Management of Patients With Rheumatoid Arthritis in Latin America A Consensus Position Paper From Pan-American League of Associations of Rheumatology and Grupo Latino Americano De Estudio de Artritis Reumatoide

Objective: A consensus meeting of representatives of 18 Latin-American and Caribbean countries gathered in Renaca, Chile, for 2 days to identify problems and provide recommendations for the care of patients with rheumatoid arthritis (RA) in Latin America, a region where poverty and other health priorities make the efforts to provide effective and high quality care difficult. This report includes recommendations for health professionals, patients, and health authorities in Latin America, with an emphasis oil education and therapeutic issues. Methods: Fifty-one rheumatologists (list available only online on the JCR website) from 18 Latin-American and Caribbean countries with a special interest in RA participated in the consensus meeting. Participants were experts identified and appointed by the National Societies of Rheumatology affiliated with the Pan-American League of Associations for Rheumatology (PANLAR) and by the Grupo Latino Americano De Estudio de Artritis Reumatoide (GLADAR)-an independent group of Latin American rheumatologist researchers were also invited to the meeting. Eight topics were identified as priorities: patient, community and allied health professional education, health policy and decision making, programs for early detection and appropriate treatment of RA, role of classic disease modifying antirheumatic drugs (DMARDs), role of biologic therapy, and drug safety surveillance. To reach consensus, a survey with questions relevant to the topic of interest was sent to all participants before the meeting. During a 2 day meeting, the answers of the survey were reviewed and discussed by each group, with final recommendations on action items. Results: The specific topic of the survey was answered by 86% of the participants and 68% of them answered the entire survey. It was agreed that RA and rheumatic diseases which are currently not but should be public health priorities in Latin America, because of their prevalence and impact on quality of life. Conclusions: Strategic areas identified as priorities for our region included: early diagnosis and access to care by multidisciplinary teams, creation of databases to identify infections with the use of biologic agents in RA which are relevant to Latin America, and overall efforts to improve the care of RA patients in accordance with international standards. Implementation of educational programs aimed to improve self-management for patients with RA was also considered crucial.

Menstrual and hormonal alterations in juvenile systemic lupus erythematosus

Menstrual cycles of 30 patients with juvenile systemic lupus erythematosus (JSLE) were compared with 30 age-matched controls. The mean age of patients with JSLE and controls was similar (17.4 +/- 3.2 vs 17.06 +/- 2.08 years, P = 0.66). The mean menarche age was higher in JSLE than controls (13.13 +/- 1.4 vs 11.56 +/- 1.5 years, P = 0.0008). On the contrary, the mean maternal menarche age was similar in both groups (P = 0.62). Menstrual abnormalities and longer length cycles were more frequently observed in JSLE than controls (63% vs 10%, P = 0.0001; 23% vs 0%, P = 0.0105, respectively). The median of follicle stimulating hormone was significantly higher in patients with JSLE compared with controls (4.6 vs 3.4 IU/L, P = 0.0207), and the median of progesterone was lower (32.5 vs 70 ng/mL, P = 0.0033). The median Of luteinizing hormone was lower in patients with JSLE with menstrual abnormalities versus normal cycles (2.9 vs 5.5 IU/L, P = 0.019) and both had a high percentage of decreased progesterone levels (63% vs 73%, P = 0.70). Our findings support the notion that menstrual disturbances are frequent and may be associated with pituitary dysfunction leading to a decreased progesterone production. We also reported that in spite of premature ovarian failure being a rare event in JSLE the follicular reserve seems to be low regardless of intravenous cyclophosphamide treatment. Lupus (2009) 18, 38-43.

