Treat-to-target (T2T) recommendations for gout.

OBJECTIVES: The treat-to-target (T2T) concept has been applied successfully in several inflammatory rheumatic diseases. Gout is a chronic disease with a high burden of pain and inflammation. Because the pathogenesis of gout is strongly related to serum urate levels, gout may be an ideal disease in which to apply a T2T approach. Our aim was to develop international T2T recommendations for patients with gout. METHODS: A committee of experts with experience in gout agreed upon potential targets and outcomes, which was the basis for the systematic literature search. Eleven rheumatologists, one cardiologist, one nephrologist, one general practitioner and one patient met in October 2015 to develop T2T recommendations based on the available scientific evidence. Levels of evidence, strength of recommendations and levels of agreement were derived. RESULTS: Although no randomised trial was identified in which a comparison with standard treatment or an evaluation of a T2T approach had been performed in patients with gout, indirect evidence was provided to focus on targets such as normalisation of serum urate levels. The expert group developed four overarching principles and nine T2T recommendations. They considered dissolution of crystals and prevention of flares to be fundamental; patient education, ensuring adherence to medications and monitoring of serum urate levels were also considered to be of major importance. CONCLUSIONS: This is the first application of the T2T approach developed for gout. Since no publication reports a trial comparing treatment strategies for gout, highly credible overarching principles and level D expert recommendations were created and agreed upon.

Medición de la calidad de vida asociada a la salud y a la capacidad funcional en pacientes con gota crónica tofácea / Measurement of health-related quality of life and functional capacity in patients with chronic tophaceous gout

Introducción: Hay pocos instrumentos en el estudio de gota validados para evaluar la actividad, la capacidad funcional o la calidad de vida de los pacientes. Se desconoce si los instrumentos genéricos como el cuestionario MOS-20 (Medical Outcomes Study Short Form Health Survey ‘Resultados médicos del formulario corto del estudio de la encuesta de salud’) o los instrumentos específicos para otras enfermedades, como el cuestionario AIMS (Arthritis Impact Measurement Scales ‘Escala de medición del impacto de la artritis’) puedan aplicarse a pacientes con gota. Objetivo: Evaluar las características clinimétricas de los cuestionarios MOS-20 y AIMS y su correlación con el cuestionario HAQ-DI (Health Assessment Questionnaire ‘Cuestionario de evaluación de salud’) así como con variables clínicas en los pacientes con gota crónica tofácea (GCT). Pacientes y métodos: Se incluyeron 49 pacientes con GCT. Se obtuvieron las variables demográficas y clínicas. Se aplicaron los 3 cuestionarios en la valoración basal. En 20 pacientes se realizó una segunda evaluación después de 8 semanas. Resultados: Todos los pacientes fueron de sexo masculino. El tiempo de evolución de la enfermedad fue de 14,9±8,3 años. El HAQ-DI fue de 0,43±0,56 con un alfa de Cronbach (αC) de 0,95 y un coeficiente de correlación intraclase (CCI) de 0,86. El MOS-20 tuvo un αC de 0,68 a 1,0 y un CCI de 0,27 a 0,61 entre las diferentes dimensiones. El AIMS tuvo un αC de 0,66 a 0,96 y un CCI de 0,11 a 0,79 entre los diferentes componentes. La reproducibilidad fue mejor en los componentes físicos que en los componentes de salud mental tanto del MOS-20 como del AIMS. Los cuestionarios MOS-20, AIMS y HAQ-DI correlacionaron con la presencia de articulaciones con limitación funcional. No se encontraron diferencias significativas entre los pacientes con articulaciones inflamadas ni con tofos. El HAQ-DI se correlacionó mejor con las variables del componente físico que con las del componente mental de los cuestionarios AIMS y MOS-20. Conclusión: Los cuestionarios AIMS, MOS-20 y HAQ-DI son útiles para valorar la capacidad funcional y la calidad de vida en los pacientes con GCT (AU)

