Maura Couto

Frequency and functional activity of Th17, Tc17 and other T-cell subsets in Systemic Lupus Erythematosus

To compare frequency and functional activity of peripheral blood (PB) Th(c)17, Th(c)1 and Treg cells and the amount of type 2 cytokines mRNA we recruited SLE patients in active (n=15) and inactive disease (n=19) and healthy age- and gender-matched controls (n=15). The study of Th(c)17, Th(c)1 and Treg cells was done by flow cytometry and cytokine mRNA by real-time PCR. Compared to NC, SLE patients present an increased proportion of Th(c)17 cells, but with lower amounts of IL-17 per cell and also a decreased frequency of Treg, but with increased production of TGF-beta and FoxP3 mRNA. Iotan active compared to inactive SLE, there is a marked decreased in frequency of Th(c)1 cells, an increased production of type 2 cytokines mRNA and a distinct functional profile of Th(c)17 cells. Our findings suggest a functional disequilibrium of T-cell subsets in SLE which may contribute to the inflammatory process and disease pathogenesis.

Classification of Systemic Lupus Erythematosus: Systemic Lupus International Collaborating Clinics Versus American College of Rheumatology Criteria. A Comparative Study of 2,055 Patients From a Real-Life, International Systemic Lupus Erythematosus Cohort.

The new Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria aimed to improve the performance of systemic lupus erythematosus (SLE) classification over the American College of Rheumatology (ACR) 1997 criteria. However, the SLICC 2012 criteria need further external validation. Our objective was to compare the sensitivity for SLE classification between the ACR 1997 and the SLICC 2012 criteria sets in a real‐life, multicenter, international SLE population.

White blood cell count abnormalities and infections in one-year follow-up of 124 patients with SLE.

The purpose of our study was to evaluate the frequency of leukocyte count abnormalities in a large cohort of SLE patients and its association with infection. To make this evaluation, we studied consecutive patients with SLE diagnosis and prospectively followed them in the Coimbra Lupus Cohort. Data about white blood cell count abnormalities and infection during one‐year follow‐up were obtained. The presence of leukopenia, lymphopenia, and neutropenia was registered for one‐year period. Infections were classified as severe or mild. We found that of the 124 patients who were included (91.1% female, mean age 41.2, mean disease duration 11.1), mild infections occurred in 43.5%, and severe in 3.2% of the patients. Twelve percent, 41.1%, and 4.8% of the patients had persistent leukopenia, lymphopenia, and neutropenia, respectively. Fourteen percent received a pneumococcal vaccination. Patients with neutropenia had a significantly higher number of infections (P= 0.033). Thus, our study showed that neutropenia was associated with an increased risk of infection during this one‐year follow‐up. Infections were frequent, but most of them were mild.

Functional characterization of peripheral blood dendritic cells and monocytes in systemic lupus erythematosus

With the purpose of contributing to a better knowledge of the APCs functional activity in SLE, we evaluated the distribution and functional ability to produce pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-12) of peripheral blood (PB) monocytes and DC (tDC), particularly myeloid (mDC) and CD14−/lowCD16+ DC subpopulations comparing them with those obtained from healthy individuals. The study was performed in 34 SLE patients with diverse disease activity scores (SLEDAI) and 13 healthy age- and sex-matched controls (NC). Our results show an overall decrease in absolute number and relative frequency of tDC in SLE patients with active disease when compared to those with inactive disease and NC, although this decrease did not seem to have an effect on the distribution of PB DC subsets. The monocytes number in SLE patients was similar to those found in NC, whereas a higher frequency of monocytes producing cytokines as well as the amount of each cytokine per cell found without stimulation was particularly observed in those patients with active disease. After stimulation, we observed a higher frequency of IL-12-producing monocytes in active SLE patients. On the other hand, we found among DCs higher frequencies of cytokine-producing CD14−/lowCD16+ DCs and a higher amount of cytokines produced per cell, particularly in active disease. These findings support an increased production of inflammatory cytokines by APCs in active SLE, mostly associated with alterations in CD14−/lowCD16+ DC subset homeostasis that might contribute to explain the dynamic role of these cells in disease pathogenesis.

Epidemiology of Systemic Lupus Erythematosus

Publisher Summary Epidemiology is the study of the distribution of illnesses and diseases and the factors affecting their incidence and clinical course in the population. Systemic lupus erythematosus (SLE), an autoimmune disease with a broad spectrum of clinical and immunological manifestations, is a major challenge to study epidemiologically, but research on SLE has been carried out in many parts of the world. These include descriptive studies of incidence and prevalence, observational studies of SLE prognosis, and the identification of potentially preventable causes of morbidity and mortality. Analytic and genetic epidemiologic studies suggest a multifactorial etiology of SLE. A better understanding of the epidemiology of SLE should help us understand its etiology, identify predictors of morbidity and mortality, and improve SLE care and outcomes. Epidemiologic clues for potential cause(s) remain elusive, not so much from lack of effort, but lack of strong signals. Even the most established risk factors, except for gender, explain the minority of cases. Overall, epidemiologic studies demonstrate a good and possibly improved prognosis since its first description, making SLE a chronic but potentially dangerous illness. Studies also indicate considerable variations in outcome and differences between ethnic groups and between industrial and preindustrial countries that are probably increasing, comprising a major research challenge and a possible public health opportunity to correct these inequalities. Long-term morbidity is appreciated but its study is only just beginning. Future studies will need to look at what is really modifiable and to test interventions rigorously.

