Lesions In Systemic Lupus Erythematosus Research Articles

Dermatomyositis: A Clinicopathological Study of 40 Patients

The histopathology of cutaneous lesions of dermatomyositis (DM) may be indistinguishable from acute cutaneous lesions of systemic lupus erythematosus (SLE). Misreported or incomplete clinical information may result in a clinicopathologic discrepancy and a delay in making a correct diagnosis of DM. The aim of this study was to systematically characterize the histopathologic findings of cutaneous lesions of DM and to determine if skin biopsy specimens of DM and SLE could be distinguished by light microscopic examination. Biopsies from 40 patients diagnosed with DM at the Wake Forest University School of Medicine from 1994 to 1999 were reviewed. The histological features by light microscopy were graded in a systematic fashion. We then assessed whether the cutaneous pathological changes of DM could be distinguished from those of SLE. Ten biopsy specimens each of DM and SLE (matched for anatomical site and lesion morphology) were randomized. Histological grading was performed in a blinded fashion, as was a histopathologic diagnosis (DM versus SLE). The most consistent histological findings of DM included increased dermal mucin, vacuolar alteration of the basal cell layer, and mild-to-moderate mononuclear cell inflammatory infiltrates. Our results show that the histological grading of SLE skin biopsies was nearly identical to that of DM. The correct histopathologic diagnosis of DM or SLE was made in 11 of the 20 skin biopsies without clinical information. Despite the limitations of our small sample size, these findings suggest that acute cutaneous lesions of SLE cannot be distinguished from DM. Clinicopathologic correlation is important for making a diagnosis of DM or SLE.

Quantitative magnetic resonance imaging analyses and clinical significance of hyperintense white matter lesions in systemic lupus erythematosus patients

To analyze the clinical significance of hyperintense white matter (WM) lesions in both symptomatic and asymptomatic systemic lupus erythematosus (SLE) patients. We studied 120 consecutive SLE patients and 44 healthy volunteers. Fluid attenuated inversion recovery and T2-weighted magnetic resonance images (MRI) were used for visual and semiautomatic volumetric measurements. At baseline, 61 MRI were normal and 59 had hyperintense WM lesions. Mean volumes of WM lesions were 96.14 (SD = 85.14) mm(3) in T2 weighted and 197.2 (161.13) mm(3) in FLAIR images. The volume of WM lesions was associated with age (r = 0.45; p = 0.01), total corticosteroid dose (r = 0.53; p = 0.001), and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index scores (r = 0.55; p = 0.002). After a median follow-up time of 24 months (SD = 2.3; range = 12-28 months), 20 patients had still normal MRIs, 30 patients had stable MRI findings, and 30 had new WM lesions. Predictors for new or increased WM lesions were past central nervous system manifestations (p = 0.001; OR = 12.2; 95% CI = 3.5-21.2), antiphospholipid antibodies (p = 0.003; OR = 6.9; 95% CI = 2.1-15.3); Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index scores (p = 0.002; OR = 7.2; 95% CI = 1.4-17.8) and higher dose of total corticosteroid dose (p = 0.01; OR = 2.4; 95% CI = 1.4-6.7). Small hyperintense WM lesions in SLE are associated with central nervous system symptoms and antiphospholipid antibodies, and progress over time in patients with more severe SLE. Therefore, in the context of SLE, these lesions are likely consequences of central nervous system damage and not mere incidental finding.

Envolvimento mucocutâneo no lúpus eritematoso sistêmico e sua associação com auto-anticorpos

FUNDAMENTOS: As manifestações mucocutâneas são comuns em pacientes com lúpus eritematoso sistêmico,podendo assumir espectro bastante variado. OBJETIVOS: Estudar a prevalência de lesões mucocutâneas no lúpus eritematoso sistêmico e verificar suas possíveis associações com auto-anticorpos. MÉTODOS: Submeteram-se 113 pacientes com lúpus eritematoso sistêmico a anamnese dirigida para envolvimento mucocutâneo e exame ectoscópico. Seus prontuários foram examinados para dados demográficos e perfil de auto-anticorpos como anti-Ro/SS-A, antiLa/SS-B, antiDNA e anti-Sm. RESULTADOS: Os achados mais prevalentes foram os de fotossensibilidade (83,1%), alopecia (65,4%), eritema em vespertílio(54,3%) e fenômeno de Raynaud (53,9%). Em 46,9% existia algum tipo de queixa mucocutânea no momento do diagnóstico da doença. Encontrou-se associação entre a ocorrência de lúpus cutâneo subagudo e presença do anti-Ro/SSA (p = 0,03), do fenômeno de Raynaud e o anticorpo anti-Sm (p = 0,05) e do eritema em vespertílio e o anticorpo antiDNA (p = 0,03). CONCLUSÃO: Os achados mucocutâneos estão presentes na maioria dos pacientes com lúpus sistêmico, existindo em aproximadamente metade deles no momento do diagnóstico. As lesões mais comuns foram fotossensibilidade, alopecia, eritema em vespertílio e fenômeno de Raynaud.

