Early Rheumatoid Arthritis in Latin America: Low Socioeconomic Status Related to High Disease Activity at Baseline

Objective. To determine the influence of socioeconomic factors on disease activity in a Latin American (LA) early rheumatoid arthritis (RA) multinational inception cohort at baseline. Methods. Clinical evaluation, ethnicity, socioeconomic status (SES), 4-variable Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR), Health Assessment Questionnaire (HAQ) disability index (DI), and erosions were recorded in 1,093 patients with early RA (<1 year from onset). Multivariate analyses evaluated influences of sex, age, marital status, education, medical coverage, SES, and ethnicity on HAQ DI, DAS28-ESR, and presence of erosions. Results. Ethnicities included 43% Mestizo, 31% Caucasian, 19% African LA, 4% Amerindian, and 3% other. Fifty-eight percent were of low/low-middle SES, 42% had <8 years of education, 21% had no medical coverage, median disease duration was 6 months (25th, 75th percentiles 4, 9 months), median HAQ DI score was 1.25 (25th, 75th percentiles 0.63, 2.00), median DAS28-ESR score was 6.2 (25th, 75th percentiles 4.9, 7.2), and 25% had erosions. Women and Mestizos, African LA, and Amerindians had earlier onset than men or Caucasians (P < 0.01). When adjusted by country, the analysis of covariance model showed that low/low-middle SES, female sex, partial coverage, and older age were associated with worse HAQ DI scores; only low/low-middle SES was associated with higher DAS28 scores. Statistically significant differences were found in HAQ DI and DAS28 scores between countries. When excluding country, low/low-middle SES, female sex, and no coverage were associated with worse HAQ DI and DAS28 scores, whereas separated/divorced/widowed status was associated with worse HAQ DI scores and age was associated with worse DAS28 scores. Logistic regression showed that older age, no coverage, and the Amerindian and other ethnic groups were associated with erosions. Conclusion. We compared early RA patients from the main LA ethnic groups. Our findings suggest that low/low-middle SES is important in determining disease activity. A more genetic-related background for erosions is possible.

Determinants of discordance in patients' and physicians' rating of rheumatoid arthritis disease activity

Objective To assess the determinants of patients' (PTGL) and physicians' (MDGL) global assessment of rheumatoid arthritis (RA) activity and factors associated with discordance among them. Methods. A total of 7,028 patients in the Quantitative Standard Monitoring of Patients with RA study had PTGL and MDGL assessed at the same clinic visit on a 0-10-cm visual analog scale (VAS). Three patient groups were defined: concordant rating group (PTGL and MDGL within >= 2 cm), higher patient rating group (PTGL exceeding MDGL by > 2 cm), and lower patient rating group (PTGL less than MDGL by > 2 cm). Multivariable regression analysis was used to identify determinants of PTGL and MDGL and their discordance. Results. The mean +/- SD VAS scores for PTGL and MDGL were 4.01 +/- 2.70 and 2.91 +/- 2.37, respectively. Pain was overwhelmingly the single most important determinant of PTGL, followed by fatigue. In contrast, MDGL was most influenced by swollen joint count (SJC), followed by erythrocyte sedimentation rate (ESR) and tender joint count (TJC). A total of 4,454 (63.4%), 2,106 (30%), and 468 (6.6%) patients were in the concordant, higher, and lower patient rating groups, respectively. Odds of higher patient rating increased with higher pain, fatigue, psychological distress, age, and morning stiffness, and decreased with higher SJC, TJC, and ESR. Lower patient rating odds increased with higher SJC, TJC, and ESR, and decreased with lower fatigue levels. Conclusion. Nearly 36% of patients had discordance in RA activity assessment from their physicians. Sensitivity to the "disease experience" of patients, particularly pain and fatigue, is warranted for effective care of RA.

