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.

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.

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.

Juvenile-onset spondyloarthropathies.

This article discusses the clinical spectrum and characteristics of juvenile-onset spondyloarthropathies and includes a review of the demographic, clinical, radiographic (and other imaging techniques), and laboratory data of conditions, syndromes, and diseases making up this group. The pathogenic role of several factors in the context of adult-onset patients, but also in regards to studies already performed in juvenile-onset patients, is discussed.

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.

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.

Desensitization to allopurinol after allopurinol hypersensitivity syndrome with renal involvement in gout.

This is a case report of a 36-year-old male with tophaceous gout for 16 years. He started therapy with 300 mg/day of allopurinol. He had received variable dexamethasone doses by self-prescription for 16 years. When allopurinol was initiated, he had hyperuricemia and normal renal function. Twenty days after starting allopurinol, he presented diffuse maculopapular rash, conjunctivitis, increase in serum creatinine values, leukocytosis and eosinophilia and the diagnosis of allopurinol hypersensitivity (AH) syndrome was made. He completely recovered from the AH and renal function normalized. However, the gout worsened over the following years in spite of treatment with benzobromarone, low doses of prednisone, and colchicine. Allopurinol desensitization was successful beginning with an oral low dose scheme (6.5 mug/day) until we reached 300mg/day. Today the patient receives allopurinol with no side effects. We believe that this is the first reported example of successful desensitization in full-blown AH with renal involvement. Our cautious regimen might be tried in other such patients.

[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.

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.

The early clinical recognition of juvenile-onset ankylosing spondylitis and its differentiation from juvenile rheumatoid arthritis.

OBJECTIVE: To determine which early clinical data differentiate juvenile-onset ankylosing spondylitis (AS) from juvenile rheumatoid arthritis (JRA). METHODS: Medical records of 35 patients with juvenile-onset AS and 75 with JRA (excluding type II pauciarticular JRA), all of whom had disease onset at age < or = 16 years, disease duration of < or = 2 1/2 years at the initial visit to the rheumatology clinic, and followup of > or = 10 years, were analyzed retrospectively with regard to features of disease found 6 months, 12 months, and 10 years after onset. RESULTS: At 6 months, various features appeared more frequently in the juvenile-onset AS group than in the JRA group, i.e., pauciarthritis (54.3% versus 30.7%; P = 0.03, odds ratio [OR] = 2.7), enthesopathy (82.9% versus 0%; P < 0.0001, OR = 321.4), tarsal disease (71.4% versus 1.3%; P < 0.0001, OR = 185.0), and lumbar/sacroiliac symptoms (11.4% versus 0%; P = 0.02, OR = 11.9). At 12 months, the features found more frequently among juvenile-onset AS patients than JRA patients were enthesopathy (88.6% versus 4.0%; P < 0.0001, OR = 186.0), tarsal disease (85.7% versus 10.7%; P < 0.0001, OR = 50.3), and knee disease (100.0% versus 82.7%; P = 0.04, OR = 8.0). Involvement of the upper extremities (especially the hands) was found in significantly fewer juvenile-onset AS patients compared with the JRA group. Definite involvement of the spine and sacroiliitis in juvenile-onset AS occurred after a mean +/- SD of 7.3 +/- 2.0 years. CONCLUSION: Regardless of axial disease, enthesopathy and tarsal disease in children who have arthritis of the lower, but not of the upper extremities differentiate juvenile-onset AS from JRA within 1 year of symptoms. The discriminative value of these parameters approaches that of axial disease (the gold standard) throughout the followup period.

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.

Exposure of anionic phospholipids upon platelet activation permits binding of beta 2 glycoprotein I and through it that of IgG antiphospholipid antibodies. Studies in platelets from patients with antiphospholipid syndrome and normal subjects.

