Differences between leukemic arthritis and juvenile idiopathic arthritis.

OBJECTIVES: To determine the clinical and laboratory differences between leukemic arthritis (LA) and juvenile idiopathic arthritis (JIA) at the onset of the disease. MATERIAL AND METHODS: Patients under 16 years of age, both genders, who presented for the first time to the pediatric rheumatology service with a diagnosis of probable JIA, with arthritis and without peripheral blood blasts, in which the final diagnosis was acute lymphoblastic leukemia (ALL) or JIA. The clinical and laboratory characteristics of the patients were compared, chi-square and relative risk were used for categorical variables, and the Mann-Whitney U and T-test for the comparison of means between groups. A binary logistic regression model was developed to differentiate leukemic arthritis from JIA. RESULTS: A total of 76 patients, 14 with LA and 62 with JIA, were analyzed. The mean age at diagnosis was lower in the leukemic arthritis group, the female gender prevailed in the JIA group, and the time to onset of symptoms was lower in the leukemic arthritis group. Patients with leukemic arthritis showed increased pain intensity, fever, weight loss, nocturnal diaphoresis, lymph node enlargement, hepatosplenomegaly, and pain that did not improve with analgesic administration. Laboratory parameters with statistical significance were the presence of anemia, leukopenia, and neutropenia. The platelet count was significant but in a low normal value, compared to the JIA. A binary logistic regression model was developed to differentiate leukemic arthritis from JIA. The probability associated with the statistic (Chi-square) was 0.000, and the Cox and Snell R2 and Nagelkerke R2 values were 0.615 and 1, respectively. The developed model correctly classified 100% of the cases. CONCLUSIONS: The diagnosis of acute lymphoblastic leukemia should be ruled out in patients who present with arthritis and hematological alterations, mainly leukopenia and neutropenia, with joint pain disproportionate to the degree of arthritis, predominantly at night and that does not improve with the use of analgesics, fever, lymph nodes, and hepatosplenomegaly. Criteria are suggested to differentiate both diseases.

Comparison of clinical features and drug therapies among European and Latin American patients with juvenile dermatomyositis.

OBJECTIVES: To compare the demographic features, presenting manifestations, diagnostic investigations, disease course, and drug therapies of children with juvenile dermatomyositis (JDM) followed in Europe and Latin America. METHODS: Patients were inception cohorts seen between 1980 and 2004 in 27 paediatric rheumatology centres. The following information was collected through the review of patient charts: sex; age at disease onset; date of disease onset and diagnosis; onset type; presenting clinical features; diagnostic investigations; course type; and medications received during disease course. RESULTS: Four hundred and ninety patients (65.5% females, mean onset age 7.0 years, mean disease duration 7.7 years) were included. Disease presentation was acute or insidious in 57.1% and 42.9% of the patients, respectively. The course type was monophasic in 41.3% of patients and chronic polycyclic or continuous in 58.6% of patients. The more common presenting manifestations were muscle weakness (84.9%), Gottron's papules (72.9%), heliotrope rash (62%), and malar rash (56.7%). Overall, the demographic and clinical features of the 2 continental cohorts were comparable. European patients received more frequently high-dose intravenous methylprednisolone, cyclosporine, cyclophosphamide, and azathioprine, while methotrexate and antimalarials medications were used more commonly by Latin American physicians. CONCLUSIONS: The demographic and clinical characteristics of JDM are similar in European and Latin American patients. We found, however, several differences in the use of medications between European and Latin American paediatric rheumatologists.

Tjalma syndrome (pseudo-pseudo Meigs') as initial manifestation of juvenile-onset systemic lupus erythematosus. / Síndrome de Tjalma (pseudo-pseudo Meigs) como manifestación inicial de lupus eritematoso sistémico de inicio juvenil.

Tjalma syndrome or pseudo-pseudo Meigs' syndrome is a clinical condition characterized by pleural effusion, ascites and elevated CA-125 with no associated benign or malignant ovarian tumor in a patient with systemic lupus erythematosus (SLE). Tjalma described the first case of a patient with SLE, pleural effusion, ascites and elevated CA-125. We report the first case in a 14-year old patient who presented with ascites and pleural effusion refractory to treatment and elevated CA-125, in the absence of an ovarian tumor, that warranted aggressive management.

Frequency of auditory involvement and of associated factors in patients with juvenile idiopathic arthritis. / Frecuencia de la afección auditiva y los factores asociados en pacientes con artritis idiopática juvenil.

