Complete urological evaluation including sperm DNA fragmentation in male systemic lupus erythematosus patients.

OBJECTIVE: To evaluate sperm DNA fragmentation analysis in non-azoospermic male systemic lupus erythematosus (SLE) patients. METHODS: Twenty-eight consecutive male SLE patients (American College of Rheumatology criteria) and 34 healthy controls were evaluated for demographic/exposures data, urological evaluation, hormone profile and sperm analysis (including sperm DNA fragmentation). Clinical features, disease activity/damage scores and treatment were also evaluated. RESULTS: The median age (33 (20-52) vs. 36.5 (25-54) years, P = 0.329) and frequency of varicocele (25% vs. 32%, P = 0.183) were similar in SLE patients and healthy controls. Sperm DNA fragmentation showed significantly higher levels of cells class III (44 (9-88) vs. 16.5 (0-80)%, P = 0.001) and cell class IV (10.5 (3-86) vs. 7 (0-36)%, P = 0.039) in SLE. The sperm DNA fragmentation index was also significantly higher in SLE patients (62 (31-97) vs. 25.5 (0-100)%, P < 0.001). Conventional sperm parameters (including sperm count, motility and morphology) were similar in both groups. In SLE patients no correlations were observed between sperm DNA fragmentation index and age, disease duration, Systemic Lupus Erythematosus Disease Activity Index 2000 and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index scores, and cumulative dose of prednisone, hydroxychloroquine, intravenous cyclophosphamide, methotrexate, azathioprine and mycophenolate mofetil ( P > 0.05). Further analysis of SLE patients treated with and without intravenous cyclophosphamide showed that total sperm motility was significantly lower in the former group (64% (15-83) vs. 72% (57-86), P = 0.024). The sperm DNA fragmentation index was alike in both groups (52.5 (31-95) vs. 67.5 (34-97)%, P = 0.185). CONCLUSIONS: To our knowledge, this is the first demonstration that male non-azoospermic SLE patients have increased sperm DNA fragmentation without evident gonadal dysfunction. Intravenous cyclophosphamide does not seem to be a major determinant for this abnormality. Future prospective study is necessary to determine the impact of this alteration in these patients' fertility.

Effectiveness of renoprotective approaches for persistent proteinuria in lupus nephritis: more than just immunosuppression.

OBJECTIVE: The objective of this study is to evaluate the efficacy of a tightly controlled renoprotective protocol in systemic lupus erythematosus (SLE) patients with persistent proteinuria. METHODS: Thirteen SLE patients with nephritis and persistent proteinuria (>1 g/24 hours) were included. The protocol consisted of regular clinical evaluations every two weeks to assess blood pressure (BP, target <130/80 mmHg), adherence to therapy, diet and smoking. No change in immunosuppressive drugs was allowed but reduction of glucocorticoid dose was permitted if indicated. Clinical, laboratory and treatment evaluations were performed at baseline and at the end of the study (after three months). RESULTS: SLE patients had a mean age of 37.85 ± 7.68 years and disease duration of 9.85 ± 7.29 years. At baseline, patients had a mean duration of maintenance therapy of 10.38 ± 7.56 months, 12 with mycophenolate mofetil (92.3%) and one with azathioprine (7.7%). At least one dose optimization of antihypertensive regimen was required in all patients during the study. Seven patients (53.8%) had BP>130/80mmHg at baseline. At the end, 11 patients (84.6%) achieved stable BP target; 92.3% were using an angiotensin-converting enzyme inhibitor, 53.9% an angiotensin receptor blocker, and 46.2% were using combined therapy. All patients had a significant reduction in proteinuria levels (2.26 ± 1.09 vs 0.88 ± 0.54 g/24 hours, p < 0.001) and 61.5% achieved proteinuria <1 g/24 hours. A significant decrease in mean prednisone dose was observed (10.96 ± 6.73 vs 5.38 ± 3.36 mg/day, p = 0.013) as well as mean Systemic Lupus Erythematosus Disease Activity Index score (4.38 ± 0.72 vs 3.08 ± 1.86, p = 0.043). No significant changes were identified in serum creatinine, albumin, potassium, complement 3 and complement 4 levels ( p > 0.05). CONCLUSION: This study provides evidence that a tightly controlled renoprotective protocol is effective in reducing persistent proteinuria in lupus nephritis. The concomitant reduction of prednisone without any change in immunosuppression reinforces the importance of strategies beyond the treatment of nephritis activity.

