bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebral blood flow and glucose metabolism in multi-infarct-dementia related to primary antiphospholipid antibody syndrome
Authors: Hilker R , Thiel A , Geisen C , Rudolf J
Published: November 2003

The primary antiphospholipid antibody syndrome (PAPS) has beendescribed in patients with a history of fetal loss,thrombocytopenia and arterial or venous thrombosis. In PAPS, a prothrombotic state is mediated by antiphospholipid antibodies (aPLs) leading to disseminated thromboembolic vascular occlusion. Today, the presence of aPLs in the serumis considered as a distinct risk factor for recurrent stroke in young adults. Some PAPS patients develop a multi-infarct-syndrome with a stepwise decline of higher cortical functions. We report on a 55-year-old man suffering from progressive dementia and PAPS, in whom cerebral glucose metabolism and blood flow were examined by positron emission tomograpy (PET). Cerebral atrophy and moderate signs of leukaraiosis were detected in magnetic resonance imaging (MRI), whereas the PET scans showed a considerable diffuse impairment of cortical glucose metabolism combined with a reduced cerebral perfusion in the arterial border zones. These findings indicate that PAPS-associated vascular dementia is accompanied by a cortical neuronal loss, presumably caused by a small-vessel disease with immune-mediated intravascular thrombosis. This case shows that pathological findings in PAPS are congruent to cerebral changes of metabolism and blood flow in systemic lupus erythematosus (SLE).
Methotrexate therapy in systemic lupus erythematosus
Authors: Sato E I
Published: November 2003

There are 12 non-controlled and only two controlled studies using methotrexate (MTX) in a total of 207 SLE patients in the literature. The majority of these studies evaluated mainly cutaneous and/or articular involvement and attained good results. Two studies evaluated a small number ofpatients with lupus nephritis, achieving discordant results. Two other studies in pediatric onset systemic lupus erythematosus (SLE) also presented conflicting results, it being relevant that the one with poor response hadthe majority of patients with nephritis. One of the controlled trials was retrospective and concluded that MTX was effective in the treatment of antimalarial-resistant lupus arthritis and that toxicity leading to discontinuation of MTX was infrequent. The other controlled study was a double-blind, randomized, placebo-controlled clinical trial that evaluated SLE patients with mild activity. The authors concluded that MTX was effective in controlling cutaneous and articular activity and permitted prednisone dose reduction. The side effects were frequent but only 10% of patients needed to discontinue the medication.

The accumulative evidence suggests that MTX in a low weekly dose may be effective in SLE patients with articular and/or cutaneous involvement with no response to antimalarials and low-dose prednisone and in patients in whom we can not reduce prednisone dose due to articular or cutaneous activity. Caution is required concerning the side effects.
Myocardial microangiopathy associated with antiphospholipid antibodies
Authors: Lauwerys B R , Lambert M , Vanoverschelde J-L , Cosyns J-P , Houssiau F A
Published: November 2003

Myocardial thrombotic microangiopathy is a well described post-mortem finding in patients with the catastrophic antiphospholipid (APL) syndrome. However, it has been only very rarely imaged in living patients. Here, we report two patients with APL antibodies presenting with scintigraphic, electrocardiographic and/or echocardiographic evidence of (sub)acute myocardial ischaemia, despite a normal coronary angiography. Formal proof of a thrombotic microangiopathy was obtained by a kidney biopsy in one patient. We emphasize the value of 99mTc-MIBI (2-methoxy isobutyl isonitrile) exercise stress myocardial scintigraphy for the detection of cardiac microangiopathy associated with the APL syndrome.
Treatment of systemic lupus erythematosus with bromocriptine
Authors: Walker S E
Published: November 2003

Prolactin, a lactogenic hormone, is a cytokine and an inportant link between the immune and endocrine systems. Prolactin stimulated disease in autoimmune NZB/NZW mice. Treatment of the mice with the prolactin-lowering dopamine agonist, bromocriptine, suppressed anti-DNA and prolonged life spans. These findings have been applied to humans with systemic lupus erythematosus (SLE). An open-label study, a double blind study, and a study comparing bromocriptine to hydroxychloroquine provided evidence that bromocriptine therapy reduced flares and suppressed disease activity in SLE.
A case of systemic lupus erythematosus complicated with multicentric reticulohistiocytosis (MRH): successful treatment of MRH and lupus nephritis with cyclosporin A
Authors: Saito K
Published: November 2003

We document the rst case of a patient who manifested systemic lupus erythematosus (SLE) complicated with multicentric reticulohistiocytosis (MRH). Neither intravenous steroid nor cyclophosphamide (CY) pulse therapies were fully effective against multiple MRH-related tumors that appeared on the left ankle joint and interphalangeal joints of both hands. In contrast, treatment with cyclosporin A (CyA) resulted in a marked regression of these nodules within one month, together with a complete remission of both MRH and lupus nephritis. We propose CyA as an alternative choice for the treatment of MRH.
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 in 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 the 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.
Lipid and lipoprotein levels in premenopausal systemic lupus erythematosus patients
Authors: Formiga F , Meco J F , Pinto X , Jacob J , Moga I , Pujol R
Published: November 2003

The purpose of this study was to assess the prevalence of dyslipoproteinemia and to analyze the clinical variables that are associated with it in a sample of premenopausal systemic lupus erythematosus (SLE) patients.