Atopic dermatitis: correlation between non-damaged skin barrier function and disease activity

Background Atopic dermatitis (AD) is a chronic dermatosis, predominant in childhood, characterized by pruritus and eczematous-type lesions with xerosis as the prominent clinical sign. Objectives To analyze the correlation between biophysical measurements of skin barrier function and other assessment criteria of clinical severity according to Rajka and Langelands criteria. Methods Biophysical measurements [transepidermal water loss (TEWL) and corneometry] were obtained from 120 patients with the diagnosis of AD. Serum levels of IgE were also evaluated. Results A significant correlation between corneometry, TEWL, and clinical severity of AD was found. Data showed an inverse correlation between corneometry, TEWL, and AD severity, and a significant difference (P < 0.001) between mean of corneometry and TEWL and AD severity (mild, moderate, and severe). As for IgE levels, corneometry had significant negative correlation, in contrast with TEWL, which showed a significant positive correlation (P < 0.001). Conclusion Biophysical measurements of skin barrier in non-lesional skin of AD may work as an evaluation factor for AD severity.

Low dynamic muscle strength and its associations with fatigue, functional performance, and quality of life in premenopausal patients with systemic lupus erythematosus and low disease activity: a case–control study

Abstract Background The purpose of the present study was to compare dynamic muscle strength, functional performance, fatigue, and quality of life in premenopausal systemic lupus erythematosus (SLE) patients with low disease activity versus matched-healthy controls and to determine the association of dynamic muscle strength with fatigue, functional performance, and quality of life in SLE patients. Methods We evaluated premenopausal (18–45 years) SLE patients with low disease activity (Systemic lupus erythematosus disease activity index [SLEDAI]: mean 1.5 ± 1.2). The control (n = 25) and patient (n = 25) groups were matched by age, physical characteristics, and the level of physical activities in daily life (International Physical Activity Questionnaire IPAQ). Both groups had not participated in regular exercise programs for at least six months prior to the study. Dynamic muscle strength was assessed by one-repetition maximum (1-RM) tests. Functional performance was assessed by the Timed Up and Go (TUG), in 30-s test a chair stand and arm curl using a 2-kg dumbbell and balance test, handgrip strength and a sit-and-reach flexibility test. Quality of life (SF-36) and fatigue were also measured. Results The SLE patients showed significantly lower dynamic muscle strength in all exercises (leg press 25.63%, leg extension 11.19%, leg curl 15.71%, chest press 18.33%, lat pulldown 13.56%, 1-RM total load 18.12%, P < 0.001-0.02) compared to the controls. The SLE patients also had lower functional performance, greater fatigue and poorer quality of life. In addition, fatigue, SF-36 and functional performance accounted for 52% of the variance in dynamic muscle strength in the SLE patients. Conclusions Premenopausal SLE patients with low disease activity showed lower dynamic muscle strength, along with increased fatigue, reduced functional performance, and poorer quality of life when compared to matched controls.

Inactive Disease and Remission in Childhood-Onset Systemic Lupus Erythematosus

Objective. To define inactive disease (ID) and clinical remission (CR) and to delineate variables that can be used to measure ID/CR in childhood-onset systemic lupus erythematosus (cSLE). Methods. Delphi questionnaires were sent to an international group of pediatric rheumatologists. Respondents provided information about variables to be used in future algorithms to measure ID/CR. The usefulness of these variables was assessed in 35 children with ID and 31 children with minimally active lupus (MAL). Results. While ID reflects cSLE status at a specific point in time, CR requires the presence of ID for >6 months and considers treatment. There was consensus that patients in ID/CR can have <2 mild nonlimiting symptoms (i.e., fatigue, arthralgia, headaches, or myalgia) but not Raynaud's phenomenon, chest pain, or objective physical signs of cSLE; antinuclear antibody positivity and erythrocyte sedimentation rate elevation can be present. Complete blood count, renal function testing, and complement C3 all must be within the normal range. Based on consensus, only damage-related laboratory or clinical findings of cSLE are permissible with ID. The above parameters were suitable to differentiate children with ID/CR from those with MAL (area under the receiver operating characteristic curve >0.85). Disease activity scores with or without the physician global assessment of disease activity and patient symptoms were well suited to differentiate children with ID from those with MAL. Conclusion. Consensus has been reached on common definitions of ID/CR with cSLE and relevant patient characteristics with ID/CR. Further studies must assess the usefulness of the data-driven candidate criteria for ID in cSLE.