Introduction: In gout there are few instruments validated for the evaluation of activity, functional capacity or quality of life. It is not known if generic instruments such as the MOS-20, or specific for other illnesses, such as the AIMS, can be applied to patients with Gout. Objective: To evaluate the clinimetric characteristic of the MOS-20 and AIMS questionnaires, and their correlation with HAQ-DI, as well as with clinical variables in patient with tophaceous gout (TG). Methods: 49 patients with TG were included. Demographic and clinical variables were obtained. The 3 questionnaires were applied at the basal evaluation. A second evaluation was applied to 20 patients, 8 weeks later. Results: All patients were male. The time of since onset of the illness was 14.9±8.3 years. The HAQ-DI was 0.43±0.56 with an alpha of Cronbach (αC) of 0.95 and the intraclass correlation coefficient (ICC) was 0.86. The MOS-20 had an αC of 0.68 to 1.0 and a ICC of 0.27 to 0.61 between the several components. The AIMS had an αC of 0.66 to 0.96, and a ICC of 0.11 to 0.79 between the several components. Reliability was better between the physical components in MOS-20 and AIMS. The MOS-20, AIMS and the HAQ-DI correlated with the presence of joints with functional limitation. There weren’t any significant differences among the patients with inflamed joints, nor in those with tophi. The HAQ-DI was best correlated with the physical component than with the mental component of the AIMS and the MOS-20. Conclusion: The AIMS, the MOS-20 and the HAQ-DI are useful in measuring the functional capacity and the quality of life in patient with TG (AU)

[Measurement of health-related quality of life and functional capacity in patients with chronic tophaceous gout]. / Medición de la calidad de vida asociada a la salud y a la capacidad funcional en pacientes con gota crónica tofácea.

INTRODUCTION: In gout there are few instruments validated for the evaluation of activity, functional capacity or quality of life. It is not known if generic instruments such as the MOS-20, or specific for other illnesses, such as the AIMS, can be applied to patients with Gout. OBJECTIVE: To evaluate the clinimetric characteristic of the MOS-20 and AIMS questionnaires, and their correlation with HAQ-DI, as well as with clinical variables in patient with tophaceous gout (TG). METHODS: 49 patients with TG were included. Demographic and clinical variables were obtained. The 3 questionnaires were applied at the basal evaluation. A second evaluation was applied to 20 patients, 8 weeks later. RESULTS: All patients were male. The time of since onset of the illness was 14.9±8.3 years. The HAQ-DI was 0.43±0.56 with an alpha of Cronbach (αC) of 0.95 and the intraclass correlation coefficient (ICC) was 0.86. The MOS-20 had an αC of 0.68 to 1.0 and a ICC of 0.27 to 0.61 between the several components. The AIMS had an αC of 0.66 to 0.96, and a ICC of 0.11 to 0.79 between the several components. Reliability was better between the physical components in MOS-20 and AIMS. The MOS-20, AIMS and the HAQ-DI correlated with the presence of joints with functional limitation. There weren't any significant differences among the patients with inflamed joints, nor in those with tophi. The HAQ-DI was best correlated with the physical component than with the mental component of the AIMS and the MOS-20. CONCLUSION: The AIMS, the MOS-20 and the HAQ-DI are useful in measuring the functional capacity and the quality of life in patient with TG.

A modified Delphi exercise to determine the extent of consensus with OMERACT outcome domains for studies of acute and chronic gout.

