Painful shoulder: comparison of physical examination and ultrasonographic findings.

BACKGROUND: High frequency ultrasonography is an accurate non-invasive imaging technique for evaluating patients with painful shoulder. OBJECTIVE: To compare the clinical diagnosis established by a physical examination with high frequency ultrasonographic findings in patients with painful shoulder. METHODS: Thirty one consecutive patients with a first flare of shoulder pain were prospectively included in the study. All had a physical examination performed by two blinded rheumatologists. Ultrasonographic examination was carried out within one week of the physical examination by a third rheumatologist experienced in this technique who had no knowledge of the clinical findings. Ultrasonography was considered the optimal diagnostic technique. RESULTS: Clinical assessment showed low accuracy in the diagnosis of periarticular shoulder lesions. CONCLUSION: Ultrasonography should be used wherever possible to improve diagnosis and treatment of painful shoulder.

Activity indices in rheumatoid arthritis.

OBJECTIVE: To determine which activity indices better correlate with assessor's (AGA) and patient's (PGA) global assessment of disease activity and to compare the improvement with American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) criteria and their association with PGA and AGA of overall improvement. METHODS: Seventy-five patients with rheumatoid arthritis (RA) were studied. Swollen and tender joints, morning stiffness, grip strength, pain, AGA, PGA, Health Assessment Questionnaire (HAQ) score, erythrocyte sedimentation rate (ESR), C-reactive protein (CPR), and hemoglobin were determined before and 6 months after treatment. Several activity indices were calculated: Disease Activity Score (DAS), DAS 3, DAS 28, DAS '28,' ACR > or = 20%, Mallya, Riel, IDA, and a modification of the Stoke index. RESULTS: All indices correlated with PGA and AGA before and after treatment (r > 0.38, p < 0.01), but better results were obtained with AGA than PGA. DAS, DAS 3, DAS 28, and modified Stoke had the best correlation with AGA (r > or = 0.77, p < 0.01). The indices that better detected the differences after treatment for AGA were DAS, DAS 3, DAS 28, and modified Stoke (r > or = -0.42, p < 0.01). The level of agreement between EULAR and ACR improvement classifications with both reduced and extensive joint counts was comparable and its association with PGA and AGA overall improvement was significant (p < 0.01). CONCLUSION: All activity indices correlated with PGA and AGA, although the best results were obtained with AGA. Although indices' correlations were similar, the DAS group and the modified Stoke seemed to be the most useful indices to measure disease activity in RA. The discriminating potential between ACR and EULAR improvement classification was comparable, as was the association with PGA and AGA overall improvement.

Tratamiento con pamidronato por vía intravenosa en la enfermedad de paget / Intravenous pamidronate treatment in Paget's disease

Objetivo. Evaluar la evolución de diversos parámetros metabólicos en pacientes con enfermedad de Paget tratados con pamidronato por vía intravenosa en uno o dos ciclos. Pacientes y métodos. Catorce pacientes recibieron 15 mg/día de pamidronato durante cinco días. Se determinaron: fosfatasa alcalina total (FAT), fosfatasa ácida tartrato resistente (FATR), piridinolina (Pyr), vitamina D, hormona paratiroidea (PTH) y calcio iónico, al inicio, a la semana, al mes, a los tres y seis meses de tratamiento. Seis pacientes recibieron un segundo ciclo de tratamiento a los dos años del primero. Resultados. Se produjo una reducción de los parámetros de formación y resorción ósea, siendo significativa para la FAT a partir del tercer mes (p<=! 0,01), la FATR a los tres y seis meses (p <= 0,01) y la Pyr al mes y tres meses (p<=! 0,05). La PTH aumentó inicialmente, reduciéndose posteriormente junto con el calcio iónico. Con el segundo ciclo se comprobó un menor descenso de todos los parámetros bioquímicos, siendo sólo significativo el descenso de la FAT a los tres (p<= 0,01) y seis meses (<= 0,05). La PTH se mantuvo siempre por encima de los niveles basales y el calcio iónico se comportó como en el primer ciclo. Conclusiones. El pamidronato es un tratamiento efectivo y seguro en la enfermedad de Paget, que consigue una reducción de los marcadores del metabolismo óseo, si bien es menos marcada con ciclos sucesivos (AU)

Low vitamin D levels in outpatient postmenopausal women from a rheumatology clinic in Madrid, Spain: their relationship with bone mineral density.