High-titer antichromatin antibody is associated with proliferative class IV of lupus nephritis

The antichromatin antibody (aCT) has been described as a useful marker for lupus nephropathy. The relevance of its nephritogenic potential may be appropriately evaluated in the context of renal histopathology. Therefore, the present study investigated the relationship of aCT with a particular histopathologic class of lupus nephritis (LN). Seventy-eight consecutive patients with systemic lupus erythematosus (ACR criteria) and active nephritis who underwent renal biopsy from 1999 to 2004 and with available frozen serum sample obtained at the time of biopsy were selected. aCT was measured by ELISA, and anti-dsDNA was measured by indirect immunofluorescence (IIF) and by ELISA. All renal biopsies were revised in a blinded manner by the same expert renal pathologist. Charts were extensively reviewed for demographic and renal features obtained at the time of biopsy. The prevalence of aCT (>= 20 U) was 59% with a mean titer of 74.3 +/- 38.7U. Both aCT-positive and aCT-negative groups of patients had similar age, gender distribution, duration of lupus, and duration of renal disease. Anti-dsDNA was detected by IIF in 29.5% and by ELISA in 42.3% of the patients. Concomitant presence of both antibodies was observed in 63% (29/46) [anti-dsDNA by ELISA] and 45.6% (21/46) [anti-dsDNA by IIF] of the patients. Lower serum levels of C3 (73% vs. 40%, P=0.0058) and C4 (82% vs. 46.7%, P=0.0021) were more commonly observed in aCT >= 20 U patients compared to the aCT-negative group. It is important to note that the use of a higher cut-off value (>= 40 U) for aCT test revealed a predominance of class IV LN (58% vs. 33%, P=0.039) in aCT >= 40 U compared to aCT<40 U group. The mean levels of proteinuria, serum albumin, and creatinine were markedly altered but were comparable in both groups (P >= 0.05). One fourth (26.3%) of the 19 patients with class IV LN and aCT >= 40 U had no detectable anti-dsDNA (ELISA). These data suggest that high-titer aCT seems to be a valuable biomarker for proliferative class IV of LN.

Auto-antibodies do not influence development of atherosclerotic plaques in rheumatoid arthritis

Background: Many questions remain unanswered about premature atherosclerosis in rheumatoid arthritis (RA). Besides inflammation, some studies have suggested the role of autoantibodies on its pathogenesis. Objective: The aim of this study was to investigate the presence of antibodies against phospholipids, beta2-glycoproteinl (beta2-gpl), lipoprotein lipase, and heat shock proteins (Hsp) in RA patients and to evaluate their possible association with subclinical carotid atherosclerosis. Methods: Seventy-one RA patients and 53 age- and sex-matched controls were selected to perform anticardiolipin antibodies (aCL) (IgG and IgM), anti-beta2-gpl (IgG, IgM, and IgA), anti-lipoprotein lipase (anti-LPL), anti-Hsp 60, and anti-Hsp 65 by ELISA tests. Intima-medial thickness (IMT) of common carotid and presence of plaques were assessed by high-resolution B-mode ultrasonography. Exclusion criteria were smoking, diabetes, and arterial hypertension. Lipoproteins, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fibrinogen levels, as well as health assessment questionnaire (HAQ) and disease activity score (DAS) 28 were also evaluated. Results: Age (48.93 +/- 12.31 vs. 45.37 +/- 9.37 years; p = 0.20) and body mass index (BMI) (p = 0.69) were similar in RA and controls, as well as female gender (p = 0.56). The mean IMT was similar between RA and controls (0. 721 +/- 0.16 vs. 0.667 +/- 0.14 turn, p = 0.07) but the frequency of plaques was higher in RA (14.1% vs. 1.9%; p = 0.02). In RA patients, IMT measurements did not differ according to the presence or absence of these antibodies: IgG aCL (0.62 +/- 0.64 vs. 0.72 +/- 0.17 mm, p = 0.24), IgM aCL (0.65 +/- 0.79 vs. 0.73 +/- 0.17 mm, p = 0.33), anti-Hsp 60 (0.78 +/- 0.20 vs. 0.71 +/- 0.16 mm, p = 0.27), anti-Hsp 65 (0.73 +/- 0.16 vs. 0.72 +/- 0.17 mm, p = 0.77), IgG anti-beta2-gpl (0.73 +/- 0.16 vs. 0.71 +/- 0.17 mm, p = 0.72), and anti-CCP (0.71 +/- 0.16 vs. 0.76 +/- 0.20 mm, p = 0.36). In addition, IMT did not correlate with antibodies titers: IgG aCL (r = -0.09, p = 0.47), IgM aCL (r = - 0.15, p = 0.21), anti-Hsp 60 (r = 0.10, p = 0.42), anti-Hsp 65 (r = 0.05, p = 0.69), IgG anti-beta2-gpl (r = - 0.07, p = 0.57), IgM anti-beta2-gpl (r = - 0.05, p = 0.69), IgA anti-beta2-gpl (r = 0.03, p = 0.79), and anti-CCP (r = - 0.07, p = 0.57). RA patients with plaques had a significantly higher age compared to those without plaques (p = 0.001), as well as higher mean IMT (p < 0.001), total cholesterol (p = 0.001), and LDL (p = 0.003). Conclusions: In RA a clear association between all autoantibodies studied herein and increased IMT or presence of plaques was not observed. The great prevalence of carotid atherosclerosis in RA was related to age, total and LDL cholesterol, as identified in normal population. (c) 2008 Elsevier Masson SAS. All rights reserved.

