Lupus current issue

Editorial: Photoprotection: does it work?

Ilchyshyn, L, Hawk, J., Millard, T. — 2008-07-14

Editorial: Oral contraceptives in systemic lupus erythematosus: the case for (and against)

Petri, M, Buyon, J. — 2008-07-14

Childhood agricultural and adult occupational exposures to organic dusts in a population-based case-control study of systemic lupus erythematosus

Parks, C., Cooper, G., Dooley, M., Park, M., Treadwell, E., Gilkeson, G. — 2008-07-14

Organic dust exposure can influence the development and symptoms of immune-related diseases such as atopy and asthma, but has rarely been examined in relation to systemic autoimmunity. The present analyses explore the association of lifetime farm and occupational organic dust exposures with systemic lupus erythematosus (SLE) in recently diagnosed patients (n = 265) compared with controls (n = 355) frequency matched by age, sex and state. Questionnaire data included childhood farm residence, childhood and adult experience with specific crops, and adult work in textiles, hog or poultry processing and paper or furniture manufacture. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression models including age, sex, state, race, education and silica exposure. Overall childhood or adult farm contact and childhood farm residence were not associated with SLE. Farm contact with livestock was inversely associated with SLE (OR = 0.55, 95% CI 0.35, 0.88). This effect was most pronounced among those with childhood farm residence and both childhood and adult livestock exposure (OR = 0.19; 95% CI 0.06, 0.63), but was difficult to separate from adult exposure to grains or corn. Other adult occupational exposures were not associated with SLE risk overall, regardless of childhood farm residence or livestock exposure, although an inverse association was seen among non-smokers (OR = 0.59; 95% CI 0.33, 1.1), particularly for textile work (OR = 0.34; 95% CI 0.19, 0.64). These exploratory findings support the development of studies to specifically investigate the effects of organic dust exposure on SLE risk, with particular attention to exposure assessment and characterization of demographics, smoking and other occupational exposures.

Circulating thrombomodulin and vascular cell adhesion molecule-1 and renal vascular lesion in patients with lupus nephritis

Yao, G., Liu, Z., Zhang, X, Zheng, C., Chen, H., Zeng, C., Li, L. — 2008-07-14

Currently, the detection of renal vascular lesions (VLS) in lupus nephritis (LN) mainly depends on biopsy examination, and lack surrogate biomarkers for clinical dynamic evaluation. The aim of the present study is to explore the correlation between circulatory endothelial damage biomarkers and VLS. Soluble E-selectin, thrombomodulin (TM) and vascular cell adhesion molecule-1 (VCAM-1) were measured by ELISA. TM and VCAM-1 levels both were significantly elevated in LN with VLS than in LN without VLS (P < 0.01). However, the serum E-selectin was not significantly changed in LN patients with and without VLS. A positive correlation was found between TM and serum creatinine (r = 0.617, P < 0.05) in patients with vascular lesions. In order to further analyse the relationship between TM level and severity degree of vascular lesions in LN patients, we subdivided the patients with vascular lesions into two groups: with thrombotic microangiopathy (TMA) and without TMA. TM level of the patients with TMA is significantly higher than those without TMA (P < 0.01). In conclusion, combined with renal pathological examination, monitoring the circulatory levels of TM and VCAM-1, can provide circulating biomarkers of VLS in LN patients.

Prevalence and clinical associations of anti-Ku antibodies in systemic autoimmune diseases

2008-07-14

We retrospectively analysed the prevalence and clinical features associated to anti-Ku antibodies in patients affected by different autoimmune diseases. Anti-Ku antibodies are detected in 147 sera out of 7239 anti-ENA positive sera (2%). They are found in 2% of patients with systemic sclerosis (SSc) (8 out of 379), 1.8% of systemic lupus erythematosus (SLE) (7 out of 372) and 1.8% of undifferentiated connective tissue disease (UCTD) (9 out of 496) and more rarely in Sjögren Syndrome and rheumatoid arthritis. Most of anti-Ku positive patients were affected by UCTD and overlap syndromes, including polymyositis, SSc and SLE. Interstitial lung disease, myositis, articular symptoms, Raynaud's phenomenon and sicca represents the main clinical features detected in our cohort. The rate and severity of pulmonary disease is similar to those found in other SSc patients. Isolated anti-Ku were detected in about 47% of sera. No clinical differences were observed between these patients and subjects with multiple anti-nuclear specificities. However, anti-Ku are usually detected in association with other serological markers in SLE and Sjögren Syndrome, while they occurred isolated in SSc and polymyositis.

