Cardiac Sarcoma Mimicking Libman-Sacks Endocarditis in a Patient with Systemic Lupus Erythematosus (SLE): A Case Report and Literature Review.

We present the case of a 39-year-old woman who was diagnosed with SLE and antiphospholipid antibodies 8 years ago. The chief manifestations of her disease included low-grade fever and polyarthritis. Eight months before presentation, she experienced symptoms attributed to a flare of SLE, leading to an increase in immunomodulatory treatment with no improvement. She presented to the emergency room with acute onset of dyspnea. Clubbing of her fingers and toes was noted. When questioned, she reported the onset of clubbing 5 months earlier. A CTA was performed to rule out pulmonary embolism, which was excluded, although it revealed a severely damaged mitral valve with severe insufficiency and a large mass on the valve, protruding into the left atrium. Antibiotics were started, with a working diagnosis of infectious endocarditis; however, the severe mitral valve dysfunction lead to emergency mitral valve replacement, revealing an organized thrombus. She was treated with anticoagulation, with a working diagnosis of Libman-Sacks endocarditis, with no improvement. Additional immunosuppression failed to improve her symptoms. Enlargement of the thrombotic mass and an increased gradient across the prosthetic mitral valve led to repeat surgery, culminating in a diagnosis of high-grade sarcoma within the left atrial mass. We further discuss cardiac sarcoma and describe the occurrence of clubbing in patients with sarcoma. This case highlights the importance of interdisciplinary collaboration and the need for vigilant monitoring in refractory cases, particularly when atypical presentations arise.

Effect of Secukinumab and Tumor Necrosis Factor Inhibitors on Humoral Response to BNT162b2 mRNA Vaccine in Patients With Spondyloarthritis Compared to Immunocompetent Controls.

OBJECTIVE: To assess the humoral response to the BNT162b2 mRNA vaccine among patients with spondyloarthritis (SpA) receiving secukinumab (SEC) compared to those receiving tumor necrosis factor inhibitors (TNFi) and immunocompetent controls. METHODS: Consecutive patients with psoriatic arthritis or axial SpA receiving SEC (n = 37) or TNFi (monotherapy, n = 109; + methotrexate [MTX], n = 16), immunocompetent controls (n = 122), and patients with rheumatoid arthritis (RA) receiving TNFi therapy (controls, n = 50) were vaccinated with 2 or 3 doses of the BNT162b2 vaccine. We evaluated humoral response, adverse events, and disease activity, and monitored for breakthrough coronavirus disease 2019 (COVID-19) postvaccination. RESULTS: The 2-dose vaccine regimen induced a comparable seropositive response in all study groups. S1/S2 antibody titers (in binding antibody units/mL; mean [SD]) were higher in the SEC group vs the TNFi + MTX-SpA and TNFi-RA groups (192.5 [68.4] vs 104.6 [46.9], P < 0.001, and 143.1 [81.9], P = 0.004). After 6 months, 96.3%, 96.6%, and 80.9% of the SEC, immunocompetent, and TNFi monotherapy-SpA groups (P = 0.10), respectively; 66.7% of the TNFi + MTX-SpA group (P = 0.03); and 63% of the TNFi-RA group (P = 0.004) remained seropositive. S1/S2 antibody titer decline was steeper in the TNFi groups than the SEC group. After the third dose, 100% of the SpA and immunocompetent and 88.9% of the TNFi-RA (P = 0.25) groups were seropositive. Rate of breakthrough COVID-19 infection was higher in the TNFi groups than in the SEC group (36-37.5% vs 10.8%). No significant between-group differences were observed for postvaccination disease activity and adverse events. CONCLUSION: SEC did not interfere with the immunogenic response to BNT162b2 vaccine in patients with SpA; however, TNFi therapy was associated with lower S1/S2-antibody titers, faster decline, and higher rate of breakthrough infections.

The association between sonographic enthesitis with sonographic synovitis and tenosynovitis in psoriatic arthritis patients.