Systemic Lupus Erythematosus

Systemic lupus erythematosus has many guises, but the unifying feature is the presence of antibodies against double-stranded DNA in almost all patients. This review provides data that show that such autoantibodies cause the renal lesions of systemic lupus erythematosus, and it emphasizes the importance of histones, histone fragments, and other nuclear autoantigens.

Neurometabolic changes in normal white matter may predict appearance of hyperintense lesions in systemic lupus erythematosus

To determine if neurometabolic changes in the white matter (WM) of systemic lupus erythematosus (SLE) patients may predict the appearance of small hyperintense lesions on T2-weighted magnetic resonance imaging (MRI) inside the magnetic resonance spectroscopy (MRS) region of interest (ROI). We included 30 SLE patients and 23 controls. We performed single voxel proton MRS over the superior-posterior region of the corpus callosum. We measured signals from N-acetyl-compounds (NAA), choline (Cho) and creatine-phosphocreatin (Cr) and determined NAA/Cr and Cho/Cr ratios. After a minimum of 12 months, MRI and MRS were repeated in all patients and nine volunteers. Twenty patients had normal MRI and 10 patients had MRI hyperintense lesions in the MRS ROI at baseline. All patients had hyperintense lesions in the MRS ROI in follow-up MRIs. All SLE patients had increased Cho/Cr values at both MRS when compared with normal controls (P = 0.001). In addition, there was an increase in Cho/Cr values when patients' baseline and follow-up MRS were compared (P = 0.001). We observed a correlation between Cho/Cr ratios and number of WM lesions (r = 0.69; P = 0.001). Increased Cho/Cr in normal appearing WM may be indicative of future appearance of hyperintense T2-weighted MRI lesions in SLE patients.

Peripheral nervous system lesion syndromes and the mechanisms of their formation in connective tissue diseases

Systemic rheumatological diseases are often accompanied by the development of central and peripheral nervous system pathology. Data providing evidence of the high incidence of peripheral nervous system lesions in systemic lupus erythematosus and systemic scleroderma are presented. These diseases in particular are characterized by polyneuropathies and tunnel syndromes. Our own observations, along with published data, revealed the following major pathogenetic mechanisms of peripheral nervous system lesions in diffuse connective tissue diseases - ischemic, immunological, and metabolic. Consideration of these mechanisms will lead to pathogenetically based treatment and improved therapeutic outcomes.

Laryngeal involvement in a patient with bullous pemphigoid

Laryngeal involvement in a patient with bullous pemphigoid

Is disturbed clearance of apoptotic keratinocytes responsible for UVB-induced inflammatory skin lesions in systemic lupus erythematosus?

Apoptotic cells are thought to play an essential role in the pathogenesis of systemic lupus erythematosus (SLE). We hypothesise that delayed or altered clearance of apoptotic cells after UV irradiation will lead to inflammation in the skin of SLE patients. Fifteen SLE patients and 13 controls were irradiated with two minimal erythemal doses (MEDs) of ultraviolet B light (UVB). Subsequently, skin biopsies were analysed (immuno)histologically, over 10 days, for numbers of apoptotic cells, T cells, macrophages, and deposition of immunoglobulin and complement. Additionally, to compare results with cutaneous lesions of SLE patients, 20 biopsies of lupus erythematosus (LE) skin lesions were analysed morphologically for apoptotic cells and infiltrate. Clearance rate of apoptotic cells after irradiation did not differ between patients and controls. Influx of macrophages in dermal and epidermal layers was significantly increased in patients compared with controls. Five out of 15 patients developed a dermal infiltrate that was associated with increased epidermal influx of T cells and macrophages but not with numbers of apoptotic cells or epidermal deposition of immunoglobulins. Macrophages were ingesting multiple apoptotic bodies. Inflammatory lesions in these patients were localised near accumulations of apoptotic keratinocytes similar as was seen in the majority of LE skin lesions. In vivo clearance rate of apoptotic cells is comparable between SLE patients and controls. However, the presence of inflammatory lesions in the vicinity of apoptotic cells, as observed both in UVB-induced and in LE skin lesions in SLE patients, suggests that these lesions result from an inflammatory clearance of apoptotic cells.