Pregnancy outcome in juvenile systemic lupus erythematosus: A Brazilian multicenter cohort study

Objective. To determine pregnancy outcome and fetal loss risk factors in patients with juvenile systemic lupus erythematosus (JSLE). Methods. A total of 315 female patients with JSLE followed in 12 Brazilian pediatric rheumatology centers were consecutively selected. Menarche was observed in 298 (94.6%) patients. Patients` medical records were reviewed for pregnancy outcomes and demographic, clinical, and therapeutic data. Results. A total of 24 unplanned pregnancies occurred in 298 (8%) patients. The outcomes were 5 (21%) early fetal losses (prior to 16 wks gestation), 18 (75%) live births, and 1 (4%) death due to preeclampsia and premature birth. The frequencies of active diffuse proliferative glomerulonephritis, proteinuria >= 0.5 g/day, and arterial hypertension at the beginning of pregnancy were higher in pregnancies resulting in fetal losses than in live births [60% vs 5% (p = 0.02), 60% vs 5% (p = 0.02), 60% vs 5% (p = 0.02), respectively]. JSLE pregnancies with fetal losses had a significantly higher mean SLE Disease Activity Index 2000 (SLEDAI-2K) at the start of pregnancy compared with those with live births (9.40 +/- 7.47 vs 3.94 +/- 6.00; p = 0.049). Four pregnancies were inadvertently exposed to intravenous cyclophosphamide therapy for renal involvement despite contraceptive prescriptions, resulting in fetal loss in 3 (p = 0.02). In multivariate analysis only intravenous cyclophosphamide use at start of pregnancy (OR 25.50, 95% CI 1.72-377.93, p = 0.019) remained as an independent risk factor for fetal loss. Conclusion. We identified immunosuppressive therapy as the major contributing factor for fetal loss in JSLE, reinforcing the importance of contraception.

Bone mineral apparent density in juvenile dermatomyositis: the role of lean body mass and glucocorticoid use

Objective: To analyse bone mineral density (BMD) in juvenile dermatomyositis (JDM) and its possible association with body composition, disease activity, duration of disease, glucocorticoid (GC) use, and biochemical bone parameters, including osteoprotegerin (OPG) and receptor activator of nuclear factor B (RANKL). Methods: Twenty girls with JDM and 20 controls matched for gender and age were selected. Body composition and BMD were analysed by dual-energy X-ray absorptiometry (DXA) and bone mineral apparent density (BMAD) was calculated. Duration of disease, cumulative GC, and GC pulse therapy use were determined from medical records. Disease activity and muscle strength were measured by the Disease Activity Score (DAS), the Childhood Myositis Assessment Scale (CMAS), and the Manual Muscle Test (MMT). Inflammatory and bone metabolism parameters were also analysed. OPG and RANKL were measured in patients and controls using an enzyme-linked immunosorbent assay (ELISA). Results: A lower BMAD in the femoral neck (p< 0.001), total femur (p< 0.001), and whole body (p=0.005) was observed in JDM patients compared to controls. Body composition analysis showed a lower lean mass in JDM compared to controls (p=0.015), but no difference was observed with regard to fat mass. A trend of lower serum calcium was observed in JDM (p=0.05), whereas all other parameters analysed, including OPG and RANKL, were similar. Multiple linear regression analysis revealed that, in JDM, lean mass (p< 0.01) and GC pulse therapy use (p< 0.05) were independent factors for BMAD in the hip region. Conclusions: This study has identified low lean mass and GC pulse therapy use as the major factors for low hip BMAD in JDM patients.