OBJECTIVES: To examine the association between sonographic enthesitis with sonographic synovitis and tenosynovitis in PsA patients, and the association between sonographic enthesitis and clinical characteristics. METHODS: Consecutive PsA patients that fulfilled the ClASsification criteria for Psoriatic ARthritis (CASPAR) were prospectively recruited. Each patient was evaluated by comprehensive clinical and sonographic assessment (greyscale and Doppler), the latter including 52 joints, 40 tendons and 14 entheses [according to MAdrid Sonography Enthesitis Index (MASEI) plus lateral epicondyles] performed by an experienced sonographer blinded to the clinical data. The US enthesitis score was further categorized to inflammatory (hypoechogenicity, thickening, bursitis and Doppler) and structural (enthesophytes/calcifications and erosions) subcategories. Multivariate linear regression models assessed the association between enthesitis and the selected variables. RESULTS: A total of 158 PsA patients [mean (s.d.) age 52.3 (13) years, 88 (55.7%) females] were analysed. Multivariate linear regression analyses showed a significant association between sonographic enthesitis and sonographic synovitis (ß = 0.18, P = 0.008) and between sonographic enthesitis and sonographic tenosynovitis (ß = 0.06, P = 0.02). These associations were derived from the enthesitis inflammatory subcategory of the MASEI (P < 0.05). Associations between enthesitis and synovitis were also demonstrated on the level of the elbow, knee and ankle joints (P < 0.05). In addition, sonographic enthesitis was significantly associated with older age, male sex, swollen joint count, CRP level and physical occupation. CONCLUSIONS: Sonographic enthesitis is associated with sonographic synovitis and tenosynovitis. The severity of sonographic enthesitis may represent a marker for inflammatory activity in other musculoskeletal domains.

Heart Valve Surgery in Antiphospholipid Syndrome Patients-Morbidity and Mortality.

OBJECTIVES: To assess valve surgery outcomes in antiphospholipid syndrome (APS). METHODS: A retrospective study assessing complications and mortality rate and possible factors associated with adverse outcomes of APS patients undergoing valve surgery in two tertiary medical centers. RESULTS: Twenty-six APS patients (median age at surgery 47.5 years) who underwent valve surgery were detected, of whom 11 (42.3%) had secondary APS. The mitral valve was most commonly involved (n = 15, 57.7%). A valve replacement was performed in 24 operations (92.3%), 16 of which (66.7%) were mechanical valves. Fourteen (53.8%) patients sustained severe complications, and four of them died. The presence of mitral regurgitation (MR) was associated with severe complications and mortality (odds ratio (95% confidence interval) 12.5 (1.85-84.442), p = 0.008, for complications. All deceased patients had MR (p = 0.033). The presence of Libman-Sacks endocarditis (LSE) (7.333 (1.272-42.294), p = 0.045), low C3 (6.667 (1.047-42.431), p = 0.05) and higher perioperative prednisone doses (15 ± 21.89 vs. 1.36 ± 3.23 mg/day, p = 0.046) were also associated with complications. A lower glomerular filtration rate (GFR) was associated with mortality (30.75 ± 19.47 vs. 70.68 ± 34.44 mL/min, p = 0.038). CONCLUSIONS: Significant morbidity and mortality were observed among APS patients undergoing valve surgery. MR was associated with mortality and complications. LSE, low complement and higher doses of corticosteroids were associated with complications, while a low GFR was associated with mortality.

Synovial monocytes from psoriatic and rheumatoid arthritis patients are modulated differently by TNF inhibitors and glucocorticoids: an ex-vivo study.