Increased corticotropin-releasing hormone (CRH) expression in cutaneous lupus lesions.

OBJECTIVE: Corticotropin-releasing hormone (CRH) and pro-opiomelanocortin (POMC) axis activation leads to the production of hormones, such as adrenocorticotrophic hormone (ACTH) and the α-melanocyte stimulating hormone (α-MSH). Data regarding the role of these hormones in systemic lupus erythematosus (SLE) are scarce. In the present study we aim to evaluate the participation of this axis in the cutaneous involvement of SLE. METHODS: Seventeen SLE patients were clinically evaluated, and biopsies from affected and unaffected skin of these patients were compared with 17 healthy control individuals. Immunohistochemical analyses for CRH, ACTH, α-MSH, and MC-1R were performed, and the serum levels of α-MSH, IL-1, IL-1ra, IL-6, IL-10, IL-12p70, IL-17, TNF-α, and IFN-γ were measured. RESULTS: The affected skin of the SLE patients exhibited higher CRH expression in the deep dermis compared to the skin of the controls (p = 0.024), whereas the tissue expression of ACTH, cortisol, α-MSH and its receptor MC-1R were comparable in SLE patients and controls. Higher serum levels of IFN-γ (p = 0.041), TNF-α (p = 0.001) and IL-6 (p = 0.049) were observed in SLE patients compared with controls, while α-MSH levels were similar in both groups. CONCLUSION: The novel finding of elevated CRH expression solely in the affected skin deep dermis supports the notion of a cutaneous local dysfunction of the CRH-POMC axis in the pathogenesis of cutaneous SLE lesions.

Podocyte injury in pure membranous and proliferative lupus nephritis: distinct underlying mechanisms of proteinuria?

Proteinuria is a major feature of lupus nephritis (LN) and reflects podocyte injury. Analysis of podocyte biomarkers was performed attempting to identify if podocyte phenotype is distinct in pure membranous and proliferative LN. Expression of synaptopodin, Wilms tumor protein 1 (WT1), glomerular epithelial protein 1 (GLEPP1) and nephrin was evaluated in 52 LN biopsies by immunohistochemistry. Preserved synaptopodin expression was observed in only 10 (19.2%) of all biopsies while 42 (80.8%) had reduced expression. Both groups had comparable proteinuria at the time of biopsy (p = 0.22); however, in the mean follow-up of four years there was a tendency toward lower mean levels of proteinuria in patients with preserved synaptopodin staining (0.26±0.23 vs. 0.84±0.90 g/24 h, p = 0.05) compared with those with diminished expression. Thirty-nine (75%) biopsies were classified as proliferative and 13 (25%) as pure membranous. Comparison of podocyte biomarkers demonstrated a predominance of preserved staining of synaptopodin (69.2%), WT1 (69.2%), GLEPP1 (53.9%) and nephrin (60%) in the pure membranous group whereas only <10% of the proliferative showed preserved expression. Our data suggest that in proliferative forms there seems to occur structural podocyte damage, whereas in the pure membranous the predominant preserved pattern suggests a dysfunctional podocyte lesion that may account for the better long-term prognosis of proteinuria outcome.

Ovarian reserve in adult patients with childhood-onset lupus: a possible deleterious effect of methotrexate?

