bluuebunny/crossref_metadata_2025 huggingface dataset:
Intramedullary tuberculosis manifested as Brown ‐ Sequard syndrome in a patient with systemic lupuserythematosus
Authors: Kim Wan-Uk , Shim Byoung-Yong , Min Jun-Ki , Hong Yeon-Sik , Park Sung-Hwan , Cho Chul-Soo , Park Chun-Kun , Kim Ho-Youn
Published: November 2003

A 25-year-old girl presented with progressive deterioration of right side weakness with decreased sensation on the left trunk. She had been treated with high dose steroid due to autoimmune thrombocytopenia for 2 months. Clinical, laboratory and immunologic studies revealed that she had systemic lupus erythematosus (SLE), MRI of spinal cord showed marginal contrast enhancing and fluid containing mass in the cord of the C5-6 level, suggesting intramedullary abcess. She underwent surgery of mass removal with biopsy. The pathologic findings from cord tissues revealed numerous acid fast bacilli (AFB) in necrotic tissues. After surgery and anti-tuberculous treatment, her neurologic symptoms were markedly improved with restoration of right side motor weakness. To our knowledge, this is the first case report of intramedullary tuberculosis in a patient with SLE. Since intramedullary tuberculosis may sometimes mimic neurologic complication of SLE itself, it may pose diagnostic and therapeutic confusion for clinicians. We report a case of spinal cord tuberculosis affecting C5, 6 level which was manifested as Brown ‐ Sequard syndrome in a patient with SLE.
Clinical outcome and predictors of disease evolution in patients with incomplete lupus erythematosus
Authors: Vila Lm , Mayor Am , Valent Ah , Garc M , Vila S
Published: November 2003

To determine the outcome and identify risk factors for evolution into systemic lupus erythematosus (SLE) in a population of incomplete lupus erythematosus (ILE) patients, we studied the clinical and serologic manifestations in a cohort of 87 ILE patients. ILE patients had at least one but less than four of the American College of Rheumatology (ACR) classification criteria of SLE and did not present distinctive clinical features or meet classification criteria of other connective tissue diseases. The patients that remained with ILE were compared with patients that evolved into SLE and with a cohort of 94 SLE patients. The mean disease duration and follow up of ILE patients were 4.44.1 and 2.2 2.4 years respectively. Eight patients evolved into SLE, but none presented major organ damage. At baseline, patients that remained with ILE were less likely to have photosensitivity, elevated anti-dsDNA and decreased C3 complement than patients that evolved into SLE. At the end of the study, malar rash and oral ulcerations were also less frequent in the ILE group. Compared with all SLE cases, ILE patients were less likely to have photosensitivity, malar rash, oral ulcers, Raynaud's phenomenon, arthritis, low C3, low C4, positive anti-dsDNA, anti-Sm, anti-RNP, anti-Ro and anti-La antibodies at baseline. Hazard analyses showed that malar rash, oral ulcers, elevated anti-dsDNA and decreased C4 were associated with SLE occurrence. In conclusion, this study suggests that ILE represents a mild spectrum of lupus in which mucocutaneous and serological abnormalities are associated with progression into SLE. Lupus (2000) 9, 110±115
The benefit of combining hydroxychloroquine with quinacrine in the treatment of SLE patients
Authors: Toubi E , Rosner I , Rozenbaum M , Kessel A , Golan T D
Published: November 2003

Background: Although the benefit of antimalarials in the treatment of cutaneous LE is well established, the effect of combined hydroxychloroquine and quinacrine treatment in systemic lupus erythematosus with major organ involvement remains underappreciated.

Patients: Six active SLE patients (SLEDAI score > 5 points), with a mean duration of illness 9.1 yr (range 2 ± 17 yr) were started on quinacrine (100 mg/d) following failure to achieve clinical remission on a therapeutic regimen which included a maintenance dose of hydroxychloroquine (400 mg/d) together with prednisone (either 10 ± 20 mg/d or higher daily doses of this agent for short periods) and azathioprine (150 mg/d) or methotrexate (7.5 mg/week).

Outcome: In 5=6 of the patients the addition of quinacrine to the previous treatment resulted in complete remission (SLEDAI 0 ± 2 points), which persisted over the follow-up period [mean 2.2 yr (range 0.5 ± 3.5)]. During this period hydroxychloroquine and azathioprine were reduced to 200 mg/d and 100 mg/d respectively, whereas prednisone was modified as follows: in 2 patients daily administration was discontinued; in one the dose was reduced to 2.5 mg/d (from that of 20 mg/d); in 2 others the previous need for an intermittent course was avoided. However, in one out of the six patients the addition for 3 months of quinacrine to the therapeutic protocol did not result in clinical improvement and was therefore discontinued.

Conclusions: The promising results of this preliminary investigation encourages the combined use of the two antimalarial drugs in appropriate candidates. This modality may induce remission, seems to be safe and possesses a steroid sparing effect.
The clinical features and prognosis of lupus with disease onset at age 65 and older
Authors: Pu S J , Luo S F , Wu Y J J , Cheng H S , Ho H H
Published: November 2003

