Clues for Previously Undiagnosed Connective Tissue Disease in Patients With Trigeminal Neuralgia

Background: Connective tissue diseases (CTD) may be associated with idiopathic trigeminal neuralgia (TN). The prevalence and diagnostic implications of this association are, however, not well established. Objectives: The objective of this study was to evaluate, in TN patients, if rheumatologic clinical and laboratory findings could contribute to the early diagnosis of rheumatic diseases. Methods: Forty-six consecutive TN patients, 67% female, mean disease duration 8.78 +/- 7.25 years, and 47 controls were initially interviewed using a standard questionnaire based on common signs/symptoms of systemic lupus erythematosus, Sjogren syndrome, mixed CTD, and systemic sclerosis. Autoantibodies were detected by standard techniques. Those with rheumatologic complaints or positive autoantibodies were referred to the Rheumatology Outpatient Clinic for a more detailed evaluation. Secondary causes of TN were excluded. Results: The frequency of Raynaud phenomenon (P = 0.026) and ANA reactivity (P = 0.04) were significantly higher in TN patients compared with controls. Fourteen TN patients were ANA positive. Seven of them reported concomitant rheumatic complaints, and interestingly, diffuse CTD was diagnosed in 4 (57%) of these patients: 1 systemic lupus erythematosus; 2 Sjogren syndrome; and 1 undifferentiated disease with scleritis and positive parotid scintigraphy. In all cases, TN preceded by at least 10 months the rheumatologic signs/symptoms. Moreover, these 4 TN patients with CTD had a higher frequency of sicca symptoms (P = 0.001) and higher titers of ANA (>= 1:320) (P = 0.006) than the remaining 42 TN patients without CTD diagnoses. Sixteen patients had isolated laboratory or clinical abnormalities, and none of them had CTD diagnoses. Conclusions: The concomitant presence of sicca symptoms and high titer ANA are clues for the early investigation of rheumatic diseases in TN patients.

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.

Spontaneous tendon rupture in systemic lupus erythematosus: association with Jaccoud`s arthropathy

Tendon rupture has rarely been described in patients with systemic lupus erythematosus. From observation of three cases of Jaccoud`s arthropathy with tendon rupture, and considering that this arthropathy is more related to an inflammatory process of the tendon sheath than to synovitis per se, the intention of this study was to review the cases of tendon rupture in patients with systemic lupus erythematosus, in the hope of determining the frequency of Jaccoud`s arthropathy associated with this complication. Systematic review using MEDLINE, Scielo and LILACS databases (1966 to 2009) and the following keywords: systemic lupus erythematosus, tendon rupture, Jaccoud`s arthropathy. Secondary references were additionally obtained. Additionally, three Brazilian systemic lupus erythematosus patients who developed tendon rupture are described. Only 40 articles obtained fulfilled the previously established criteria. They were all case reports; the number of cases reported was 52 which, together with the three cases presented herein add up to 55 cases. Forty-six patients were women aged between 19 and 71 years, with a mean age of 40.1 +/- 12.4 years, and the average duration of the disease was 10 years. The most frequently observed rupture sites were the patellar and Achilles` tendons. While almost all patients described were on various doses of corticosteroids, 16 patients concomitantly had Jaccoud`s arthropathy (29%). In conclusion, the association between Jaccoud`s arthropathy and tendon rupture in systemic lupus erythematosus has been underestimated. As almost one-third of the systemic lupus erythematosus patients with tendon rupture also have Jaccoud`s arthropathy, this arthropathy may be recognized as risk marker for tendon rupture. Lupus (2010) 19, 247-254.