OBJECTIVES: To assess ovarian reserve markers and anti-corpus luteum antibodies (anti-CoL) in adult patients with childhood-onset systemic lupus erythematosus (c-SLE). METHOD: Fifty-seven adult c-SLE female patients and 21 healthy controls were evaluated for anti-CoL. Ovarian reserve was assessed by: follicle stimulating hormone (FSH), luteinizing hormone (LH), oestradiol, anti-Müllerian hormone (AMH), and antral follicle count (AFC). Demographic data, menstrual abnormalities, disease activity, damage, and treatment were also analysed. RESULTS: The median current age was similar in adult c-SLE patients and controls (27.7 vs. 27.7 years, p = 0.414). The medians of AMH (1.1 vs. 1.5 ng/mL, p = 0.037) and AFC (6 vs. 16, p < 0.001) were significantly reduced in SLE patients compared to controls without significant menstrual abnormalities. Anti-CoL were solely observed in c-SLE patients (16% vs. 0%, p = 0.103) and were not associated with demographic data, ovarian reserve parameters, disease activity/damage, and treatment. Further evaluation of c-SLE patients treated with cyclophosphamide revealed a higher median of FSH levels compared to c-SLE patients not treated with cyclophosphamide and controls (8.8 vs. 5.7 vs. 5.6 IU/L, p = 0.032) and lower median AMH (0.4 vs. 1.5 vs. 1.5 ng/mL, p = 0.004) and AFC (4.0 vs. 6.5 vs. 16 IU/L, p = 0.001) levels. Nineteen patients treated exclusively with methotrexate demonstrated a negative correlation between the cumulative dose and AMH levels (p = 0.027, r = -0.507). CONCLUSIONS: The present study demonstrated for the first time that a high cumulative methotrexate dose is a possible cause of subclinical ovarian dysfunction in adult c-SLE patients. Further studies are required to confirm this deleterious effect in other rheumatic diseases, particularly juvenile idiopathic arthritis and idiopathic inflammatory myopathy.

Clinical and immunological features of 888 Brazilian systemic lupus patients from a monocentric cohort: comparison with other populations.

Epidemiological studies with systemic lupus erythematosus (SLE) patients have been reported worldwide but, until now, a large evaluation had not been performed in Brazil. Therefore, we determined the clinical and immunological features of 888 SLE patients followed at our service from 2008 to 2012. The mean age at SLE onset and the mean disease duration were 29.9 ± 9.5 years old and 14.5 ± 8.4 years, respectively. A predominance of female gender (91.9%) and Caucasian ethnicity (69.9%) were observed. Cumulative mucocutaneous manifestations (90.7%) were most commonly identified (malar rash (83.2%), photosensitivity (76.9%)) followed by articular (87.4%), hematological (44.0%) and renal (36.9%) involvements. Antinuclear antibody was detected in all patients, followed by anti-dsDNA (35.1%), anti-Sm (21.8%) and anti-ribosomal P protein antibodies (19.8%). Additional comparison of clinical and laboratory features between genders revealed that malar rash was observed more in female SLE patients (84.5% vs. 69.4%, p = 0.001). Male lupus patients presented a higher frequency of anti-dsDNA (45.8% vs. 34.2%, p = 0.047) and a trend of more nephritis (47.2% vs. 36.0%, p = 0.059). In conclusion, we identified a high prevalence of mucocutaneous manifestations in this Brazilian SLE cohort compared to other countries, mainly malar rash that was most commonly observed in female patients. Anti-dsDNA and other specific SLE autoantibodies were also identified in a higher frequency, predominantly in the male gender.

Impaired aerobic exercise capacity and cardiac autonomic control in primary antiphospholipid syndrome.

