Distinct antibody profile: a clue to primary antiphospholipid syndrome evolving into systemic lupus erythematosus?

We have performed a retrospective study to determine if patients with antiphospholipid syndrome that developed systemic lupus erythematosus (APS/SLE) had distinct clinical and/or serological features. All 80 primary APS (PAPS) patients followed up at our APS unit were included in the study and divided into two groups: 14 APS/SLE and 66 PAPS. Prior or at onset of lupus manifestations, six patients were uniformly negative for lupus and Sjögren autoantibodies, and the other eight patients had persistent positive. In the first year after diagnosis of SLE, three patients remained with negative antibodies, the other seven patients maintained the same antibodies, and four patients developed other antibodies. APS/SLE group had a significant lower mean age at PAPS diagnosis (26.0?±?8.0 vs. 34.2?±?11.9 years, p?=?0.03) and a longer disease duration (14.0?±?7.0 vs. 6.0?±?5.0 years, p?<?0.0001). The mean time for PAPS to develop SLE was 5.2?±?4.3 years. The typical clinical and laboratorial findings of APS did not discriminate both groups of patients. At lupus onset, antinuclear antibodies were more frequently observed in those who evolved to SLE (100 vs. 51.5 %, p?=?0.0005). Anti-double-stranded DNA (dsDNA), anti-ribosomal P, anti-Ro/SS-A, anti-La/SS-B, and anti-U1RNP antibodies were exclusively found in the APS/SLE patients, whereas anti-Smith (Sm) antibodies were not detected in both groups. The detection of a distinct subgroup of lupus-associated autoantibody in PAPS patients seems to be a hint to overt SLE disease, particularly in those patients with young age at diagnosis.     

Estrogen receptor alpha gene polymorphism and systemic lupus erythematosus: a possible risk?

Estrogens and their receptors may play a role in the pathogenesis of systemic lupus erythematosus. Genetic alterations in the exon 8-coding region of the estrogen receptor alpha alter the intracellular signalling of estrogens, leading in enhanced or diminished activity. We investigated whether genetic alterations in exon 8 of ERalpha gene are associated with the occurrence and clinical features of lupus disease. The coding region of ERalpha exon 8 was subjected to mutation analysis using the polymerase chain reaction, denaturing gradient gel electrophoresis and sequence analysis, using DNA isolated from whole blood of 36 female patients and 38 healthy females. Clinical and laboratory parameters were available from the patients' files. We identified the codon 594 polymorphism either in homozygous for the wild type gene (ACG/ACG) or heterozygous (ACG/ACA), both in patients and healthy females. Statistical analysis of the genotype and allele distribution revealed that there was a significant difference (chi2 test, P = 0.02 and P = 0.04, respectively) between patients and healthy women. Odds ratio estimate revealed that carriers of ACG/ACA genotype have three-fold higher risk of developing lupus disease (OR = 3.129, 95% CI 1.181-8.292). Moreover, in patients the heterozygous genotype was associated with rash, mouth ulcers and serositis (Fisher's exact test, P = 0.055, P = 0.083, P = 0.065, respectively). The heterozygous patients were associated significantly with an early age at disease onset (ANOVA test, P < 0.05). We conclude that estrogen receptor alpha codon 594 genotype may influence the development of systemic lupus erythematosus at a younger age, as well as a certain disease clinical pattern.     

Arterial occlusion in systemic lupus erythematosus: a good prognostic sign?

Arterial occlusion with subsequent amputation of extremities is a rare manifestation of systemic lupus erythematosus (SLE). It may be caused by local arteritis and/or thrombosis. We describe the clinical and laboratory manifestations and treatment administered to six SLE patients who developed peripheral arterial necrosis necessitating amputation of extremities secondary to the arterial occlusion. All patients were female, with ages ranging from 16 to 65 years. Arterial occlusion took place in the initial months of disease (median: 7 months). Only one of five patients tested for antiphospholipid antibodies had these antibodies who also had vasculitis and thrombosis in a histopathological study. Most patients presented a very benign outcome after the amputation of extremities and stayed in remission for several years. The satisfactory outcome of most patients after the vascular phenomenon allows us to consider the possibility that such a complication could be, for unknown reasons, a marker for good prognosis in SLE or, alternatively, that the aggressive therapy administrated for patients with this complication at the beginning of the disease could recover the balance of the immune system, avoiding future relapses.     