Systemic lupus erythematosus (SLE) in the elderly is uncommon and rarely reported with disease onset at age 65 and older. The aim of this study is to retrospectively analyze the influence of age at disease onset on the clinical features and prognosis of SLE. From 1988 to 1998, we encountered 21 lupus patients with disease onset at age 65 and older (all are included in group A). For comparison, 21 lupus patients with disease onset between 50 ± 64 years of age (group B)and 152 lupus patients with disease onset before 50 years of age (group C) were obtained by a simple random sampling method from the hospital registry. Clinical features as included in the 1982 ARA revised criteria for classification of SLE and survival rate were analyzed and compared among these three groups. Group A had a smaller female to male ratio, longer duration from disease onset to diagnosis, less malar rash, more discoid lupus, and shorter survival rate that group C. There was no statistically significant difference in clinical features and survival between groups A and B, as well as between female and male patients of these two groups. The main cause of death in group A was septic shock. In conclusion, the clinical features and prognosis of SLE were influenced by the age at disease onset. However, clinical features and prognosis of SLE were similar in both late-onset lupus groups.
A longitudinal study of human cytomegalovirus serology and viruria fails to detect active viral infection in 20 systemic lupus erythematosus patients
Authors: Bendiksen Signy , Van Ghelue Marijke , Rekvig Ole Petter , Gutteberg Tore , Haga Hans-Jacob , Moens Ugo
Published: November 2003

In this study, we investigated whether active human cytomegalovirus infection could be detected in 20 systemic lupus erythematosus (SLE) patients over a one-year observation period by polymerase chain reaction on serial urine specimens and by monitoring of IgG and IgM HCMV-specific antibody profiles in serial serum samples. Of 788 urine samples analysed for the presence of human cytomegalovirus DNA, only 2 specimens (0.25%) collected from two different patients contained genuine human cytomegalovirus sequences as determined by polymerase chain reaction and subsequent sequencing of the PCR products. These two patients had one positive sample out of 36 samples or 40 samples, respectively. Nineteen of the patients (95%) possessed IgG antibodies against human cytomegalovirus, while 9 (45%) produced IgM antibodies. However, none of the patients showed signs of an active virus infection as judged by the stable anti-HCMV IgG or IgM antibody levels during the observation period, nor was any correlation between disease activity and HCMV serology/viruria observed. Of single serum samples of 26 age-and sex-matched blood donors, 21 (81%) were HCMV IgG positive and 1 (3.8%) was IgM seropositive. In conclusion, our data fail to establish an active human cytomegalovirus infection in SLE patients.
Mixed cryoglobulinemia: new concepts
Authors: Ramos-Casals Manuel , Trejo Olga , García-Carrasco Mario , Cervera Ricard , Font Josep
Published: November 2003

The most documented extrahepatic manifestation of hepatitis C virus (HCV) infection is mixed cryoglobulinemia (MC). MC is characterised by the presence of temperature-sensitive protein complexes: in type II MC, cryoglobulins are composed of a monoclonal rheumatoid factor (usually, IgMk) against polyclonal IgG. In type III MC, all components are polyclonal. The presence of microheterogeneity and other new types of cryoglobulins is a novel and recent observation. The production of different autoantibodies and circulating immune complexes, including the cryoglobulins, are responsible for systemic vasculitis and various organ damage. In a limited number of MC patients, a malignancy, that is B-cell non-Hodgkin's lymphoma or hepatocellular carcinoma, may also develop. Finally, results of interferon and/or ribavirin treatments in MC patients represent an indirect proof for the pathogenetic link between MC and HVC infection. The discovery of the relation between HCV infection and MC shows the striking association between a viral infection and an autoimmune disease and, thus, a potential link between the systemic autoimmune and lymphoproliferative disorders.
Epidemiology of cardiovascular disease in systemic lupus erythematosus
Authors: Aranow C , Ginzler E M
Published: November 2003

Awareness of the impact of cardiovascular disease on the late morbidity and mortality in patients with Systemic Lupus Erythematosus (SLE) is increasing. Clinical events secondary to accelerated atherosclerosis have been documented in lupus cohorts across the globe. We review the history and epidemiology of cardiovascular disease in patients with SLE.
Lipids, cardiovascular disease and atherosclerosis in systemic lupus erythematosus
Authors: Wierzbicki As
Published: November 2003

Systemic lupus erythematosus is commonly associated with early onset cardiovascular disease and is often associated with hyperlipidaemia. This review examines the evidence for an increased prevalence of both CHD and hyperlipidaemia in SLE and mechanisms by which autoimmunity in SLE could accelerate the progression of atheroma. It postulates how lipid lowering therapies used in cardiological disease might help reduce the incidence of CHD in SLE.
Normal endothelial cell function
Authors: Pearson J D
Published: November 2003

Endothelial cell functions, primarily involving regulated mediator secretion or altered surface protein expression, are vital for normal homeostasis. Endothelial cells secrete the potent vasodilator and anti-platelet agent prostacyclin and nitric oxide, and also the potent vasoconstrictor peptide endothelin-1; they control the selective adhesion and emigration of leukocytes from the bloodstream; and they are the source of circulating von Willebrand factor, tissue plasminogen activator and type 1 plasminogen activator inhibitor. The properties of healthy endothelium ensure that an antithrombotic and anticoagulant balance is maintained in the bloodstream, and provide a tonic vasodilator action that controls blood flow and pressure on a minute-to-minute basis. Disturbances of normal endothelial function are strongly implicated in the pathogenesis of atherosclerosis and autoimmune vasculitic diseases including lupus.
Sex hormone binding globulins and atherosclerotic risk in systemic lupus
Authors: Merrill J T , Lahita R G
Published: November 2003

Sex hormone binding globulin (SHBG) is a transport protein in human plasma which regulates the bioavailability of sex hormones, mediates membrane receptor signaling and may affect inflammatory processes, suggesting a regulatory role for this protein in the prevention of atherosclerosis. The current report summarizes literature implicating several members of the SHBG family in the regulation of hormonal and inflammatory processes which may be pertinent to the accelerated atherosclerosis seen in systemic lupus.
Anti-telomere antibodies in systemic lupus erythematosus: a new ELISA test for anti-DNA with potential pathogenetic implications
Authors: Wallace D J , Salonen E-M , Avaniss-Aghajani E , Morris R , Metzger A L , Pashinian N
Published: November 2003

Background: Telomeric hexamer repeats (TTAGGG/CCCTAA)n are highly repetitive sequences of DNA. They cap the termini of eukaryotic chromosomes and stabilize them, preventing degradation or fusion. Anti ds-DNA is one of the most specific tests for systemic lupus erythematosus (SLE). Of related importance, a preliminary report has suggested that anti-telomere antibodies are also highly specific for the presence of SLE.