Genetic susceptibility and haplotype analysis between Fc{gamma} receptor IIB and IIIA gene with systemic lupus erythematosus in Chinese population

Pan, F, Tang, X, Zhang, K, Li, X, Xu, J, Chen, H, Ye, D. — 2008-07-14

The objective of this study is to understand the role of FcRIIB and FcRIIIA gene in susceptibility to systemic lupus erythematosus (SLE), and to examine possible susceptible haplotypes between two genes. A total of 119 patients with SLE from 95 nuclear families, aged from 14 to 78 years, were selected according to 1997 criteria of American College of Rheumatology. In addition, 316 family members of these patients were also genotyped. A family-based association study was used to explore the relationship between gene polymorphism and SLE. We studied 13 single-nucleotide polymorphisms (SNPs) encoding non-synonymous substitution in the FcRIIB and FcRIIIA gene (four SNPs in the FcRIIB gene and nine SNPs in the FcRIIIA gene) with respect to genetic susceptibility to SLE. All SNPs were genotyped by restriction fragment length polymorphism method. Among 13 SNPs, univariate (single-marker) family-based association tests showed that variant alleles at only four SNPs (rs10917661 and rs1050501, in exon 2 and exon 5 of FcRIIB gene, rs403016 and rs428888, in exon3 of FcRIIIA gene respectively) were significantly associated with genetic susceptibility to SLE. Furthermore, the haplotype-specific FBATs showed 50Ter-225Thr (34.1%, in FcRIIB gene) and 72Arg-118Asn (40%, in the FcRIIIA gene) haplotype were more frequently transmitted in SLE than other haplotypes (Z = 3.539, P = 0.00042; Z = 2.678, P = 0.007412 respectively). But haplotypes were not found between FcRIIB and FcRIIIA gene Our results suggest that there were meaningful haplotype in FcRIIIA and FcRIIB gene respectively. FcRIIIA and FcRIIB genes in the pathogenesis of SLE may play an independent role in Chinese population.

Haemolytic anaemia in a multi-ethnic cohort of lupus patients: a clinical and serological perspective

2008-07-14

Systemic lupus erythematosus is a chronic autoimmune disease that can be associated with a variety of haematological manifestations. We identified 76 patients with haemolytic anaemia in a cohort of 1251 unrelated female lupus patients enrolled in our studies. The presence of the various American College of Rheumatology clinical criteria for lupus and serological specificities were determined in lupus patients with haemolytic anaemia and compared with a group of race-matched control lupus patients without haemolytic anaemia. Clinical data were obtained from medical records, and serological specificities were determined in our clinical immunology laboratory at OMRF. The presence of haemolytic anaemia in lupus patients was associated with a higher frequency of proteinuria (OR = 2.70, P = 0.000031), urinary cellular casts (OR = 2.83, P = 0.000062), seizures (OR = 2.96, P = 0.00024), pericarditis (OR = 2.21, P = 0.0019), pleuritis (OR = 1.72, P = 0.028) and lymphopenia (OR = 1.79, P = 0.015). These findings were independent of the presence of thrombocytopenia, which was approximately five times more common in lupus patients with haemolytic anaemia. Lupus patients with haemolytic anaemia were about 8 years younger than lupus patients without haemolytic anaemia at the time of disease onset (P = 0.000001). In the absence of thrombocytopenia, lupus patients with haemolytic anaemia were approximately two times more likely to have anti-dsDNA antibodies (P = 0.024). The presence of haemolytic anaemia is associated with a subset of lupus characterized by a younger age of disease onset, and a more severe disease with a higher likelihood of renal involvement, seizures, serositis and other cytopenias.

Efficacy of enteric-coated mycophenolate sodium in patients with resistant-type lupus nephritis: a prospective study

2008-07-14

The role of mycophenolate mofetil (MMF) is still controversial in the treatment of cyclophosphamide-resistant proliferative lupus nephritis (PLN). Enteric-coated mycophenolate sodium (EC-MPS) has less gastrointestinal adverse effects than MMF and is, therefore, increasingly utilised in organ transplantation. The aim of this study was to compare the efficacy and safety of EC-MPS versus an extended-course of intravenous cyclophosphamide (ED-IVCY) in resistant-type PLN. Thirty-one, biopsy-proven PLN, patients who failed to respond to an induction of IVCY were enrolled in a prospective, open-labelled, historically controlled study. Patients received 6 month of EC-MPS (720 mg b.i.d.) treatment. The patients in the ED-IVCY group, collected from a database, received a repeated 6-month course of monthly IVCY 0.5–1 g/m² of body surface area. Both groups received 0.5–1 mg/kg/day of prednisolone. Primary outcomes were partial or complete responses. A repeated kidney biopsy was performed to evaluate the histological response. No serious adverse events or patient deaths were observed during the study. Both groups had comparable baseline characteristics. At 6 months, the EC-MPS group had a comparable response rate with the ED-IVCY group. There were significantly less adverse events in the EC-MPS group. Repeated biopsies showed significant improvement in the EC-MPS group. EC-MPS provides salutary efficacy and safety in the treatment of resistant-type PLN and can be a suitably alternative treatment to ED-IVCY.