Treat-to-target in systemic lupus erythematosus: Where are we?

Systemic lupus erythematosus (SLE) is the most paradigmatic disorder within systemic autoimmune diseases. The concept and principles of treat-to-target (T2T) in SLE were established half a decade ago and, since then, remarkable advances have been made. An international consensus was organized in order to define and unify the term remission, although plurality, with subtle nuances still exists and has not been overcome. Also, lupus low disease activity state (LLDAS) was coined as an alternative and, perhaps, more realistic target. Both of them have proven to be meaningful in terms of improving several outcomes, and have opened the path for future research in clinical trials. This review arises from the need to summarize the current state of some of the recommendations of the T2T task force.     

Malignancy in systemic lupus erythematosus: what have we learned?

So far, we know that there is a slight increased risk in SLE for all cancers combined compared to that in the general population. However, this is largely driven by an increased risk for haematological malignancies, particularly NHL. Hodgkin's lymphoma may be increased as well. There is a moderately increased risk of lung cancer, and some evidence for increased risk of rarer cancer types, such as hepatobiliarly cancer and vulvar/vaginal malignancies.There is also very good evidence that cervical dysplasia is increased in women with SLE. This may be mediated by decreased clearance of HPV, which some suggest is an innate characteristic of SLE patients. However, an increased risk of cervical dysplasia is also associated with immunosuppressive medication exposures, particularly cyclophosphamide. Regardless of the source of increased risk for developing cervical dysplasia, it is important that women with SLE follow established guidelines for cervical cancer screening.Unfortunately, one of the most clinically relevant questions, the mechanism underlying the association between lymphoma and SLE, remains largely unanswered. Recent data suggest that disease-related factors may be at least as important as drug exposures. Work is in progress to further elucidate the relative importance of these two very important, and interrelated, factors.

• there is evidence that immune system activity plays a role in the development of some lymphomas, but there is also evidence that immunosuppressive medications can influence the development of certain cancers, and pre-cancerous states such as cervical dysplasia, in autoimmune rheumatic disease populations

• in many cases the benefits of immunosuppressive exposures in SLE probably outweigh the relatively small absolute risk of precipitating a malignancy

• regarding cervical dysplasia, there is evidence of increased risk related to some medication exposures, particularly to cyclophosphamide; women with SLE should follow the established guidelines for cervical cancer screening

• much has been learned recently regarding the association between cancer and SLE; however, important questions remain regarding the independent influences of medication exposures versus disease activity on lymphoma risk in SLE

• establishing which molecular pathways mediate the association between lymphoma and SLE will also be of great value

• a related research priority is the development of effective SLE treatments that could take the place of toxic agents such as cyclophosphamide

High risk of tuberculosis in systemic lupus erythematosus?

The incidence and severity of tuberculosis (TB) in patients with systemic lupus erythematosus (SLE) varies greatly among different series. In addition, prospective data are scarce. The aim of this study is to analyse the frequency and severity of TB in our cohort of lupus patients. We analysed data from a prospective database of a single center cohort of 232 patients with SLE (ACR criteria). Prophylaxis with isoniazid was not regularly administered. We identified all cases of TB diagnosed during 10 years (January 1994 to December 2003). The following variables were analysed: annual incidence of TB, location of infection and response to therapy. Data from published series reporting on the incidence of TB among SLE patients were extracted. Three patients (1.3%) suffered clinically manifest TB in 1603 patient-years of follow-up, resulting in an incidence of 187 cases/100,000 patient-years (95% CI 39-547). The pooled annual incidence of TB infection in our area during this period was 30/100,000 individuals. We recorded two cases of pulmonary TB and one case of tuberculous pleurisy. All patients had good response to therapy. The annual incidence of TB among SLE patients in other series, most of them from developing countries, varied between 150/100,000 patients in Turkey and 2450/100,000 patients in India. Of note, high prevalence of extrapulmonary forms as well as elevated TB-associated mortality was reported in most series. TB was more frequent in SLE patients than expected in the general population. We did not see any cases of disseminated infection and all patients had good response to treatment. Our data compare favourably in terms of incidence, severity and outcome with those from highly endemic areas.     