Methods: 220 patients with SLE, 79 with rheumatoid arthritis (RA), 54 with other rheumatic diseases and 99 healthy controls were tested for anti-telomere antibody as measured by enzyme immunoassay detecting 30and 60-mer telomeric repeats (5 ± 10 hexamers). 48 of the 220 SLE patients charts were abstracted for 90 separate clinical, laboratory and treatment parameters. Comparisons were made between SLE and non-SLE patients, and within the lupus group for telomere positivity and among the latter 48 patients for anti-DNA (Farr) levels and SLEDAI scores.

Results: Anti-telomere antibody was present in 48.6% of the overall SLE group (220), 71% of our cohort (48), 11% with primary Sjogren's (2=18), 7.6% with RA (6=79) and 2% of normal controls (2=99) (P < 0.001 comparing SLE to all other groups). In the 48 patient cohort, anti-telomere antibody was more sensitive than anti-dsDNA (Farr) (71% vs 50%), but did not correlate with other clinical parameters, SLEDAI scores, or other autoantibodies.

Conclusions: The detection of anti-telomere antibody appears to be more sensitive and may be as specific as anti-dsDNA (Farr) in SLE. The detection of telomeric repeats may be as accurate as other anti-DNA assay methodologies and more specific for the presence of SLE. The immunogenic potential of telomere biology related to the pathogenesis and/or diagnosis of SLE deserves further investigation.
Fever and pneumonia in a steroid treated patient with systemic lupus erythematosus
Authors: Goodman S M , Russell L , Kagen L , Schneider R
Published: November 2003

Systemic lupus erythematosus is reported to affect the lungs in almost half of patients, but pleuritis is most commonly encountered. Acute pneumonitis is an uncommon but recognized manifestation of SLE. Infection and drug reactions are more frequently diagnosed. The case discussed below permits consideration of the dilemmas typical of the SLE patient who presents with an acute pulmonary process.
Primary and secondary pulmonary hypertension in systemic lupus erythematosus
Authors: Pan T Ling-Te , Thumboo J , Boey M-L
Published: November 2003

Objectives: To describe the aetiology and clinical profile of primary and secondary pulmonary hypertension (PHT) in SLE patients.

Methods: A retrospective study of SLE patients with PHT identified from a cohort of 786 SLE patients seen at Tan Tock Seng Hospital, Singapore.

Results: 22 patients had primary and 24 patients had secondary PHT, with similar clinical features at presentation and a similar degree of pulmonary pressure elevation. Secondary PHT was due to valvular heart disease (50%), pulmonary embolism (13%), interstitial lung disease (8%) or a combination of these factors (29%). Primary PHT tended to present after a shorter duration of lupus than secondary PHT (8.8 vs 43.2 months, P = 0.118). At presentation, Raynaud's phenomenon was present in 34.8% of subjects with primary or secondary PHT. Among those with secondary PHT, the presence of Raynaud's phenomenon was associated with a trend towards higher pulmonary artery systolic pressures (51.0 vs 40.5 mmHg, P = 0.101). 17% of patients with PHT died, but from causes unrelated to PHT.

Conclusion: Primary and secondary PHT are equally common in SLE patients. Secondary PHT is often multi-factorial, and Raynaud's phenomenon may be a marker for the severity of PHT in this group of patients.
Alterations of cerebral glucose metabolism indicate progress to severe morphological brain lesions in neuropsychiatric systemic lupus erythematosus
Authors: Weiner S M , Otte A , Schumacher M , Brink I , Juengling F D , Sobanksi T , Nitzsche E U , Peter H H
Published: November 2003

Neuropsychiatric systemic lupus erythematosus (SLE) is frequently associated with deficits in brain glucose metabolism, even if morphological imaging by magnetic resonance imaging (MRI) shows no abnormalities. In these patients it is unclear whether or not the changes of brain metabolism measured by F-18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) may progress to lesions of cerebral structure. We describe a 20-year-old woman with SLE who presented with depression, headache and impairment of memory. Initially, a cranial MRI was negative, but FDG-PET revealed significant hypometabolism in the frontal and parieto-temporo-occipital regions on both sides as well as hypermetabolism in the nuclei caudati. Within two months the patient developed an acute confusional state, seizures, visual disturbances and cranial MRI became positive showing hyperintensities at the basal ganglia and the temporo-occipital regions. Focal cerebral symptoms responded to treatment with high dose corticosteroids and brain lesions in MRI disappeared. However, a second FDG-PET showed persistent hypometabolism at frontal regions in accordance with the persistence of subclinical depression. To our knowledge, this is the first SLE case report showing that functional brain lesions visualized by FDG-PET may be a risk factor for subsequent structural brain damage seen in MRI. Thus, FDG-PET may help to verify cerebral involvement of SLE earlier than MRI.
Kingella endocarditis and meningitis in a patient with SLE and associated antiphospholipid syndrome
Authors: Wolak T , Abu-Shakra M , Flusser D , Liel-Cohen N , Buskila D , Sukenik S
Published: November 2003

