Psoriatic arthritis: genetics and pathogenesis

Psoriatic arthritis is a complex disease affecting primarily peripheral and axial joints and entheses together with the skin. The pathogenesis is characterized by a genetic background and by inflammatory mechanisms which may be triggered by environmental factors. Several susceptibility genes have been investigated; they include HLA genes, genes within the HLA region and genes outside the HLA region. T cells, including the recently described subset Th17, are thought to play an important role in the acute and chronic phases of the disease. Some of these findings allowed novel therapeutic interventions or opened new promising approaches in treatment. The most relevant data of the literature are summarized and discussed

Failure to achieve lupus low disease activity state (LLDAS) six months after diagnosis is associated with early damage accrual in Caucasian patients with systemic lupus erythematosus

Background: The aim was to assess the attainability and outcome of the lupus low disease activity state (LLDAS) in the early stages of systemic lupus erythematosus (SLE). Methods: LLDAS prevalence was evaluated at 6 (T1) and 18 (T2) months after diagnosis and treatment initiation (T0) in a monocentric cohort of 107 (median disease duration 9.7 months) prospectively followed Caucasian patients with SLE. Reasons for failure to achieve LLDAS were also investigated. Multivariate models were built to identify factors associated with lack of LLDAS achievement and to investigate the relationship between LLDAS and Systemic Lupus International Collaboration Clinics (SLICC)/Damage Index (SDI) accrual. Results: There were 47 (43.9%) patients in LLDAS at T1 and 48 (44.9%) at T2. The most frequent unmet LLDAS criterion was prednisolone dose >7.5 mg/day (83% of patients with no LLDAS at T1). Disease manifestations with the lowest remission rate during follow up were increased anti-double-stranded DNA (persistently present in 85.7% and 67.5% of cases at T1 and T2, respectively), low serum complement fractions (73.2% and 66.3%) and renal abnormalities (46.4% and 28.6%). Renal involvement at T0 was significantly associated with failure to achieve LLDAS both at T1 (OR 7.8, 95% CI 1.4-43.4; p = 0.019) and T2 (OR 3.9, 95% CI 1.4-10.6; p = 0.008). Presence of any organ damage (SDI â\u89¥1) at T2 was significantly associated with lack of LLDAS at T1 (OR 5.0, 95% CI 1.5-16.6; p = 0.009) and older age at diagnosis (OR 1.05 per year, 95% CI 1.01-1.09; p = 0.020). Conclusion: LLDAS is a promising treatment target in the early stages of SLE, being attainable and negatively associated with damage accrual, but it fit poorly to patients with renal involvement

Severe neuropsychiatric systemic lupus erythematosus successfully treated with rituximab: An alternative to standard of care

Demyelinating syndrome secondary to systemic lupus erythematosus (DS-SLE) is a rare encephalomyelitis burden with a high risk of disability and death. We report on a 49-year-old Caucasian woman with systemic lupus erythematosus (SLE) complicated by severe cognitive dysfunction, brainstem disease, cranial nerve palsies, weakness and numbness in limbs and multiple discrete magnetic resonance imaging (MRI) areas of damage within the white matter of semioval centers, temporal lobe, external capsule, claustrum, subinsular regions and midbrain. She also had multiple mononeuritis diagnosed through sensory and motor nerve conduction study. She was diagnosed with severe DS-SLE prominently involving the brain and was treated with 500 mg methylprednisolone (PRE) pulses for 3 consecutive days, followed by one single pulse of 500 mg cyclophosphamide, and 1 g rituximab, which was then repeated 14 days later. PRE 25 mg/day, rapidly tapered to 7.5 mg/day in 6 months, and mycophenolate mofetil 1 g/day were prescribed as maintenance therapy. She had progressive and sustained improvement in neurological symptoms with almost complete resolution of brain MRI lesions after 1 year. B-cell depleting therapy could be considered as a possible alternative to standard of care in the management of severe inflammatory neuropsychiatric SLE but it should be associated with a conventional immunosuppressant as maintenance treatment to reduce the risk of flare and reduce corticosteroids dose

Polymyalgia rheumatica: an autoinflammatory disorder?