OBJECTIVES: To reach consensus with recommendations made by an OMERACT Special Interest Group (SIG). METHODS: Rheumatologists and industry representatives interested in gout rated and clarified, in three iterations, the importance of domains proposed by the OMERACT SIG for use in acute and chronic gout intervention studies. Consensus was defined as a value of less than 1 of the UCLA/RAND disagreement index. RESULTS: There were 33 respondents (61% response rate); all agreed the initial items were necessary, except "total body urate pool". Additional domains were suggested and clarification sought for defining "joint inflammation" and "musculoskeletal function". Items that demonstrated no clear decision were re-rated in the final iteration. There were six highly rated items (rating 1-2) with four slightly lower rating items (rating 3) for acute gout; and 11 highly rated items with eight slightly lower ratings for chronic gout. CONCLUSIONS: Consensus is that the following domains be considered mandatory for acute gout studies: pain, joint swelling, joint tenderness, patient global, physician global, functional disability; and for chronic gout studies: serum urate, gout flares, tophus regression, health-related quality of life, functional disability, pain, patient global, physician global, work disability and joint inflammation. Several additional domains were considered discretionary.

Decreased levels of uric acid after oral glucose challenge is associated with triacylglycerol levels and degree of insulin resistance.

Hyperuricaemia is one of the components of metabolic syndrome. Both oxidative stress and hyperinsulinism are important variables in the genesis of this syndrome and have a close association with uric acid (UA). We evaluated the effect of an oral glucose challenge on UA concentrations. The study included 656 persons aged 18 to 65 years. Glycaemia, insulin, UA and plasma proteins were measured at baseline and 120 min after an oral glucose tolerance test (OGTT). The baseline sample also included measurements of total cholesterol, triacylglycerol (TAG) and HDL-cholesterol. Insulin resistance was calculated with the homeostasis model assessment. UA levels were significantly lower after the OGTT (281.93 (sd 92.19) v. 267.48 (sd 90.40) micromol/l; P < 0.0001). Subjects with a drop in UA concentrations >40.86 micromol/l (>75th percentile) had higher plasma TAG levels (P = 0.0001), baseline insulin (P = 0.02) and greater insulin resistance (P = 0.034). Women with a difference in plasma concentrations of UA above the 75th percentile had higher baseline insulin levels (P = 0.019), concentration of plasma TAG (P = 0.0001) and a greater insulin resistance index (P = 0.029), whereas the only significant difference in men was the level of TAG. Multiple regression analysis showed that the basal TAG levels, insulin at 120 min, glycaemia at 120 min and waist:hip ratio significantly predicted the variance in the UA difference (r2 0.077). Levels of UA were significantly lower after the OGTT and the individuals with the greatest decrease in UA levels are those who have greater insulin resistance and higher TAG levels.

Molecular analysis of the SLC22A12 (URAT1) gene in patients with primary gout.

OBJECTIVE: To analyse the SLC22A12 (URAT1) gene in primary gout patients, first-grade relatives and healthy controls and the possible association of them with demographic and clinical data. SUBJECTS AND METHODS: We included 69 consecutive patients with diagnosis of primary gout, as well as 29 first-grade relatives and 120 healthy volunteers. Demographic and clinical data were obtained from the patients and relatives. DNA was purified from peripheral blood and all 10 exons of the SLC22A12 (URAT1) gene were sequenced. RESULTS: We found six different mutations in the SLC22A12 gene in 16 out of 69 (23%) patients with primary gout. Five mutations were in exon 5 and one in exon 4; five out of six mutations were heterozygous (one compound heterozygous) and one homozygous. The C850G mutation (exon 5) was found in 11 gout patients, these patients have lower levels of triglycerides than the rest of the group: 160 +/- 56 vs 292 +/- 203 mg/dl (P = 0.038). In one family, we found SLC22A12 mutations in three relatives within exon 5. We did not find mutations in the other exons studied (1-3 and 6-10), nor in any of the 10 exons of the 120 healthy volunteers. CONCLUSIONS: We found several mutations in SLC22A12 gene associated with primary gout, the definite role of these mutations in URAT1 activity needs to be further studied.

