamylation is a post translational modification of proteins by an enzyme-independent modification of lysine residues against which autoantibodies are subsequently induced. In this article we hypothesise that, like citrullination, carbamylation of proteins and associated antibody production during the gingival inflammation associated with gingivitis and periodontitis may play a role in the pathogenesis of rheumatoid arthritis.

Asunto(s)

RESUMEN

OBJECTIVE: To examine effects of the COX-2 inhibitor market withdrawals on NSAID utilization among patients at increased risk of gastrointestinal (GI) and cardiovascular (CV) toxicities. METHODS: A prospective cohort study was conducted using patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) Registry. The study population included rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients prescribed NSAIDs by rheumatologists from 1/1/2003 to 12/31/2005. Three cohorts were defined based on calendar year. The primary outcome assessed whether or not an NSAID gastroprotective strategy was prescribed. Secondary outcomes included rates of COX-2 inhibitor utilization and gastroprotective co-therapy utilization, stratified by the presence of cardiac and GI risk factors. RESULTS: NSAID gastroprotection utilization decreased from 65.1% in 2003 to 47.7% (p<0.001) in 2005. COX-2 inhibitor use decreased from 55.1% to 29.2% (p<0.001), whereas nonselective NSAIDs (nsNSAIDs) use increased from 50.2% to 73.9% (p=<0.01). Among patients with two or more risk factors for NSAID related GI bleeding, gastroprotection decreased from 74.4% in 2003 to 60.9% (p<0.01). For patients with two or more CV risk factors from 2003 to 2005, COX-2 inhibitor utilization decreased significantly, whereas nsNSAID utilization increased significantly. CONCLUSIONS: The COX-2 inhibitor withdrawals resulted in a rapid decline in NSAID gastroprotection prescribed by participating U.S. rheumatologists despite the availability of other gastroprotective options. Channeling toward nsNSAID use was widespread, including among patients at increased CV risk. Longer term follow-up is required to determine the clinical significance of these changes in NSAID prescribing, particularly for NSAID-related GI and CV-related toxicities.

Asunto(s)

RESUMEN

OBJECTIVE: Scleroderma-related interstitial lung disease (SSc-ILD) has limited therapeutic options due to unclear pathogenesis. Recently, PDGF receptor (PDGFR) amplification has been postulated to cause fibrosis. We hypothesized that a combination of immunosuppressive agents, e.g. cyclophosphamide (CYC) and imatinib (PDGFR inhibitor), might be useful for treating SSc-related ILD. Our objective was to evaluate the safety and efficacy of this combination therapy in scleroderma-related pulmonary disease. METHODS: Five patients with advanced SSc-ILD underwent comprehensive cardiopulmonary evaluation, followed by administration of oral imatinib (200 mg/day) and intravenous CYC (500 mg every 3 weeks). Safety was assessed by close monitoring of complete blood count, liver and cardiac functions. Efficacy was evaluated by measuring pulmonary functions at 6 and 12 months. RESULTS: Of the five patients in the study, four had severe and one had mild restrictive lung disease. All patients tolerated the combination treatment without myelosuppression, deterioration of liver functions or cardiac status. Only one patient had mild fluid overload requiring diuretics. Two patients completed 1 yr of treatment. Only the patient with mild restrictive lung disease showed improvement in pulmonary function. CONCLUSION: The combination of intravenous CYC and oral imatinib was well-tolerated without major side effects. Clinical improvement was seen in only the patient with mild restrictive disease. To our knowledge, this is the first study examining the safety, tolerability and efficacy of imatinib in combination with CYC in scleroderma-related pulmonary disease. Large prospective trials are needed to further determine optimal timing, dose and duration of this regimen.

Asunto(s)

RESUMEN

PURPOSE: Although aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) exert inhibitory effects on platelets in vitro and in vivo, there are insufficient data to substantiate the use of NSAIDs alone as antiplatelet drugs in patients already taking aspirin. We therefore sought to determine whether aspirin, added to NSAID therapy, further suppresses platelet function. SUBJECTS AND METHODS: We enrolled 25 healthy adult volunteers who were administered ketoprofen (extended-release capsules, 200 mg daily) for 1 week, followed by ketoprofen (200 mg daily) and aspirin (325 mg daily) or ketoprofen (200 mg daily) alone during the second week. Platelet aggregation, stimulated by epinephrine and arachidonic acid, and cyclooxygenase activity, measured by thromboxane B(2), were measured at baseline, on day 8, and on day 15. RESULTS: On day 8, all subjects demonstrated abnormal platelet aggregation (>50% inhibition), which persisted at day 15 in both the aspirin and no aspirin groups. One week of ketoprofen treatment reduced thromboxane B(2) levels by 84% in the aspirin group and by 85% in the no aspirin group (P = 0.8), without any further inhibition measured on day 15. CONCLUSION: Extended-release ketoprofen significantly inhibited platelet aggregation and thromboxane B(2) production in healthy volunteers. Addition of aspirin had no additional effect. Trials are warranted to determine whether these in vitro effects result in clinical antiplatelet activity in patients who require chronic treatment with NSAIDs, thereby avoiding the toxicity of NSAID/aspirin combination therapy.