Persistent Periodontal Disease Hampers Anti-Tumor Necrosis Factor Treatment Response in Rheumatoid Arthritis

Objective: This study aimed to evaluate prospectively the influence and the evolution of periodontal disease (PD) in rheumatoid arthritis (RA) patients submitted to anti-tumor necrosis factor (TNF) therapy. Methods: Eighteen patients with RA (according to the American College of Rheumatology criteria) were assessed for PD before (BL) and after 6 months (6M) of anti-TNF treatment: 15 infliximab, 2 adalimumab, and 1 etanercept. Periodontal assessment included plaque and gingival bleeding indices, probing pocket depth, cementoenamel junction, and clinical attachment level. Rheumatologic evaluation was performed blinded to the dentist's assessment: demographic data, clinical manifestations, and disease activity (Disease Activity Score using 28 joints [DAS28], erythrocyte sedimentation rate [ESR], and C-reactive protein [CRP]). Results: The median age and disease duration of patients with RA were 50 years (25-71 y) and 94% were female. Periodontal disease was diagnosed in 8 patients (44.4%). Comparing BL to 6M, periodontal parameters in the entire group remained stable (P > 0.05) throughout the study (plaque and gingival bleeding indices, probing pocket depth, cementoenamel junction, and clinical attachment level), whereas an improvement in most analyzed RA parameters was observed in the same period: DAS28 (5.5 vs. 3.9, P = 0.02), ESR (21 vs. 12.5 mm/first hour, P = 0.07), and CRP (7.8 vs. 2.8 mg/dL, P = 0.25). Further analysis revealed that this improvement was restricted to the group of patients without PD (DAS28 [5.5 vs. 3.6, P = 0.04], ESR [23.0 vs. 11.5 mm/first hour, P = 0.008], and CRP [7.4 vs. 2.1, P = 0.01]). In contrast, patients with PD had lack of response, with no significant differences in disease activity parameters between BL and 6M: DAS28 (5.2 vs. 4.4, P = 0.11), ESR (17.0 vs. 21.0, P = 0.56), and CRP (9.0 vs. 8.8, P = 0.55). Conclusions: This study supports the notion that PD may affect TNF blocker efficacy in patients with RA. The possibility that a sustained gingival inflammatory state may hamper treatment response in this disease has high clinical interest because this is a treatable condition.

Juvenile onset systemic lupus erythematosus: a possible role for vitamin D in disease status and bone health

Purpose: In juvenile onset systemic lupus erythematosus (JoSLE), evidence for the association between vitamin D status, lupus activity, and bone health is very limited and not conclusive. The aim of this study was, therefore, to assess in JoSLE patients the possible relevance of vitamin D deficiency in disease and bone parameters. Methods: Fifty-seven JoSLE patients were initially compared to 37 age, race and body mass index (BMI) -matched healthy controls. The serum concentration of 25 hydroxyvitamin D (25OHD) was determined by radioimmunoassay. Patients with 25OHD deficiency (acurrency sign20 ng/mL) were compared to those with levels > 20 ng/mL. Disease activity was evaluated by SLE Disease Activity Index (SLEDAI). Bone mineral density (BMD) and body composition (BC) were measured using dual-energy X-ray absorptiometry (DXA). Results: 25OHD levels were similar in patients and controls (21.44 +/- 7.91 vs 22.54 +/- 8.25 ng/mL, p = 0.519), regardless of supplementation (65% of patients and none in controls). Thirty-one patients with 25OHD deficiency (acurrency sign20 ng/mL) were further compared to the 26 JoSLE patients with levels > 20 ng/mL. These two groups were well-balanced regarding vitamin D confounding variables: age (p = 0.100), ethnicity (p = 1.000), BMI (p = 0.911), season (p = 0.502), frequency of vitamin D supplementation (p = 0.587), creatinine (p = 0.751), renal involvement (p = 0.597), fat mass (p = 0.764), lean mass (p = 0.549), previous/current use of glucocorticoids(GC) (p = 1.0), immunosuppressors (p = 0.765), and mean current daily dose of GC (p = 0.345). Patients with vitamin D deficiency had higher SLEDAI (3.35 +/- 4.35 vs 1.00 +/- 2.48, p = 0.018), lower C4 levels (12.79 +/- 6.78 vs 18.38 +/- 12.24 mg/dL, p = 0.038), lower spine BMD (0.798 +/- 0.148 vs 0.880 +/- 0.127 g/cm2, p = 0.037) and whole body BMD (0.962 +/- 0.109 vs 1.027 +/- 0.098 g/cm2, p = 0.024). Conclusion: JoSLE vitamin D deficiency, in spite of conventional vitamin D supplementation, affects bone and disease activity status independent of therapy and fat mass reinforcing the recommendation to achieve adequate levels. Lupus (2012) 21, 1335-1342.