We studied 53 premenopausal (34.5 y) SLE outpatients and 45 controls. Clinical variables studied included patient age, weight, height, body mass index (BMI), age at disease onset, disease duration, clinical activity of SLE, renal involvement and drug therapy. Total cholesterol (TC), high-and low-density lipoprotein cholesterol (HDL-C and LDL-C), and triglycerides were measured using standard enzymatic techniques. Apolipoproteins (apo) A-I and B were determined by radial immunodiffusion.

Twenty-nine patients (55%) and 14 controls (30%) had dyslipoproteinemia. An increase in TC, triglycerides, HDL3-C, apo A-I and apo B, and a decrease in HDL2-C and HDL-C/TC index was found in SLE patients in comparison with controls. TC (P ‘ 0.007), apo B (P ‘ 0.02), LDL-C (P ‘ 0.03) and triglycerides (P ‘ 0.0001) were significantly correlated with proteinuria. Patients on prednisone therapy had higher triglycerides levels (P ‘ 0.03) than untreated patients. TC (P ‘ 0.01), LDL-C (P ‘ 0.006) and triglycerides (P ‘ 0.04) were also correlated with the dose of prednisone.

Dyslipoproteinemia is a common feature in adult SLE premenopausal patients which is characterized by an increase in TC, triglycerides and apo B, and an abnormal distribution of HDL subclasses. Corticosteroid therapy and proteinuria are the best predictors of dyslipoproteinemia in these patients.
Antiphospholipid syndrome induced by HIV
Authors: Leder A N , Flansbaum B , Zandman-Goddard G , Asherson R , Shoenfeld Y
Published: November 2003

A 24-y-old male who developed necrotic lesions on the lower extremities together with testicular thrombosis necessitating orchiectomy, demonstrated high level IgG anticardiolipin (aCL) associated with acute HIV infection. This is one of the first cases describing a close relationship between viral infection and the classic antiphospholipid syndrome (APS). It is well documented that HIV patients may produce antiphospholipid antibodies (aPL), but the full-blown picture of the APS is distinctly uncommon with HIV or any other viral infection, possibly due to the overproduction of the IgM isotype rather than IgG aCL as in this case. The induction of thrombosis following infections has been well described in patients with catastrophic antiphospholipid syndrome (CAPS) but not in patients with the ‘classic or simple’ APS.
Echocardiography and pulmonary function testing in childhood onset systemic lupus erythematosus
Authors: Al-Abbad A-JA , Cabral D A , Sanatani S , Sandor G GS , Seear M , Petty R E , Malleson P N
Published: November 2003

The aim of this paper was to investigate the frequency of echocardiography (ECHO) and pulmonary function test (PFT) abnormalities in childhood onset systemic lupus erythematosus (SLE), and to determine the relationship of these abnormalities to disease activity. The charts of 50 patients with childhood onset SLE attending a pediatric rheumatology clinic were reviewed for ECHO and PFT studies. The frequency and description of ECHO and PFT abnormalities were documented. Possible associations of PFT and ECHO abnormalities with clinical cardiopulmonary disease, radiographic findings, and measures of lupus disease activity were evaluated. Forty patients (80%) had at least one ECHO study. Twenty-seven (68%) had an abnormal initial study. Nine of 14 patients with an initial abnormal ECHO had normal findings on repeated study. Three abnormalities were considered moderately severe. Thirty-three patients (66%) had at least one PFT performed. Sixteen (48%) were abnormal initially. Four of these ‘abnormal’ studies were repeated and the abnormalities persisted. Nine patients (27%) were considered to have a severe abnormality. Thirty-one children (62%) had both studies performed. An initial abnormal ECHO and abnormal PFT was found in 10 (32%) of these children. No relationship between ECHO or PFT abnormality and any measure of disease activity (physician's global assessment, anti DNA, C3 or ESR) could be found. Occult cardiac and pulmonary disease as demonstrated by ECHO or PFT occurs frequently in childhood onset SLE. If we wish to understand the natural history of these abnormal heart and lung findings, it will be necessary to do serial testing with ECHO and PFTs in this population.
Lupus nephritis in Lebanon
Authors: Uthman I W , Muffarij A A , Mudawar W A , Nasr F W , Masri A-FM
Published: November 2003

This is a retrospective study of the clinicopathological characteristics of 50 systemic lupus erythematosus patients with nephritis who underwent a kidney biopsy and were admitted to the American University of Beirut Medical Center, in Lebanon, between 1979 and 1999. There were 43 females and seven males, with a median age of 24 y. Renal histology slides from these patients were assessed according to the World Health Organization classification, and were distributed as follows: class I (n = 3, 6%); class II (n = 14, 28%); class III (n = 11, 22%); class IV (n = 19, 38%); class V (n = 1, 2%); class VI (n = 2, 4%). All the patients received oral prednisone, in addition the following treatments were used: pulse intravenous (IV) cyclophosphamide (n = 23, 46%); azathioprine (n = 22, 44%); pulse IV steroids (n = 19, 38%); chloroquine sulfate (n = 17, 34%); methotrexate (n = 5, 10%); and plasmapheresis (n = 2, 4%). The median duration of follow-up was 5 y (range 1-33 y). On their last evaluation, out of 37 patients who were followed, 20 patients (54%) had controlled disease, eight patients (22%) were still on active medical treatment, four patients (11%) were on chronic hemodialysis, and five patients (13%) had died. Unlike three other Arab populations studies from Kuwait, United Arab Emirates and Saudi Arabia, where the most frequent histopathologic abnormality was class III, diffuse proliferative LN (class IV) was the most common type of lupus nephritis in Lebanon, similarly to reports from USA, France, Netherlands, South Africa, Thailand and Taiwan.
Anti-cardiolipin and anti-beta 2 glycoprotein Iantibodies in Indian patients with systemic lupus erythematosus: association with the presence of seizures
Authors: Shrivastava A , Dwivedi S , Aggarwal A , Misra R
Published: November 2003