Patients with antiphospholipid syndrome, whether primary or secondary to systemic lupus erythematosus, may have thrombocytopenia. Their antibodies to anionic phospholipids might bind to phospholipids on the platelet wall but anionic phospholipids are asymmetrically located in the inner leaflet. In addition, antibodies to anionic phospholipids may require beta 2 glycoprotein I (beta 2GPI) as a cofactor in order to bind to phospholipids. In turn, beta 2GPI has high affinity for anionic phospholipids. Loss of this asymmetry occurs upon platelet activation and could thus permit such antibody-beta 2GPI-platelet interaction. We studied this by flow cytometry using purified beta 2GPI-FITC labelled and similarly labelled affinity-purified polyclonal antibodies to cardiolipin or phosphatidylserine (aPL) obtained from sera of patients with primary antiphospholipid syndrome. Five percent of resting platelets were bound by aPL in the presence of beta 2GPI. Such binding increased when we activated platelets with various agonists, reaching 31% with the concurrent use of thrombin and the calcium ionophore A23187. Platelet activation resulted in the expression of GMP140 but this did not correlate with aPL binding. This probably reflects that the expression of GMP140, which depends on their secretion of alpha granules, has different agonist responses and occurs at different times than do microvesicle formation and expression of prothrombinase activity which coincide with the loss of phospholipid asymmetry on the platelet wall. When we studied the binding of purified beta 2GPI we also found that it binds preferentially to activated platelets and that it seems to be a prerequisite for the binding of aPL onto them. Our findings indicate that aPL from patients with antiphospholipid syndrome may bind to activated platelets through beta 2GPI.

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.

Genuine ankylosing spondylitis in children: a case-control study of patients with early definite disease according to adult onset criteria.

OBJECTIVE: To describe a group of children with spinal and sacroiliac (SI) joint involvement since the initial year of disease, who fulfilled current adult onset ankylosing spondylitis (AS) diagnostic criteria within 3 years of onset. METHODS: We conducted a case-control study of 44 patients with juvenile onset definite AS. 14 cases (Group A) and 30 controls (Group B) were studied; groups were matched by age at onset (age < or = 16 years), duration of disease at the time of admission to our clinic (< or = 1 year), diagnostic criteria (New York criteria), and period of observation. We compare demographic characteristics, as well as peripheral joint disease 6 and 12 months after onset, and analyze Group A at time of diagnosis. In contrast to Group A, patients in Group B had a syndrome of peripheral arthritis and enthesitis (SEA syndrome), but no axial symptoms or definite diagnosis of AS in the first 5 years of disease. RESULTS: Patients in Group A were HLA-B27 positive boys with peripheral arthritis and enthesitis who differed from those in Group B in the frequency of pauciarthritis and polyarthritis at one year of disease (0 vs 36.7% and 100.0 vs 63.3%; p = 0.008) and age at diagnosis (9.03 +/- 1.13 vs 16.5 +/- 3.3 years; p > 0.0001). Six patients in Group A had lumbar pain and 3 SI joint pain 6 months after onset; at the end of the first year, the number increased to 10 and 6 patients, respectively. At time of diagnosis (2.36 +/- 0.72 yrs after onset), all patients in Group A had radiographic sacroiliitis and spinal, SI, and/or costosternal pain, 11 reduced anterior spinal flexion, and 6 reduced chest expansion. CONCLUSION: There is a less common subgroup of adult-like juvenile onset AS who develop clinical and radiographic evidence of disease affecting the axial skeleton earlier than children progressing from SEA syndrome to AS 5 to 10 years after onset.

A proposal for the classification of patients for clinical and experimental studies on reactive arthritis.

OBJECTIVE: To propose classification criteria for patients entering clinical and basic studies on reactive arthritis (ReA). METHODS: From a MEDLINE search of articles published between 1980 and 1996, we identified reports on HLA-B27 related ReA and Reiter's syndrome as study groups and analyzed the items that constituted the diagnostic, classification, and inclusion (or entry) criteria of patients. We developed disease categories that constituted our classification proposal. RESULTS: We reviewed 175 articles containing 110 study groups of patients with ReA and 94 with Reiter's syndrome. Most articles (89.7%) relied on arthritis for diagnosis, but only 48.0% relied on infection. Only 22.5% of articles used published criteria for diagnosis. Articles including a bacterial name to further describe a group of patients with ReA relied on cultures at the site of infection, serum antibodies, or both to confirm the diagnosis. There were inter/intra-group variations and overlapping of diagnostic criteria, at least 32 different terms referring to ReA or Reiter's syndrome, and 6 patterns of disease. According to these data, we propose 3 categories of disease for patients entering clinical and basic studies on ReA: probable ReA (2 subgroups); definite ReA triggered by bacteria (2 subgroups); and bacterial-associated undifferentiated oligoarthritis or spondyloarthropathy. CONCLUSION: This proposal provides a rationale for reducing the heterogeneity found in criteria for including patients with ReA in research and to facilitate scientific communication. In contrast to diagnostic criteria, this proposal does not restrict the study population to a minority of patients, but allows the investigator to include several forms of disease and to analyze results according to different categories.

Intradermal tophi in gout: a case-control study.