Primary antiphospholipid syndrome (PAPS) is associated with increased risk of cardiovascular disease and mortality. Aerobic capacity and cardiac autonomic control are also associated with these risks. The aim of our study was to assess aerobic capacity and cardiac autonomic control in PAPS patients. Thirteen women with PAPS and 13 healthy controls matched for age, gender, and body mass index were enrolled for the study. Both groups were sedentary and were not under chronotropic, antidepressants and hypolipemiant drugs. All subjects performed a treadmill-graded maximal exercise. Aerobic capacity was assessed by peak oxygen uptake (VO2peak), time at anaerobic ventilatory threshold (VAT) and respiratory compensation point (RCP) and time-to-exhaustion, whereas cardiac autonomic control was assessed by chronotropic reserve (CR) and heart rate recovery at the first and second minutes after graded exercise (HRR1min and HRR2min, respectively). All aerobic capacity indexes were reduced more in PAPS patients than in healthy subjects: VO2peak (30.2 ± 4.7 vs 34.6 ± 4.3 ml.kg(-1).min(-1), p = 0.021), time at VAT (3.0 ± 1.5 vs 5.0 ± 2.0 min, p = 0.016), time at RCP (6.5 ± 2.0 vs 8.0 ± 2.0 min, p = 0.050), time-to-exhaustion (8.5 ± 2.0 vs 11.0 ± 2.5 min, p = 0.010). HRR1min (22 ± 9 vs 30 ± 7 bpm, p = 0.032) and HRR2min (33 ± 9 vs 46 ± 8 bpm, p = 0.002) were delayed in PAPS patients compared to healthy controls but CR was not significantly different (p = 0.272). In conclusion, an impaired aerobic capacity and cardiac autonomic control was identified in PAPS.

Increased arterial stiffness assessed by pulse wave velocity in Behçet's disease and its association with the lipid profile.

OBJECTIVE: To evaluate the structural and functional properties of vessels in Behçet's Disease (BD) using carotid-femoral pulse wave velocity (PWV) and an echo-tracking system. METHODS: BD patients without traditional cardiovascular risk factors were selected. All BD patients performed PWV and carotid ultrasound. BD patients were divided into groups based on the presence of systemic (vascular and/or ocular and/or central nervous system involvement) and vascular involvement. Healthy controls age- and sex-matched with the same exclusion criteria were selected. RESULTS: A total of 23 BD patients (mean age 35.0 ± 7.6 years) had significantly higher PWV levels compared with controls (8.48 ± 1.14 vs. 7.53 ± 1.40 m/s, P = 0.017). Intima-media thickness (594.87 ± 138.61 vs. 561.08 ± 134.26 µm, P = 0.371), diastolic diameter (6383.78 ± 960.49 vs. 6447.65 ± 1159.73 µm, P = 0.840), distension (401.95 ± 117.72 vs. 337.91 ± 175.36 µm, P = 0.225) and relative distension (6.26 ± 2.83 vs. 5.42 ± 2.46 µm, P = 0.293) were similar in both groups. The systemic disease group had significantly higher levels of PWV (8.79 ± 1.21 vs. 7.88 ± 0.72 m/s, P = 0.036) compared to those with exclusive mucocutaneous manifestations. BD patients with vascular involvement had similar PWV and echo-tracking parameters compared to those without vascular involvement (P > 0.05), but had higher total and LDL cholesterol levels (P = 0.019 and P = 0.012, respectively). The multivariate linear regression analysis identified triglycerides as the most important factor in increasing PWV levels (P = 0.001) in BD. CONCLUSIONS: PWV is more useful than carotid ultrasound in detecting structural and functional vascular damage in BD and emphasizes the role of the disease itself in promoting these alterations. Our findings also reinforce the need for rigorous control of all risk factors in BD, particularly lipoproteins.

Hydroxychloroquine reduces low-density lipoprotein cholesterol levels in systemic lupus erythematosus: a longitudinal evaluation of the lipid-lowering effect.