We describe a patient with SLE and antiphospholipid syndrome who presented with severe headache and fever. Lumbar puncture analyses indicated meningitis. Kingella kingae was isolated from her blood cultures. A large mobile vegetation was seen on her mitral valve. The association between SLE, Libman – Sacks endocarditis and bacterial endocarditis is discussed.
Differences in clinical sensitivity of ELISA tests for autoantibodies with human and bovine extractable nuclear antigens
Authors: Kapogiannis B , Gussin H AE , Teodorescu M R , Teodorescu M
Published: November 2003

Bovine antigens are routinely used in indirect ELISA tests to detect autoantibodies against extractable nuclear antigens (ENA). Here we investigate the difference in clinical sensitivity between ELISA tests prepared with native human and bovine antigens. SSA and SSB were obtained from spleen and nRNP/Sm complex from thymus. Each antigen was extracted with the same immunoaffinity column. ELISA tests with human and bovine antigens were set up under the same conditions of clinical specificity established on 50 blood bank donors. Of 109 random SLE and Sjogren's syndrome sera 49% and 35% were positive, respectively, for human and bovine SSA, 26% and 16% for SSB. Of 98 random SLE sera 52% and 41% were positive for human and bovine nRNP/Sm, respectively. A few specimens reacted only with bovine antigens, probably false positive reactions. The relative clinical sensitivity for all specimens identified as positive by human and/or bovine antigens was significantly higher with human than with bovine SSA, (93% vs 67%; P < 0.001, χ2), SSB (93% vs 50%; P < 0.001), and for nRNP/Sm (96% vs 75%; P < 0.01). However, for values that exceeded 2.5–4 times the upper normal limit, the levels were similar for human and bovine antigens. We concluded that native human antigens offer clinical sensitivity superior to native bovine antigens for the measurement of anti-ENA antibodies by ELISA.
Maintaining remission of lupus erythematosus profundus (LEP) with cyclosporin A
Authors: Saeki Y , Ohshima S , Kurimoto I , Miura H , Suemura M
Published: November 2003

We report a young female patient with recurrent lupus erythematosus profundus (LEP) who has successfully maintained remission of LEP with cyclosporin A (CsA), although conventional treatments such as systemic corticosteroids (low-dose), dapsone, and other immunosuppressive drugs (azathiopurine, cyclophosphamide) could not maintain remission.
Endpoints: consensus recommendations from OMERACT IV
Authors: Strand V , Gladman D , Isenberg D , Petri M , Smolen J , Tugwell P
Published: November 2003

The goal of the ‘Outcome Measures in Rheumatology’ (OMERACT) process is to select domains and/or outcome measures for clinical trials in each defined disease category according to truth, discrimination and feasibility. OMERACT IV, held in Cancun, Mexico, April 1998, included the module ‘Systemic Lupus Erythematosus (SLE)’, designed to define a preliminary core set of outcome domains for randomized controlled trials and longitudinal observational studies (LOS). Although specific measures to be used in clinical trials of SLE have yet to be determined, both randomized controlled trials and longitudinal observation studies groups recommended that outcome be assessed in terms of disease activity and damage in all organ systems involved, as well as by health related quality of life, meaningful to patients, and adverse events. These recommendations were ratified by the majority of participants. In a heterogeneous patient population such as SLE, it is recognized that any individual measure of clinical response may reflect only a portion of what might be termed the ‘true outcome’. A responder index could integrate such relatively independent measures of outcome into a single assessment, potentially increasing statistical power and decreasing sample size. Results from randomized controlled trials currently underway assessing these outcome domains are eagerly awaited, and are expected to rapidly advance the field
The variation in anti-ENA characteristics between different ethnic populations with systemic lupus erythematosus over a 10-year period
Authors: Tench C M , Isenberg D A
Published: November 2003

Objective: To assess how anti-ENA characteristics change in patients with systemic lupus erythematosus from different ethnic backgrounds over a 10-year period follow-up study.

Results: There were 61 patients, of whom 37 were Caucasian, 12 were Asian and 12 were AfroCaribbean. At the first available bleed 12=37 (32%) Caucasians were anti-ENA positive compared to 6=12 (50%) Asians and 9=12 (75%) of Afro-Caribbeans (Chi-squared P ‘ 0.01 for Caucasian vs Afro-Caribbean) and these proportions remained essentially unchanged after 10 y of follow-up. However, over the 10 y of follow-up anti-ENA patterns did change, with anti-Ro being the commonest antibody pattern to emerge and anti-Ro/La the commonest antibody pattern to disappear. There were 20=37(54%) Caucasians, 1=12(8%) Afro-Caribbeans and 5=12(42%) Asians who remained negative for anti-ENA throughout the 10-year follow-up (Chi-squared P ‘ 0.03 for Caucasian vs Afro-Caribbean).

Conclusion: Anti-ENA were more commonly found in the Afro-Caribbean than the Caucasian population. The commonest patterns of anti-ENA differ between ethnic groups and, over a 10-year period, anti-ENA patterns in individual patients changed in a significant number of individuals. However, Caucasians were more likely to remain anti-ENA negative over 10 y of follow-up than Afro-Caribbeans.
Down-regulation of natural killer cells and of g/d T cells in systemic lupus erythematosus. Does it correlate to autoimmunity and to laboratory indices of disease activity?
Authors: Riccieri V , Spadaro A , Parisi G , Taccari E , Moretti T , Bernardini G , Favaroni M R , Strom R
Published: November 2003

A depletion of natural killer (NK) cells seems to play a role in the course of systemic lupus erythematosus (SLE) whereas the possible involvement in this disease of T cell receptor (TCR) g/d positive T cells is still debated.