Dyspeptic symptoms and delayed gastric emptying of solids in patients with inactive Crohn's disease

Background: Patients with Crohn's disease (CD) have been shown to present dyspeptic symptoms more frequently than the general population. Some of these symptoms could be related to motility disorders to some degree. Then, we propose to investigate whether gastric emptying of solids in patients with inactive CD is delayed and to determine the relationships between gastric emptying and dyspeptic symptoms in inactive CD. Methods: Twenty-six patients with inactive Crohn's disease, as defined by a Crohn's Disease Activity Index (CDAI) < 150, underwent a gastric emptying test by breath test using C-13 octanoic acid coupled to a solid meal and answered a validated questionnaire (The Porto Alegre Dyspeptic Symptoms Questionnaire) to assess dyspeptic symptoms. Patients with scores >= 6 were considered to have dyspepsia. The control group was composed by 19 age-and sex-matched healthy volunteers. Results: Patients with CD had a significantly longer t 1/2 and t lag (p<0.05) than the controls. CD patients with dyspepsia had significantly (p<0.05) prolonged gastric emptying when compared to patients without dyspeptic symptoms. When the individual symptom patterns were analyzed, only vomiting was significantly associated with delayed gastric emptying (p<0.05). There was no difference between the subgroups of patients with respect to gender, CDAI scores, disease location, clinical behavior (obstructive/obstructive) or previous gastrointestinal surgery. Conclusion: Delayed gastric emptying in inactive Crohn's disease patients seems to be associated with dyspeptic symptoms, particularly vomiting, even without any evidence of gastrointestinal obstruction.

Fluctuation of Anti-Endothelial Cell Antibody Titers in Mixed Connective Tissue Disease

Background: Antibodies directed against endothelial cell surface antigens have been described in many disorders and have been associated with disease activity. Since the most prominent histopathologic feature in mixed connective tissue disease (MCTD) is the widespread and unique proliferative vascular lesion, our aim was to evaluate the frequency of anti-endothelial cell antibodies (AECA) in this condition. Objectives: To evaluate the frequency of AECA in this disease and assess its clinical and laboratory associations. Methods: Seventy-three sera from 35 patients with MCTD (Kasukawa's criteria), collected during a 7 year period, were tested for immunoglobulins G and M (IgG and IgM) AECA by cellular ELISA, using HUVEC (human umbilical vein endothelial cells). Sera from 37 patients with systemic lupus erythematosus (SLE), 22 with systemic sclerosis (SSc) and 36 sera from normal healthy individuals were used as controls. A cellular ELISA using HeLa cells was also performed as a laboratory control method. Results: IgG-AECA was detected in 77% of MCTD patients, 54% of SLE patients, 36% of SSc patients and 6% of normal controls. In MCTD, IgG-AECA was associated with vasculitic manifestations, disease activity and lymphopenia, and was also a predictor of constant disease activity. Immunosuppressive drugs were shown to reduce IgG-AECA titers. Since antibodies directed to HeLa cell surface were negative, AECA was apparently unrelated to common epitopes present on epithelial cell lines. Conclusions: AECA are present in a large proportion of patients with MCTD and these antibodies decrease after immunosuppressive treatment. IMAJ 2012; 14:84-87