Polymyalgia rheumatica: an autoinflammatory disorder

Prognostic impact of coronary microcirculation abnormalities in systemic sclerosis: a prospective study to evaluate the role of non-invasive tests

INTRODUCTION: Microcirculation dysfunction is a typical feature of systemic sclerosis (SSc) and represents the earliest abnormality of primary myocardial involvement. We assessed coronary microcirculation status by combining two functional tests in SSc patients and estimating its impact on disease outcome. METHODS: Forty-one SSc patients, asymptomatic for coronary artery disease, were tested for coronary flow velocity reserve (CFR) by transthoracic-echo-Doppler with adenosine infusion (A-TTE) and for left ventricular wall motion abnormalities (WMA) by dobutamine stress echocardiography (DSE). Myocardial multi-detector computed tomography (MDCT) enabled the presence of epicardial stenosis, which could interfere with the accuracy of the tests, to be excluded. Patient survival rate was assessed over a 6.7- ± 3.5-year follow-up. RESULTS: Nineteen out of 41 (46%) SSc patients had a reduced CFR (≤2.5) and in 16/41 (39%) a WMA was observed during DSE. Furthermore, 13/41 (32%) patients showed pathological CFR and WMA. An inverse correlation between wall motion score index (WMSI) during DSE and CFR value (r = -0.57, P <0.0001) was observed; in addition, CFR was significantly reduced (2.21 ± 0.38) in patients with WMA as compared to those without (2.94 ± 0.60) (P <0.0001). In 12 patients with abnormal DSE, MDCT was used to exclude macrovasculopathy. During a 6.7- ± 3.5-year follow-up seven patients with abnormal coronary functional tests died of disease-related causes, compared to only one patient with normal tests. CONCLUSIONS: A-TTE and DSE tests are useful tools to detect non-invasively pre-clinical microcirculation abnormalities in SSc patients; moreover, abnormal CFR and WMA might be related to a worse disease outcome suggesting a prognostic value of these tests, similar to other myocardial diseases

Predictors of musculoskeletal flares and Jaccoud׳s arthropathy in patients with systemic lupus erythematosus: A 5-year prospective study

Objective To investigate the prognostic value of US in predicting musculoskeletal flares and Jaccoud׳s arthropathy (JA) in systemic lupus erythematosus (SLE). Methods A total of 80 out of 94 patients (76 female; age 45.5 ± 13.2 years) with non-deforming non-erosive (NDNE) arthritis and 48/60 healthy controls (42 female; age 49.6 ± 11.6 years) completed the 5-year follow-up study. Each patient was prospectively assessed for the occurrence of musculoskeletal flares using BILAG2004 and hand deformities according to Jaccoud׳s articular index. Baseline clinical, serological, semi-quantitative (0–3 scale) ultrasound (US) findings, PD-synovitis and PD-tenosynovitis scores were used as covariates to identify predictors of study outcomes. Short Form 36 v2 (SF36v2) health survey questionnaire was administered. Results Overall, 12 MS flares in 10 (12.5%) patients were recorded and the incidence rate was 3.0 per 100 patient-year. Baseline PD-synovitis score independently predicted MS flare (p < 0.001; RR = 2.0; 95% CI: 1.4–3.0) within 2 years since US examination. In all, 5 (6.2%) patients developed JA whose incidence rate was 1.25 per 100 patient-year. Independent risk factors for development of JA were higher longitudinal BILAG score in the musculoskeletal domain (p = 0.005; RR = 2.4; 95% CI: 1.3–4.6) and longer disease duration (p = 0.013; RR 1.2; 95% CI: 1.1–1.3). JA and active musculoskeletal inflammation (BILAG ≥ C), but not US erosions, were associated with lower results in SF36v2 physical and mental summary components. Conclusions Performing musculoskeletal US can be useful in order to predict MS flares. Jaccoud׳s deformities may arise in patients with long-standing SLE and prolonged, even subclinical, joint and tendon inflammation