UNLABELLED: The influence of antimalarials on lipids in systemic lupus erythematosus (SLE) has been identified in several studies but not in many prospective cohorts. The aim of this study was to longitudinally determine the effect of antimalarials on the lipoprotein profile in SLE. PATIENTS AND METHODS: Fasting total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein cholesterol (LDL) plasma levels were determined at entry and after 3 months of hydroxychloroquine (HCQ) treatment in a longitudinal evaluation of 24 patients with SLE. RESULTS: a significant decrease in TC (198 ± 33.7 vs. 183 ± 30.3 mg/dl, p = 0.023) and LDL levels (117 ± 31.3 vs. 101 ± 26.2 mg/dl, p = 0.023) were detected after the 3 months of HCQ therapy. The reduction of 7.6% in TC (p = 0.055) and 13.7% in LDL levels (p = 0.036) determined a significant decrease in the frequency of dyslipidemia (26% vs. 12.5%, p = 0.013) after HCQ therapy. CONCLUSION: This longitudinal study demonstrated the beneficial effect of antimalarials on lipids in SLE since this therapy induced a reduction of atherogenic lipoproteins.

Alveolar hemorrhage: distinct features of juvenile and adult onset systemic lupus erythematosus.

We compared outcomes of alveolar hemorrhage (AH) in juvenile (JSLE) and adult onset SLE (ASLE). From 263 JSLE and 1522 ASLE, the AH occurred in 13 (4.9%) and 15 (1.0%) patients, respectively (p < .001). Both groups had comparable disease duration (2.6 ± 3.0 vs. 5.6 ± 7.0 years, p = .151) and median SLEDAI scores [17.5 (2 to 32) vs. 17.5 (3 to 28), p = 1.000]. At AH onset, a higher frequency of JSLE were already on a high prednisone dose ( > 0.5 mg/kg/day) compared to ASLE (54% vs. 15%, p = .042). The mean drop of hemoglobin was significantly lower in JSLE (2.9 ± 0.9 vs. 5.5 ± 2.9 g/dL, p = .006). Although treatments with methylprednisolone, plasmapheresis, intravenous immunoglobulin and cyclophosphamide were similar in both groups (p > .050), regarding outcomes, there was a trend in high frequency of mechanical ventilation use (85% vs. 47%, p = .055) and also significant mortality (69% vs. 13%, p = .006) in JSLE compared to ASLE. The sepsis frequency was comparable in both groups (50% vs. 27%, p = .433). We have identified that AH in JSLE has a worse outcome most likely related to respiratory failure. The AH onset in JSLE already treated with high-dose steroids raises the concern of inadequate response to this treatment and reinforces the recommendation of early aggressive alternative therapies in this group of patients.

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 pleuritis: a relevant risk factor for pulmonary tuberculosis.

The objective of the study was to evaluate risk factors for pulmonary tuberculosis in systemic lupus erythematosus (SLE). Clinical/laboratorial features of 1283 SLE patients (ACR criteria) followed at the Lupus Clinic were obtained from the electronic register database from 2001 to 2009. Pulmonary tuberculosis was diagnosed in 20 patients (1.6%) (TB+ group). As control group (TB-), 40 patients without tuberculosis matched for age, gender, ethnicity, age at SLE diagnosis, and disease duration were arbitrarily selected. All 20 patients of the TB+ group presented confirmed pulmonary tuberculosis from 1 to 23 years after SLE diagnosis (7.6 ± 8.1 years). Frequencies of previous SLE involvements (cutaneous, articular, hematological, renal, pericarditis, pneumonitis, and central nervous system) were alike in TB+ and TB- groups (p > 0.05). In contrast, prior pleuritis was more frequent in the TB+ group (40% vs. 5%, p = 0.001). In fact, pulmonary tuberculosis was diagnosed in 8/10 patients with previous pleuritis. Immunosuppressive and corticosteroid therapies at the moment of tuberculosis diagnosis were also similar in both groups (p > 0.05). We have identified pleuritis as a relevant risk factor for pulmonary tuberculosis, suggesting that previous pleural injury is a critical part of the complex interplay between altered immune system, socio-economic conditions, and increased susceptibility to this mycobacterial infection.