To evaluate a possible relationship between vitamin D levels and bone mineral density (BMD) and the prevalence of hypovitaminosis in a population of postmenopausal women from a rheumatologic outpatient clinic in Madrid, Spain, 171 postmenopausal women (aged 47-66 years) divided into two groups (osteoporotic and nonosteoporotic, according to WHO criteria) were studied between November and June. Liver and kidney function were normal in all subjects. Serum parathyroid hormone (PTH) and calcidiol levels were determined and bone densitometry carried out at the lumbar spine and hip level. PTH and calcidiol serum levels did not show any correlation. Serum PTH was inversely related to BMD at both hip and lumbar spine in the total group, and at the hip with calcidiol levels lower than 37 nmol/l. Calcidiol was directly related to hip BMD only when levels were lower than 37 nmol/l. Results of a stepwise multiple regression analysis showed that the single factor which affected BMD at the hip was calcidiol in the subgroup with serum calcidiol levels below 37 nmol/l, while in the subgroup with serum calcidiol levels above 37 nmol/l, the main factor affecting hip BMD was serum PTH. The prevalence of vitamin D deficiency at a cutoff of 37 nmol/l was 64%. In summary, calcidiol serum levels below 37 nmol/l seem to affect bone mass, regardless of the effect of PTH. Vitamin D deficiency is a frequent finding in the postmenopausal women who attend a rheumatology outpatient clinic in Madrid. Vitamin D supplementation should therefore be considered in this population during the winter season.

Antiperinuclear factor as a prognostic marker in rheumatoid arthritis.

OBJECTIVE: Antiperinuclear factor (APF) is an autoantibody detected in >50% of patients with rheumatoid arthritis (RA); it shows a specificity of roughly 90%. We investigated the possible role of APF as a prognostic marker in RA. METHODS: A series of 103 patients with RA who fulfilled the 1987 American College of Rheumatology criteria (88 women and 15 men; mean age 55.5 yrs, mean disease duration 9 yrs) were prospectively followed. Sixteen variables were assessed in each patient at inclusion and over a 3 year period. APF was determined by indirect immunofluorescence assay using human buccal mucosal cells as substrate. APF assays were done at entry and at the end of followup without knowledge of the clinical status of the patients. Mann-Whitney U, chi-squared tests, variance analysis, and kappa index were used for statistical analysis. RESULTS: Eighty of 103 patients completed followup. APF was detected in 40 of 80. At inclusion, APF correlated with the visual analog scale (VAS) of pain (p = 0.02). However, patients who showed APF positivity at entry had a less favorable course than APF negative individuals, as shown by a worse VAS of well being (p = 0.01), Ritchie index (p = 0.01), number of painful joints (p = 0.03), grip strength (p = 0.01), C-reactive protein (p = 0.04), and Health Assessment Questionnaire score (p = 0.03) at the end of the study. In addition, APF positive patients showed a worse radiological course (p = 0.03). CONCLUSION: Our results suggest APF is a possible marker of poor prognosis in RA.

Interpreting the clinical significance of the differential inhibition of cyclooxygenase-1 and cyclooxygenase-2.

The International Consensus Meeting on the Mode of Action of COX-2 Inhibition (ICMMAC) brought together 17 international experts in arthritis, gastroenterology and pharmacology on 5 6 December 1997. The meeting was convened to provide a definition of COX-2 specificity and to consider the clinical relevance of COX-2-specific agents. These compounds are a new class of drugs that specifically inhibit the enzyme COX-2 while having no effect on COX-1 across the whole therapeutic dose range. The objectives of the meeting were to review the currently available data regarding the roles and biology of COX-1 and COX-2, and to foster a consensus definition on COX-2 specificity. At the present time, no guidelines exist for the in vitro and in vivo assessment of COX specificity, and it was felt that consensus discussion might clarify some of these issues. The meeting also reviewed recent clinical data on COX-2-specific inhibitors. The following article reflects discussion at this meeting and provides a consensus definition of COX-2-specific inhibitors.

[Polymorphism of the gene of vitamin D receptor and bone mineral density in postmenopausal women]. / Polimorfismo del gen del receptor de la vitamina D y densidad mineral ósea en mujeres posmenopáusicas.