Ultrasonographic assessment of bone erosions in the different subtypes of systemic lupus erythematosus arthritis: Comparison with computed tomography

Background: The aim was to determine the accuracy of high-resolution ultrasonography (US) for detecting erosion in the metacarpophalangeal (MCP) and wrist joints of patients with different subtypes of systemic lupus erythematosus (SLE) arthritis, using computed tomography (CT) as the gold-standard reference method. Method: The ulnar head, radiocarpal and second to fifth MCP joints in 26 patients with SLE - 9 classified as having rhupus syndrome, 10 as having Jaccoud's arthropathy (JA) and 7 as having non-deforming non-erosive (NDNE) arthritis - were subdivided into areas and bilaterally evaluated for the presence of bone erosion by CT and US. On CT, erosion volume was scored according to the outcome measures in rheumatology-rheumatoid arthritis magnetic resonance imaging (OMERACT-RAMRIS) score. On US, erosions were semi-quantitatively scored 0-3 according to scoring by ultrasound structural erosion (ScUSSe) systems. Results: Erosions were detected by CT in 92/728 areas (12.6 %) and by US in 43/728 areas (5.9 %). Sensitivity, specificity and accuracy of US overall was 36 %, 98 % and 90 % compared with 57 %, 98 % and 93 % in the dorsal and lateral aspects of the second and fifth MCP, which were identified as areas with the best US reliability. Adding wrist joints would capture a larger number of erosions without affecting the accuracy. US detected 90.0 % of CT erosions with bone volume loss >20 % and 51.2 % of erosions with bone volume loss >10 %. Patients with rhupus had a greater number of larger erosions than those with JA or NDNE arthritis, with prevalent involvement of the MCP joints. Overall reliability of US in detecting bone erosions was moderate for rhupus syndrome (0.55) and JA (0.58), but poor for NDNE arthritis (0.10). Conclusion: US had moderate sensitivity and excellent specificity for detection and semi-quantitative assessment of bone erosions in SLE

Long-term glucocorticoid treatment and high relapse rate remain unresolved issues in the real-life management of polymyalgia rheumatica: a systematic literature review and meta-analysis

A systematic review and meta-analysis were conducted, according to the PRISMA methodology, to summarize current evidence on the prevalence and predictors of long-term glucocorticoid (GC) treatment and disease relapses in the real-life management of polymyalgia rheumatica (PMR).Out of 5442 retrieved studies, 21 were eligible for meta-analysis and 24 for qualitative analysis. The pooled proportions of patients still taking GCs at 1, 2, and 5&nbsp;years were respectively 77% (95%CI 71-83%), 51% (95%CI 41-61%), and 25% (95CI% 15-36%). No significant difference was recorded by distinguishing study cohorts recruited before and after the issue of the international recommendations in 2010. The pooled proportion of patients experiencing at least one relapse at 1&nbsp;year from treatment initiation was 43% (95%CI 29-56%). Female gender, acute-phase reactants levels, peripheral arthritis, starting GCs dosage, and tapering speed were the most frequently investigated potential predictors of prolonged GC treatment and relapse, but with inconsistent results. Only a few studies and with conflicting results evaluated the potential role of early treatment with methotrexate in reducing the GC exposure and the risk of relapse in PMR.This study showed that a high rate of prolonged GC treatment is still recorded in the management of PMR. The relapse rate, even remarkable, can only partially explain the long-term GC treatment, suggesting that other and not yet identified factors may be involved. Additional research is needed to profile patients with a higher risk of long-term GC treatment and relapse and identify more effective steroid-sparing strategies. Key Points: • High rate of long-term glucocorticoid (GC) treatment is recorded in polymyalgia rheumatica (PMR), being 77%, 51%, and 25% of patients still on GCs after respectively 1, 2, and 5 years. • A pooled relapse rate of 43% at 1 year, even remarkable, can only partially explain the long-term GC treatment in PMR. • Several studies have attempted to identify potential predictors of prolonged treatment with GCs and relapse, but with inconsistent results. • Additional research is needed to profile patients with a higher risk of long-term GC treatment and relapse and identify more effective steroid-sparing strategies