Premature coronary artery calcification is associated with disease duration and bone mineral density in young female systemic lupus erythematosus patients.

Our objective was to evaluate the relevance of traditional and disease-related cardiovascular risk factors and of bone mineral density for premature coronary artery calcification in young patients with systemic lupus erythematosus. Ninety-four female patients with systemic lupus erythematosus with disease durations >5 years and <45 years were consecutively selected. Cardiovascular risks (diabetes mellitus, arterial hypertension, dyslipoproteinemia, smoking, family history, body mass index, ovarian and renal insufficiency) and systemic lupus erythematosus-related risk factors (disease duration, ACR criteria, modified SLICC/ ACR, SLEDAI and treatment) were evaluated. Bone mineral density was assessed by dual X-ray absorptiometry. Coronary artery calcification was determined by computed tomography. Coronary artery calcification was identified in 12 (12.7%) patients and was associated with a higher frequency of patients with cardiovascular risks (p = 0.001), higher number of cardiovascular risks (p = 0.002), age (p = 0.025), disease duration (p = 0.011) and SLICC (p=0.011). Individual analysis of cardiovascular risks demonstrated that menopause (p = 0.036), dyslipidemia (p = 0.003) and hypertension (p = 0.006) were significantly associated with coronary artery calcification. In addition, coronary artery calcification was associated with a lower whole body bone mineral density (p = 0.013). Multiple logistic regression analysis using cardiovascular risks, age, disease duration, SLICC and whole body bone mineral density revealed that only disease duration (p = 0.038) and whole body bone mineral density (p = 0.021) remained significant for coronary artery calcification. In conclusion, we found that disease duration and decreased bone mineral density are independent predictors for premature coronary calcification in young women with systemic lupus erythematosus, suggesting a common underlying mechanism.

Lymphocytic prolactin does not contribute to systemic lupus erythematosus hyperprolactinemia.

OBJECTIVES: 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). CONCLUSIONS: 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.

Digital vasculitis in systemic lupus erythematosus: a minor manifestation of disease activity?

The objective of this study is to determine if digital vasculitis (DV), a clinical manifestation with a high systemic lupus erythematosus disease activity index (SLEDAI) score, is associated with lupus severity. DV and other clinical manifestations defined according to the SLEDAI were evaluated in 168 consecutive patients with systemic lupus erythematosus (SLE). Two groups were defined according to presence (DV+, n = 27) or absence of DV (DV-, n = 141) at the time of evaluation. The exclusion criterion was the presence of antiphospholipid syndrome (Sapporo's criteria). The two groups were comparable with regard to age (P = 0.09), gender (P = 1.00), white race (P = 0.81), and disease duration (P = 0.78). Compared to the DV- group, the DV+ group had a significantly higher frequency of mucocutaneous manifestations (66.7 vs. 39.0%, P = 0.01), haematological abnormalities (22.2 vs. 6.4%, P = 0.02) and constitutional symptoms (11.1 vs. 0.7%, P = 0.01). Renal and neurological involvements were similar in both groups (P = 0.57 and P = 1.00, respectively). The evaluation of each SLEDAI parameter confirmed that the DV+ group had higher frequencies of mild manifestations, such as new rash (P = 0.02), alopecia (P = 0.02), oral ulcers (P = 0.045), fever (P = 0.01) and leucopenia (P = 0.005). In contrast, both groups had similarly increased anti-dsDNA (P = 0.78) and decreased complement levels (P = 0.29). In conclusion, DV in patients with SLE identifies a subgroup of a mild disease. The high 'weighted' index attributed to this alteration in the SLEDAI score should therefore be revised.

Validation of the Spanish, Portuguese and French versions of the Lupus Damage Index questionnaire: data from North and South America, Spain and Portugal.

