Development and Implementation of a Pilot Registry for Monitoring the Efficacy and Safety of Novel Therapies in Patients with Systemic Lupus Erythematosus.

The therapeutic armamentarium in Systemic Lupus Erythematosus (SLE) is expanding with the introduction of novel biologic and small-molecule agents. Complementary to randomized controlled trials, registry-based studies are advantageous due to the inclusion of a wider range of patients from daily practice and the potential for long-term monitoring of the efficacy and safety of therapies. Moreover, data from registries can be used to identify disease phenotypes that best respond to biologic agents, and to correlate clinical response with parameters such as co-administered therapies and comorbidities. In this project, we will use the configuration of the Hellenic Registry of Biologic Therapies for inflammatory arthritides in order to design a dedicated SLE module with variables pertaining to global and organ-specific disease activity, severity, flares, organ damage/outcome, comorbidities and adverse events. The second stage will involve the pilot implementation of this platform for the multicentric registration of SLE patients who are treated with belimumab. The significance lies in the development of a structured registry that enables the assessment of the disease burden and the long-term efficacy and safety of existing and future biological agents in SLE. Piloting the registry can serve as a basis for establishing nationwide collaborative efforts.

Cognitive deficits early in the course of rheumatoid arthritis.

OBJECTIVE: The aim was to examine the severity and prevalence of cognitive difficulties in persons with rheumatoid arthritis (RA) within the first three years of diagnosis. METHOD: One hundred consecutive RA patients aged 28-67 years (90% women) were administered a battery of 6 neuropsychological tests yielding 14 cognitive indices. Self-reported measures of trait anxiety, depression, impact of disease on daily activities, and pain severity were also obtained along with physician-rated disease severity. RESULTS: Twenty percent of RA patients were classified as cognitively impaired, defined as age- and education-adjusted scores at least 1.5 standard deviations below the population mean on 3 or more cognitive indices. Impaired performance, controlling for age, education, and premorbid cognitive capacity, was detected primarily on measures of short-term memory, immediate and delayed episodic recall, and phonemic fluency. There were modest negative associations between cognitive indices and measures of perceived disease severity (pain level, impact of disease on daily functionality, and overall health quality). CONCLUSIONS: Cognitive deficits on several domains are frequently encountered in relatively young RA patients during the first few years of the disease and may need to be taken into account as important correlates of disease severity and progression.

Adaptation to an autoimmune disorder: Does mental flexibility impact illness-related self-regulation?

OBJECTIVE: To examine whether mental flexibility moderates the relationship between illness representations of control and coping behaviour in individuals suffering from rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). DESIGN: Recently, diagnosed RA (N = 80) and SLE (N = 75) patients completed questionnaires about illness representations of personal and treatment control and four coping behaviours: instrumental coping, adherence to medical advice, palliative coping and wishful thinking. Mental flexibility was assessed with the Trail Making Test Part B (TMT-B), while visuomotor processing speed, as a confounder, was assessed with the Trail Making Test Part A (TMT-A). Moderated mediation models were tested within a bootstrapped multiple regression framework. RESULTS: TMT-A scores had no statistically significant moderation effects on the relation between representations and coping behaviour. Conversely, in those participants with SLE, TMT-B scores moderated the relation of personal control to wishful thinking and palliative coping, as well as the relation of treatment control to both wishful thinking and palliative coping. All significant effects were restricted to the SLE group. CONCLUSION: Interactions between neurocognitive factors and the process of illness adaptation may emerge early during the course of SLE. The present findings highlight the role of cognitive functioning as an integral part of the illness-related self-regulation mechanism.

Diagnostic criteria for systemic lupus erythematosus: has the time come?

Systemic lupus erythematosus (SLE) is a multiorgan disease with protean manifestations. Because SLE is uncommon and heterogeneous, its diagnosis can pose a considerable challenge, especially for clinicians with limited expertise of the disease. This is particularly true at the early stages of SLE, when an inadequate number of features to secure the diagnosis might be present, and for patients presenting with uncommon features, which can nonetheless be severe and require prompt treatment. Furthermore, the suboptimal performance of immunological testing in patients referred for possible SLE has been highlighted. As a result, SLE remains largely a clinical diagnosis that is made after excluding alternative diagnoses. Diagnostic criteria can expedite diagnosis and treatment, but are not available for SLE. Thus, SLE classification criteria are often used, but strict adherence to these criteria could delay diagnosis. Therefore, while eagerly awaiting diagnostic criteria for this disease, we propose interim potential solutions to facilitate its diagnosis.

Interleukin-21 is increased in active systemic lupus erythematosus patients and contributes to the generation of plasma B cells.

OBJECTIVES: Excessive interleukin- (IL-) 21 production by T cells has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). We explored the expression and function of IL-21 in human SLE. METHODS: IL-21 and IL-21 receptor (IL-21R) expression was assessed by real-time PCR and flow cytometry in peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls. PBMCs, purified CD19+CD27- naïve and CD19+CD27+ memory B cells were stimulated with IL-21 and CpG-ODN2006 (TLR-9 agonist) to examine generation of memory and plasma (CD19+CD38highIgD-) B cells. Apoptosis was assessed by 7AAD staining. RESULTS: Active SLE patients had 4-fold higher IL-21 mRNA and increased levels of intracellular IL-21 in peripheral blood CD4+ T cells (mean±SD fluorescence intensity, 1.7±0.1 in active versus 0.9±0.3 in inactive SLE and controls, p=0.035). IL-21R mRNA was comparable between SLE and healthy controls. Stimulation of PBMCs with IL-21 increased the proportion of memory and plasma cells; addition of CpG-ODN2006 enhanced these effects. Both naïve and memory B cells responded to IL-21/TLR-9 by increased generation of memory and plasma B cells, respectively; an anti-apoptotic effect was observed. In active SLE, PBMCs stimulation with IL-21 and/or CpG-ODN increased memory and plasma B cells, comparable to healthy controls. Addition of IL-21 to lupus autologous mixed lymphocyte cultures induced significant IgG production, and treatment with IL-21R.Fc to block IL-21/IL-21R interaction reduced the proportion of plasma cells. CONCLUSIONS: Increased IL-21 may synergise with TLR-9 signalling and contributes to generation of plasma cells in active SLE patients.

Imported human tungiasis in Greece.

BACKGROUND: Tungiasis is a parasitic skin disease caused by the sand flea Tunga penetrans. It is widespread in poor urban and rural communities in sub-Saharan Africa, the Caribbean and South America. Imported cases of tungiasis are increasingly being reported due to the increased numbers of travelers visiting the affected areas. CASE REPORT: A 28-year-old woman presented with a lesion on the subungual area of the right fourth toe, covered with a central dark crust. The lesion appeared two weeks after returning from Tanzania. The flea Tunga penetrans was identified by histopathological examination of a biopsy material. This is the first case of tungiasis in Greece. CONCLUSIONS: Tungiasis should be considered in the differential diagnosis of parasitic infections in travelers returning from endemic geographical areas.