OBJECTIVE: To describe the characteristics of intradermal tophi in patients with gout and search for factors associated with their development. METHODS: This is a case-control study of patients with gout: cases (Group A, n = 21) had intradermal (not subcutaneous) plaques of monosodium urate (MSU) crystals located in sites distant to articular or paraarticular structures, and controls (Group B, n = 42) had gout but no intradermal tophi. Both Group A and Group B were paired by sex, age (+/-5 years), and duration of the disease (+/-3 years). Analysis included serum and urinary uric acid levels at first visit, radiographic stage of gout, the presence of associated diseases, and previous therapy, specifically, chronic glucocorticoid and diuretic usage. RESULTS: Intradermal tophi were located in the legs, forearms, buttocks, thighs, arms, and abdominal wall. Patients in Group A had a greater number of nonintradermal tophi in common sites (11.9+/-12.5 vs. 4.2+/-7.9, mean +/- SD; p = 0.018), decreased glomerular filtration rate (46.74+/-25.11 vs. 70.87+/-30.18 ml/min; p = 0.042), advanced radiographic changes (57.2 vs. 7.1%; p = 0.0001), and longterm glucocorticoid self-medication (76 vs. 36%; p = 0.006). We found no differences in other associated diseases between groups. CONCLUSION: Intradermal tophi were commonly found in the legs and forearms, and less frequently in the buttocks, thighs, and abdominal wall of gouty patients, and were associated with longterm self-prescribed glucocorticoids and chronic renal failure. The occurrence of intradermal tophi in these patients appeared to correlate with advanced disease.

Immunoregulatory defects in juvenile rheumatoid arthritis. Comparison between patients with the systemic or polyarticular forms.

Studies of cellular immunity in juvenile chronic arthritis (juvenile rheumatoid arthritis, JRA) have been scant, controversial, or have not addressed the issue of the different forms of the disease. We studied 23 patients with JRA of either systemic (n = 8) or polyarticular (n = 15) type of onset and compared the findings to those made in 10 healthy children of similar age. Both groups of patients with JRA were found to have increased CD8 T cells, normal production of interleukin-1 and 2 and decreased production of B cell stimulatory factor in their peripheral blood. In addition, patients with systemic JRA were found to have decreased spontaneously expanded and concanavalin-A induced suppressor functions. These findings in both forms of JRA are distinguishable from those that have been made in other connective tissue diseases including the adult form of rheumatoid arthritis.

Comparison of two schedules for administering oral low-dose methotrexate (weekly versus every-other-week) in patients with rheumatoid arthritis in remission: a twenty-four week, single blind, randomized study.

OBJECTIVE: To compare the efficacy of 2 low-dose oral methotrexate (MTX) schedules in maintaining remission in patients with rheumatoid arthritis (RA). METHODS: Patients with RA were included if they were receiving treatment with weekly MTX for at least 9 months and the RA was in remission (defined by American College of Rheumatology [ACR] criteria) for at least 6 months. Patients were stratified by treatment and randomly assigned to weekly or every-other-weekly (EOW; reducing their monthly dose by half) treatment with MTX. Patients were evaluated by a rheumatologist (blinded to the treatment schedule) at baseline and at 6, 12, and 24 weeks. The evaluations included joint counts, Ritchie Articular Index, Health Assessment Questionnaire Disability Index, physician's and patient's global health assessments, visual analog scale for pain, and incidence of adverse effects. Laboratory evaluations were done at baseline and at week 24. RESULTS: Fifty-one patients were included (26 taking weekly MTX, 25 taking EOW MTX). Baseline comparisons showed no differences between the groups. The mean duration of RA was <3 years in both groups, and they had been started on weekly MTX treatment early after diagnosis. After 24 weeks, >90% of the patients in both groups continued in remission. Evaluations of disease activity at 6 and 12 weeks showed no between-group differences. EOW MTX patients who experienced relapse were switched back to weekly MTX, and after a few weeks, their RA was again controlled. The incidence of adverse effects was slightly higher in the weekly MTX group, although the difference did not reach statistical significance. The observed laboratory values were very similar for both groups, except for the serum aspartate aminotransferase and alanine aminotransferase levels, which decreased in the EOW MTX group and were statistically significant at week 24 (P = 0.04 and P = 0.006, respectively). CONCLUSION: EOW MTX represents a valid therapeutic alternative for a specific subgroup of RA patients, as outlined by the ACR remission criteria. Patients with a short disease duration who were treated early after disease onset with weekly MTX and who achieve sustained remission have a higher probability of success with the EOW MTX schedule.