The aim of this study was to evaluate the peripheral blood mononuclear cells (PBMCs) that express NK surface markers CD16 and CD56 or g/d TCR antigen in 58 SLE patients, investigating the possible role of these cell subsets involved in non-MHC-restricted cytotoxicity and their relationship with the main clinical and laboratory parameters.

SLE patients had, with respect to controls, considerably decreased values of NK cells (P < 0.0004 in percentage and P < 0.00004 as absolute number), of non-MHC-restricted T cytotoxic lymphocytes (P < 0.007 and P < 0.0015, respectively) and of T cells expressing g/d TCR (P < 0.02 and P < 0.004, respectively). The absolute numbers of these cell subsets positively correlated to each other (P < 0.009). g/d T cells inversely correlated with higher ESR values, both percentually (P < 0.006; r ‘ 70.367) and in absolute number (P < 0.009; r ‘ 70.350). Moreover, the percentage values of this cell subset inversely correlated with higher levels of CRP (P < 0.05; r ‘ 70.256) while SLE patients with anti-SSB/La antibodies had lower values of T lymphocytes bearing g/d TCR, both as percentage (P < 0.008) and as absolute number (P < 0.02).

Our study indicates that non-MHC-restricted cytotoxicity, shared by NK, NK-like and g/d T cells, may be down-regulated in SLE patients, owing to a significant reduction of these PBMC subsets. These specific cell subset impairments seem to affect only some aspects of the disease, suggesting a weakening of the regulatory properties of these cells in the control of different immunological and inflammatory features of SLE, that could be of importance in its clinical expression.
PRISM (Pictorial Representation of Illness and Self Measure) - a novel visual method to assess the global burden of illness in patients with systemic lupus erythematosus
Authors: Büchi S , Villiger P , Kauer Y , Klaghofer R , Sensky T , Stoll T
Published: November 2003

Objective: For patients with chronic illnesses the global burden of illness is a crucial health measure hitherto neglected in research studies and clinical practice. We tested the application and validity of PRISM (Pictorial Representation of Illness and Self-Measure), a novel visual method for assessing the burden of illness, in patients with systemic lupus erythematosus (SLE).

Method: PRISM was applied in a cross sectional sample of 60 patients with SLE. Correlations were assessed between a quantitative measure derived from PRISM (Self-Illness Separation  SIS) and sociodemographic factors, measures of disease activity, damage, physical and psychological disability variables, as well as coping resources.

Results: The PRISM task was understood by all but one patient, and was in every instance completed in less than 3 minutes. SIS correlated with SF-36 physical health, coping resources as assessed by Sense of Coherence (SOC), and age, but not with disease activity or damage. In multiple regression analyses, independent contributions to SIS were observed for SF-36 physical component scale (contributing 12% of the variance). SOC (10%) and age (14%).

Conclusion: PRISM is a new non-verbal measure to assess burden of illness. As in previous studies, PRISM was well accepted and understood by patients with SLE, quick to complete, and yielded meaningful information consistent with that in earlier research work.
Systemic lupus erythematosus with myocardial dysfunction due to microvasculopathy
Authors: Nanke Y , Kotake S , Shimamoto K , Fukasawa C , Hara M , Kamatani N
Published: November 2003

A 25-year-old Japanese woman with systemic lupus erythematosus (SLE) had myocardial dysfunction. Heart catheterization showed normal coronary anatomy. Left ventricular cineangio-graphy demonstrated hypokinesis in the anterior and posterior segments. Myocardial scintigraphy revealed patchy defects in the regions unrelated to coronary arteries. These data suggested that the myocardial dysfunction was due to microvasculopthy. In addition, it was speculated that the microvasculopathy was caused by vasculitis but not by thrombi, since she did not have antiphospholipid syndrome. In support of this speculation, corticosteroid therapy without any thrombolytic agents was effective. This report represents the first live patient with SLE in whom myocardial dysfunction due to microvasculopathy has been demonstrated.
Chronic intestinal pseudo-obstruction in systemic lupus erythematosus due to intestinal smooth muscle myopathy
Authors: Hill P A , Dwyer K M , Power D A
Published: November 2003

We report the case of a woman with systemic lupus erythematosus initially manifesting with fever, rash and arthritis, and two years later with Class IV lupus nephritis. Following treatment with cyclophosphamide she developed symptoms and signs of chronic intestinal pseudo-obstruction (CIPO) that was initially thought to be due to a neutropenic enterocolitis. However, persistence of symptoms resulted in segmental resection of the ileum which showed widespread myocyte necrosis and active inflammation within the muscularis propria. A subsequent, more extensive ileocolic resection showed severe diffuse atrophy and fibrosis of the muscularis propria throughout the resected bowel. The absence of mesenteric vasculitis and the clinical response of the CIPO to the immunosupressive regimen of prednisolone and cyclosporin A suggest that the bowel muscle coat changes reflect an intestinal myopathy secondary to systemic lupus erythematosus, and may have an auto-immune etiology.
Hydroxychloroquine has no significant effect on lipids and apolipoproteins in Chinese systemic lupus erythematosus patients with mild or inactive disease
Authors: Tam L S , Li E K , Lam C WK , Tomlinson B
Published: November 2003

Objective: To investigate the effects of hydroxychloroquine (HCQ) in Chinese patients with systemic lupus erythematosus who were either on a low dose of prednisone or not on prednisone.