Influencia de factores sociodemográficos en actividad de enfermedad, estadofuncional y calidad de vida de pacientes con artritis psoriásica / Influence of sociodemographic features on clinical manifestations, disease activity, functional status and quality of life of patients with psoriatic artritis

Objetivo: Determinar la influencia de factores sociodemográficos en las manifestaciones clínicas, actividad de la enfermedad, estado funcional y calidad de vida de pacientes con artritis psoriásica (APs). Métodos: Se incluyeron 148 pacientes con APs reclutados de varios centros de reumatología de Argentina. Se determinaron factores sociodemográficos: edad, sexo, raza, nivel de educación, fuentes de ingreso personal, escala de Graffar y clases sociales. Al inicio de la enfermedad se evaluaron las siguientes variables: edad al inicio, duración de la enfermedad, manifestaciones clínicas y forma clínica de presentación. La actividad de la enfermedad fue evaluada mediante número de articulaciones activas, escala visual análoga (EVA) global del paciente y BASDAI. El estado funcional y la calidad de vida de los pacientes se determinó por medio de BASFI, ASQoL y SF-12 (Versión 1.0). Para el análisis estadístico de los datos obtenidos se utilizó test de Chi-cuadrado, test exacto de Fisher y test de Kruskal-Wallis. Resultados: De los 148 pacientes, 58,8% fueron mujeres con una edad media al inicio de la enfermedad de 53,2 ± 13,6 años y una duración media de enfermedad de 9,3 ± 8,9 años. La edad al inicio, el sexo, la raza y la escala de Graffar no estuvieron asociados con manifestaciones clínicas, actividad de la enfermedad, estado funcional y calidad de vida

Severe tophaceous gout. Characterization of low socioeconomic level patients from México.

OBJECTIVE: To describe a group of patients with frequent tophaceous gout, the variables associated with severe tophaceous gout and to compare them with other patients with gout described elsewhere. METHODS: We looked for 65 demographic clinical and paraclinical variables from patients with gout who attended our gout clinic from 1995-2000 and were evaluated by the same group of physicians. RESULTS: Three hundred and sixteen patients were included, 98% males, 82% live in México city, the mean age at onset, educational level and disease duration were 37.5 +/- 12.4, 6.3 +/- 3.9 and 12.6 +/- 10.3 years respectively. Tophaceous gout was present in 62% of the patients with a mean tophi number of 4.7 +/- 6.3 and mean HAQ score 0.13 +/- 0.37. Severe tophaceous gout (>or= 5 tophi) was found in 34% and these patients had significantly: earlier age at onset, longer duration of the disease, lesser frequency of obesity and higher frequency of: intradermal tophi, HAQ > 0.5, hospitalizations, radiographic score III/IV, uric acid under-excretion, renal function impairment and previous (oral and parenteral) auto-prescribed chronic glucocorticoid treatment compared with patients with non-severe tophaceous gout. In the multiple logistic regression the significant variables were renal function impairment (p = 0.000) and previous chronic parenteral glucocorticoid treatment (p = 0.011) . CONCLUSION: Our patients compared with those from other countries who have earlier age at onset, very low frequency of gout among females, frequent tophaceous gout and severe tophaceous gout. Severe tophaceous gout in this group is associated with renal function impairment and previous chronic parenteral glucocorticoid treatment.

Relationship between disease activity and infection in patients with spondyloarthropathies.

OBJECTIVE: To assess the relationship between disease activity and signs and symptoms of infection in Mexican patients with spondyloarthropathies (SpA). METHODS: A cross sectional study of 95 non-selected patients with SpA (62 men; mean age 26.4 years), who were examined for signs and symptoms of infection and their association with disease activity. 52 had ankylosing spondylitis (AS), 32 undifferentiated SpA (uSpA), 6 chronic reactive arthritis (ReA), and 5 psoriatic arthritis (PsA). Categorical data were analysed by chi(2) or Fisher's tests. RESULTS: 53 (56%) patients had infections: 41 (43%) upper respiratory tract (URT), 34 (36%) enteric, and 20 (21%) genitourinary infections. More infections occurred in HLA-B27 positive patients as a whole (39 v 5; p = 0.003) and in uSpA (12 v 2; p = 0.005). In AS and uSpA, infections occurred in approximately 50%. 30/39 (77%) patients with active disease (group A) and 23/56 (41%) (group B) (p = 0.001) had infection. There were more enteric infections in group A (47%; p<0.001) and more URT infections in group B (52%; p = NS). 22/30 (73%) patients attributed disease activity to infection. CONCLUSION: Enteric, and less commonly, URT infections in Mexican patients with SpA, particularly those who were HLA-B27 positive, seem to have a role in the active phase of AS and uSpA.