Effect of phototherapy with low intensity laser on local and systemic immunomodulation following focal brain damage in rat

Brain injury is responsible for significant morbidity and mortality in trauma patients, but controversy still exists over therapeutic management for these patients. The objective of this study was to analyze the effect of phototherapy with low intensity lasers on local and systemic immunomodulation following cryogenic brain injury. Laser phototherapy was applied (or not-controls) immediately after cryogenic brain injury performed in 51 adult male Wistar rats. The animals were irradiated twice (3 h interval), with continuous diode laser (gallium-aluminum-arsenide (GaAlAs), 780 nm, or indium-gallium-aluminum-phosphide (InGaAlP), 660 nm) in two points and contact mode, 40 mW, spot size 0.042 cm(2), 3 J/cm(2) and 5 J/cm(2) (3 s and 5 s, respectively). The experimental groups were: Control (non-irradiated), RL3 (visible red laser/ 3 J/cm(2)), RL5 (visible red laser/5 J/cm(2)), IRL3 (infrared laser/ 3 J/cm(2)), IRL5 (infrared laser/5 J/cm(2)). The production of interleukin-1IL-1 beta (IL-1 beta), interleukin6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-alpha) was analyzed by enzyme immunoassay technique (ELISA) test in brain and blood samples. The IL-1 beta concentration in brain of the control group ;was significantly reduced in 24 h (p < 0.01). This reduction was also observed in the RL5 and IRL3 groups. The TNF-alpha and IL-6 concentrations increased significantly (p < 0.01 and p < 0.05, respectively) in the blood of all groups, except by the IRL3 group. The IL-6 levels in RL3 group were significantly smaller than in control group in both experimental times. IL-10 concentration was maintained stable in all groups in brain and blood. Under the conditions of this study, it is possible to conclude that the laser phototherapy can affect TNF-alpha, IL-1 beta and IL-6 levels in the brain and in circulation in the first 24 h following cryogenic brain injury. (C) 2009 Elsevier B.V. All rights reserved.

Ovarian necrotizing vasculitis in a patient with lupus

Ovarian vasculitis is a rare complication seen in the reproductive system and has been described in only one patient with lupus and a few patients with other rheumatic conditions (polyarteritis nodosa, giant cell arteritis, scleroderma). Three additional cases following gynecology procedures have also been reported. We report the second case of a patient with systemic lupus erythematosus, who developed ovarian vasculitis. The diagnosis was made at the age of 12 and confirmed by laparoscopy and histopathology in the presence of disease activity. She experienced late menarche at the age of 16, and she experienced a good clinical evolution after disease treatment with regular menstrual cycles and normal levels of sexual hormones. Lupus (2009) 18, 1313-1315.

Vaccination, atherosclerosis and systemic lupus erythematosus

Atherosclerosis is an inflammatory disease, leading to the formation of pro-inflammatory and pro-oxidative lipids that generate an immune response. Several antigens have been shown to activate the immune response and affect the development of atherogenesis. Systemic lupus erythematosus is an autoimmune and inflammatory disease strongly associated with premature development of atherosclerotic plaques. Modulation of the immune system could represent a useful approach to prevent and/or treat atherosclerosis. A vaccination-based approach might be a useful, effective tool in the modern arsenal of cardiovascular therapies and could be used on a large scale at a low cost. In non-systemic lupus erythematosus populations, vaccines against oxidized low-density lipoprotein, beta-2-glycoprotein I, heat shock proteins, lipoproteins, cholesterol, molecules involved in cholesterol metabolism, and other molecules (CD99, vascular endothelial growth factor-receptor, and interleukin-2) have been tested, with promising results. However, there are no studies of vaccination against atherosclerosis in systemic lupus erythematosus. Lupus (2009) 18, 1209-1212.

A systemic parvo-like virus in the freshwater crayfish Cherax destructor

Systemic Cowdry Type A inclusions (CAs) were observed in a moribund Cherax destructor collected at an aquaculture farm in South Australia. Inclusions were most common in the gills and were associated with multifocal necrosis of the main gill axis and lamellae. The hepatopancreas was necrotic; however, only one CA was observed in the interstitial tissues. CAs were associated with necrosis in the abdominal and gut musculature. CAs were also observed in the spongy connective tissues and the epicardium. Empty capsids (17.5 +/- 0.5 nm) and microfilaments were most commonly observed within these inclusions by transmission electron microscopy. Complete icosahedral viral particles (20.8 +/- 1.2 nm) were difficult to distinguish within the viroplasm, but were visualised better in aggregates between the viroplasm and the inner nuclear membrane. The nucleolus was closely associated with the developing viroplasm, and was hypertrophied and segregated into its fibrillar and granular components. The virus was named Cherax destructor systemic parvo-like virus (CdSPV) on the basis of its histopathology, cytopathology and morphology. CdSPV is the first systemic virus described in a freshwater crayfish.