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is a chronic autoimmune disease characterized by the presence of arthritis in children under 16 years of age for more than 6 weeks in the absence of any other known cause. The extra-articular manifestations, especially in the audiovestibular system, are related to the involvement of the joints of the ossicular chain as a result of the inflammatory process in the synovium. Previous clinical studies in pediatric patients have shown conductive or sensorineural hearing loss. OBJECTIVE: The aim of this study was to assess the frequency of hearing impairment and of associated factors in patients with JIA. METHODOLOGY: A prospective, analytical study was conducted from January 2013 to August 2014 in 62 patients with JIA aged between 5 and 15 years. The study was approved by the local ethics committee and parents signed their informed consent. All subjects underwent audiological examination involving otomicroscopy, audiometry, tympanometry, stapedius reflex and test for transient otoacoustic emissions (TOAE); rheumatologic evaluation included joint examination and the application of a measure of functional ability (disability) using the Childhood Health Assessment Questionnaire (CHAQ). Measures of central tendency and of dispersion were used (chi-square for associations and P<.05 for statistical significance). RESULTS: Sixty-two patients were included: 56 girls and 6 boys, mean age 11.9 years and mean disease duration of 3.4 years; 46% had rheumatoid factor (RF)- positive polyarticular JIA, 40% had RF-negative polyarticular JIA, 15% had disease of systemic onset and 3% had oligoarthritis. Active disease was found in 29 patients and 33 were in remission with medication. Of the total of 124 ears evaluated according to the Jerger classification for tympanometry, abnormal findings were observed in 78 that were type As and in 1 that was type Ad, whereas there were 45 type A ears. Hearing loss was disclosed by speech audiometry, rather than by pure tone audiometry. The TOAE were absent in 4% of those assessed and the stapedius reflex was absent in less than 10%. Factors that had a positive correlation with hearing impairment were RF-positive polyarticular JIA, disease duration, degree of disability and the erythrocyte sedimentation rate level (P<.000). CONCLUSION: The presence of an abnormal tympanogram suggested early involvement in the structure of the tympanic-ossicular complex; however, 3.4 years later, no hearing loss had been reported.

Association of PDCD1 polymorphisms with childhood-onset systemic lupus erythematosus.

A regulatory single nucleotide polymorphism (SNP) PD1.3G/A located on programmed cell death 1 (PDCD1) gene, was shown to be involved in susceptibility to systemic lupus erythematosus (SLE) in Swedish, European American, and Mexican cases. However, association to childhood-onset SLE has not been analyzed. The aim of this study was to investigate the association of PDCD1 polymorphisms and haplotypes with susceptibility to childhood-onset SLE in Mexican population. Three PDCD1 SNPs, PD1.3G/A, PD1.5C/T, PD1.6G/A, were analyzed in 250 childhood-onset SLE Mexican patients and 355 healthy controls in a case-control association study. Polymorphisms were genotyped by TaqMan technology. Stratification analysis was performed on the SLE cohort to investigate the SNP association with renal disorder. In addition, haplotypes were constructed with these three SNPs. The PD1.3A allele was significantly associated to childhood-onset SLE (P=0.0019, odds ratio (OR) 2.73, 95% confidence interval (95% CI) 1.35-5.56). The other PDCD1 SNPs did not show association. A total of 155 patients (62%) had nephritis, and no association was observed with PDCD1 SNPs. The ACG haplotype (PD1.3A, PD1.5C, PD1.6G) included almost all PD1.3A alleles, and it was more frequent in SLE patients (5.5%) than in controls (2.1%) (P=0.003; OR 2.73, 95% CI 1.37-5.46). The haplotype structure in Mexican controls was significantly different from those reported in Spanish and Swedish. Our results support association of the PD1.3A SNP to susceptibility of childhood-onset SLE in Mexican population and does not show association to lupus nephritis in this age group.

Performance of an objective structured clinical examination in a national certification process of trainees in rheumatology.

OBJECTIVE: To assess reliability and validity of the objectively-structured clinical examination (OSCE) applied in postgraduate certification processes by the Mexican Board of Rheumatology. METHOD: Thirty-two (2013) and 38 (2014) Rheumatology trainees (RTs) underwent an OSCE consisting of 12 and 15 stations respectively, scored according to a validated check-list, as well as 300-multiple-choice 300 question examination (MCQ). Previously, 3 certified rheumatologists underwent a pilot-OSCE. A composite OSCE score was obtained for each participant and its performance examined. RESULTS: In 2013, OSCE mean score was 7.1±0.6 with none RT receiving a failing score while the MCQ score was 6.5±0.6 and 7 (21.9%) RTs receiving a failing (< 6) score. In 2014, the OSCE score was 6.7±0.6, with 3 (7.9%) RTs receiving a failing score (2 of them also failed MCQ) while the MCQ score was 6.4±0.5 and 7 (18.5%) RTs were disqualified (2 of them also failed OSCE). A significant correlation between the MCQ and the OSCE scores was observed in the 2013 (r=0.44; P=0.006). Certified rheumatologists performed better than RTs at both OSCE. Overall, 86% of RTs obtaining an OSCE passing score also obtained a MCQ passing score, while this was only 67% (P=.02) among those who obtained an OSCE failing score. Nine stations were applied at both consecutive years. Their performance was similar in both certification processes, with correlation coefficients ranging from 0.81 to 0.95 (P≤0.01). CONCLUSION: The OSCE is a valid and reliable tool to assess the Rheumatology clinical skills in RTs.