The aim of this study was to examine whether the clinical features of antiphospholipid antibody syndrome are associated with anti-cardiolipin and anti-beta2 glycoprotein I antibodies in Indian patients with SLE. Seventy-six patients (71 females), who fulfilled 1982 ACR criteria for SLE, were prospectively studied for the clinical features of antiphospholipid antibody syndrome (APS), and their sera were analysed for the presence of IgG/IgM/IgA anti-cardiolipin antibodies (aCL) by an in-house ELISA and, in 65 of them, for the presence of IgG anti-beta2 glycoprotein I antibodies (anti-beta2 GPI)by a commercial kit. Thirty-nine (51%) patients were positive for aCL, all of which were positive for IgG aCL, either alone (79.6%) or along with IgM and/or IgA. Twenty-seve(69.3%) out of 39 aCL-positive and seven (26.9%) out of 26 aCL-negative sera were positive for IgG antibodies to beta2 GPI. There was a significant corr elation (r = 0.66, P > 0.05) between the levels of aCL and anti-beta2 GPI antibodies. Forty-one patients had features of definite or suggestive APS. Thrombocytopenia, recurrent pregnancy loss and CNS manifestations (seizures eight, infarct one) were seen in 20, 13 and nine patients, respectively. Thrombosis of the peripheral vessels was seen in only one patient. Only the presence of seizures was significantly associated with the presence of aCL and anti-beta2 GPI antibodies (P > 0.05). The characteristic association of definite APS (recurrent pregnancy loss and arterial/venous thrombosis) was lacking.
Vaccination and systemic lupus erythematosus: the bidirectional dilemmas
Authors: Aron-Maor A , Shoenfeld Y
Published: November 2003

Vaccination has been perhaps the most important achievement in medicine of the last century. A hoard of infectious diseases that used to claim the lives of many, especially children, have been prevented and some even eradicated. However, it is possible that within this gift there is hidden a ‘Trojan Horse’. During the last decade increasing numbers of reports regarding possible autoimmune side effects of vaccination, have been published. The existing data does not link the vaccines and the autoimmune phenomena observed in a causal relationship, nevertheless a temporal connection has been described. In this article we wish to address in particular the possible link between vaccines andsystemic lupus erythematosus (SLE), namely two aspects of this inter-relationship: the occurrence of SLE following vaccination and outcome of immunization of known SLE patients.
Grand Rounds from International Lupus Centres
Authors: Lane S E , Gaffney K , Ball R Y , Marshall T J
Published: November 2003

We report a case of long-standing SLE which presented with symptomatic muscle vasculitis on a background of photosensitivity, arthralgia and myalgia. The diagnosis was complicated by cardiomyopathy, nephrotic syndrome and diabetes. We highlight the benefits of aggressive treatment in severe disease and the importance of recognising and treating comorbidity especially in relation to atherosclerosis.
In vitro-activated human lupus T cells express normal estrogen receptor proteins which bind to the estrogen response element
Authors: Suenaga R , Rider V , Evans M J , Abdou N I
Published: November 2003

We have shown that estrogen receptor (ERa,ERb) transcripts are expressed in SLE and normal T cells. In this study, T cell nuclear extracts from female lupus patients and normal donors were tested for biologically active ER proteins capable of binding to the human estrogen response element (hERE) by electrophoretic mobility shift assays. When peripheral blood T cells were stimulated with 17b-estradiol (E2), PMA and ionomycin, two major retarded bands in T cell nuclear extracts exhibited a migration pattern similar to slow migrating protein-ERE complexes in human breast cancer cell extracts. T cells cultured only with E2 did not have these complexes. The formation of the complexes was inhibited by competition with the hERE cold oligonucleotide and partially with anti-ERa antibodies. There was no notable difference in the migration pattern of ERE-binding proteins between the SLE and normal T cell extracts. Together, these results suggest that activated human T cells, whether lupus-derived or normal-derived, contain biologically active ERa proteins. Other factors may be responsible for differential sensitivity of lupus T cells to estrogen.
Prevalence and isotype distribution of antiphospholipid antibodies in Chilean patients with systemic lupus erythematosus (SLE)
Authors: Aguirre V , Cuchacovich R , Barria L , Aris H , Trejo C , Massardo L , Pasten R , Espinoza L
Published: November 2003