BACKGROUND: Conflicting results have been reported on the association between restriction fragment length polymorphism at the vitamin D receptor (VDR) gene locus and bone mineral density (BMD). Population differences in environmental factors, such as calcium intake and calcidiol levels which have strong influence in BMD, may alter this association. PATIENTS AND METHODS: We analyzed the Bsml RFLP at the eight introm of the VDR gene in a population sample (n = 204) of postmenopausal Spanish women aged 50-65 years being seen clinically and studied calcium intake (dietetic questionnaire) and biochemical parameters (PTH and calcidiol). In parallel bone densitometry were measured in lumbar spine and proximal femur. RESULTS: We identified low BMD of the proximal femur in the BB group. This effect was not observed at other body locations. The calcium intake was lees than 500 mg/day in 60% of the studied population as calcidiol levels were lower than 10 ng/l in 36% of it. The total group population with normal calcium intake (> 1,000 mg/day) showed higher BMD (proximal femur and spine) than the group with low calcium intake, this variation not being observed in group BB alleles. Interestingly, we observed significant differences in BMD proximal femur between genotype groups BB versus Bb + bb when calcidiol levels were < 10 ng/l. Moreover, within the BB subgroup, those subjects with normal calcidiol levels have higher proximal femur BMD compared with those with low calcidiol levels. CONCLUSIONS: Our results indicate an effect of the VDR genotype on BMD proximal femur which is clearly influenced by calcium intake and calcidiol serum levels.

Benign familial hyperphosphatasemia: a report of two families and review of the literature.

Benign familial hyperphosphatasemia is a rare biochemical abnormality of hereditary nature, characterized by the presence of persistently elevated levels of serum alkaline phosphatase in several members of the same family, in the absence of disease or any known cause of hyperphosphatasemia. To date, there have been 29 pedigrees reported in the literature. Another two families affected with hyperphosphatasemia, originating in an increase in the bone isoenzyme, are described. The epidemiology, inheritance, isoenzymatic patterns, postulated mechanisms and clinical significance of this entity are discussed.

[Efficacy and safety of nabumetone in the treatment of knee osteoarthritis: a comparative clinical trial versus aceclofenac. Study Group of Nabumetone for Osteoarthritis of the Knee]. / Eficacia y seguridad de la nabumetona en el tratamiento de la gonartrosis: ensayo clínico comparativo con aceclofenaco. Grupo de Estudio de Nabumetona en Artrosis de Rodilla.

BACKGROUND: Non-steroidal antiinflammatory drugs are extensively prescribed for the symptomatic treatment of osteoarthritis (OA). This study compared the efficacy and safety of nabumetone with aceclofenac in patients with active knee osteoarthritis. PATIENTS AND METHODS: Phase IV, multicentre, prospective, open-label, parallel-group, randomized, three-month treatment, clinical trial, of nabumetone (1-2 g once a day) vs aceclofenac (100 mg two times each day). The main efficacy variable was intensity of pain, evaluated on a Visual Analogic Scale (VAS). In addition: Gonarthrosis Severity Index (GSI)-baseline score > 5 and < 17-, patient and physician Global Assessment of OA Activity, patient and physician Global Assessment of OA progression were assessed. Adverse events incidence and severity were assessed. Three study visits were made on a monthly basis. The main statistical analysis was by intention to treat (ITT). RESULTS: In 12 centres 274 patients were recruited (137/group), aged 62.5 +/- 8.4 years, of whom 189 completed the trial (97 nabumetone and 92 aceclofenac). 90% were female, and 83% of the patients had both knees affected. In both groups the intensity of pain at month 3 improved significantly (p < 0.001) with respect to baseline: VAS of the nabumetone group: 6.1 +/- 1.9 to 4.3 +/- 2.8 cm; VAS of the aceclofenac group: 6.1 +/- 1.9 to 4.4 +/- 2.7 cm. There were no significant differences in any of the intergroup comparisons made. 15 nabumetone-treated and 23 aceclofenac-treated patients withdrew from the study due to moderate to severe adverse events. Gastrointestinal adverse events were the reason for withdrawal in 7 nabumetone and 14 aceclofenac-treated patients. CONCLUSIONS: The efficacy and safety of nabumetone are similar to those of aceclofenac in the treatment of knee osteoarthritis.

Joint symptoms in relapsing polychondritis.