Azithromycin does not prevent six-month myointimal proliferation but attenuates the transient systemic inflammation occurring after coronary stenting

Stent implantation produces a systemic increase of inflammatory markers that correlates with Chlamydophila pneumoniae infection in atherosclerotic plaque. We performed a clinical intervention study to investigate the effect of antibiotic treatment on 6-month follow-up angiographic minimal luminal diameter after stenting. Ninety patients were randomly assigned to oral azithromycin or placebo in a double-blinded and randomized fashion. Medication was initiated 2 weeks before a pre-scheduled stenting procedure and maintained 12 weeks thereafter. Angiographic outcomes were evaluated by a six-month follow-up angiography and laboratorial parameters were accessed by blood sampling 2 weeks before stenting, within the first 24 h after procedure and additional samples after four weeks and 6 months. Minimal luminal diameter (1.76 +/- A 0.56 mm Vs. 1.70 +/- A 0.86 mm; P = 0.7), restenosis rate, diameter stenosis, late loss, and binary restenosis rates were comparable in placebo and azithromycin group in the 6 months follow-up. Serum levels of C-reactive protein presented a three fold significant increase in the control group one day after stenting but did not change in the azithromycin group (8.5 [3.0;16.4] Vs. 2.9 [1.7;6.6]-median [25;75 percentile] P < 0.01). Azithromycin does not improve late angiographic outcomes but attenuates the elevation of C-reactive protein levels after stenting, indicating an anti-inflammatory effect.

Effects of bilateral adrenalectomy on systemic kainate-induced activation of the nucleus of the solitary tract. Regulation of blood pressure and local neurotransmitters

Glutamatergic transmission through metabotropic and ionotropic receptors, including kainate receptors, plays an important role in the nucleus of the solitary tract (NTS) functions. Glutamate system may interact with several other neurotransmitter systems which might also be influenced by steroid hormones. In the present study we analyzed the ability of systemic kainate to stimulate rat NTS neurons, which was evaluated by c-Fos as a marker of neuronal activation, and also to change the levels of NTS neurotransmitters such as GABA, NPY, CGRP, GAL, NT and NO by means of quantitative immunohistichemistry combined with image analysis. The analysis was also performed in adrenalectomized and kainate stimulated rats in order to evaluate a possible role of adrenal hormones on NTS neurotransmission. Male Wistar rats (3 month-old) were used in the present study. A group of 15 rats was submitted either to bilateral adrenalectomy or sham operation. Forty-eight hours after the surgeries, adrenalectomized rats received a single intraperitoneal injection of kainate (12 mg/kg) and the sham-operated rats were injected either with saline or kainate and sacrificed 8 hours later. The same experimental design was applied in a group of rats in order to register the arterial blood pressure. Systemic kainate decreased the basal values of mean arterial blood pressure (35%) and heart rate (22%) of sham-operated rats, reduction that were maintained in adrenalectomized rats. Kainate triggered a marked elevation of c-Fos positive neurons in the NTS which was 54% counteracted by adrenalectomy. The kainate activated NTS showed changes in the immunoreactive levels of GABA (143% of elevation) and NPY (36% of decrease), which were not modified by previous ablation of adrenal glands. Modulation in the levels of CGRP, GAL and NT immunoreactivities were only observed after kainate in the adrenalectomized rats. Treatments did not alter NOS labeling. It is possible that modulatory function among neurotransmitter systems in the NTS might be influenced by steroid hormones and the implications for central regulation of blood pressure or other visceral regulatory mechanisms control should be further investigated.