Previous studies have demonstrated that ethnicity plays a role in the prevalence, isotype distribution, and clinical significance of anticardiolipin (aCL) and anti-β2 glycoprotein I (aβ2-GPI) antibodies in systemic lupus erythematosus (SLE) patients. Few studies have been done in Latin American populations. Serum samples from 129 Chilean SLE patients were tested for IgG, IgM and IgA aCL and aβ2-GPI by ELISA. Clinical data were reviewed with the focus on clinical manifestations of antiphospholipid syndrome (APS). Positivity for at least one isotype of aCL was found in 30% of patients, while only 10% were positive for at least one isotype of aβ2-GPI. IgG was the most prevalent isotype for aCL (16%), and the isotype distribution was similar (4%) for aβ2-GPI. In general, the presence of aCL was significantly associated with the presence of aβ2-GPI, but a number of samples were positive for only one antibody, some of them associated with clinical manifestations of APS. ACL antibodies at medium-high titers were significantly correlated with thrombosis (P/0.0007) and fetal loss (P/0.009); however, the sensitivity of aβ2-GPI for detecting thrombosis and fetal loss was lower than aCL (19 and 17% vs 56 and 50%, respectively), and the specificity slightly higher (91 and 90% vs 84 and 82%). In Chilean SLE patients, aCL and aβ2-GPI antibodies are important in the evaluation of patients with APS. However, the utility of aβ2-GPI antibodies was limited by the low prevalence of these antibodies in comparison with other ethnic groups. Further studies are needed to define the basis of the observed differences among ethnic groups.
Pinguecula and Sjögren's syndrome: two cases
Authors: de Roux-Serratrice C , Conrath J , Serratrice J , Granel B , Disdier P , Weiller P-J
Published: November 2003

A pinguecula is a small, raised conjunctival nodule at the temporal or nasal limbus classically associated with conjunctival microtrauma from exposure to sunlight and/or to dust. We report two cases occurring during the course of Sjögren's syndrome. To our knowledge this association has never been described.
Ultraviolet therapy in lupus
Authors: Millard T P , Hawk J LM
Published: November 2003

This review examines the use of ultraviolet (UV) therapy in lupus erythematosus (LE), a disorder usually associated with abnormally increased photosensitivity. In addition to the abnormal cutaneous response to ultraviolet radiation (UVR) exposure, photo-aggravation of systemic disease activity in systemic LE (SLE) may also occur. However, courses of UVR exposure may also be used in the treatment or prophylaxis of various photodermatoses, and LE now appears to be included in that group. Thus, several studies have reported apparent benefits of phototherapy in both cutaneous and systemic LE, although the underlying mechanisms remain obscure and final confirmation of such efficacy is still awaited in continuing studies.
Suppression of experimental systemic lupus erythematosus (SLE) in mice via TNF inhibition by an anti-TNFα monoclonal antibody and by pentoxiphylline
Authors: Segal R , Dayan M , Zinger H , Mozes E
Published: November 2003

We have previously shown that the clinical manifestations of experimental systemic lupus erythematosus (SLE) correlate with an early increased secretion of TNFα and IL-1. In the present study, we examined the efficacy of two therapeutic modalities which lower TNFα production or activity, on the clinical manifestations of the disease. Experimental SLE was induced in naive C3H.SW mice by injection of the human anti-DNA monoclonal antibody (mAb) bearing the common idiotype, 16/6 Id. Two weeks after booster injections, treatment with either an anti-TNFα mAb, or pentoxiphylline (PTX) was started, for a period of 6 weeks. Production of TNFα (by splenocytes) and IL-1 (by peritoneal macrophages) was determined 3 and 7 months after disease induction. The experimental mice were also followed for disease manifestations. Both treatment protocols, with anti-TNFα mAb and with PTX, reduced the production of the two pro-inflammatory cytokines, TNFα and IL-1, in mice with experimental SLE. Anti-DNA antibodies were significantly lower in the mice treated with either protocol. In addition, a significantly lower rate of leukopenia, proteinuria and immune complex deposition was observed in treated mice. Abrogation of TNFα and IL-1 production in the early stages of experimental SLE by an anti-TNFα mAb or by PTX improves the clinical status of mice affiicted with this autoimmune disease.
Update on therapy — thalidomide in the treatment of lupus
Authors: Karim M Y , Ruiz-Irastorza G , Khamashta M A , Hughes G RV
Published: November 2003

Thalidomide has been shown to be an effective treatment for cutaneous forms of lupus erythematous refractory to other therapies. Thalidomide has very serious side effects, including teratogenicity and neuropathy, which limit its clinical use in lupus to such severe refractory cases. Efficacy has been confirmed in several studies, although recurrence after discontinuation of treatment is frequent. More recent experience suggests that lower doses than originally used may be effective, which may result in a reduction in side effects. Much effort has been expended in studying the mechanisms of action of thalidomide, although as yet it is unclear which of the mechanisms identified to date contribute to its efficacy in treating cutaneous forms of lupus erythematosus. Identification of patients suitable for thalidomide therapy requires a rigorous selection process. Potential side effects should be clearly explained, particularly teratogenicity as many patients are young women. Written consent and a negative pregnancy test must be obtained prior to commencement of therapy. Reliable contraceptive measures should be strictly observed by patients taking thalidomide. Close clinical and neurophysiological supervision using nerve conduction studies should be undertaken.
Alternative therapies in rheumatic diseases—pros and cons
Authors: Aron-Maor A , Shoenfeld Y
Published: November 2003

We have reviewed several types of alternative therapy used in the treatment of rheumatic diseases. The data provided by most available research does not show significant results of these therapies in comparison with Western treatment protocols. However, there has been some symptomatic relief reported by patients who have turned to these alternative remedies. Alternative medicine is not without potential harm or danger, especially in the herbal remedies used. Acupuncture is a relatively safe means of therapy, and even though its effect in rheumatic diseases has not been very impressive in terms of influence on the course of disease or laboratory parameters, it has provided some symptomatic relief where pain was involved. Even though acupuncture has not been very effective in rheumatic conditions, there are other published claims for success in migraines, electro-acupuncture in depression, in the prevention of post-operative nausea and vomiting, and for nausea caused by chemotherapy as well as for analgesia in childbirth.

