L. Massaro

Flare, Persistently Active Disease, and Serologically Active Clinically Quiescent Disease in Systemic Lupus Erythematosus: A 2-Year Follow-Up Study

Objective Several indices have been proposed to assess disease activity in patients with Systemic Lupus Erythematosus (SLE). Recent studies have showed a prevalence of flare between 28–35.3%, persistently active disease (PAD) between 46%–52% and serologically active clinically quiescent (SACQ) disease ranging from 6 to 15%. Our goal was to evaluate the flare, PAD and SACQ rate incidence in a cohort of SLE patients over a 2-year follow-up. Methods We evaluated 394 SLE patients. Flare was defined as an increase in SLEDAI-2K score of ≥4 from the previous visit; PAD was defined as a SLEDAI-2K score of ≥4, on >2 consecutive visits; SACQ was defined as at least a 2-year period without clinical activity and with persistent serologic activity. Results Among the 95 patients eligible for the analysis in 2009, 7 (7.3%) had ≥1 flare episode, whereas 9 (9.4%) had PAD. Similarly, among the 118 patients selected for the analysis in 2010, 6 (5%) had ≥1 flare episode, whereas 16 (13.5%) had PAD. Only 1/45 patient (2.2%) showed SACQ during the follow-up. Conclusion We showed a low incidence of flare, PAD and SACQ in Italian SLE patients compared with previous studies which could be partly explained by ethnic differences.

Ultrasound evaluation of hand, wrist and foot joint synovitis in systemic lupus erythematosus

OBJECTIVES To assess the prevalence and severity of inflammatory abnormalities of the hand, wrist and foot joints in SLE patients by US and to correlate them with clinical, laboratory and disease activity score parameters. METHODS Sixty-two consecutive SLE patients were enrolled in the present study and underwent clinical evaluation, laboratory tests and bilateral high-resolution US of the hand, wrist and foot joints. Joint effusion (JE), synovial hypertrophy (SH) and local pathological vascularization [power Doppler (PD)] were evaluated according to both a dichotomous score and a semi-quantitative (0-3) grading system. In addition, a global US score was calculated by summing the values given to each elementary lesion for every single joint and every joint group. US findings were correlated with physical examination, serological parameters (CRP, ANA, anti-dsDNA, ENA, aPL, C3 and C4 serum levels) and disease activity indexes (SLEDAI-2K, ECLAM). RESULTS US detected inflammatory joint abnormalities in 54/62 patients (87.1%); 72.6% presented involvement of the MTP joints, 46.7% the MCP joints, 19.3% the PIP joints and 53% the wrists. A total of 1984 joints were examined highlighting JE in 19.1% of cases, SH in 6.9% and positive PD in 1.1%. The global US inflammatory score had a mean value of 10.9 (s.d. 15.2). No correlations were found between US findings and SLE disease activity parameters. CONCLUSION US demonstrated a high prevalence of inflammatory joint abnormalities in SLE that were also present in asymptomatic patients. Interestingly, the foot joints were the most frequently involved. US is a valuable tool for detecting subclinical synovitis in SLE.

International consensus: What else can we do to improve diagnosis and therapeutic strategies in patients affected by autoimmune rheumatic diseases (rheumatoid arthritis, spondyloarthritides, systemic sclerosis, systemic lupus erythematosus, antiphospholipid syndrome and Sjogren's syndrome)?: The unmet needs and the clinical grey zone in autoimmune disease management

Autoimmune diseases are a complex set of diseases characterized by immune system activation and, although many progresses have been done in the last 15years, several unmet needs in the management of these patients may be still identified. Recently, a panel of international Experts, divided in different working groups according to their clinical and scientific expertise, were asked to identify, debate and formulate a list of key unmet needs within the field of rheumatology, serving as a roadmap for research as well as support for clinicians. After a systematic review of the literature, the results and the discussions from each working group were summarised in different statements. Due to the differences among the diseases and their heterogeneity, a large number of statements was produced and voted by the Experts to reach a consensus in a plenary session. At all the steps of this process, including the initial discussions by the steering committee, the identification of the unmet needs, the expansion of the working group and finally the development of statements, a large agreement was attained. This work confirmed that several unmet needs may be identified and despite the development of new therapeutic strategies as well as a better understanding of the effects of existing therapies, many open questions still remain in this field, suggesting a research agenda for the future and specific clinical suggestions which may allow physicians to better manage those clinical conditions still lacking of scientific clarity.