Asunto(s)

RESUMEN

Autoantibodies to the insulin receptor have been demonstrated to antagonize the physiologic actions of insulin, most often resulting in hyperglycemia unresponsive to massive doses of insulin (type B insulin resistance). Patients with these anti-insulin receptor antibodies typically have a coexistent autoimmune disorder, most commonly systemic lupus erythematosus (SLE) or undifferentiated autoimmune syndromes. Attempting to determine the prevalence and significance of anti-insulin receptor antibodies, sera from consecutive patients with SLE and early undifferentiated connective tissue disease (UCTD) were tested for the presence of anti-insulin receptor antibodies by radio-immuno assay. Thirty-eight patients participated in the study. Twenty-six had SLE and 12 had UCTD. One patient with SLE (2.6%) was positive for anti-insulin receptor antibodies. None of the patients demonstrated evidence of insulin resistance, hypoglycemia, ovarian hyperandrogenism, or acanthosis nigricans, findings commonly linked with the presence of anti-insulin receptor antibodies. The results presented here indicate that the incidence of anti-insulin receptor antibodies in patients with SLE or UCTD, without associated history of altered glucose metabolism, is quite low. Because in most cases the disturbance of glucose metabolism dominates the clinical picture at presentation and the associated systemic autoimmune syndrome presents either simultaneously with or subsequent to the diagnosis of diabetes, the measurement of anti-insulin receptor antibodies should be reserved for patients with indications of disordered glucose homeostasis.

RESUMEN

OBJECTIVE: To increase awareness of giant cell myocarditis (GCM), its pathogenesis, and treatment. METHODS: Review of relevant publications from the English-language literature. RESULTS: GCM is a rare, frequently fatal inflammatory disorder of cardiac muscle of unknown origin, characterized by widespread degeneration and necrosis of myocardial fibers.Congestive heart failure and ventricular tachycardia are common clinical manifestations. GCM occurs primarily in previously healthy adults, although it is frequently associated with various systemic diseases, primarily of autoimmune causes. The inflammatory infiltrate is characterized by the presence of multinucleated giant cells and is distinct from cardiac sarcoidosis. Animal models of GCM are similar to models of other autoimmune disorders such as rheumatoid arthritis. The prognosis, which is poor despite partial responsiveness to immunosuppressive medications, is improved with cardiac transplantation. CONCLUSIONS: The clinical and immunopathogenetic similarities with classical rheumatologic diseases, the differential diagnosis with sarcoidosis and other inflammatory conditions, and the use of standard immunosuppressive medications make GCM a disease process that should be added to the rheumatologist's expertise.

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

Topical drug delivery may be the optimal route for the treatment of localized musculoskeletal disorders because higher drug concentrations can be achieved at the sites of clinical significance. The rationale for the use of topical salicylates and other nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of soft-tissue rheumatic complaints and osteoarthritis is reviewed. Topical capsaicin offers another potentially beneficial therapy for the treatment of osteoarthritis of selected joints. Although there are extensive, uncontrolled experiences with DMSO that suggests its effectiveness in the treatment of musculoskeletal disorders, controlled trials yield conflicting results. The basis for the use of physical modalities such as phonophoresis and iontophoresis to improve topical drug efficacy is summarized.

Asunto(s)

RESUMEN

The role of trace metallic elements (copper, selenium, zinc, gold) in chronic inflammatory states is of great interest because many of them are co-factors in metabolic processes involving articular tissues and immune system function. Deficiencies of several of these have been documented in patients with rheumatoid arthritis. Other than for the clinically approved gold compounds, there exists only inconsistent evidence for a therapeutic role of trace metallic elements in the management of rheumatoid arthritis.

Asunto(s)

RESUMEN

Multicentric reticulohistiocytosis (MR) is a rare disease in which an infiltration of histiocytic cells causes destructive polyarthritis and characteristic cutaneous lesions. It predominantly affects women between the ages of 40 and 50 years. Effective treatment has not been well established. We describe a case diagnosed in a 6-year-old girl. This is the youngest patient with MR reported to date.