Clofazimine is as effective as chloroquine for the treatment of cutaneous lesions in systemic lupus erythematosus

Clofazimine is as effective as chloroquine for the treatment of cutaneous lesions in systemic lupus erythematosus

Efficacy of topical tacrolimus in the treatment of various cutaneous manifestations of lupus erythematosus

Efficacy of topical tacrolimus in the treatment of various cutaneous manifestations of lupus erythematosus

Increased prevalence of squamous intraepithelial lesions in systemic lupus erythematosus: Association with human papillomavirus infection

To compare the prevalence of abnormal Pap smears in patients with systemic lupus erythematosus (SLE) with that in a large group of healthy controls, and to determine whether SLE itself is an independent risk factor. The association of human papillomavirus (HPV) infection and the use of immunosuppressive agents with abnormal Pap smears in SLE was also assessed. Eighty-five SLE patients participated in this cross-sectional study. A sample of cervical cells was collected from each patient for routine cytologic examination. HPV was typed by restriction and sequencing analysis. A structured questionnaire was administered to the subjects to ascertain the possible behavioral and biologic risk factors associated with cervical atypia. Data on 2,080 healthy female subjects were retrieved for comparison. The mean (+/-SD) age of SLE patients and controls was 42 +/- 9 years and 44 +/- 10 years, respectively. The prevalence of abnormal Pap smears was significantly increased in SLE patients compared with controls (16.5% versus 5.7%). The prevalence of squamous intraepithelial lesions was increased approximately 6-fold in SLE patients (11.8%) compared with controls (2.0%). SLE itself remained an independent risk factor for abnormal Pap smears (odds ratio 3.5, 95% confidence interval 1.8-6.9). The overall prevalence of HPV infection in SLE patients and controls was 11.8% and 7.3%, respectively. However, 10.6% of SLE patients were infected with at least 1 high-risk type of HPV, compared with 4.2% of controls. Multiple infections were also more common in SLE patients than in controls (4.7% versus 1.1%). There were no significant differences in the use of immunosuppressive agents between SLE patients with normal Pap smears and those with abnormal Pap smears. Abnormal Pap smears were more common among SLE patients than controls, even after adjusting for HPV status. SLE-associated immunosuppression increases susceptibility to high-risk HPV infection and multiple HPV infections. The use of immunosuppressant agents was not associated with abnormal Pap smears.

Avaliação do índice de danos permanentes através de SLICC/ACR-DI em pacientes com mais de cinco anos de diagnóstico de lúpus eritematoso sistêmico

to evaluate the frequency of different types of irreversible lesions in systemic lupus erythematosus (SLE) patients with more than five years of disease. ninety female SLE patients with more than five years of disease were evaluated concerning the irreversible damage score using Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for systemic lupus erythematosus (SLICC/ACR/DI). patients mean age was 38 ± 10 years old (60% white). The average time after diagnosis was 128 ± 59 months, the mean number of ACR criteria was 7 ± 1, and the mean SLICC/ACR-DI score was 2 ± 2. Seventy-two percent of patients presented SLICC/ACRDI score > 1. We found a tendency to association between actual older age and presence of damage (p = 0.06). We did not find association between age at time of SLE diagnosis, disease duration or number of ACR criteria and presence of irreversible damage (p > 0.05), but we found a significant association between discoid lesion and presence of damage (p = 0.049) as well as between positive double strand anti-DNA antibody and damage (p = 0.013). Concerning the type of irreversible lesions, we found cardiovascular damage in 21%, dermatological lesions in 21%, musculoskeletal lesions in 17%, gonadal lesions in 16%, neuropsychiatric damage in 13%, eye lesions in 12%, renal lesions in 12%, peripheral vascular lesions in 10%, pulmonary damage in 6%, endocrinological damage in 6% and malignances in 3%. There was no significant association between duration of prednisone use and damage (p = 0.725), however we found a significant association between prednisone cumulative dose and presence of damage (p = 0.013). We found a tendency to association between lower duration of antimalarial drugs and irreversible damage (p = 0.068). irreversible lesions were found in 72% of SLE patients with more than five years of disease. The more prevalent lesions were cardiovascular, dermatological, musculoskeletal and gonadal. The cumulative dose of prednisone showed significant association with presence of damage, suggesting the importance of spare steroid strategies.