The influence of lean mass in trabecular and cortical bone in juvenile onset systemic lupus erythematosus

The aim of this study was to evaluate risk factors for low bone mineral density (BMD) and vertebral fractures, in juvenile systemic lupus (JSLE). Thirty-one consecutive patients with JSLE were compared with 31 gender- and age-matched healthy controls. BNID and body composition from all participants were measured using dual-energy X-ray absorptiometry. Vertebral fractures were defined as a reduction of >= 20% of the vertebral height for all patients. Lumbar spine and total femur BMD was significantly decreased in patients compared with controls (P = 0.021 and P = 0.023, respectively). A high frequency of vertebral fractures (22.58%) was found in patients with JSLE. Analysis of body composition revealed lower lean mass (P = 0.033) and higher fat mass percentage (P = 0.003) in patients than in controls. Interestingly, multiple linear regression using BMD as a dependent variable showed a significant association with lean mass in lumbar spine (R(2) = 0.262; P = 0.004) and total femur (R(2) = 0.419, P = 0.0001), whereas no association was observed with menarche age, SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics/American College of Rheumatology, and glucocorticoid. This study indicates that low BMD and vertebral fractures are common in JSLE, and the former is associated with low lean mass, suggesting that muscle rehabilitation may be an additional target for bone therapeutic approach.

Penile anthropometry in systemic lupus erythematosus patients

The aim of this study was to evaluate penile anthropometry in systemic lupus erythematosus (SLE) patients compared with healthy controls and the possible relevant pubertal, clinical, hormonal and treatment factors that could influence penile dimensions. Twenty-five consecutive SLE patients were assessed by urological examination, sexual function, testicular ultrasound, hormones, sperm analysis, genetic analysis, clinical features and treatment. The control group included 25 age-matched healthy males. SLE patients had a lower median penis length and circumference [8 (7.5-10) vs. 10 (8-13) cm, p = 0.0001; 8 (7-10) vs. 10 (7-11) cm, p = 0.001; respectively], lower median testicular volume by right and left Prader [15 (10-25) vs. 20 (12-25) ml, p = 0.003; 15 (10-25) vs. 20 (12-25) ml, p = 0.006; respectively], higher median of follicle-stimulating hormone [5.8 (2.1-25) vs. 3.3 (1.9-9) IU/l, p = 0.002] and lower morning total testosterone levels (28% vs. 0%, p = 0.009) compared with controls. In spite of that, erectile dysfunction was not observed in patients or controls. Analyses of lupus patients revealed that the median penis circumference was lower in patients with disease onset before first ejaculation compared with those with disease onset after first ejaculation [7.8 (7-10) vs. 9.0 (7.5-10) cm, p = 0.026]. No differences were observed in the median penile anthropometry regarding sexual dysfunction (p = 0.610), lower morning total testosterone levels (p = 0.662), oligo/azoospermia (p = 0.705), SLE Disease Activity Index >= 4 (p = 0.562), Systemic Lupus International Collaborating Clinics/ACR Damage Index >= 1 (p = 0.478), prednisone cumulative dose (p = 0.789) and intravenous cyclophosphamide therapy (p = 0.754). Klinefelters syndrome (46XY/47XXY) was diagnosed in one (4%) SLE patient with decreased penile size whereas Y-chromosomal microdeletions was absent in all of them. In conclusion, we have identified reduced penile dimensions in SLE patients with no deleterious effect in erectile function. Disease onset before first ejaculation seems to affect penis development in pre-pubertal lupus. Lupus (2011) 20, 512-518.