Methods: 65 consecutive Chinese lupus patients without features of nephritis underwent assessment of the fasting serum lipid profile, including total cholesterol (TC), triglycerides (TG), HDL-cholesteorl (HDL-C), LDL-cholesterol (LDL-C), apolipoprotein A-1 (apo A-1), apolipoprotein B (apo B) and lipoprotein (a) (Lp(a)).

Results: 44/65 (67.7%) patients were on HCQ with a dose of 244 86 mg daily and 34/65 (52.3%) patients were on 4.3 + 2.6 mg daily of prednisone. The percentages of patients taking prednisone and the mean dose in those patients receiving this treatment were not different between the groups with or without HCQ treatment. TG tended to be lower in those patients on HCQ (median and interquartile range) (1.0 (0.7-1.4) mmol/L vs 1.2 (0.8-1.6) mmol/L), but there were no significant differences in TC or other lipid parameters including Lp(a) between the 2 groups of patients with or without HCQ treatment.

Conclusion: HCQ had no significant effect on the serum lipid profile in these lupus patients with mild or inactive disease. This finding probably reflects the low doses of corticosteroid used and a lower background lipid level in this population.
The spectrum of cutaneous manifestations in lupus erythematosus—the Italian experience
Authors: Cardinali C , Caproni M , Bernacchi E , Amato L , Fabbri P
Published: November 2003

We have evaluated the incidence of lupus erythematosus (LE)-specific skin disease in 186 patients with LE, seen retrospectively over a 1 0-year period at our Dermatology Department and determined the correlation of LE-nonspecific skin disease in patients with systemic involvement.

Chronic cutaneous LE (CCLE) with classical discoid lesions (localized, 70%; generalized, 30%) was the most common cutaneous manifestation (72.5%). Subacute cutaneous LE (SCLE) represented only 8% of LE skin disease (annular-polycyclic type, 73%; papulo-squamous type, 27%). Acute cutaneous LE (ACLE) was detected in 15% of our patients: the butterfly erythema was the most frequent skin lesion (96%) while only one case of bullous LE and one case of widespread maculo-papular eruption in association with malar erythema were demonstrated. In 8 patients no LE-specific skin lesions (lupus sine lupo) were found.

LE-nonspecific skin lesions were found in 31% of our patients with systemic LE (SLE): Raynaud's phenomenon was found in 23/58 (39.6%), cutaneous small vessel leukocytoclastic vasculitis in 8/58 (13.7%), nonscarring alopecia in 18/58 (31%), lupus pernio in 6/58 (10.3%), hemorrhagic lesions in 4/58 (6.8%), livedo reticularis in 5/58 (8.6%), mucosal ulcers in 3/58 (5.1%) and periungual telangiectasia in 12/58 (20.6%) SLE patients. LE-nonspecific skin lesions are detected only in patients with SLE and usually in the active phases of the disease.
Lupus nephritis: a challenging cause of rapidly progressive crescentic glomerulonephritis
Authors: Sumethkul V , Chalermsanyakorn P , Changsirikulchai S , Radinahamed P
Published: November 2003

The outcomes of 32 lupus patients with rapidly progressive crescentic glomerulonephritis were studied. Lupus nephritis accounted for 51.6% (32/62) of all patients with biopsy proven rapidly progressive crescentic glomerulonephritis during a six year observation period that includes 961 consecutive native kidney biopsies. Median entry serum creatinine was 221 imol/1. All patients received induction therapy with pulse methylprednisolone (n = 27) or intravenous cyclophos-phamide (n = 5). Maintenance therapies included prednisolone alone (group 1), prednisolone plus intermittent pulse intravenous cyclophosphamide (IVCY) (group 2) and prednisolone plus daily oral cytotoxic drugs (group 3). Twelve patients eventually had uremia. Seven further patients died of infection during therapy. One patient still had renal insufficiency and twelve patients had favorable clinical outcome (serum creatinine < 200 lmol/ 1). Patients in group 3 were more likely to have favorable clinical outcome than group 2 (P = 0.01; Fisher's exact test). Survival analysis found that the three year survival of ‘group 2 was 27.6% while that of ‘group 3’ was 83.3%. Our results suggest that lupus nephritis is not an infrequent cause of crescentic glomerulonephritis. Therapy with IVCY is not necessary associated with good outcome. Selected patients can be effectively treated with daily oral cytotoxic drugs as a reasonable alternative therapy.
Preservation of fertility and ovarian function and minimizing gonadotoxicity in young women with systemic lupus erythematosus treated by chemotherapy
Authors: Blumenfeld Z , Shapiro D , Shteinberg M , Avivi I , Nahir M
Published: November 2003

Background: Premature ovarian failure (POF) is a common long-term consequence of chemotherapy. Whereas the cytotoxic-induced damage is reversible in other tissues of rapidly dividing cells such as bone marrow, gastrointestinal tract and thymus, it appears to be progressive and irreversible in the ovary, where the number of germ cells is limited, fixed since the fetal life, and cannot be regenerated. The gonadal toxicity of cyclophosphamide is well known. In patients with lupus nephritis, premature ovarian failure (POF) was reported in half of all treated women after cyclophosphamide pulse therapy, affecting 100% of those older than 30y, about 50% of the patients between the ages of 20-30y and only 13% of the patients younger than 20y of age. Following our preliminary encouraging experience in women with lymphoma, whereby the temporary induction of a prepubertal hormonal milieu, during chemotherapy, has significantly decreased the risk of POF, we have administered a monthly injection of gonadotropin-releasing hormone agonistic analogue (GnRH-a) to eight young women in parallel to alkylating agent chemotherapy.