Neuropsychological Functioning and Its Relationship to Antiphospholipid Antibodies in Patients With Systemic Lupus Erythematosus

While it is clear that central nervous system (CNS) lesions in systemic lupus erythematosus (SLE) adversely affect cognitive functioning, it is also evident that patients without visible lesions (non-CNS SLE) may also exhibit subtle cognitive impairment. The presence of antiphospholipid antibodies (aPLs) has been proposed as a marker of disease severity and hence should be correlated with neuropsychological dysfunction in this population. The current study compared groups of non-CNS lupus patients who were positive (LA+) or negative (LA-) for aPLs on selected measures of neuropsychological functioning. In addition, we attempted to characterize the pattern of cognitive impairment that is associated with LA status in these patients. No coherent neuropsychological pattern emerged, but LA+ patients performed worse than LA- patients on measures assessing attention, concentration, and visual search, as well as spatial learning and memory.

Cytomegalovirus infection induces expression of 60 KD/Ro antigen on human keratinocytes

To investigate the effect of human cytomegalovirus (CMV) infection on the expression of Ro autoantigen in human keratinocytes, the binding of anti-Ro peptide antibodies (anti-60 KD/Ro, anti-52 KD/Ro and anti-calreticulin) to cultured human keratinocytes was detected by fixed cell enzyme-linked immunoassay (ELISA), immunofluorescence, flow cytometry (FACS) analysis and immunoblotting. There was a significant increase in the binding of anti-60 KD/Ro antibody but not anti-52 KD/Ro or anti-calreticulin antibody to the surface of cultured keratinocytes at 24 h after CMV infection compared with uninfected cells, by ELISA and immunofluorescence. Surface binding of anti-60 KD/Ro was found in 71.2% (+/- 5.5%) of CMV-infected cells compared with 26.2% (+/- 4.1%) of untreated cells (P < 0.05) by FACS analysis. Similar observations were made with a human serum which contained anti-60 KD/Ro antibodies. Immunoblotting was used to analyse total cellular 60 KD/Ro antigen expression in keratinocytes infected with CMV or without infection. No increase in the intensity of the 60 KD band was found in extracts of the CMV-infected cells, suggesting that the 60 KD/Ro antigen is redistributed from the cytoplasm to the cell surface after viral infection. The effects of CMV infection on cell cultures were compared with those of ultraviolet B (UVB) irradiation. The 60 KD/Ro, 52 KD/Ro and calreticulin were all induced on the UVB-irradiated cell surface but not significant synergistic effect of UVB and CMV was found. This study provides evidence that CMV infection induced 60 KD/Ro antigen expression on the surface of human keratinocytes, suggesting that CMV may play a role in development of skin lesions in systemic lupus erythematosus (SLE).

Magnetic resonance imaging in systemic lupus erythematosus patients without a history of neuropsychiatric lupus erythematosus

To determine the prevalence of magnetic resonance imaging (MRI) lesions in systemic lupus erythematosus (SLE) patients without a history of neuropsychiatric symptoms and to correlate any MRI abnormalities with the patient's other disease manifestations or treatment. Prospective study of 32 consecutive patients with SLE without a history of neuropsychiatric symptoms, from inpatient and outpatient rheumatology services, who underwent MRI scan during a 3-year period. Five patients had MRI abnormalities consisting of white matter lesions or periventricular hyperintensities; this is similar to the prevalence of these abnormalities in the general population. The prevalence of silent brain MRI abnormalities is not increased in SLE patients who do not have a history of neuropsychiatric manifestations.

IgG Subclass Deposits in Glomeruli of Lupus and Nonlupus Membranous Nephropathies