Cutaneous vasculitis in systemic lupus erythematosus: association with anti-ribosomal P protein antibody and Raynaud phenomenon

Ninety-one consecutive systemic lupus erythematosus (SLE) patients (American College of Rheumatology criteria) with a history of cutaneous vasculitis were compared to 163 SLE controls without this clinical manifestation from July to December 2007 in order to determine the possible clinical and serological association of this manifestation. Data were obtained in an ongoing electronic database protocol and autoantibodies to anti-double-stranded DNA, anti-Sm, anti-RNP, anti-Ro/SS-A, anti-La/SS-B, and anticardiolipin and ribosomal P protein antibody (anti-P) were detected by standard techniques. Exclusion criteria were the presence of anti-phospholipid syndrome or antibodies, Sjogren syndrome, and a history of thrombosis. The mean age (38.5 +/- 11.5 vs. 37.8 +/- 11.6 years, p = 0.635), disease duration (12.5 +/- 7.8 vs. 11.8 +/- 7.9 years, p = 0.501), and frequency of white race (71.4% vs. 70.5%, p = 0.872) and female sex (96.8% vs. 93.7%, p = 0.272) were comparable in both groups. The vasculitis group had a higher frequency of malar rash (97.9% vs. 87.4%, p = 0.004), photosensitivity (91.4% vs. 81.6%, p = 0.030), and Raynaud phenomenon (RP; 27.7% vs. 7.5%, p < 0.001), whereas all other clinical manifestation including renal and central nervous system involvements were similar to the control group. Laboratorial data revealed that only anti-P (35.1% vs. 12.1%, p < 0.001) was more frequent in patients with vasculitis. In a multivariate logistic regression model, cutaneous vasculitis was associated to the presence of RP (OR = 3.70; 95% confidence interval [CI] = 1.73-8.00) and anti-P (OR = 3.42; 95% CI = 1.76-6.66). In summary, SLE cutaneous vasculitis characterizes a subgroup of patients with more RP and anti-P antibodies but not accompanied by a higher frequency of renal and central nervous system involvements.

Hormone profile in juvenile systemic lupus erythematosus with previous or current amenorrhea

To identify the underlying mechanism of amenorrhea in juvenile systemic lupus erythematosus (JSLE) patients, thirty-five (11.7%) JSLE patients with current or previous amenorrhea were consecutively selected among the 298 post-menarche patients followed in 12 Brazilian pediatric rheumatology centers. Pituitary gonadotrophins [follicle-stimulating hormone (FSH) and luteinizing hormone (LH)] and estradiol were evaluated in 32/35 patients, and prolactin and total testosterone in 29/35 patients. Patient`s medical records were carefully reviewed according to demographic, clinical and therapeutic findings. The mean duration of amenorrhea was 7.2 +/- A 3.6 months. Low FSH or LH was observed in 7/32 (22%) JSLE patients and normal FSH or LH in 25 (78%). Remarkably, low levels of FSH or LH were associated with higher frequency of current amenorrhea (57% vs. 0%, P = 0.001), higher median disease activity (SLEDAI) and damage (SLICC/ACR-DI) (18 vs. 4, P = 0.011; 2 vs. 0, P = 0.037, respectively) and higher median current dose of prednisone (60 vs. 10 mg/day, P = 0.0001) compared to normal FSH or LH JSLE patients. None of them had decreased ovarian reserve and premature ovarian failure. Six of 29 (21%) patients had high levels of prolactin, and none had current amenorrhea. No correlations were observed between levels of prolactin and SLEDAI, and levels of prolactin and SLICC/ACR-DI scores (Spearman`s coefficient). We have identified that amenorrhea in JSLE is associated with high dose of corticosteroids indicated for active disease due to hypothalamic-pituitary-ovary axis suppression.