Translation, cross-cultural adaptation, and validation of the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Dougados Functional Index (DFI) in a Spanish speaking population with spondyloarthropathies.

OBJECTIVES: The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Dougados Functional Index (DFI) are the most commonly used instruments to measure disease activity and functioning in ankylosing spondylitis (AS). The aim of this study was to translate, adapt and validate these instruments into the Spanish language. METHODS: The BASDAI, BASFI, and DFI questionnaires were translated into Spanish by three independent bilingual physicians who were familiar with the medical aspects of AS and by one professional translator. Two rheumatologists familiar with instrument validation, and who were aware of the purpose of the study, examined semantic, idiomatic and conceptual issues and produced by consensus unified versions of each instrument. English back-translations from the Spanish were done by a professional translator unaware of the original version. Both English versions were compared, and where needed, modifications to the Spanish versions were made. The Spanish versions were administered to 61 ambulatory patients with AS and to 80 patients with undifferentiated spondyloarthropathy for validation purposes. Reliability and responsiveness were measured in 28 patients participating in a physiotherapy program. RESULTS: Reliability showed an acceptable 24-hour test-retest intraclass correlation coefficient (ICC)--BASFI ICC: 0.68, 95% CI: 0.29-0.85; BASDAI ICC: 0.74, 95% CI: 0.52-0.88 and DFI ICC: 0.87, 95% CI: 0.73-0.94. The construct validity of the instruments was evaluated, and BASDAI was correlated with disease activity measured by the total enthesis count (rs: 0.34); general well being in the last week (rs: 0.7); spinal pain (rs: 0.53) and duration of morning stiffness (rs: 0.64). BASFI correlated with Schöber's test (rs: -0.4); occipital-wall distance (rs: 0.38) and thoracic expansion (rs: -0.3). DFI correlated with Schöber's test (rs: -0.36); occipital-wall distance (rs: 0.29) and chest expansion (rs: -0.3). The correlation among DFI and BASFI was rs: 0.83. All instruments showed clinical responsiveness in the physiotherapy program (baseline and end of program; mean +/- SD): BASDAI: 6.25 +/- 1.97 and 3.07 +/- 2.04 (p = 0.0001); BASFI: 5.68 +/- 2.29 and 2.88 +/- 1.77 (p = 0.0001); DFI: 16 +/- 7.6 and 8.0 +/- 5.5 (p = 0.001) with effect sizes and standardized effect sizes > 1. CONCLUSIONS: The Mexican Spanish versions of the BASDAI, BASFI, and DFI showed adequate reliability, validity and responsiveness to clinical change. These instruments can be used in the clinical evaluation of Spanish-speaking patients with AS.

A short-term follow-up of enthesitis and arthritis in the active phase of juvenile onset spondyloarthropathies.