Since the public demand for alternative types of therapy is increasing, and since people will go to alternative medicine therapists, it makes sense for medical doctors to become acquainted with these subjects.
Prevention of autoantibody formation and prolonged survival in New Zealand Black/New Zealand White F1 mice with an ancient Chinese herb, Ganoderma tsugae
Authors: Lai N-S , Lin R-H , Lai R-S , Kun U-C , Leu S-C
Published: November 2003

For centuries, Chinese medicine has regarded Ganoderma, a fungus (Myceteae, Amastigomycota, Basidomycetes, Aphyllophorales, Polyporaceae, Ganoderma) also known as ‘Ling Zhi’ in Mandarin, as a premium remedy for many diseases. Until now, no convincing data regarding its therapeutic effects in vivo on autoimmune diseases have been demonstrated. In this study, a controlled protocol was conducted in which New Zealand Black/White F1 mice were fed standard chow with prednisolone (0.5 mg/kg/day) or Ganoderma tsugae extract, commencing at 2 months of age. It was found that the F1 mice responded well to Ling Zhi extract. Ling Zhi improved the survival rate of lupus mice, decreased the amount of proteinuria, decreased serum levels of anti-dsDNA autoantibody, and showed evidence of decreased perivascular and parenchyma mono-nuclear cell infiltration in vital organs.
FcγRIIa/IIIa polymorphism and its association with clinical manifestations in Korean lupus patients
Authors: Yun H R , Koh H K , Kim S-S , Chung W T , Kim D W , Hong K P , Song G G , Chang H K , Choe J-Y , Bae S-C , Salmon J E , Yoo D-H , Kim T-Y , Kim S Y
Published: November 2003

The aim of this study was to determine the distribution of the FcgRIIa and FcgRIIIa polymorphisms and their association with clinical manifestations in Korean lupus patients.

Three hundred SLE (systemic lupus erythematosus) patients (48 male, 252 female) meeting 1982 ACR criteria and 197 Korean disease-free controls were enrolled. Genotyping for FcgRIIa 131 R/H and FcgRIIIa 176 F/V was performed by PCR of genomic DNA using allele-specific primers and the FcgRIIIa genotype was confirmed by direct sequencing of PCR product in some cases.

There was significant skewing in the distribution of the three FcgRIIa genotypes between the SLE and the controls (P=0.002 for R =R131 vs R/H131 and H/H131, OR 2.5 (95% CI 1.4–4.5), but not in FcgRIIIa genotypes. FcgRIIa-R allele was a significant predictor of lupus nephritis, as compared with SLE patients without nephritis (P=0.034 for R131 vs H131, OR 1.4 (95% CI 1.03–1.9)), but proliferative nephritis (WHO class III and IV) was less common in patients with FcgRIIa-R/R131 and in FcgRIIa-R allele. In 300 SLE patients, high binding allele combination H131=V176 was less common in SLE with nephritis than in SLE without nephritis. Hemolytic anemia was less common in R131=F176 allele combination among four FcgRIIa/FcgRIIIa allelic combinations. Male SLE patients showed a higher frequency of renal involvement, serositis, thrombocytopenia, malar rash and discoid rash than female SLE, and male SLE had a higher frequency of FcgRIIa-R/R131 or R131-allele than male controls, but FcgRIIa or FcgRIIIa genotypes had no association with renal involvement in male SLE patients. FcgRIIa-H/H131 showed a higher frequency of hemolytic anemia and less pulmonary complications in male SLE. Female SLE patients showed higher frequency of any hematologic abnormality, lymphopenia, anti-cardiolipin antibody (/) and anti-Ro antibody (/) than male SLE, and had earlier onset of first symptoms. There was no skewing in FcgRIIa or FcgRIIIa genotypes between female SLE and female controls, but FcgRIIa-R131 allele showed skewing between female SLE with nephritis and female SLE without nephritis. The age at onset of thrombocytopenia was earlier in FcgRIIa-R/R131 among three FcgRIIa genotypes, and serositis in FcgRIIIa-F/F176 among three FcgRIIIa genotypes.

FcgRIIa-R131 homozygote was a major predisposing factor to the development of SLE and FcgRIIa-R131 homozygote and R131 allele were a predisposing factor, and H131=V176 was a protective allele combination in lupus nephritis. In contrast to other ethnic patients, in our study cohort, clinical manifestation was different between male and female, and FcgRIIa and FcgRIIIa showed somewhat different clinical associations between the genders.
Polymorphic light eruption and the HLA DRB1*0301 extended haplotype are independent risk factors for cutaneous lupus erythematosus
Authors: Millard T P , Kondeatis E , Vaughan R W , Lewis C M , Khamashta M A , Hughes G RV , Hawk J LM , Mcgregor J M
Published: November 2003