We have previously developed and validated a self-administered questionnaire, modelled after the Systemic Lupus International Collaborating Clinics Damage Index (SDI), the Lupus Damage Index Questionnaire (LDIQ), which may allow the ascertainment of this construct in systemic lupus erythematosus (SLE) patients followed in the community and thus expand observations made about damage. We have now translated, back-translated and adapted the LDIQ to Spanish, Portuguese and French and applied it to patients followed at academic and non-academic centres in North and South America, Portugal and Spain while their physicians scored the SDI. A total of 887 patients (659 Spanish-speaking, 140 Portuguese-speaking and 80 French-speaking patients) and 40 physicians participated. Overall, patients scored all LDIQ versions higher than their physicians (total score and all domains). Infrequent manifestations had less optimal clinimetric properties but overall agreement was more than 95% for the majority of items. Higher correlations were observed among the Spanish-speaking patients than the Portuguese-speaking and French-speaking patients; further adjustments may be needed before the Portuguese and French versions of the LDIQ are applied in community-based studies. The relationship between the LDIQ and other outcome parameters is currently being investigated in a different patient sample.

Testicular Sertoli cell function in male systemic lupus erythematosus.

OBJECTIVE: To assess the testicular Sertoli cell function in male SLE patients. METHODS: Thirty-four consecutive patients were prospectively selected to evaluate serum inhibin B. Clinical features, treatment, semen analysis, urological evaluation, testicular ultrasound, hormones and anti-sperm antibodies were determined. RESULTS: Patients were subdivided into two groups: low serum inhibin B (Group 1, n = 8) and normal levels (Group 2, n = 26). The median sperm concentration (P = 0.024), total sperm count (P = 0.023) and total motile sperm count (P = 0.025) were lower in Group 1. Inhibin B levels were positively correlated with sperm concentration (r = 0.343), total motile sperm count (r = 0.357), and negatively correlated with follicule-stimulating hormone (FSH) (r = 0.699) and luteinizing hormone (r = 0.397). The median serum inhibin B was lower in SLE patients treated with intravenous cyclophosphamide (IVCYC) compared with those without this therapy (P = 0.031). Further evaluation of the 26 SLE patients with normal inhibin B and FSH levels revealed that medians of inhibin B/FSH ratio were lower in SLE patients with oligozoospermia compared with normozoospermia (P = 0.004). This ratio was also lower in SLE patients treated with IVCYC than those without this therapy (P = 0.04). In contrast, inhibin B serum level alone did not discriminate the later group of patients (P = 0.12). CONCLUSIONS: This is the first study to identify a high frequency of testicular Sertoli cell dysfunction in male SLE associated with semen abnormalities. Further prospective studies are necessary to determine if inhibin levels and inhibin B/FSH ratio will be an earlier and useful marker of IVCYC toxicity in these patients.

[Primary erythromelalgia]. / Eritromelalgia primária.

Erythromelalgia is a rare disease characterized by intense erythema, burning pain and increased temperature in the distal of the extremities. Primary forms and secondary forms have been described, most commonly with essential thrombocythemia and policythemia vera. The authors describe a fifteen year old patient with primary erythromelalgia and discuss the pathogenic, clinical and therapeutic features of this disease.

[Low complement levels in urticarial vasculitis as first manifestation of systemic lupus erythematosus]. / Vasculite urticariforme hipocomplementêmica como primeira manifestação do lúpus eritematoso sistêmico.

Hypocomplementaemic urticarial vasculitis syndrome is a leukocytoclastic vasculitis characterized by urticarial lesions, associated with fever, arthralgias, arthritis and abdominal pain. Other systemic manifestations include glomerulonephritis, uveitis, episcleritis, chronic obstructive pulmonary disease and neurological abnormalities. Some case associated with systemic lupus erythematosus have been described and SLE diagnosis was made by previous or concomitant diagnostic criteria before onset of urticarial vasculitis. Urticarial vasculitis prior to SLE diagnosis is rare. The development of anti-Ro/SS-A antibody for the diagnosis of SLE is emphasized. The authors alert to the importance of periodically searching for this marker in patients with urticarial vasculitis.

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.