Materials and methods: A monthly intramuscular depot injection of 3.75 mg D-TRP6-GnRH-a (Decapeptyl C.R.) was administered after informed consent to eight women with autoimmune, severe connective tissue diseases (seven SLE patients and one woman with nephrotic syndrome) in parallel to chemotherapy, for up to six months. The institutional committee for human experimentation approved the protocol. The concentrations of FSH, LH, progesterone, and 17-/3-estradiol (E2) were measured before, during and after the GnRH-a/chemotherapy treatment. A transvaginal (or transabdominal) sonography (TVS) was performed on each patient before and after treatment. These eight treated patients (study group) were compared to a group of nine women similarly treated by cyclophosphamide pulses (CPT) or chlorambucil for SLE/connective tissue disease but were not referred for the GnRH-a adjuvant treatment.

Results: Whereas none of the eight women receiving GnRH-a in parallel to alkylating agent chemotherapy (cyclophosphamide (7) or chlorambucil (1)) suffered POF and hypergonadotropic amenorrhea, five of the nine ( > 50%) patients treated by alkylating agents (cyclophosphamide (8) or chlorambucil (I)) experienced POF. Whereas two of these five women were 35 y old, the other three were < 23 y old at the time of the chemotherapeutic insult.

Conclusions: Our present results, extrapolating this encouraging experience from hematological malignant diseases to severe connective tissue diseases, such as SLE associated nephropathy or others, suggests that the beneficial effect of GnRH-a co-treatment may be exploited towards preservation of future fertility and ovarian function in every young woman of reproductive age, exposed to alkylating agents, such as cyclophosphamide and chlorambucil.
Central nervous system involvement in systemic lupus erythematosus: cerebral imaging and serological profile in patients with and without overt neuropsychiatric manifestations
Authors: Sanna G , Piga M , Terryberry J W , Peltz M T , Giagheddu S , Satta L , Ahmed A , Cauli A , Montaldo C , Passiu G , Peter J B , Shoenfeld Y , Mathieu A
Published: November 2003

The aim of this study was to evaluate morphological and functional abnormalities by cerebral imaging in a series of systemic lupus erythematosus (SLE) patients with and without overt central nervous system (CNS) manifestations, and to detect possible relationships with clinical parameters and a large panel of autoantibodies, including those reactive against neurotypic and gliotypic antigens. 68 patients with SLE were investigated in a cross-sectional study which included clinical evaluation of symptoms, cerebral magnetic resonance imaging (MRI) and brain single photon emission tomography (SPECT) analysis, electroencephalography (EEG), and serological tests for antibodies directed against nuclear, cytoplasmic neuronal and glial cell-related antigens.

The results of this study showed: (1) a significant positive association of (a) anti-glial fibrillary acidic protein (GFAP) serum antibodies with neuropsychiatric (NP) manifestations and (b) antiserin proteinase 3 (anti-PR3/c-ANCA) serum antibodies with pathological cerebral SPECT; (2) the presence of significantly higher values of (a) SLICC organ damage index in patients with abnormal MRI and (b) SLAM activity index in patients with abnormal SPECT; and (3) the association of (a) abnormal MRI with nonactive NP manifestations and (b) combined abnormality of brain SPECT and MRI with the occurrence of overall overt NP manifestations and with those of the organic/major type.

Neuropsychiatric manifestations, namely those of the organic/major type, appeared to be significantly associated to the presence of a serum antibody against GFAP, a gliotypic antigen. There was also evidence of an association between SPECT abnormality and the presence of anti-PR3 (c-ANCA). Furthermore, brain imaging by MRI and SPECT applied to SLE patients appears to express CNS involvement significantly related to specific categories of NP manifestations. The abnormalities detected by the two tests seem to be preferentially associated with different activity phases of the NP disorder or of the lupus disease.
Autoantibody responses to cardiolipin and DNA in infancy: association with lymphocytic panniculitis
Authors: Miyagawa S , Uchida Y , Taira K , Higuchi M , Hashimoto K , Yoshioka A , Shirai T
Published: November 2003

We report an infant with anticardiolipin (aCL) antibodies who presented with erythematous nodular skin lesions and elevated liver enzyme levels. The cutaneous manifestation was histologically lymphocytic lobular panniculitis with vasculitic and hemorrhagic changes. The infant also had low levels of anti-double stranded DNA (dsDNA) and anti-single stranded DNA (ssDNA) antibodies. There were no detectable antibodies to small nuclear ribonucleoproteins including Ro/SSA and La/SSB. His mother was consistently seronegative for any of these antibodies. Without corticosteroid therapy, cutaneous lesions resolved and anticardiolipin antibodies, but not anti-dsDNA and ssDNA antibodies, normalized within 16 months after the onset of the disease. Our patient demonstrated an uncommon presentation of aCL related cutaneous manifestation, the presentation with panniculitis being only the third such patient reported in the literature. Of great interest was the appearance of aCL antibodies and skin lesions during very early infancy.
CD45 autoantibodies mediate neutralization of activated T cells from lupus patients through anergy or apoptosis
Authors: Mamoune A , Kerdreux S , Durand V , Saraux A , Le Goff P , Youinou P , Le Corre R
Published: November 2003

The objectives were to provide estimates of the prevalence of autoantibody (Ab) directed to CD45 in lupus patients, identify the target autoantigen(s), and determine the ability of such reactivity to mediate neutralization of T lymphocytes.