Assessment of disease activity in Systemic Lupus Erythematosus: Lights and shadows

The assessment of disease activity in patients affected by Systemic Lupus Erythematosus (SLE) represents an important issue, as recommended by the European League Against Rheumatism (EULAR). Two main types of disease activity measure have been proposed: the global score systems, providing an overall measure of activity, and the individual organ/system assessment scales, assessing disease activity in different organs. All the activity indices included both clinical and laboratory items, related to the disease manifestations. However, there is no gold standard to measure disease activity in patients affected by SLE. In this review, we will analyze the lights and shadows of the disease activity indices, by means of a critical approach. In particular, we will focus on SLE Disease Activity Index (SLEDAI) and British Isles Lupus Assessment Group (BILAG), the most frequently used in randomized controlled trials and observational studies. The evaluation of data from the literature underlined some limitations of these indices, making their application in clinical practice difficult and suggesting the possible use of specific tools in the different subset of SLE patients, in order to capture all the disease features.

Seronegative Autoimmune Diseases

A close relationship exists between autoimmunity and autoantibodies; despite this, some patients are persistently negative for disease‐specific autoantibodies. These conditions have been defined as seronegative autoimmune diseases. Although the prevalence of seronegative autoimmune diseases is low, they may represent a practical problem because they are often difficult cases. There are also situations in which autoantibodies are positive in healthy subjects. In particular, three different conditions can be described: latent autoimmunity, preclinical autoimmunity, and postclinical autoimmunity. Here, we analyze briefly the meaning of autoantibody negativity in the seronegative autoimmune diseases, focusing in particular on the specificities associated with systemic lupus erythematosus, antiphospholipid syndrome, and rheumatoid arthritis.

Rituximab infusion-related adverse event rates are lower in patients with systemic lupus erythematosus than in those with rheumatoid arthritis

OBJECTIVES Rituximab (RTX) is a therapeutic option for patients with SLE or RA. We conducted a prospective, longitudinal, observational study to compare rates of RTX-related adverse events (AEs) in these two patient groups. METHODS RTX was used in 23 patients with SLE that was refractory to conventional therapy and in 31 patients with RA that had been unsuccessfully treated with TNF-α inhibitors. Infusion-related and infectious AE rates were calculated for each group. RESULTS Seven (22.5%) RA patients experienced an infusion-related reaction. These AEs involved 7/91 (7.7%) infusions administered in the RA group. None of the 102 infusions administered to SLE patients was associated with infusion-related AEs (P = 0.038 vs RA group). The mean daily glucocorticoid dose administered during the week preceding RTX treatment in the SLE group was higher than that for the RA group [0.25 (0.2) vs 0.18 (0.14) mg/kg, P = not significant] and significantly higher than that received by the subgroup of the seven RA patients who experienced infusion-related AEs [0.10 (0.02) mg/kg; P = 0.0017]. Infectious AE rates were also lower (but not significantly so) in the SLE group (8.7 vs 12.9% in RA). CONCLUSIONS Repeated cycles of RTX in combination with different immunosuppressants is a safe therapeutic option for SLE and RA patients. The lower incidence of infusion-related AEs in the SLE patients might reflect the higher dosage glucocorticoid therapy they received during the week before RTX infusion.

Longterm Outcome of Patients with Primary Antiphospholipid Syndrome: A Retrospective Multicenter Study

Objective. To assess the longterm frequency of thrombotic recurrences, obstetrical complications, organ damage, severe comorbidities, and evolution toward connective tissue disease (CTD) in primary antiphospholipid syndrome (PAPS). Methods. Medical records of patients with PAPS followed in 6 centers for ≥ 15 years were retrospectively reviewed. Results. One hundred fifteen patients were studied: 88% women, followed between 1983 and 2014 with a mean (± SD) age at diagnosis of 33 (± 10) years. During a median followup of 18 years (range 15–30), 50 patients (44%) had at least a thrombotic event for a total of 75 events and an annual incidence of 3.5%. Thromboses were more frequent in patients with previous thrombotic history (p = 0.002). A catastrophic antiphospholipid syndrome occurred in 6 patients (5%). The use of oral anticoagulants in patients with thrombotic onset did not appear to be protective against recurrences (p = 0.26). Fifty-two women had 87 pregnancies, successful in 78%. Twenty-nine percent of patients accrued functional damage. Damage was significantly associated with a thrombotic history (p = 0.004) and with arterial events (p < 0.001), especially stroke, but not with demographics, serology, or treatment. Twenty-four major bleeding episodes were recorded in 18 patients, all receiving anticoagulants. Severe infections affected 6 patients (5%), with 1 fatality. A solid cancer was diagnosed in 8 patients (7%). Altogether, 16 patients (14%) developed an autoimmune disease and 13 (11%) a full-blown picture of CTD. Conclusion. Despite therapy, a high proportion of patients experienced new thrombotic events and organ damage, while evolution toward CTD was infrequent.