Lymphocytic prolactin does not contribute to systemic lupus erythematosus hyperprolactinemia

Introduction Lymphocytic prolactin (PRL) gene expression is detected in the majority of the immune cells and it is not known if this source contributes to hyperprolactinemia in systemic lupus erythematosus (SLE). We have therefore evaluated lymphocytic PRL secretion and gene expression in SLE and healthy controls. Methods Thirty SLE patients (ACR criteria) and 10 controls were selected for the study. Serum levels of PRL and macroprolactin were detected by immunofluorometric assay and gel filtration chromatography, respectively. The lymphocytic biological activity was determined by Nb2 cells bioassays. Lymphocytic PRL gene expression was evaluated by RT-PCR assay. Results The median serum PRL levels of the 30 SLE patients was higher than the control group (9.65 (1.9-38.9) vs. 6.40 (2.4-10.3) ng/mL, p=0.03). A significant difference was detected between median serum PRL levels of active SLE, inactive SLE and controls (10.85 (5-38.9) vs. 7.65 (1.9-15.5) vs. 6.40 (2.4-10.3) ng/mL), p=0.01). The higher frequency of mild hyperprolactinemia was detected among active SLE in comparison with inactive SLE and controls (7(38.9%) vs. 1 (8.3%) vs. 0(0%)), with statistical significance (p=0.02). Nb2 cells assay revealed uniformly low levels of lymphocytic PRL in active, inactive and control groups without statistical significance among them (24.2 (8-63) vs. 27 (13.6-82) vs. 29.5 (8-72) ng/mL), p=0.84). Furthermore, median lymphocytic PRL gene expression evaluated by RT-PCR assay was comparable in both active and inactive SLE groups (p=0.12). Conclusion This is the first study to exclude a lymphocytic source of PRL, pointing out a pituitary etiology for hyperprolactinemia in SLE. However, other sources from the immune system cannot be ruled out.

Gingival capillary changes and oral motor weakness in juvenile dermatomyositis

Objective. We assessed the orofacial involvement in JDM, and evaluated the possible association of gingival and mandibular mobility alterations with demographic data, periodontal indices, clinical features, muscle enzyme levels, JDM scores and treatment. Methods. Twenty-six JDM patients were studied and compared with 22 healthy controls. Orofacial evaluation included clinical features, dental and periodontal assessment, mandibular function and salivary flow. Results. The mean current age was similar in patients with JDM and controls (P > 0.05). A unique gingival alteration characterized by erythema, capillary dilation and bush-loop formation was observed only in JDM patients (61 vs 0%, P = 0.0001). The frequencies of altered mandibular mobility and reduced mouth opening were significantly higher in patients with JDM vs controls (50 vs 14%, P = 0.013; 31 vs 0%, P = 0.005). Comparison of the patients with and without gingival alteration showed that the former had lower values of median of cementoenamel junction (-0.26 vs -0.06 mm, P = 0.013) and higher gingival bleeding index (27.7 vs 14%, P = 0.046). This pattern of gingival alteration was not associated with periodontal disease [plaque index (P = 0.332) and dental attachment loss (P = 0.482)]. The medians for skin DAS and current dose of MTX were higher in JDM with gingival alteration (2.5 vs 0.5, P = 0.029; 28.7 vs 15, P = 0.012). A significant association of lower median manual muscle testing with a reduced ability to open the mouth was observed in patients with JDM than those without this alteration (79 vs 80, P = 0.002). Conclusions. The unique gingival pattern associated with cutaneous disease activity, distinct from periodontal disease, suggests that gingiva is a possible target tissue for JDM. In addition, muscle weakness may be a relevant factor for mandibular mobility.

Menstrual and hormonal alterations in juvenile dermatomyositis

Objective To evaluate age at menarche, menstrual cycles and hormone profile in juvenile dermatomyositis (JDM) patients and controls. Methods Twelve consecutive JDM patients were compared to 24 age-matched healthy subjects. Age at menarche and age of maternal menarche were recorded. Menstrual cycle was evaluated prospectively for 6 consecutive months and the mean cycle length and flow were calculated. The hormone profile was collected on the last menstrual cycle. Demographic data, clinical features, muscle enzymes, JDM scores and treatment were analysed. Results The median of current age of JDM patients and controls was similar (18 vs. 17 years, p=0.99). The median age at menarche of the JDM patients was higher than in the control group (13 vs. 11 years, p=0.02) whereas the median age of maternal menarche was alike in both groups (12 vs. 13 years, p=0.67). Menstrual disturbances were not observed, except for one patient who had longer length of menstrual cycle. The median of follicle stimulating hormone (FSH) was significantly higher in JDM patients compared to controls (4.5 vs. 3.0 IU/L, p=0.02) and none of them had premature ovarian failure (POF). The median of progesterone was significantly lower in JDM patients (0.3 vs. 0.7 ng/mL, p=0.01) with a higher frequency of decreased progesterone compared to controls (75% vs. 29%, p=0.01). Conclusions Our study identifies in JDM patients delayed menarche with normal cycles and low follicular reserve. The decreased progesterone levels may suggest an underlying subclinical corpus luteum dysfunction in this disease.