Anaphylaxis to mefenamic acid in a patient with new onset of systemic lupus erythematosus.

Many studies have addressed the frequency of drug allergy (DA) in systemic lupus erythematosus (SLE) patients. Some studies suggest that there may be an increased risk in these patients while others do not confirm this. The conflicting results may be due to differences in definition of drug allergy; in the means of ascertaining allergic manifestations; and in the choice of controls. SLE patients are more frequently exposed to drugs, which, ‘‘per se’’, represent a risk factor for drug allergy. Prompt recognition of DA, particularly anaphylaxis, is crucial, as it may be life-threatening and the appropriate treatment cannot be delayed. In a patient with SLE, the differential diagnosis of drug allergy is challenging. Features such as rash, fever and cytopenia may result from drug allergy but may also be part of SLE manifestations. Furthermore, drugs like sulphonamides are well known to exacerbate, or even induce SLE. The authors report a case of a 32-year-old Caucasian female housewife who presented at the emergency room with rash, diffuse myalgias, dry mouth, paraesthesia and dizziness. The symptoms started 90 minutes after taking a 250 mg tablet of mefenamic acid. She was thought to have an allergic drug reaction and was treated with intramuscular clemastin and IV methylprednisolone 250 mg. She was alert, her blood pressure was 100/57 mmHg, her heart rate was 124 per minute and her temperature was normal. Despite receiving clemastin and methylprednisolone, two hours later she had a clinical deterioration starting with generalised pruritus and worsening of generalised exanthema, myalgias and arthralgias. She rapidly developed angio-oedema and anaphylactic shock. Her temperature was 37.4 1C, her blood pressure dropped to 73/45 mmHg and her heart rate was 120 per min. She was given dopamine, epinephrine and 250 mg of IV methylprednisolone and intravenous fluids. Blood cell count revealed a haemoglobin level of 7.9 g/dl [11.5–16.5], a white blood cell count of 5.4 10/mL [4–11], prothrombin time 22 s [13], d-dimers of 7.17 mg/L [0–0.6], fibrinogen of 2.6 g/L [2–5.0], SGPT 219 U/l [5 55]; SGOT 337 U/l [5–34]; SGGT 15 U/l [9–36], total bilirubin 0.8 mg/dl

AB1364 Adaptation and validation of the rheumatoid arthritis quality of life (RAQOL) scale for portugal

Background Rheumatoid Arthritis (RA) is a chronic inflammatory disease that has a major impact on patients’ quality of life. The Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL) is a patient-centric outcome measure, specific to RA. The measure has not previously been available for use with Portuguese RA patients. Objectives To produce a Portuguese version of the RAQoL that is acceptable to Portuguese patients and demonstrates sound psychometric properties. Methods The dual panel methodology was used to translate the UK RAQoL into Portuguese. This involved conducting a bilingual panel (providing the initial translation into Portuguese) followed by a lay panel (where items are assessed for comprehension and acceptability). Cognitive debriefing interviews were conducted with Portuguese RA patients to determine the face and content validity of the translated scale. A large-scale postal validation survey was carried out to establish the psychometric properties of the Portuguese RAQoL. The measure was administered on two occasions to RA patients, alongside a comparator instrument – the Nottingham Health Profile (NHP). Internal consistency was assessed using Cronbach’s alpha coefficient. Spearman’s Rank correlation coefficient was employed to assess test-retest reliability. Convergent validity was tested by correlating RAQoL scores with those on the NHP sections. Known group validity was assessed using non-parametric tests for independent samples. This involved determining the ability of the RAQoL to distinguish between patients that differed according to their self-perceived severity of RA and general health. Results The translation panels produced a Portuguese version of the RAQoL that was easily understood and considered natural by native speakers. Interviewees considered the new language version to be relevant and appropriate. One hundred and seventy-eight RA patients (82% female) took part in the postal validation survey with a mean age of 56.6 (range 25 to 79) years. The Portuguese RAQoL demonstrated excellent internal consistency (Cronbach’s α=0.95) and test-retest reliability (r=0.92), indicating that the measure produces low levels of random measurement error. RAQoL scores correlated most strongly with scores on the NHP Physical mobility scale (r=0.77) and showed moderately strong correlations with the Emotional reactions, Pain and Energy level section scores. Non-parametric tests for independent samples demonstrated significant differences in RAQoL scores between patients who differed according to their self-perceived RA severity (p<0.001) and general health (p<0.001). Conclusions The Portuguese version of the RAQoL was found to be a comprehensive, reliable and valid questionnaire. The new language version is recommended for use in routine clinical practice and for research purposes, to assess quality of life in Portuguese RA patients. Disclosure of Interest None declared