Recent evidence suggests that polymorphic light eruption (PLE) is an inherited photosensitivity disorder which may predispose to cutaneous lupus erythematosus (LE). In this study we examine the relative risk (RR) attributable to the presence of PLE, together with the effect of the major histocompatibility complex (MHC) in the development of cutaneous LE. Eighty-five Caucasian patients with annular subacute cutaneous LE (SCLE) and discoid LE (DLE) were recruited, together with 102 first degree relatives and 200 healthy local Caucasian controls. Symptoms suggestive of PLE were elicited in patients and relatives, and human leukocyte antigen (HLA) typing determined by PCR-SSP. Standard association analysis and family transmission disequilibrium testing (TDT) were then used to compare the HLA frequencies between groups. We found a significant (P < 0.05) association of the HLA A*01, B*08, DRB1*0301 extended haplotype with both SCLE and DLE and also significant association of DLE with the HLA A*03, B*07, DRB1*15 haplotype, with a possible protective effect in SCLE for HLA B*44 and DRB1*04 (P=0.002 and 0.001 respectively). Association was observed between PLE and cutaneous LE (P < 0.001), but not between PLE and any HLA allele. From these figures we estimate, for the general population, that the RR of developing SCLE given the presence of (a) PLE, (b) DRB1*0301 and (c) both PLE and DRB1*0301 is 3.37, 5.45 and 12.03, respectively. For DLE, equivalent RRs are 3.11, 2.15 and 6.94. In conclusion, these data imply the involvement of both PLE and HLA DRB1*0301 in the development of SCLE and DLE. They form a basis for examining the genetic architecture of photosensitivity, some aspects of which may be common to both cutaneous LE and PLE.
Benefyts of lefiunomide in systemic lupus erythematosus: a pilot observational study
Authors: Remer C F , Weisman M H , Wallace D J
Published: November 2003

The objective of this study was to retrospectively explore the safety and efficacy of leflunomide (LEF) in outpatients with systemic lupus erythematosus (SLE).

Eighteen SLE females received LEF, open label, 100 mgday loading dose for 3 days followed by 20 mg per day. Patients were evaluated for safety and efficacy after 2—3 months of therapy.

The mean age was 42.6 y and mean disease duration 7.9 y. ACR criteria were met by 1518. Four patients stopped LEF during the observation period. Ten of 14 LEF-treated patients had subjective improvement with 914 patients achieving lower SLEDAI scores. The mean SLEDAI decreased by 2.1 (P=0.005) and the mean ESR decreased by 9 mm h(P=0.02). Prednisone dosages could be reduced in 25 subjects without a flare. No organ-threatening or life-threatening side effects were seen in our patients. Diarrhea occurred in seven patients (two stopped LEF), rash occurred in one patient (stopped LEF), one patient stopped LEF for reasons not related to therapy. Blood pressure was unchanged.

Leflunomide was efficacious and safe in this cohort of SLE patients after 2—3 months of therapy. Placebo-controlled trials of longer duration are indicated.
Presence of cutaneous interferon-a producing cells in patients with systemic lupus erythematosus
Authors: Blomberg S , Eloranta M L , Cederblad B , Nordlind K , Alm G L , Rönnblom L
Published: November 2003

Systemic lupus erythematosus (SLE) patients have increased levels of interferon-alfa (IFN-a) in the circulation but a reduced number of functionally intact natural IFN-a producing cells (IPC) in peripheral blood. In search for tissue localisation of activated IPC, we investigated skin biopsies from SLE patients for the occurrence of such cells.

Eleven SLE patients with inflammatory skin lesions and six healthy controls were biopsied. An immunohistochemical technique (IH) and in situ hybridisation (ISH) were used to detect intracellular IFN-a protein and IFN-a mRNA, respectively.

In all 11 biopsies from SLE lesions, a high number of IPC were detected by IH. In the nonlesional SLE biopsies we could also demonstrate IPC in 10=11 patients. In 6=11 SLE patients, IFN- a mRNA containing cells could be detected in the specimens. A low number of IPC were detected in 1=6 healthy controls by IH, but no ISH positive cells were seen.

Our results demonstrate that SLE patients have active IPC in both dermal lesions and in noninflammatory skin. A recruitment of IPC from blood to peripheral tissues may explain the low number of circulating natural IPC in SLE patients. Because the type I IFN system is involved in the SLE disease process, these results are of interest for the understanding of the pathogenesis in SLE.
Hyperactivity in a mouse model of the antiphospholipid syndrome
Authors: Katzav A , Pick C G , Korczyn A D , Oest E , Blank M , Shoenfeld Y , Chapman J
Published: November 2003

In the antiphospholipid syndrome (APS), antibodies to a complex of phospholipids and beta2-glycoprotein I (β2-GPI) are associated with recurrent thromboembolic events, spontaneous abortions, thrombocytopenia and central nervous system (CNS) disturbances. Animals immunized with b2-GPI develop the systemic manifestations of APS but the involvement of the (CNS) in these animals has not been studied. The objective of the present study was to examine mice with induced experimental APS for behavioral changes. Female Balb/C mice were immunized once with β2-GPI in complete Freund's adjuvant (CFA) or with CFA alone. Four months after immunization the mice were tested in the staircase apparatus and the following two variables were measured: (1) number of rears; and (2) number of stairs climbed by the mice. Immunization with β2-GPI resulted in elevated levels of circulating anti-negatively charged phospholipids and anti-β2-GPI antibodies. The APS mice exhibited hyperactive behavior as reflected by more frequent rears (P < 0.023) and higher number of stairs climbed (P < 0.019) by the mice in 3 min. This simple test demonstrated that experimental APS animals are significantly hyperactive and may serve as a marker for CNS involvement in this model.
Lupus profundus: not a benign disease
Authors: Grossberg E , Scherschun L , Fivenson D P
Published: November 2003