Folic acid in systemic lupus erythematosus – a new aspect

Clinical Rheumatology -     

Health disparities in systemic lupus erythematosus—a narrative review

Clinical Rheumatology - To describe root causes of health disparities by reviewing studies on incidence and outcomes of systemic lupus erythematosus (SLE) related to ethnic, race, gender, or...     

Microchimeric cells in systemic lupus erythematosus: targets or innocent bystanders?

During pregnancy maternal and fetal cells commute back and forth leading to fetal microchimerism in the mother and maternal microchimerism in the child that can persist for years after the birth. Chimeric fetal and maternal cells can be hematopoietic or can differentiate into somatic cells in multiple organs, potentially acting as targets for 'autoimmunity' and so have been implicated in the pathogenesis of autoimmune diseases that resemble graft-versus-host disease after stem cell transplantation. Fetal cells have been found in women with systemic lupus erythematosus, both in the blood and a target organ, the kidney, suggesting that they may be involved in pathogenesis. Future studies will address how the host immune system normally tolerates maternal and fetal cells or how the balance may change during autoimmunity.     

Biomarkers in systemic lupus erythematosus: Do they make the mark?

Biomarkers are indicators of biological processes. In lupus we especially require activity biomarkers to look at predicting flares, differentiating damage from activity, and assessing response to treatment. There are numerous molecules that have been evaluated for these purposes, but studies suffer from limitations of design, statistical rigor, and outcome measure. The best biomarker remains the oldest one, double-standard deoxyribonucleic acid (dsDNA) and has many longitudinal studies to back it, and shows the ability to predict renal flares. Apart from this anti-C1q, cell-bound complement activation products and urinary molecules-chemokines and neutrophil gelatinase—associated lipocalin (NGAL)—are promising. The interferon signature has not lived up to its promise; however, microRNA (miRNA) signature is newly coming up as a marker of activity. Even if we do come up with better biomarkers, there is lack of clarity on issues of socio-economic impact as well as psychological impact of frequent testing for biomarkers.     

Lymphopenia in systemic lupus erythematosus patients: Is it more than a laboratory finding?

Aim of the workTo investigate the relation between lymphopenia and clinical manifestations, laboratory findings, disease activity and damage index in systemic lupus erythematosus (SLE) patients.Patients and methods124 SLE patients were recruited from the Rheumatology Department in-patient and outpatient clinic, Faculty of medicine, Cairo University Hospitals. SLE disease activity index (SLEDAI) and the systemic lupus international collaborating clinics damage index (SLICC-DI) were assessed. Patients were divided into two groups according to presence or absence of lymphopenia (lymphocyte count ≤1500 cells/mm³⁾, and were compared as regards different disease parameters.ResultsThe 124 patients were 113 females (91.1%) and 11 males (8.9%). Their mean age was 28.54 ± 8.25 years and median disease duration was 48 (24–105) months. 86 (69.4%) had renal involvement, complement C3 was consumed in 84 (67.7%) and C4 in 44 (35.5%). All were receiving steroids and a high dose was more frequent in those with lymphopenia (17 (29.8%) compared to those without (in 9 (13.4%). Lymphopenia was found in 57 (46%) patients. Lymphopenic patients had higher frequency of renal involvement (p = 0.002) (OR = 3.37, CI = 1.5–7.8), complement consumption (p = 0.03), 24 h urinary proteins (p = 0.034), higher steroid doses (p = 0.012) and cyclophosphamide administration (p = 0.03). SLEDAI was severe in 29.8% of lymphopenic patients (p = 0.16), and SLICC-DI median was 2 in both groups (p = 0.4).ConclusionLymphopenia is a common finding in SLE patients and was significantly associated with lupus nephritis, complement consumption, higher steroid doses and cyclophosphamide administration. Lymphopenia might be a promising marker for renal involvement in SLE.     

Dubin-Johnson syndrome with systemic lupus erythematosus: a case report

Introduction Dubin-Johnson syndrome (DJS) is a rare recessively inherited conjugated hyperbilirubi- nemia caused by deficiency of the canalicular multi-drug resistance/multi-specific organic anionic transporter protein (MDR2/cMOAT). Thus bilirubin is conjugated but inefficiently secreted into bile, which results in accumulation of conjugated and, to some extent, unconjugated bilirubin in blood, leading to hyperbilirubinemia and bilirubinuria. But, the results of liver function tests are no…