Posterior Ankle Impingement Syndrome

We present a case of a 38-year-old female with a history of right posterior ankle pain for 2 months which worsened with walking and standing up for a long time. There were no complaints in other joints. On physical examination the patient presented swelling of the posterior ankle and complained of pain with forced flexion of the right feet. There was no increase of inflammation parameters in blood tests. Radiographic lateral view of the right ankle demonstrated an enlarged Stieda’s process (Fig. 1). The magnetic resonance imaging (MRI) of the right ankle confirmed the Stieda’s process (Fig. 1) being able to originate posterior conflict, with a subtle bone marrow edema. A slight effusion was observed in the anterior and posterior compartments of the tibiotalar joint as well as edema of the subcutaneous fat. The patient was told to rest and NSAID were prescribed with resolution of the hindfoot pain. The posterior ankle impingement syndrome is a condition resulting from soft tissue compression between the posterior process of the calcaneus and the posterior tibia during ankle plantar flexion.1 An important cause of the syndrome is a prominent posterolateral talar process (Stieda’s process) or the presence of os trigonum, due to its impact on adjacent structures.2 Patients usually report chronic or recurrent posterior ankle pain caused or exacerbated by forced plantar flexion.3 Other causes of this syndrome may result from flexor hallucis longus tenosynovitis, ankle osteochondritis, subtalar joint disease, and fracture.

AB0608 Greater Organ Involvement and Disease Activity in Childhood-Onset than Adult-Onset With SLE (DATA from Reuma.Pt/Les)

Background Systemic lupus erythematosus (SLE) is a multi-organ immune-mediated disease that affects predominantly women at reproductive age but may present itself at any age. Age at disease onset has a strong modulating effect on clinical presentation and course of disease. Although young patients may have a more aggressive disease, controversies persist regarding the impact of age at disease onset on SLE outcome. Objectives Characterize childhood-onset, adult-onset and late-onset SLE and assess whether disease outcome differs in these three patient groups. Methods Patients with childhood-onset (diagnosis ≤18 years) SLE fulfilling ACR 1997 criteria were identified in the Portuguese registry Reuma.pt/SLE and compared with adult-onset (≥19y and ≤49 years) and late-onset (≥50 years) SLE patients paired for disease duration. Results Two hundred and sixty seven SLE patients with mean disease duration of 11.9±9.3 years were analyzed (Table 1). The number of fulfilled ACR criteria was significantly higher in childhood-onset SLE. A greater proportion of women, higher prevalence of arthritis and anti-SSA antibodies were noted in the adult-onset group. Hypertension, diabetes and thyroid disease were significantly more prevalent in late-onset SLE. Disease activity at last visit evaluated using the SLEDAI-2K was significantly higher in childhood-onset group than in the late-onset counterparts. SLICC/ACR damage index was numerically higher in late-onset SLE and significantly more patients in this group had irreversible damage. Cyclophosphamide and mycophenolate mophetil were used more frequently in childhood-onset SLE patients.Table 1. Demographic and clinical characteristics of childhood-onset, adult-onset and late-onset SLE Childhood-onset Adult-onset Late-onset P N=89 N=89 N=89 Female n (%) 77 (87) 85 (96) 78 (88) 0.039 Current mean age (years) 25.1±9.1 40.0±13.1 68.3±7.3 <0.001 Number of ACR criteria fulfilled 5.8±1.3 5.3±1.3 5.2±1.1 0.005  Malar rash (%) 55 (62) 32 (36) 33 (37) <0.001  Arthritis (%) 62 (70) 79 (89) 71 (80) 0.005  Renal involvement (%) 52 (58) 28 (31) 14 (16) <0.001  Neurologic disorder (%) 10 (11) 5 (6) 2 (2) 0.039  Hematologic disorder (%) 68 (76) 53 (62) 67 (75) 0.029 Anti-SSA positivity (%) 13 (15) 30 (34) 19 (21) 0.006 Low complement (%) 74 (83) 60 (67) 46 (52) <0.001 SLEDAI-2K at last visit 3.4±3.8 2.2±2.7 1.6±2.8 0.004 SLICC-DI 0.5±0.9 0.7±1.3 0.9±1.3 0.116 SLICC-DI ≥1 (%) 18 (20) 23 (26) 36 (40) <0.001 Hypertension (%) 17 (19) 16 (18) 43 (48) <0.001 Diabetes (%) 0 (0) 7 (8) 15 (17) 0.008 Thyroid disease (%) 3 (3) 13 (26) 20 (23) 0.004 Conclusions The skin, kidney and neurological involvement are most common in childhood-onset, as well as the use of immunosuppressants, supporting the concept of a more severe disease. In contrast, patients with late-onset SLE have more comorbidities and irreversible damage. The age of SLE onset has a significant impact not only on the clinical characteristics and disease activity, but is also important for disease outcome. Disclosure of Interest None declared