Anti-C1q Antibodies in Juvenile-Onset Systemic Lupus Erythematosus

The objective of this study was to evaluate the presence of anti-C1q antibodies Hospital Israelita Albert Einstein Research Institute, Sao Paulo, Brazil in 67 juvenile Systemic lupus erythematosus (JSLE) patients and 26 healthy controls and to assess the association of these antibodies with disease activity, nephritis, and presence of anti-double-stranded (ds)DNA. Anti-C1q antibodies were detected by ELISA. A higher frequency of anti-C1q antibodies was observed in JSLE patients compared to controls (20% vs. 0%, P = 0.016). Specificity of these antibodies was 100% [95% confidence interval (CI) 86.7-100%] and sensitivity was 19.4% (95% CI 10.7-30.8%) for a lupus diagnosis. The median anti-C1q antibodies was higher in JSLE patients compared to controls [median (range) 9.4 (5.5-127) vs. 7.3 (5-20) units, P = 0.004]. Remarkably, a positive Spearman`s coefficient was found between anti-dsDNA and anti-C1q units (r = 0.42, P = 0.0004, 95% CI 0.19-0.60). Our results confirm a low frequency of anti-C1q antibody in our lupus populations, but the presence of anti-C1q antibodies appears to be a good marker for JSLE diagnosis.

Understanding systemic lupus erythematosus physiopathology in the light of primary immunodeficiencies

Introduction Associations between systemic lupus erythematosus (SLE) and primary immunodeficiencies (PIDs) were analyzed to gain insight into the physiopathology of SLE. Some PIDs have been consistently associated with SLE or lupus-like manifestations: (a) homozygous deficiencies of the early components of the classical complement pathway in the following decreasing order: in C1q, 93% of affected patients developed SLE; in C4, 75%; in C1r/s, 57%; and in C2, up to 25%; (b) female carriers of X-linked chronic granulomatous disease allele; and (c) IgA deficiency, present in around 5% of juvenile SLE. Discussion In the first two groups, disturbances of cellular waste-disposal have been proposed as the main mechanisms of pathogenesis. On the other hand and very interestingly, there are PIDs systematically associated with several autoimmune manifestations in which SLE has not been described, such as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), immunedys-regulation polyendocrinopathy enteropathy X-linked (IPEX), and autoinumme lymphoproliferative syndrome (ALPS), suggesting that mechanisms considered as critical players for induction and maintenance of tolerance to autoantigens, such as (1) AME-mediated thymic negative selection of lymphocytes, (2) Foxp3+ regulatory T cell-mediated peripheral tolerance, and (3) deletion of auto-reactive lymphocytes by Fas-mediated apoptosis, could not be relevant in SLE physiopathology. The non-description of SLE and neither the most characteristic SLE clinical features among patients with agammaglobulinemia are also interesting observations, which reinforce the essential role of B lymphocytes and antibodies for SLE pathogenesis. Conclusion Therefore, monogenic PIDs represent unique and not fully explored human models for unraveling components of the conundrum represented by the physiopathology of SLE, a prototypical polygenic disease.

Mucosal and systemic anti-GAG immunity induced by neonatal immunization with HIV LAMP/gag DNA vaccine in mice

Vaccines capable of inducing mucosal immunity in early postnatal life until adulthood, protecting early sexual initiation, should be considered as strategies to vaccination against HIV. The HIV-1 GAG protein as a chimera with the lysosome-associated membrane protein (LAMP/gag), encoded by a DNA vaccine, is targeted to the endosomal/lysosomal compartment that contains class II MHC molecules and has been shown to be immunogenic in adult mice. Assuming that one such strategy could help to overcome the immunological immaturity in the early postnatal period, we have evaluated the systemic and mucosal immunogenicity of LAMP/gag immunization in neonatal mice. Intranasal immunization with LAMP/gag vaccine induced higher levels of sIgA and IgG anti-GAG antibodies in intestinal washes than did the gag vaccine. The combination of ID injections and the IN protocol with the chimeric vaccine promoted the increase of Ab levels in sera. Both vaccines induced splenic IFN-gamma- secreting cells against GAG peptide pools, as well as in vivo cytotoxic T lymphocyte (CTL) function, and increased the percentage of CD8+ T cells to the immunodominant class I peptide in gut and spleen. However, only the chimeric vaccine was able to enhance Th1/Th2 cytokine secretion in response to class II GAG peptide and to enhance IL-4-secreting cells against GAG peptides and p24 protein stimuli. Long-lasting humoral and cellular responses were detected until adult age, following neonatal immunization with the chimeric vaccine. The LAMP/gag vaccination was able to induce potent GAG-specific T and B cell immune responses in early life which are essential to elicit sustained and long-lasting mucosal and systemic humoral response. (C) 2010 Elsevier GmbH. All rights reserved.