OBJECTIVE: To describe the characteristics of enthesitis and arthritis in the active inflammatory stage of juvenile onset spondyloarthropathies (SpA) during a short-term follow-up. PATIENTS AND METHODS: The study group included data of 33 patients with juvenile-onset SpA with enthesitis in > or = 3 sites, arthritis in > or = 4 joints, and erythrocyte sedimentation rate (ESR) of > or = 25 mm/h despite treatment, who participated in a 26-week, double-blind, sulfasalazine versus placebo trial that showed no significant differences between groups in regard to enthesitis and arthritis. RESULTS: Twenty-seven boys and 6 girls (mean age: 15.3 +/- 3.5 years; mean disease duration: 4.1 +/- 2.7 years) with the seronegative enthesopathy and arthropathy (SEA) syndrome (n = 20) or ankylosing spondylitis (AS; n = 13) comprised the group. Throughout the study, the mean (+/- SD) number of swollen joints and tender entheses were 4.6 +/- 2.5 and 8.3 +/- 5.4. The entheses and joints most frequently involved were the calcaneal attachments of the plantar fascia (87.9%) and Achilles tendon (81.8%) and the ankle (87.9%) and knee (72.7%), respectively. There was pain in the cervical, thoracic, and lumbar spine in 39.4%, 69.7%, and 63.6% of patients and in the sacroiliac joints in 48.5%. Mid-foot involvement (or tarsitis) occurred in 29 patients (87.9%). Except for the feet, the simultaneous occurrence of enthesitis and arthritis in other sites was rare. Overall, there were no significant differences between SEA syndrome and AS patients. CONCLUSIONS: Disease activity shows a significant trend for entheses and joints of the feet and a significant prevalence of axial enthesitis in juvenile onset SpA. Mid-foot involvement appears to be the most characteristic and potentially, the most severe form of disease in these patients.

Development of a radiographic index to assess the tarsal involvement in patients with spondyloarthropathies.

OBJECTIVE: To develop and test an index to evaluate the radiographic changes that occur in the tarsus and adjacent areas of the foot in patients with spondyloarthropathies (SpA). METHODS: The spondyloarthropathy tarsal radiographic index (SpA-TRI) was developed in three consecutive steps: (a) detection of descriptors after reviewing 70 radiographic files; (b) descriptor gradation and subsequent modifications performed by a consensus committee, and (c) interobserver variability assessed by three blinded and independent observers on 272 radiographs: anteroposterior 118, lateral 90, oblique 64 from 121 patients with SpA, and intraobserver variability on 75 radiographs from 25 patients with SpA. Statistical analysis included percentage of agreement and kappa test. SpA-TRI score ranges from 0 to 4 (0=normal; 1=osteopenia or suspicious findings; 2=definite joint space narrowing, bony erosion(s), periosteal whiskering, or enthesophyte(s) in the plantar fascia or Achilleal tendon attachments; 3=para-articular enthesophyte(s); 4=bony ankylosis (joint space fusion or complete bridging)). RESULTS: Complete agreement for every evaluation was >40%, and discordance >1 grade was <15%. The kappa scores among the three observers were acceptable for all the single projections: oblique (0.52, 0.36, 0.35), lateral (0.50, 0.42, 0.56), and anteroposterior (0.40, 0.41, 0.21) views. The combination of lateral and oblique views achieved the highest concordance rates (0.72, 0.33, 0.66), surpassing that of the three projections altogether (0.34, 0.58, 0.37). In every case the concordance was comparable with that of sacroiliac joints (0.47, 0.41, 0.34); intraobserver concordance showed a similar trend. CONCLUSION: The SpA-TRI is an index that includes the most prominent features of tarsal disease and adjacent areas of the foot in SpA and grades them accordingly, it has an adequate reproducibility, and is suitable for use with two or more projections, preferably the combination of oblique and lateral.

Dermatomiositis asociado a adenocarcinoma de vesicula biliar: reporte de un caso / Dermatomyositis associated to gallbladder adenocarcinoma: a case report

La dermatomiositis asociada a neoplasias ha sido reportada en el 11.8 por ciento de los casos. Hasta el momento, solo se ha descrito en la literatura un caso de asociación entre dermatomiositis y adenocarcinoma de vesícula biliar. Presentamos el caso de una paciente de 53 años con debilidad muscular proximal de cinturas escapular y pélvica, manifestaciones cutáneas (Gottron y eritema en heliotropo), e incremento de enzimas musculares, en quién se hizo el diagnóstico de Dermatomiositis y se le prescribió el tratamiento adecuado sin embargo, a los 3 meses de evolución acudió con pérdida de peso, mala respuesta a esteroides y metotrexate, síndrome ictérico, hemorragia de tubo digestivo; se le realizó ultrasonido de hígado y vías biliares reportándose datos compatibles con coledocolitiasis y daño hepático difuso, se le realizó colecistectomía y el reporte histopatológico fue de adenocarcinoma de vesícula biliar. El objetivo de este reporte es la presentación del segundo caso en que asocia la dermatomiositis y el adenocarcinoma de vesícula biliar en la literatura médica internacional.