Lupus profundus is an unusual clinical variant of cutaneous lupus erythematosus that has previously been described as a benign disease that follows a mild course. This report describes the extent of disease and associated comorbidities in patients with severe lupus profundus and systemic lupus erythematosus. Four cases of lupus profundus are reviewed and their associated systemic disease complications are highlighted. All four patients fulfylled at least four of the 11 criteria for systemic lupus erythematosus. One patient suffered from severe facial disfygurement and Parry-Romberg syndrome. Two patients developed nonhealing ulcers on the scalp. All four patients had scarring alopecia as well as depressed areas over large areas of their body surfaces. All patients were resistant to conservative therapy, and required long-term aggressive therapy. Clinical depression secondary to disfygurement was a major problem in three patients. Extensive lupus profundus may be associated with more serious systemic disease and warrants aggressive treatment early on to prevent permanent disfygurement and its resultant psychological consequences.
Selected serum cytokines in systemic lupus erythematosus treated with quinagolide
Authors: Hrycek A , Cieślik P , Tustanowski J , Nowak S , Jedynak P
Published: November 2003

The objective of this study was to determine the effect of quinagolide (Norprolac) on serum level of cytokines in systemic lupus erythematosus (SLE) patients. In 20 SLE patients treated with a low dose of quinagolide, and in 17 healthy persons who constituted the control group, concentration of serum prolactin (PRL), interleukins (ILs), soluble tumor necrosis factor receptors (sTNF Rs) preceded by calculation of disease activity index (SLEDAI) were tested at entry and then after 3 months in 16 patients and after 6 months in 11 patients who completed the study. Serum PRL level was higher (though insignificantly) in the SLE group than in the controls and decreased significantly after 6 months of therapy. A raised SLEDAI score at entry was significantly reduced during therapy but a weak correlation with PRL level was revealed. A significant increase in IL-6 level in SLE group as compared to controls was observed (respectively 14.57±13.25 and 5.04± 3.35 pg =ml) as well as a significantly decreased level after 6 months of treatment (4.30±2.51 pg =ml). There was a significant difference between sTNF RI concentration before and after 3 months of quinagolide treatment (respectively 1140.83 312.08 and 1454.58±465.54 pg =ml). After 6 months of treatment a statistically significant correlation between concentration of PRL and level of IL-6 and a negative correlation between PRL and sTNF RI was revealed. Quinagolide treatment may have a role in the management of SLE patients. Lupus (2001) 10, 424–430.
Systemic lupus erythematosus in Aborigines and Caucasians in central Australia: a comparative study
Authors: Segasothy M , Phillips P A
Published: November 2003

The objective of this study was to determine whether there are differences in the prevalence, clinical and laboratory manifestations, and morbidity and mortality of systemic lupus erythematosus (SLE) between Aborigines and Caucasians in Central Australia.

The medical records of all patients diagnosed with SLE upto December 1999 were reviewed retrospectively.

Prevalence of SLE was 1:1360 for Aborigines and 1:5170 for Caucasians. The prevalences of malar rash, discoid rash, photosensitivity, oral ulcers, pleuritis, anticardiolipin antibodies and lupus anticoagulant were higher in Caucasians than in Aborigines. The prevalences of anti-Sm antibody and anti-RNP antibody were higher in Aborigines than in Caucasians. These differences did not attain statistical significance. There was a low prevalence of renal disease in Aborigines and Caucasians. Mortality was low in Aborigines and nil in Caucasians.

Although there is a high prevalence of SLE in Aborigines in Central Australia, renal involvement and mortality are low.
Lupus flare associated with growth hormone
Authors: Bae Y-S , Bae S-C , Lee S-W , Yoo D-H , Kim T Y , Kim S Y
Published: November 2003

This case illustrates a young man with an 11 y history of systemic lupus erythematosus who developed lupus flare after a 9-month use of growth hormone (GH) for the treatment of growth retardation. The course of disease was improving after GH cessation and treatment with high dose corticosteroids and intravenous cyclophosphamide pulse therapy.
Atherosclerosis and autoimmunity
Authors: Gordon P A , George J , Khamashta M A , Harats D , Hughes G , Shoenfeld Y
Published: November 2003

Novel risk factors for the progression of atherosclerosis such as C-reactive protein (CRP) and adhesion molecules have stimulated much recent interest in the role of inflammation in athero-sclerotic disease. There is also evidence emerging that autoimmunity may have a role in the pathogenesis of atherosclerosis. In this article we explore the evidence for the role of autoimmunity in human atherosclerosis, both in the general population and in the context of the antiphospholipid syndrome. In particular we will focus on several autoantigens, review the evidence for their role in the process of atherosclerosis and the nature of the immune responses.
Assessing depression in systemic lupus erythematosus: determining reliable change
Authors: Iverson G L , Sawyer D C , McCracken L M , Kozora E
Published: November 2003