Systemic lupus erythematosus exhibits a dynamic and continuum spectrum of effector/regulatory T cells

Objective: The identification of regulatory T cells (Treg cells) as CD4(+)CD25(high) cells may be upset by the increased frequency of activated effector T cells (Teff cells) in inflammatory diseases such as systemic lupus erythematosus (SLE). This study aimed to evaluate the frequency of T-cell subsets according to the expression of CD25 and CD127 in active (A-SLE) and inactive SLE (I-SLE). Methods: Peripheral blood mononuclear cells (PBMCs) from 26 A-SLE patients (SLE Disease Activity Index (SLEDAI) = 10.17 +/- 3.7), 31 I-SLE patients (SLEDAI = 0), and 26 healthy controls (HC) were analysed by multicolour flow. cytometry. Results: CD25(high) cell frequency was increased in A-SLE (5.2 +/- 5.7%) compared to I-SLE (3.4 +/- 3.4%) and HC (1.73 +/- 0.8%) (p < 0.01). However, the percentage of FoxP3(+) cells in the CD25(high) subset was decreased in A-SLE (24.6 +/- 16.4%) compared to I-SLE (33.7 +/- 16) and HC (45 +/- 25.1%) (p < 0.01). This was partly due to the increased frequency of Teff cells (CD25(high)CD127(+)FoxP3(empty set)) in A-SLE (10.7 +/- 7.3%) compared to I-SLE (8.5 +/- 6.5) and HC (6.1 +/- 1.8%) (p = 0.02). Hence the frequency of Treg cells (CD25(+/high)CD127(low/empty set)FoxP3(+)) was equivalent in A-SLE (1.4 +/- 0.8%), I-SLE (1.37 +/- 1.0%), and HC (1.13 +/- 0.59%) (p = 0.42). A-SLE presented an increased frequency of CD25(+)CD127(+)FoxP3(+) and CD25(empty set)FoxP3(+)CD127(low/empty set) T cells, which may represent intermediate phenotypes between Treg and Teff cells. Conclusions: The present study has provided data supporting normal Treg cell frequency in A-SLE and I-SLE as well as increased frequency of Teff cells in A-SLE. This scenario reflects a Treg/Teff ratio imbalance that may favour the inflammatory phenotype of the disease. In addition, the increased frequency of T cells with putative intermediate phenotypes may be compatible with a highly dynamic immune system in SLE.

Irreversible blindness in juvenile systemic lupus erythematosus

Blindness caused by severe vasculitis or uveitis is rare in juvenile systemic lupus erythematosus (JSLE) patients. In a 27-year period, 5367 patients were followed at our Paediatric Rheumatology Division and 263 (4.9%) patients had JSLE (American College of Rheumatology criteria). Of note, two (0.8%) of them had irreversible blindness. One of them presented with cutaneous vasculitis and malar rash, associated with pain and redness in both eyes, impairment of visual acuity due to iridocyclitis and severe retinal vasculitis with haemorrhage. Another patient had peripheral polyneuropathy of the four limbs and received immunosuppressive drugs. Three weeks later, she developed diffuse herpes zoster associated with acute blindness due to bilateral retinal necrotizing vasculitis compatible with varicella zoster virus ocular infection. Despite prompt treatment, both patients suffered rapid irreversible blindness. In conclusion, irreversible blindness due to retinal vasculitis and/or uveitis is a rare and severe lupus manifestation, particularly associated with disease activity and viral infection. Lupus (2011) 20, 95-97.