Exercise training in juvenile dermatomyositis

Objective. To investigate the effects of a supervised exercise training program on health parameters, physical capacity, and health-related quality of life in patients with mild and chronic juvenile dermatomyositis (DM). Methods. This was a prospective longitudinal study following 10 children with mild and chronic juvenile DM (disease duration >1 year). The exercise program consisted of twice-a-week aerobic and resistance training. At baseline and after the 12-week intervention, we assessed muscle strength and function, aerobic conditioning, body composition, juvenile DM scores, and health-related quality of life. Results. Child self-report and parent proxy-report Pediatric Quality of Life Inventory scores were improved after the intervention (-40.3%; P = 0.001 and -48.2%; P = 0.049, respectively). Importantly, after exercise, the Disease Activity Score was reduced (-26.9%; P = 0.026) and the Childhood Muscle Assessment Scale was improved (+2.5%; P = 0.009), whereas the Manual Muscle Test presented a trend toward statistical significance (+2.2%; P = 0.081). The peak oxygen consumption and time-to-exhaustion were increased by 13.3% (P = 0.001) and 18.2% (P = 0.003), respectively, whereas resting heart rate was decreased by 14.7% (P = 0.006), indicating important cardiovascular adaptations to the exercise program. Upper and lower extremity muscle strength and muscle function were also significantly improved after the exercise training (P < 0.05). Both the whole-body and the lumbar spine bone mineral apparent density were significantly increased after training (1.44%; P = 0.044 and 2.85%; P = 0.008, respectively). Conclusion. We showed for the first time that a 12-week supervised exercise program is safe and can improve muscle strength and function, aerobic conditioning, bone mass, disease activity, and health-related quality of life in patients with active and nonactive mild and chronic juvenile DM with near normal physical function and quality of life.

Gender characterization in a large series of Brazilian patients with spondyloarthritis

An increasing number of women have been diagnosed with spondyloarthritis (SpA) in recent decades. While a few studies have analyzed gender as a prognostic factor of the disease, no studies have addressed this matter with a large number of patients in South America, which is a peculiar region due to its genetic heterogeneity. The aim of the present study was to analyze the influence of gender on disease patterns in a large cohort of Brazilian patients with SpA. A prospective study was carried out involving 1,505 patients [1,090 males (72.4%) and 415 females (27.6%)] classified as SpA according to the European Spondyloarthropaties Study Group criteria who attended at 29 reference centers for rheumatology in Brazil. Clinical and demographic variables were recorded and the following disease indices were administered: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Radiologic Index (BASRI), Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), and Ankylosing Spondylitis Quality of Life (ASQoL). Ankylosing spondylitis (AS) was the most frequent disease in the group (65.4%), followed by psoriatic arthritis (18.4%), undifferentiated SpA (6.7%), reactive arthritis (3.3%), arthritis associated to inflammatory bowel disease (3.2%), and juvenile SpA (2.9%). The male-to-female ratio was 2.6:1 for the whole group and 3.6:1 for AS. The females were older (p<0.001) and reported shorter disease duration (p=0.002) than the male patients. The female gender was positively associated to peripheral SpA (p<0.001), upper limb arthritis (p<0.001), dactylitis (p=0.011), psoriasis (p<0.001), nail involvement (p<0.001), and family history of SpA (p=0.045) and negatively associated to pure axial involvement (p< 0.001), lumbar inflammatory pain (p=0.042), radiographic sacroiliitis (p<0.001), and positive HLA-B27 (p=0.001). The number of painful (p<0.001) and swollen (p=0.006) joints was significantly higher in the female gender, who also achieved higher BASDAI (p<0.001), BASFI (p=0.073, trend), MASES (p=0.019), ASQoL (p=0.014), and patient's global assessment (p=0.003) scores, whereas the use of nonsteroidal anti-inflammatory drugs (p<0.001) and biological agents (p=0.003) was less frequent in the female gender. Moreover, BASRI values were significantly lower in females (p<0.001). The female gender comprised one third of SpA patients in this large cohort and exhibited more significant peripheral involvement and less functional disability, despite higher values in disease indices.

Sexual activity in ankylosing spondylitis

Objective: To assess the sexual activity of patients with ankylosing spondylitis, correlating it with disease activity and functional indices. Patients and methods: Thirty-two patients with ankylosing spondylitis and 32 healthy controls were assessed regarding pain, fatigue, sexual activity (by use of pictures of seven sexual positions), disease activity (by use of Bath Ankylosing Spondylitis Disease Activity Index - BASDAI), and functional capacity (by use of Bath Ankylosing Spondylitis Functional Index - BASFI). After the interview, the patients were divided into two groups: group A (with sexual activity) and group B (no sexual activity). Results: Group B showed statistical association with longer disease duration (P = 0.01), and higher BASFI (P = 0.0007) and BASDAI (P = 0.03) scores. No correlation was observed between age and functional capacity. Man lying on his back and woman on top was the most frequent, enjoyable and least painful position. The position with the woman on her back and a man lying on top was the least chosen. Control individuals reported a higher frequency of sexual activity, longer duration of intercourse, and less pain and fatigue; the reported frequency of orgasms, however, was similar in both groups. Conclusion: The chronic nature of ankylosing spondylitis, with poor functional capacity and higher disease activity, interferes with sexual intercourse. When sexual activity was possible, orgasm and sexual satisfaction did not differ from those of healthy controls.