Possible familial Mediterranean fever in a Caucasian patient with systemic lupus erythematosus

Schreiber, B., Lachmann, H., Mackworth-Young, C. — 2008-07-14

We report the case of a Caucasian man with systemic lupus erythematosus who had recurrent fevers and abdominal pain. He was later found to carry E148Q polymorphism of MEFV, the gene responsible for familial Mediterranean fever.

Rituximab treatment of pulmonary arterial hypertension associated with systemic lupus erythematosus: a case report

Hennigan, S, Channick, R., Silverman, G. — 2008-07-14

Abstract

Pulmonary hypertension is a common but underdiagnosed complication of systemic lupus erythematosus, which can be associated with significant morbidity and early mortality. Although often associated with anti-phospholipid antibodies, the etiology remains poorly understood. In case reports and small open trials, the anti-CD20, B-cell targeted therapeutic antibody, rituximab, has been reported to provide benefits for systemic lupus erythematosus patients with glomerulonephritis, anti-phospholipid antibody syndrome, vasculitis, arthritis, and refractory skin disease. However, the outcome of rituximab treatment of pulmonary arterial hypertension associated with systemic lupus erythematosus has not been described. We, therefore, present a case of a young systemic lupus erythematosus patient with early onset of pulmonary arterial hypertension during the disease course, refractory to multiple treatment modalities, who had significant improvement with rituximab therapy.

Successful treatment of life-threatening Evans syndrome due to antiphospholipid antibody syndrome by rituximab-based regimen: a case with long-term follow-up

Ruckert, A, Glimm, H, Lubbert, M, Grullich, C — 2008-07-14

An association of antiphospholipid antibody syndrome with antibodies directed against either phospholipids or plasma proteins strongly suggest that B-cell dysfunction may be involved in its pathogenesis. Antiphospholipid antibody syndrome with autoimmune cytopenias shows a poor response rate to conventional treatment with anticoagulants, glucocorticosteroids, immunosuppressive agents, intravenous immunoglobulin or plasmapheresis. We report a case of life-threatening antiphospholipid antibody syndrome with Evans syndrome receiving successful multimodal treatment including anti-CD20 monoclonal antibody rituximab with long-term follow-up.

Factors influencing adherence to medications in a group of patients with systemic lupus erythematosus in Jamaica

Chambers, S, Raine, R, Rahman, A, Hagley, K, De Ceulaer, K, Isenberg, D — 2008-07-14

The objective of this study was to examine the factors influencing adherence to medications in a group of patients with systemic lupus erythematosus (SLE) in Jamaica. A qualitative study was designed using a screening questionnaire and semi-structured interviews. The study was conducted in the rheumatology clinic at the University Hospital of the West Indies, Kingston, Jamaica. 75 patients with SLE including 20 interviewees, who had SLE for at least 1 year participated in the study. The main outcome measures were: (i) level of self-reported adherence in a sample of the clinic attendees and (ii) interviewees explanations of the reasons for taking or not taking drugs as prescribed by their physician. 56% of the 75 study participants reported taking their medications more than 85% of the time. High cost and poor availability of medications were the main reasons for poor adherence, but some patients chose not to take their medications because of side effects, perceived mild severity of their disease and/or a preference to take drugs only when symptomatic. Patients used herbal medicines to counteract side effects of Western medicines, to ‘purge the blood' and to manage lupus symptoms when they had no medications. Religious beliefs were used as a coping strategy. Traditional use of herbal medicines is common particularly in patients from rural Jamaica, and may explain the observed use of herbal medicines in those who have emigrated to developed countries. Socio-economic constraints and poor drug availability are particularly important influences on poor adherence in Jamaican patients with SLE. Religious beliefs and use of herbal remedies do not seem to affect adherence adversely but are used when drugs cannot be obtained.

Some concerns about the Sydney criteria for antiphospholipid syndrome

Carvalho, J. — 2008-07-14