OBJECTIVE: To study articular symptoms in relapsing polychondritis (RP) and their relationship to other clinical manifestations and prognosis. METHODS: Fourteen patients who met the diagnostic criteria proposed by Damiani and Levine for RP were studied. Clinical symptoms were recorded and laboratory and radiologic examinations were carried out. In one patient a synovial histology was obtained. RESULTS: Twelve patients had joint symptoms affecting the peripheral joints (9), the chondrocostal junctions (5), or both sites together (2). Peripheral arthritis was the most frequent finding, affecting 6 patients, while peripheral arthralgia was the only articular manifestation in 3 patients. The development of joint symptoms (arthralgia, arthritis and costochondritis) was unrelated to the appearance of chondritis at other sites and no correlation was found between articular involvement and age at onset, duration of the disease, number of flares, or severity of the disease, either in terms of the number of organs involved or fatal outcome (p > 0.05). However, when articular symptoms were analysed separately arthritis was associated with a longer duration (50 months vs 30), more affected organs (4.5 vs 3.3) and a poorer prognosis compared with patients with arthralgias alone or chondrocostal symptoms. CONCLUSION: Articular symptoms are common in RP but the presence of peripheral arthritis is associated with widespread disease and a poorer prognosis.

[Hormonal changes in fertile women with quiescent systemic lupus erythematosus]. / Alteraciones hormonales en mujeres fértiles con lupus eritematoso sistémico quiescente.

The hypophyseal-adrenal-ovarian axis was studied in 29 women of childbearing age with systemic lupus erythematosus, as well as in a control group of 14 healthy women. Hormonal levels were measured on days 7th and 21st of menstrual cycle. Women with systemic lupus erythematosus had not significatively lower testosterone levels, but progesterone and 17-alfa-hydroxiprogesterone levels were markedly lower when compared to controls. These facts suggest a decrease in progesterone levels, which could act as a predisposing factor for lupic disease.

Aceclofenac in comparison to ketoprofen in the treatment of rheumatoid arthritis.

The efficacy and tolerability of aceclofenac, a new non-steroidal anti-inflammatory drug (NSAID) was compared to that of ketoprofen in a multicentre, double-blind, prospective, randomized study of 3-months duration in patients with rheumatoid arthritis. One hundred and sixty-nine patients, aged between 22 and 70 years, were included in the study. Patients were randomly assigned to two treatment groups; either aceclofenac 100 mg b.i.d. (87 patients) or ketoprofen 50 mg t.i.d. (82 patients). A placebo tablet was administered to aceclofenac-treated patients to maintain the double-blind conditions of the study. Patients were examined at 15 days and at 1, 2 and 3 months. Efficacy was assessed by the following clinical parameters: Ritchie index, pain on a visual analogue scale, grip strength, morning stiffness, spontaneous morning pain, pain on movement and nocturnal pain, together with functional capacity. Efficacy was demonstrated for both drugs, with progressive improvement in the main clinical evaluation parameters until the end of the treatment period. This was particularly pronounced at 15 days in the aceclofenac group, with a rapid improvement in the Ritchie index (baseline vs 15 days: P < 0.001). Laboratory analyses performed were all within the normal range for both drugs. Eleven patients in the ketoprofen group abandoned the study because of inefficacy, whilst only 4 patients discontinued the treatment for this reason in the aceclofenac group. Eleven patients in the ketoprofen group and 2 patients in the aceclofenac group withdrew from the study because of adverse events. In summary, this study demonstrated that aceclofenac, a new NSAID, is effective in the symptomatic treatment of RA with a minor number of patient withdrawals because of inefficacy and a better safety profile than ketoprofen.

Antiperinuclear factor: a useful test for the diagnosis of rheumatoid arthritis.

The objective of this study was to determine: (1) the diagnostic value of antiperinuclear factor (APF), (2) the types of immunoglobulins involved in the reaction and (3) the presence of the antibody in paired samples of serum and synovial fluid (SF). We studied 408 serum samples from the following: healthy controls (n = 68), patients with rheumatoid arthritis RA; n = 160, 106 RF-positive and 54 RF-negative and patients with other rheumatic diseases (n = 180). We examined paired serum and SF samples in 27 patients (8 with RA and 19 with other rheumatic conditions). APF was determined by an indirect immunofluorescence assay. A group of 30 APF-positive serum samples was incubated with fluorescent-labelled antisera against IgG, IgM and IgA independently. APF was positive in 55.7% of patients with RF-positive RA, in 35.2% of patients with RF-negative RA, in 11.1% of patients with other rheumatic diseases and in 5.9% of healthy controls. Statistical differences were found between RF-positive RA and the other three groups (P = 0.02, P = 0.0001, P = 0.0001, respectively) and between RF-negative RA and the groups of other rheumatic diseases (P = 0.0001) and healthy controls (P = 0.005). The specificity of the test for RA was 90.2%. APF was present in three SF samples from RA patients (37.5%). The reaction was mediated by immunoglobulins of the IgG class in 100% of those tested, and, in addition, 30% were of IgA and 6.7% of IgM classes. We concluded that APF is a good diagnostic test that could be included in the classification criteria of RA, it can be present in SF and it is predominantly an antibody of the IgG class.