Relation between adverse events associated with allopurinol and renal function in patients with gout.

BACKGROUND: Because serious adverse reactions to allopurinol have been related to a reduce creatinine clearance rate and prolonged half life of oxypurinol, it has been recommended that the dose should be adjusted according to the rate of creatinine clearance. However, in some patients with gout the dose is not sufficient to reduce serum levels of uric acid (< or =390 micromol/l) and to halt disease progression. OBJECTIVE: To determine the prevalence of adverse reactions attributable to allopurinol in patients with primary gout according to dose and creatinine clearance rate. METHODS: Data on 120 patients with gout receiving allopurinol, in whom the starting dose was adjusted according to creatinine clearance rate and later increased in some patients to control the disease, were retrospectively reviewed. Two groups were compared: group A, 52 patients receiving creatinine clearance adjusted maintenance doses of allopurinol and group B, 68 patients receiving non-adjusted higher maintenance doses of allopurinol. RESULTS: During follow up 57% required higher allopurinol doses than those recommended according to their creatinine clearance rate. Only five (4%) of 120 consecutive patients developed allopurinol related adverse reactions: four minor skin reactions and one allopurinol hypersensitivity syndrome (AHS). Three of these (including the case of AHS) occurred in group A and two in group B (p=NS). The duration of allopurinol treatment was the same in both groups (group A: 2.3 (3.3) years; group B: 3.7 (4.8) years). No patient in group A, but 44% in group B had a creatinine clearance rate of <50 ml/min. None of the patients received concomitant diuretics, ampicillin, or azathioprine. CONCLUSIONS: No increase was seen in the prevalence of adverse reactions to allopurinol in patients who received higher allopurinol maintenance doses than those recommended according to creatinine clearance rate.

Bacterial DNA in synovial fluid cells of patients with juvenile onset spondyloarthropathies.

OBJECTIVE: To identify bacterial DNA in synovial fluid cells of patients with active juvenile onset spondyloarthropathy (SpA). METHODS: The main group of study constituted 22 patients with juvenile onset SpA. In addition, five patients with adult onset SpA and nine with rheumatoid arthritis (RA) were studied. Polymerase chain reaction (PCR) with either genus- or species-specific primers was performed on synovial fluid cells to detect DNA sequences of Chlamydia trachomatis, Yersinia enterocolitica, Salmonella sp., Shigella sp., Campylobacter sp. and Mycobacterium tuberculosis. The presence of antibacterial antibodies in sera and synovial fluid was also determined by enzyme-linked immunoassay. RESULTS: The synovial fluid of nine patients with juvenile onset SpA, three with adult onset SpA and one with RA contained bacterial DNA. Five juvenile onset SpA samples had DNA of one single bacterium; two juvenile onset SpA and three adult onset SpA had DNA of two bacteria and two juvenile onset SpA had DNA of three bacteria. Overall, Salmonella sp. DNA was detected in seven synovial fluid samples, Shigella sp., Campylobacter sp. and M. tuberculosis were found in four samples each, and C. trachomatis was found in two. The bacterial DNA findings correlated with neither diagnosis nor disease duration. One RA synovial fluid had DNA of Campylobacter sp. Neither serum nor synovial fluid antibacterial antibodies correlated with DNA findings or clinical diagnosis. CONCLUSION: In this study, single and several combinations of bacterial DNA were identified in the synovial fluid of patients with long-term undifferentiated and definite juvenile onset SpA and adult onset SpA. Of relevance is that bacterial DNA corresponds to bacteria producing endemic disease in our population.