Asunto(s)

RESUMEN

A 33-year-old woman with longstanding rheumatoid arthritis and Sjögren's syndrome developed type B insulin resistance (diabetes mellitus due to anti-insulin receptor antibodies) simultaneous with the evolution of her rheumatic disease to mixed connective tissue disease. Cyclosporine therapy induced a remission of receptor antibody mediated insulin resistance and controlled clinical manifestations of her systemic lupus erythematosus and dermatomyositis, but had no effect on the sclerodermatous features of her illness.

Asunto(s)

Asunto(s)

RESUMEN

Three women with breast carcinoma were treated with combination chemotherapy, including cyclophosphamide, 5-fluorouracil, and methotrexate, after mastectomy. Within two months of termination of chemotherapy, all 3 patients developed florid synovitis. Two patients had prior clinical manifestations consistent with rheumatoid arthritis; one patient had no antecedent history of arthritis. We suggest that this presentation may represent exacerbation of mild or subclinical rheumatoid arthritis as a consequence of withdrawal of methotrexate therapy.

Asunto(s)

Asunto(s)

RESUMEN

The authors describe a 22-year-old man with osteolytic mandibular and maxillary lesions. Biopsy substantiated the presence of Langerhans cell histiocytosis (eosinophilic granuloma). Levels of serum angiotensin-converting enzyme (ACE) were elevated repeatedly. After definitive therapy with excision and bone grafting, ACE levels returned to normal. The role of histiocytes in ACE production is discussed. Langerhans cell histiocytosis should be considered in the diagnosis of conditions occurring with elevation of serum ACE levels and clinical findings similar to sarcoidosis.

Asunto(s)

RESUMEN

Certain health care reform proposals emphasize "primary" rather than specialty care, so it is important to document whether these changes might affect patients with rheumatic diseases. We therefore assessed outcome and costs of patients who were hospitalized with acute arthritis, comparing management by rheumatologists with nonrheumatologists. We reviewed charts retrospectively from 1991 to 1993 at our community medical center. Twenty patients with acute arthritis were managed by rheumatologists and 35 were managed by nonrheumatologists. Demographic, clinical, and rheumatologic features of patients were comparable.Rheumatologists ordered joint radiographs (65%) and performed diagnostic arthrocentesis (75%) significantly more often than nonrheumatologists (31 and 34%, respectively; p < 0.05). Rheumatologists' initial recorded diagnostic impressions were usually confirmed at discharge, whereas nonrheumatologists' more often were not (p < 0.05). Rheumatologists established definite diagnoses by American College of Rheumatology criteria significantly more often (75%) than nonrheumatologists (34%;p < 0.05). Nonrheumatologists selected antibiotics, systemic corticosteroids, nonsteroidal anti-inflammatory drugs, and allopurinol more often and intra-articular steroids (p < 0.05) and adrenocorticotropic hormone less often for a similar case mix than rheumatologists. Rheumatologists' clinical evaluations (p < 0.001), selection of diagnostic studies (p < 0.001), and therapeutic decisions (p < 0.005) were significantly more complete. Trends strongly favored rheumatologists' patients improving more rapidly (3.5 vs. 6.6 days; p = 0.06) and being hospitalized for shorter stays (7.4 vs. 14.7 days; p = 0.08) and favored rheumatologists' patients as managed at considerably less hospital cost ($8756 vs. $14,750).These limited observations suggest caution about equating nonspecialty with rheumatologic care and are consistent with suggestions that, at least for certain patients and as defined by our criteria above, rheumatologists offer more complete evaluation, more accurate diagnosis, more rational therapy, and better clinical outcome at lower cost than do nonrheumatologists.

RESUMEN

We report the case of a 60-year-old man who presented with fever, weight loss, generalized aching, left temporal and ear pain, and an erythrocyte sedimentation rate of 125 mm/hour. Due to the presumed diagnosis of giant cell arteritis (GCA), the patient was treated with prednisone (60 mg daily), with immediate improvement in his symptoms. Biopsy of the temporal arteries revealed no significant inflammatory infiltrate. Further evaluation included assessments of thyroid function, which revealed an elevated T4 level, low thyroid-stimulating hormone level, and suppressed radioactive iodine uptake on thyroid scintigraphy. A diagnosis of subacute thyroiditis was made, prednisone therapy was tapered over 3 weeks, and treatment with beta blockers was instituted. The patient remained asymptomatic and returned to a euthyroid state. This case illustrates that subacute thyroiditis should be considered in the differential diagnosis of GCA.

Asunto(s)