Leg bone pain syndrome due to cyclosporine in a renal transplant patient.

A leg bone pain syndrome of unclear etiology has been recently described in renal transplant patients receiving cyclosporine A. Herein we report a 54-year-old woman treated with cyclosporine A (CsA), corticosteroids and azathioprine who developed two months after renal transplantation severe symmetric pain with periarticular soft tissue swelling in the knees and metatarsophalangeal joints. Scintigraphy showed periarticular radionuclide activity. Clinical onset was associated with both the high dosage and with the plasma levels of CsA. Symptoms improved when the dosage of CsA was reduced and the plasma levels declined to less than 150 ng/ml.

The effect of gold salts on substance P levels in rheumatoid arthritis.

The effect of gold salt therapy on substance P immunoreactivity levels in plasma and synovial fluid was studied in 42 patients with rheumatoid arthritis. Decreased levels of synovial fluid substance P, although not statistically significant, were found in rheumatoid patients who were currently receiving gold therapy when compared to either those patients previously treated or to those who never received this therapy. In addition, we found that patients who received more than 1000 mg of gold salts had significantly lower levels of substance P in synovial fluid than those treated with lower doses. Our results, therefore, seem to support the hypothesis that gold salts appear to be slow-acting neurotoxic drugs that significantly decrease the intrasynovial concentrations of substance P, a well-known inflammatory neuropeptide, in arthritis patients.

Neuropeptides and interleukin-6 in human joint inflammation relationship between intraarticular substance P and interleukin-6 concentrations.

Plasma and synovial fluid concentrations of interleukin-6 (IL-6), using an enzyme-linked immunosorbent assay, as well as immunoreactive levels of calcitonin gene-related peptide (CGRP), substance P and vasoactive intestinal peptide (VIP) were measured in 18 patients with rheumatoid arthritis and 20 with osteoarthritis of the knee. The concentrations of IL-6 were elevated in both plasma and synovial fluids from patients with rheumatoid arthritis whereas higher levels of substance P-, CGRP- and VIP-like immunoreactivities were found in the synovial fluid, but not in plasma, from patients with rheumatoid arthritis when compared with those in osteoarthritis. Furthermore, IL-6 and substance P levels in synovial fluid were significantly correlated both in rheumatoid arthritis and osteoarthritis patients. Our data seem to support the idea of an important role shared by neuropeptides and IL-6 in the pathogenesis of human inflammatory joint disease.

Evidence of hepatitis C virus antibodies in the cryoprecipitate of patients with mixed cryoglobulinemia.

OBJECTIVE: To describe the clinical features of 8 patients with mixed cryoglobulinemia and hepatitis C virus (HCV) infection. METHODS: A clinical study of the patients was performed. Anti-HCV antibodies were determined by ELISA and confirmed by immunoblot (RIBA) in the sera and in the cryoprecipitate. RESULTS: All patients had liver dysfunction, while most had arthralgias and/or arthritis, purpura, peripheral nervous system involvement and renal disorders. Cryocrits ranged from 1 to 6%. Six patients had type III mixed cryoglobulinemia and the remaining 2 had type II. History of blood transfusion was recorded in 2 patients. Hepatitis B virus (HBV) markers were negative in all sera samples. The cryoprecipitate of 7 patients was negative for HBV markers, but anti-HCV antibodies were positive by both ELISA and RIBA. CONCLUSION: After reviewing published reports and discussing the possible role that hepatitis C virus plays in the pathogenesis of mixed cryoglobulinemia, we conclude that HCV may stimulate immune complex formation and produce cryoglobulinemia. Therefore its investigation is recommended before the diagnosis of "essential" mixed cryoglobulinemia is established.