Sera from 64 patients were studied using 2 assays: Western blot and an ELISA with CD45 eluted from 3 cell lines as antigen (U937, Jurkat and Daudi). The role of carbohydrate specificity was investigated using enzyme digestion of blotted glycans, competition with sugars, and inhibition with lectins. Apoptosis was studied through annexin V binding, and cell cycle analysis using the propidium iodide method.

AutoAb to CD45 were detected in 16/64 sera (25%) by Western blot, and 21/32 sera (66%) found positive in the ELISA. CD45 purified from Daudi cells was identified in the ELISA, but not in the blot. AutoAb were of the IgM and the IgG isotypes, but not specific for a particular cell type or CD45 isoform: 2 dominant specificities were recognized, one against p180, and another against high MW isoforms. Neuraminidase-induced enhancement of reactivity, together with the inhibitory effect of N-acetyl galactosamine and Dolichos diflorus lectin suggest that the epitopes are carbohydrates. AutoAb which were specific for activated CD4 + T cells triggered the annexin V binding, and, in 2 of 4 cases, lymphocytes underwent apoptosis.

In conclusion, carbohydrate conformational epitopes may be important as target antigens, and some CD45 autoAb have the capacity to neutralize activated T cells through anergy or apoptosis.
Nonsteroidal anti-inflammatory drugs in systemic lupus erythematosus
Authors: østensen M , Villiger P M
Published: November 2003

Up to 80% of patients with systemic lupus erythematosus (SLE) are treated with nonsteroidal anti-inflammatory drugs (NSAID) for musculoskeletal symptoms, serositis and headache. This survey reviews the literature on non-selective and selective inhibitors of cyclooxygenases, with an emphasis on the efficacy and safety profile reported in SLE patients. No lupus-specific data on gastro-intestinal side effects of NSAID exist. Both non-selective Cox inhibitors and selective Cox-2 inhibitors induce renal side effects, including sodium retention and reduction of the glomerular filtration rate. Lupus nephritis is a risk factor for NSAID-induced acute renal failure, but not for rare idiosyncratic toxic renal reactions to NSAID. In refractory nephrotic syndrome, NSAID have been used successfully. Cutaneous and allergic reactions to NSAID are increased in SLE patients as well as hepatotoxic effects, particularly with high dose aspirin. Whereas a variety of central nervous system side effects of NSAID are probably no more common in SLE patients than others, aseptic meningitis has been reported more frequently. Ovulation and pregnancy can be adversely affected by Cox inhibitors. The antiplatelet effect of aspirin and non-selective Cox inhibitors has a therapeutic potential in patients with antiphospholipid syndrome (APS). In summary, treatment of SLE with NSAID requires awareness for the increased frequency of some side effects and close monitoring of toxicity.
Profile of sex hormones in male patients with systemic lupus erythematosus
Authors: Mok C C , Lau C S
Published: November 2003

Objective: To study the profile of sex hormones in male patients with systemic lupus erythematosus (SLE).

Method: Serum prolactin (PRL), testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were obtained from 35 males with SLE and compared with 33 age-matched normal controls.

Results: No significant differences in serum T, E2, PRL levels and E2/T ratio were observed between male SLE patients and controls. However, patients with SLE had significantly higher levels of gonadotrophins (FSH, LH). Five (14%) SLE patients, but none of the controls, had both low testosterone and elevated LH. Hypoandrogenic male SLE patients did not have overt features of hypogonadism but had a higher prevalence of central nervous system disease and serositis than those with normal androgen levels. Disease flares, on the other hand, were not significantly more frequent in these patients. Although PRL or T levels per se did not correlate with disease activity in our patients, the ratio of PRL to T showed a significant correlation with SLEDAI scores ( p = 0.42, p = 0.01).

Conclusions: Hypoandrogenism is present in some male patients with SLE and may be relevant in disease pathogenesis. However, whether these hormonal abnormalities are intrinsic to SLE or the consequence of any non-specific chronic disorders cannot be distinguished from the current data. Further studies involving a larger number of subjects and inclusion of other disease controls are needed.
The family history of patients with primary or secondary antiphospholipid syndrome (APS)
Authors: Weber M , Hayem G , DeBandt M , Palazzo E , Roux S , Kahn M-F , Meyer O
Published: November 2003

Objective: To evaluate familial history for evidence of antiphospholipid syndrome (APS) and autoimmune disease in rheumatology department patients with primary or secondary APS.

Methods: We retrospectively studied patients with APS and systemic lupus erythematosus (SLE) managed at the Rheumatology Department of the Bichat University Hospital, Paris, between 1987 and 1996. Data were collected by chart review and by a 1997 standardized telephone interview.

Results: We identified 108 patients with APS managed during the ten-year study period. According to classical classification criteria, 39 patients had primary antiphospholipid syndrome (PAPS) and 69 secondary antiphospholipid syndrome (SAPS). Family history data were obtained for 29 (74%) and 55 (80%) PAPS and SAPS patients, respectively (78% of the 108 patients). Twelve PAPS (41%) and 19 SAPS (35%) patients had one or more relatives with evidence of at least one clinical feature of APS such as thrombosis or recurrent fetal loss; of these patients, seven in the PAPS (24%) and 11 in the SAPS (20%) group had two or more relatives with evidence of a clinical feature of APS. Three PAPS (10%) and 14 SAPS (25%) patients had one or more family members with an autoimmune disease.

Conclusion: A positive family history for autoimmune disease and/or antiphospholipid syndrome is common in patients with PAPS or SAPS. This finding supports a genetic contribution to APS. The percentage of a positive family history for autoimmune disease tend to be higher in patients with SAPS than in those with PAPS.