Macrophage activation syndrome as the initial manifestation of severe juvenile onset systemic lupus erythematosus. Favorable response to cyclophosphamide.

The macrophage activation syndrome is a rare but potentially fatal complication of patients with autoimmune rheumatic diseases. This is a clinicopathological entity characterized by activation of histiocytes with prominent hemophagocytosis in the bone marrow and other reticuloendothelial systems. In patients with lupus it may mimic an exacerbation of the disease or infection. We report the case of a 7-year-old girl in whom the diagnosis of lupus erythematosus and macrophage activation syndrome was simultaneously made with response to the use of cyclophosphamide.

[Ying-Yang (YY-1) expression and Fas in biopsies of children with type IV lupus nephritis correlates with the clinical condition]. / La expresión de Yin-Yang-1 (YY-1) y Fas en las biopsias de niños con nefritis lúpica tipo IV se correlaciona con la condición clínica.

BACKGROUND: It has been demonstrated that Fasmediated apoptosis participates in the physiopathology of lupus nephritis, although it is not clear whether it contributes to the development of the tissue damage.Since YY-1 down regulates Fas in cancer cell lines, it is reasonable to consider that this transcription factor may control Fas expression in lupus nephritis. The objective was to determine the correlation between YY-1 and Fas expression in renal biopsies from children with type IV lupus nephritis, and their association with the clinical condition of the patients. MATERIAL AND METHODS: Eighteen biopsies from children with type IV lupus nephritis and 5 controls were studied. Fas and YY-1 expression were determined by immunochemistry and quantified by densytometric analysis. The clinical conditions at the moment the biopsy were obtained from the clinical records and the results were analyzed through a one-way ANOVA with p<0.005. RESULTS: The results of the densytometric analysis showed an inverse relationship between YY-1 and Fas expression. YY-1 was grouped according to the intensity of expression in low, moderate and high and compared with the expression of Fas. The lupus nephritis biopsies, which revealed high expression of YY-1, corresponded to patients with less number of clinical complications,better outcome and fewer alterations on renal function.In contrast, low expression of YY-1 correlated with high Fas expression and worst clinical conditions. CONCLUSIONS: The present study suggests that YY-1regulates Fas expression in lupus nephritis and that it is associated with the clinical outcome of the patients,although further studies are necessary to determine weather it factor may serve as a prognosis factor. This is the first evidence of YY-1 participation in the physiopathology of lupus nephritis.

High insulin levels and increased low-density lipoprotein oxidizability in pediatric patients with systemic lupus erythematosus.

OBJECTIVE: To examine low-density lipoprotein (LDL) size, LDL susceptibility to oxidation, and plasma insulin levels in children with systemic lupus erythematosus (SLE). METHODS: Fifty-nine SLE patients and 59 healthy, age-matched control subjects were studied. LDL size was determined by gradient gel electrophoresis. LDL oxidizability was assessed by lag time for conjugated diene formation during copper incubation. Plasma levels of fasting insulin, glucose, lipids, lipoproteins, apolipoproteins B and A-I, and fatty acids were also measured. RESULTS: Compared with control subjects, SLE patients showed significantly higher plasma insulin levels and increased susceptibility of LDLs to oxidation. Patients with active disease were more likely than patients with inactive disease or control subjects to have the following lipid characteristics: small, dense LDL subclass, elevated total cholesterol levels, elevated LDL cholesterol levels, elevated triglyceride levels, and low levels of high-density lipoprotein cholesterol (HDL-C). Statistically significant direct correlations were observed between disease activity and triglyceride levels and between disease activity and lag time, whereas significant inverse correlations were found between disease activity and HDL-C levels and between disease activity and LDL size. Prednisone dosage explained only 15.6% of the variance in insulin levels. CONCLUSION: SLE patients have higher plasma insulin levels and increased LDL oxidizability compared with healthy control subjects. These abnormalities may contribute to the accelerated atherosclerosis observed in patients with SLE.