Monocyte Chemoattractant-1 as a Urinary Biomarker for the Diagnosis of Activity of Lupus Nephritis in Brazilian Patients

Objective. Monocyte chemotactic protein (MCP-1), involved in the pathogenesis of lupus nephritis (LN), has recently been indicated as a new biomarker of kidney activity in systemic lupus erythematosus (SLE). Our aim was to assess urinary MCP-1 (uMCP-1) as a biomarker of renal activity in patients with SLE and to compare it to other disease activity markers, using the ELISA. Methods. Seventy-five female Brazilian patients with SLE and a control group participated in our study. Patients with SLE were distributed among 3 groups according to kidney involvement and classified according to disease activity based on clinical and laboratory measures such as urinary sediment, proteinuria, kidney function, C3, C4, anti-dsDNA, disease activity index, and renal SLE disease activity index. The serum and uMCP-1 concentrations were measured by sandwich ELISA. Results. In the A-LN group (active lupus nephritis: SLE with kidney involvement), the concentration of uMCP-1 was significantly higher than in other groups. A cutoff point was established using the results of the control group to apply this test in the detection of LN. A-LN had a higher frequency of positive results for uMCP-1 in comparison to the other groups (p < 0.001). To detect disease activity in patients with LN, a new cutoff was determined based on the results of patients with SLE with kidney involvement. Setting specificity at 90%, the sensitivity of the test was 50%. Conclusion. The high specificity makes uMCP-1 a useful test as a predictor of kidney activity in SLE, especially when associated to other measures used in clinical practice. (First Release Sept 1 2012; J Rheumatol 2012;39:1948-54; doi :10.3899/jrheum.110201)

Indocyanine green angiography findings in patients with long-standing Vogt-Koyanagi-Harada disease: a cross-sectional study

Background: To investigate indocyanine green angiography (ICGA) findings in patients with long-standing Vogt-Koyanagi-Harada (VKH) disease and their correlation with disease activity on clinical examination as well as with systemic corticosteroid therapy. Methods: Twenty-eight patients (51 eyes) with long-standing (>= 6 months from disease onset) VKH disease whose treatment was tapered based only in clinical features were prospectively included at a single center in Brazil. All patients underwent standardized clinical evaluation, which included fundus photography, fluorescein angiography and ICGA. Clinical disease activity was determined based in the Standardization in Uveitis Nomenclature Working Group. Fisher exact test and logistic regression models were used for statistical analysis. Results: Disease-related choroidal inflammation on ICGA was observed in 72.5% (31 of 51 eyes). Angiographic findings suggestive of (choroidal and/or retinal) disease activity were not observed on FA. Clinically active disease based on clinical evaluation was observed in 41.2% (21 of 51 eyes). In these 21 eyes, disease-related choroidal inflammation on ICGA was observed in 76.2% (16 of 21 eyes); in the remaining eyes (without clinical active disease) disease-related choroidal inflammation on ICGA was observed in 70.0% (21 of 30 eyes). In respect to systemic corticosteroid therapy, 10 patients (18 of 51 eyes) were under treatment with prednisone. In these 10 (18 of 51 eyes) patients, disease-related choroidal inflammation on ICGA was observed in 83.3% (15 of 18 eyes); in the remaining patients (33 of 51 eyes) disease-related choroidal inflammation on ICGA was observed in 66.7% (22 of 33 eyes). Conclusion: ICGA findings suggestive of disease-related choroidal inflammation were observed in a considerable proportion of patients with long-standing VKH disease, independent of the inflammatory status of the disease on clinical examination or current use of systemic corticosteroid. Therefore, the current study reinforces the crucial role of ICGA to assist the management and treatment of patients with long-standing VKH disease.