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.     

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.     

Can systemic lupus erythematosus be the cause of collapsing glomerulopathy?

Collapsing glomerulopathy is a severe form of glomerular injury, closely associated with HIV infection, characterized by the collapsing feature of glomerular damage with frequent tubulointerstitial involvement and rapid progression to terminal renal failure. The etiopathogenesis in non-HIV infected patients remains obscure. We reported a patient whose diagnosis of collapsing glomerulopathy (CG) and systemic lupus erythematosus (SLE) was done simultaneously and described the diseases characteristics suggesting that SLE could be an etiologic factor for the induction of this glomerulopathy, clinical evolution and treatment.     

Skin lesions--an indicator of disease activity in systemic lupus erythematosus?

Cutaneous manifestations have great diagnostic value for systemic lupus erythematosus (SLE). In this study we tried to establish a correlation between lupus erythematosus LE-specific and LE-nonspecific cutaneous lesions and disease activity measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Sixty-six patients with SLE were evaluated. They were divided into three groups having: (1) only LE-specific lesions (38 or 58.46%); (2) only LE-nonspecific lesions (4 or 6.15%); and (3) both types of lesions (23 or 35.38%). Results were analyzed using the Student t-test. Patients with LE-nonspecific skin manifestations had significantly increased disease activity compared to those with only LE-specific lesions. The number of different skin lesion types also correlated with disease activity. It was significantly increased in a group with three different types of lesion, either specific or nonspecific. Patients with only one type of lesion had mild disease. An intermediate disease activity was found in the group with two different lesion types. Lupus-specific skin manifestations serve primarily as an important diagnostic clue. In conclusion, patients with LE-nonspecific lesions have significantly more active SLE than those with LE-specific lesions and may therefore require more intensive therapy and disease monitoring.     

How do patients and doctors-to-be perceive systemic lupus erythematosus?

The aim of the present study was to assess and compare illness perception of systemic lupus erythematosus (SLE) held by 6th-year medical students and patients suffering from SLE. The study group consisted of 104 students (66 women; 63.5 %), mean age 24.7 (±1), and 64 outpatients with SLE (60 women; 93.7 %). All patients were treated at a university rheumatology outpatient clinic. Mean patients’ age was 44.3 years (±12.5). Mean duration of the disease was 11 years (±6.8). The Polish version of Brief Illness Perception Questionnaire (B-IPQ) was used to assess five dimensions of illness perception. The students were asked to complete a modified version of B-IPQ designed to measure health professionals’ illness perception. Significant differences were found in all but one B-IPQ scores. The students obtained significantly higher scores than the SLE patients in consequences, identity, concern and emotional response, whereas significantly lower scores in personal control, treatment control and understanding were noted among students. No differences were found in timeline scores. Medical students’ perception of SLE is more threatening and more negative than that of patients’. Doctors-to-be perceive SLE as being less controllable, more burdensome and having more consequences than patients do. Additionally, they believe the disease causes more emotional concern. The article discusses possible explanations together with positive and negative aspects of the discrepancies.     

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.     

Leflunomide: friend or foe for systemic lupus erythematosus?

Leflunomide is a new immunosuppressive medicine that has been effectively used in the therapy of rheumatoid arthritis and subsequently used with success in animal models and patients with systemic lupus erythematosus (SLE). However, its use has also been associated with significant and serious adverse reactions involving hematological, hepatic, immune, dermatological and respiratory systems. In the current review, we attempt to describe the two sides of this drug in the treatment of SLE.     

Neuropsychiatric systemic lupus erythematosus: where are we now?

When dealing with Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) there are still many controversial topics. In 1999 the American College of Rheumatology gave classification criteria for 19 clinical syndromes. However major problems are still related to low specificity of some of them such as headache, cognitive impairment or mood disorders. Even though a frequency of CNS involvement from 14 to 75% has been described, depending on both the population studied and the methodology of assessment, a lower frequency ranging from 21 to 28 % derived by larger case series seems more realistic. The introduction of the concept of "borderline cases", proposed by Italian Study Group for NP-SLE, is based both on clinical and instrumental evaluation and could represent a useful tool when dealing with conditions which do not fulfil ACR classification. Also the relationship between SLE activity and NP involvement is a debated issue. Concerning pathogenesis, it seems reasonable to consider multifactorial mechanisms related to antibody-mediated damage, antiphospholipid pro-thrombotic effect, non-inflammatory vasculopathy and cytokines mediated cytotoxycity. However, direct and unequivocal evidence for the implication of any of the above-mentioned mechanisms is still lacking. Although a wide range of neuroimaging tools have been used to evaluate CNS involvement, no single technique has proven to be definitive and, when dealing with a patient with suspected NPSLE, it is important to combine different diagnostic techniques. Due to the lack of effective imaging along with limitation in knowledge of underlying pathogenetic mechanisms and paucity of histopathologic findings, therapeutic approach in NPSLE remains a difficult issue and is currently based on personal experience. Italian Study Group for NP-SLE proposes the creation of a national registry on NPSLE to validate ACR classification criteria. Furthermore, the possibility to collect large series and stratifying them for each of the included neuro-psychiatric syndromes seems a good strategy for planning multicentric controlled therapeutic trials in the near future.     

Koebner’s phenomenon in systemic lupus erythematosus

Koebner phenomenon is defined as a nonspecific skin stimulus eliciting a disease skin reaction. The nature of the skin trauma varies greatly and includes areas of thermal injury, excoriations, surgical incisions, and scars. We report a patient with recent onset of systemic lupus erythematosus who developed Herpes zoster on immunosuppressant medication. Two weeks after resolution of the vesicles, the patient presented with new ulcerative reddish lesions over the herpes zoster scare and worsening of her malar rash without evidence of worsening of any other organ. Koebner phenomenon was suspected. We review the literature on Koebner phenomenon in SLE.     

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

Do current arterial hypertension treatment guidelines apply to systemic lupus erythematosus patients? A critical appraisal

Objective

Arterial hypertension (HTN) is reported to burden up to 74% of systemic lupus erythematosus (SLE) patients and contributes significantly to accelerated atherosclerosis and increased cardiovascular (CV) risk. Current HTN treatment guidelines have not incorporated lupus patients in their recommendations; whether these guidelines can be fully implemented in SLE is doubtful.

Methods

A critical appraisal of the existing HTN guidelines in regard to SLE is presented in this review, based upon clinical and experimental data. Particular issues addressed are the time of antihypertensive therapy initiation, the optimal blood pressure level, the antihypertensive agent of first-choice and the need for reduction of the total cardiovascular risk in SLE.

Results

Antihypertensive therapy should be recommended at levels of 140/90 mmHg (systolic and diastolic BP, respectively) in newly diagnosed lupus patients without overt target organ involvement. In the case of lupus nephritis (LN) or diabetes mellitus (DM), therapy should be implemented at lower levels, such as 130/80 mmHg. Hypertensive lupus patients should be considered at high or very high CV risk and, consequently, the optimal BP level should be less than 130/80 mmHg. Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) seem to be a safe and efficacious first-choice antihypertensive treatment in lupus patients. Total CV risk should be considered and co-morbidities (dyslipidemia, antiphospholipid syndrome, etc.) should be managed promptly.

Conclusions

Current HTN therapeutic guidelines, lacking data from large-scale clinical trials, may not adequately apply to SLE patients. The assessment of the aforementioned recommendations in randomized clinical trials is expected to confirm their value in reducing CV risk in SLE.