Membranous nephropathy (MN) accounts for approximately 10% of all renal lesions of systemic lupus erythematosus (SLE). These membranous lesions often have a clinical presentation similar to that of idiopathic MN and may present before SLE is apparent clinically. However, unlike proliferative lesions of lupus nephritis (LN), membranous LN often does not show a "full-house" pattern of glomerular immunoglobulin and complement (C) deposits by immunofluorescence (IF); only nine of 14 such lesions that we examined stained for all of the following: IgG, IgA, IgM, C3, and C1q. Iskandar et al reported in 1992 that most cases of diffuse proliferative LN showed IgG3 as the major IgG subclass present in glomerular deposits; by contrast, IgG4 predominated in six of seven cases of MN of unspecified etiology. If IgG subclass deposition is similar in membranous and proliferative lesions of LN, then IF staining for IgG3 and IgG4 may be helpful in distinguishing lupus from nonlupus lesions in patients with MN who are lacking a firm diagnosis of SLE. We therefore stained cryostat sections of renal biopsies from 14 patients with SLE and MN (without a proliferative component; World Health Organization [WHO] classes Va and Vb) and 28 non-SLE patients with MN for IgG subclasses by direct IF; the observer was blind to the diagnosis for each case until all were read. The intensity of glomerular staining was graded on a 0 to 4+ scale with increments of 0.5+.(ABSTRACT TRUNCATED AT 250 WORDS)

Thalidomide for cutaneous lesions of systemic lupus erythematosus

Thalidomide for cutaneous lesions of systemic lupus erythematosus

Oral lesions in systemic lupus erythematosus: Do ulcerative lesions represent a necrotizing vasculitis?

It has been suggested that oral lesions in patients with systemic lupus erythematosus (SLE) may be grouped clinically as erythema, discoid lesions, or oral ulcerations. Oral ulcerations have been said to foretell a severe systemic disease flare and the proposal that oral ulcers represent a mucosal vasculitis has been suggested to explain this hypothesis. Our objective was to test the hypothesis that oral ulcers in patients with SLE result from vasculitis. We studied 10 patients with American College of Rheumatology (ACR) criteria for a diagnosis of SLE who had oral lesions of lupus (six prospectively and four retrospectively) clinically and by routine and immunofluorescence microscopy. Biopsy specimens were reviewed in a single-blinded fashion. In our patients, no oral lesion, regardless of morphology, demonstrated vasculitis histologically. All lesions demonstrated an interface mucositis. Our data strongly contradict the hypothesis that leukocytoclastic vasculitis explains a possible unproven correlation between oral ulceration and disease flares in patients with SLE.

Anti-DNA Idiotypes Deposited in Renal Glomeruli of Patients With Lupus Nephritis

Idiotypes (Id) of human anti-DNA antibodies, designated as O-81 Id, were specifically detected on the immune deposits of renal glomeruli in 46% of patients with lupus nephritis. Id-binding to anti-Id antibodies was blocked by free O-81 Id and to some extent by free DNA. DNase or acid buffer treatment failed to reveal new Id determinants on the deposits. O-81 Id and NE-1 Id activity were also detected on the renal eluate-derived IgG, but not IgM from the autopsy cases with lupus nephritis. The incidences of O-81 Id were not associated with histological features in the glomeruli, but the distribution patterns were similar to those of IgG deposits. Our study also showed that 65% to 70% of patients with IgG deposits either in the subendothelium or in the subepithelial area of the glomerular basement membrane (GBM) showed positive tests for O-81 Id. It was also noted that most patients with massive proteinuria had O-81 Id in their glomeruli. It is concluded that O-81 Id deposits are relatively specific for active lupus nephritis and that immunofluorescence studies using anti-Id antibodies may be clinically useful for specifying the renal lesions of systemic lupus erythematosus (SLE).

Lupus Nephritis in Autoimmune‐prone NZBxNZW F1 Mice and Mechanisms of Transition of the Glomerular Lesions

The pattern of renal glomerular lesions in systemic lupus erythematosus (SLE)-prone NZB x NZW (B/W) F1 mice shows an age-associated transition, as is often seen in human lupus nephritis during the clinical course of the disease. Observations revealed that the earliest lesions were confined to the mesangium associated mainly with IgM deposits, and to a lesser degree with IgG. In mice over 5 months of age, the lesions extended gradually to the capillary wall with fine granular subepithelial deposits of IgG, but not of IgM. The ultimate pattern of the glomerular lesion was one of diffuse proliferation with diffusely distributed deposits of both IgG and IgM in the mesangium and along the capillary wall. Even at this stage, subepithelial deposits were composed of IgG, but not of IgM. The pattern of glomerular deposits of endogenous retroviral envelope glycoprotein gp70, which is highly anionic, virtually coincided with that of IgG. Taking these findings collectively, it is suggested that the progression of glomerular lesions in B/W F1 mice depends largely on the age-associated appearance of retroviral gp70-IgG anti-gp70 immune complexes in the circulation and their deposition along peripheral subepithelial, and eventually subendothelial areas.