Systemic lupus erythematosus (SLE) can follow an unpredictable course. Clinicians and researchers use various self-report inventories to track aspects of the patient's functioning during the course of the illness (eg health status, pain, fatigue, quality of life and psychological status). These self-report inventories are used to measure improvement or deterioration as a function of the natural history of the disease process, or as a function of response totreatment. Proper interpretation of scores derived from these inventories requires an understanding of their psychometric properties, in particular, their reliability. It is important to calculate reliable change difference scores fortests commonly used in rheumatology so clinicians can determine if a change score is a reliable indicator of improvement or deterioration in individual patients (ie the change score is not likely to be due to measurement error). The purpose of this article is to illustrate the use of the reliable change difference scores when assessing depression in patients with SLE using the Beck Depression Inventory (BDI).
A possible role of apoptosis for regulating autoreactive responses in systemic lupus erythematosus
Authors: Funauchi M , Sugiyama M , SukYoo B , Ikoma S , Ohno M , Kinoshita K , Kanamaru A
Published: November 2003

It has been reported that apoptotic cells are increased inthe peripheral blood from patients with systemic lupuserythematosus (SLE), where dysfunctions of T helper 1 (Th1) cells are known. In order to study whether apoptosis of Th1cells is associated with the pathogenesis of SLE, earlyapoptotic cells in various T-cell subsets were detected using fluorescence-labeled annexin V (AnV). AnV binding was most frequently observed in CD4/CCR5/ T cells, andAnV binding rate (%) in this subset was higher in SLE thanin normal controls (14.7 2.6), although that in activeSLE(43.6 7.3) tended to be lower than that in inactive SLE (48.0 6.8). CD95=Fas expression was also increased i both active and inactive SLE. In some SLE patients, AnV binding rate changed in inverse proportion to titer of the serum anti-DNA antibody and in proportion to serum complement activity. These data suggest that apoptosis in Th1 cells is important in the pathogenesis of SLE and might play arole in regulating over-activation or autoreactive responses by T cells.
The effects of a human IgM monoclonal anticardiolipin antibody on pregnancy in a transgenic mouse model
Authors: Mason A N , Mageed R A , Mackworth-Young C G
Published: November 2003

The clinical features of antiphospholipid (or Hughes') syndrome (APS) are most commonly seen in individuals who have raised levels of IgG anticardiolipin antibodies. Most murine models of the syndrome have involved the administration of such antibodies to normal mice. However, APS can occur in the presence of raised levels of serum IgM anticardiolipin antibodies alone. The present study was designed to see if an IgM monoclonal antibody can induce changes in mice similar to those seen in human APS. This antibody, BH1, has previously been derived from a patient with primary APS. In its ligand-binding and idiotypic characteristics it is representative of antiphospholipid antibodies (aPL) found in the serum of patients with APS.

In order to minimise the immune response to human IgM, we used transgenic mice (F15) which express, and are predicted to be tolerant of, human immunoglobulin m chains. The features of APS may develop more readily in individuals who have an existing autoimmune disorder, such as systemic lupus erythematosus (SLE). We therefore crossed these transgenic mice with New Zealand Black (NZB, SLE-prone) mice, and used the progeny (F15 × NZB/F1) in our experiments. Twenty-four F15 × NZB/F1 mice were given BH1, or a control IgM antibody, (A5566) immediately preceding and then three times during pregnancy

There was a reduction in the mean number of foetuses in animals given BH1 compared with those given A5566 (8.6 vs 11.0; P 0.05), and a similar reduction in mean total foetal weight per pregnancy (9.05 vs 12.73 g; P 0.05). Two mice showed a marked reduction in platelet count. No evidence of thrombosis was detected macroscopically or histologically.

Our results show a lower incidence of APS-type features compared to previous studies in which mice have been administered aPL. This may be because BH1 is an IgM antibody. Nevertheless, the data support the concept that IgM aPL of particular ligand-binding specificities may have a direct pathogenetic role in certain cases of human APS.
Severe bone marrow failure associated with the use of alternating steroid with chlorambucil in lupus membranous nephropathy in Chinese
Authors: Wang A YM , Li P KT , Lai F MM , Chow K M , Szeto C C , Leung C B , Lui S F
Published: November 2003

Severe pancytopenia associated with the use of alternating steroid with chlorambucil regimen was described in six patients with nephrotic syndrome secondary to lupus membranous nephropathy (WHO class V). We believe this is the first report describing the life-threatening degree of marrow toxicity associated with this regimen of alternating steroid with chlorambucil in a Chinese population. Our data suggests that the susceptibility to marrow toxicity with the use of chlorambucil may only be applicable to Chinese patients with underlying systemic lupus erythematosus as a similar degree of toxicity has neither been reported in lupus patients of other ethnic groups nor in non-lupus patients of Chinese origin.
Lupus pregnancy: is heparin a risk factor for osteoporosis?
Authors: Ruiz-Irastorza G , Khamashta M A , Nelson-Piercy C , Hughes G RV
Published: November 2003

Regulation of calcium homeostasis during pregnancy is complex. Clinically significant bone mass loss is infrequent; however a subset of women may develop symptomatic osteoporosis related to pregnancy. Lactation is a period of special risk for bone loss. Whatever the effect of heparin on bone loss, vertebral fractures are rare in women treated with heparin during pregnancy. Low molecular weight heparins may have a less deleterious effect on bone than unfractionated heparin. Women with autoimmune diseases, particularly those with lupus and/or the antiphospholipid syndrome may receive heparin throughout pregnancy. Corticosteroids must be reduced as much as possible in these women, and calcium plus vitamin D are recommended. Finally, indications for heparin use must be clearly justified and advice regarding breastfeeding must be offered.