Evaluation of the Patient Acceptable Symptom State (PASS) in Italian Patients Affected by Systemic Lupus Erythematosus: Association with Disease Activity Indices

Objectives The aim of this study was to evaluate the discriminant capability of the patient acceptable symptom state (PASS) according to disease activity, in a cohort of Italian patients affected by systemic Lupus erythematosus (SLE). Methods Consecutive SLE patients were enrolled. At each visit, the patients underwent a complete physical examination and the clinical/laboratory data were collected in a standardized, computerized, and electronically-filled form. The evaluation of serum complement C3 and C4 levels and determination of autoantibodies was obtained. Disease activity was assessed with the SLEDAI-2K and ECLAM, while chronic damage was measured with the SLICC. Finally, PASS was assessed in all patients by asking to answer yes or no to a single question. Results One hundred sixty-five patients were enrolled (M/F 12/153; mean age 40.4±11.8 years, mean disease duration 109.1±96.2 months). No patients refused to answer, suggesting the acceptability of PASS. A total of 80% of patients rated their state as acceptable. The patients with an acceptable status had significantly lower mean SLEDAI-2K and ECLAM scores than the others [1.8±2.7 versus 3.4±2.3(P=0.004); 0.7±0.9 versus 1.4±1.1(P=0.0027)]. No significant differences were observed when considering chronic damage, evaluated with SLICC. Conclusions In the clinical practice, SLE patients assessment performed by using complex disease activity indices such as SLEDAI-2K and ECLAM, could be time consuming. In our study, for the first time, we used PASS, a quick and easily comprehensible tool, to evaluate the patients’ status, this single question seems to be able to discriminate patients with different disease activity, especially when this is determined by musculoskeletal involvement.

Ultrasonographic Evaluation of Renal Resistive Index in Patients with Lupus Nephritis: Correlation with Histologic Findings

We analyzed the association between the renal arterial resistive index (RI) and the histologic features of lupus nephritis. All consecutive patients with systemic lupus erythematosus (SLE) who required a kidney biopsy were enrolled. The study protocol included ultrasonographic assessment to measure the RI and kidney biopsy (International Society of Nephrology/Renal Pathology Society classification). A RI > 0.7 was considered pathologic. Patients with non-renal SLE and healthy patients were studied as control groups. We enrolled 42 patients with renal SLE, 10 with non-renal SLE and 14 healthy patients: their mean (±standard deviation) RI values were 0.64 ± 0.08, 0.60 ± 0.04 and 0.59 ± 0.01, respectively (p = not significant). RIs > 0.7 were recorded only in patients with renal SLE (5/42, 11.9%). The percentage of patients with a pathologic RI was significantly higher in class IV nephritis in comparison with other classes (p < 0.009). In conclusion, we found a significant correlation between pathologic RI and class IV nephritis, suggesting a role for RI as a severity marker.

The role of disease activity score 28 in the evaluation of articular involvement in systemic lupus erythematosus.

Objectives. To evaluate the application of Disease Activity Score 28 (DAS28) to assess joint involvement in Systemic Lupus Erythematosus (SLE). Methods. Sixty-nine SLE patients, complaining of joint symptoms, and 44 rheumatoid arthritis (RA) patients were enrolled. In SLE patients disease activity was assessed with SLEDAI-2K. DAS28 was calculated in all the patients. Results. Thirty SLE patients (43.5%) showed clinical signs of arthritis. Mean DAS28 was 4.0 ± 1.4, 22 patients (31.9%) had low disease activity, 29 (42.0%) moderate, and 18 (26.1%) high. We dichotomized SLE patients according to the presence (Group 1) or absence (Group 2) of articular involvement according to SLEDAI-2K: 56.3% of the patients of the second group had a moderate/high activity according to DAS28. We compared SLE patients with 44 RA patients (M/F 9/35, mean age 55.6 ± 14.5 years; mean disease duration 140.4 ± 105.6 months). No significant differences were found regarding the values of DAS28 between SLE and RA patients. On the contrary, the values of tender and swollen joint count were significantly higher in RA compared to SLE patients (P = 0.0002 and P = 0.0001, resp.). Conclusions. We suggest the use of the DAS28 in the assessment of joint involvement in SLE patients.