Association of the MCP-1-2518 A/G Polymorphism and No Association of Its Receptor CCR2-64 V/I Polymorphism with Lupus Nephritis

Objective. To evaluate whether the A/G polymorphism at position 2518 in the regulatory region of the monocyte chemoattractant protein-1 (MCP-1) or the V/I polymorphism at position 64 of the receptor. CCR2, are associated with lupus nephritis (LN) or any clinical characteristics of the disease or with renal survival in a patient population. Methods. We selected 197 patients with lupus nephritis and 220 matched healthy controls for study. MCP-1 and CCR2 genotyping was performed by polymerase chain reaction. Clinical and laboratory data were compiled from patients` charts over followup that ranged from 6 months to 10 years. Results. The GIG genotype of MCP-1 was more common in LN patients (p = 0.019), while the A allele was associated with healthy controls (p = 0.007) as was the V allele of CCR2 (p = 0.046) compared to LN patients. Clinical index measures [SLE Disease Activity Index (SLEDAI)], immunological markers, renal histology, renal function at enrollment, and renal survival were not influenced by these polymorphisms. A less aggressive renal disease, measured by renal SLEDAI index, was associated with the V allele of the CCR2 gene polymorphism. Conclusion. These findings support that MCP-1 2518 GIG is associated with LN but there was no association of this genotype with renal function or renal survival. When studying CCR2 64 V/I polymorphism we showed a positive association of the V allele with healthy controls but no association of the genotype with LN patients. (First Release March 152010; J Rheumatol 2010;37:776-82; doi:10.3899/jrheum.090681)

Incidence, Risk Factors, and Outcome of Herpes Zoster in Systemic Lupus Erythematosus

Background: The incidence and outcome of Herpes zoster (HZ) in systemic lupus erythematosus (SLE) are not completely defined as well as the relevance to HZ of disease and therapy factors. Objective: To determine HZ features in SLE. Patients and Methods: SLE patients ( 1997 update of the American College of Rheumatology classification criteria) with definitive HZ infection were identified from our Lupus Clinic computerized database of 1145 patients. Results: HZ was diagnosed in 51 SLE patients (4.45%) with an annual incidence rate of 6.4 events/1000 patient-years. At HZ diagnosis, mean disease duration was 9.78 +/- 8.37 years, median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was 1, and only 17.6% had SLEDAI >= 8. Frequency of manifestations and immunosuppressor use were similar between patients with and without HZ. Forty-two patients (82.5%) with HZ were under prednisone with concomitant immunosuppressive therapy in 66.7%. Thirty-five patients (68.6%) were using immunosuppressors: azathioprine (39.2%), cyclophosphamide (9.8%), and mycophenolate mofetil ( 9.8%). The mean lymphocyte count was 1219 +/- 803/mm(3) (43.1% < 1000/mm(3) and 17.6% < 500/mm(3)). Only patients using azathioprine and cyclophosphamide had lymphocyte counts < 500/mm(3) (15% and 40%). All patients received acyclovir, 19.6% had postherpetic neuralgia, and recurrence occurred in only 7.8%. Thoracic nerves were the most involved site (56.8%) followed by lumbar (23.5%). Bacterial suprainfection occurred in 11.7% but was not associated with therapy, lymphocyte count, or SLEDAI scores ( P > 0.05). Conclusion: This is the largest cohort to determine that HZ is a late SLE complication with some peculiar features, such as good prognosis and typical dermatomal distribution. In addition, we have identified that the major trigger factor for this viral infection in SLE is therapy, particularly the concomitant use of corticosteroid and immunosuppressors, and not active disease.