OBJECTIVES: Synovial monocytes (expressing CD14+CD16+) affect pro-inflammatory responses in the synovium microenvironment of psoriatic arthritis (PsA) and rheumatoid arthritis (RA). The effect of various drugs on those cells was evaluated. METHODS: Synovial fluid mononuclear cells (SFMCs) from PsA (n=29) and RA (n=11) patients were cultured with biologics or glucocorticoids (GCs). CD14+CD16+ cells were analysed by flow cytometry. TNF secretion was assessed by ELISA and changes in cytokine and matrix metalloproteinase-9 (MMP-9) mRNA by qPCR. RESULTS: TNF inhibitors (i) [adalimumab (ADA) and infliximab (IFX)] significantly reduced the %CD14+CD16+ cells (p<0.04 and p<0.02, respectively) compared to IL-17Ai, IL-12/23i, and GCs in PsA patients' SFMCs. Similarly, those TNFi reduced the %CD14+CD16+ cells (p<0.05 and p<0.02, respectively) compared to IL-6Ri, CD20i and GCs in RA patients' SFMCs. TNFi (ADA p<0.01, IFX p=0.0003), and GCs (p<0.05) reduced TNF levels in PsA patients SFMCs supernatants. IFX down-regulated IL-1ß mRNA (p<0.005) while GCs betamethasone (BET) (p<0.01) and methylprednisolone acetate (MPA) (p<0.005) led to IL-1ß up-regulation. IFX down-regulated IL-8 and MMP-9 (p<0.01) and up-regulated IL-10 (p<0.005), and GCs did so to a greater extent (for IL-8, BET p<0.0001 and MPA p<0.005, for MMP-9, BET and MPA p<0.0001 and for IL-10, BET and MPA p<0.0001). CONCLUSIONS: TNFi but not GCs reduced the inflammatory monocytes. Both TNFi and GCs inhibited TNF secretion but differently modulated IL-1ß, IL-8, MMP-9 and IL-10 gene expression. Our data point to TNFi as a modulator of synovial monocytes.

Sex-Based Differences in Sonographic and Clinical Findings Among Patients With Psoriatic Arthritis.

OBJECTIVE: To investigate sex-based sonographic differences in patients with psoriatic arthritis (PsA). METHODS: The study population included consecutive prospectively recruited patients with PsA, as determined by the CASPAR (Classification for Psoriatic Arthritis) criteria, who underwent clinical and physical examinations, followed by a detailed ultrasound (US) evaluation (greyscale and Doppler). US evaluation included 52 joints, 40 tendons, and 14 points of entheses (Modified Madrid Sonographic Enthesis Index [MASEI] plus lateral epicondyles) performed by an experienced sonographer blinded to the clinical data. The US score was based on the summation of a semiquantitative score for synovitis, tenosynovitis, and enthesitis. The US enthesitis score was categorized into inflammatory lesions (ie, hypoechogenicity, thickening, bursitis, and Doppler) and structural lesions (ie, enthesophytes/calcifications and erosions). RESULTS: The study population of 158 patients included 70 males and 88 females. The males had higher rates of employment (P = 0.01), Psoriasis Area and Severity Index scores (P = 0.04), and mean swollen joint counts (P = 0.04). The total US score and its subcategory scores-the synovitis and tenosynovitis scores-were similar for both sexes, whereas the total enthesitis score and its subcategory score-the inflammatory enthesitis score-were significantly higher for the males compared to the females (P = 0.01 and P = 0.005, respectively). Hypoechogenicity, thickening, and enthesophytes were more prevalent in males compared to females (P < 0.05). Multivariate ordinal logistic regression models showed that male sex was associated with a higher US inflammatory enthesitis score compared to female sex (odds ratio 1.96, P = 0.02). CONCLUSION: Sonographic enthesitis was more prevalent in males compared to females with PsA. These differences were not reflected by enthesitis disease activity scores derived from clinical assessment.

T cell functions of psoriatic arthritis patients are regulated differently by TNF, IL-17A and IL-6 receptor blockades in vitro.

OBJECTIVES: The impact of biologics used in PsA management on T cells is unknown. This study evaluated the effect of tumour necrosis factor-alpha (TNFα), interleukin-17A (IL-17A), and IL-6 receptor (IL-6R) blockers on T cell function in PsA patients and healthy controls peripheral blood mononuclear cells (PBMCs). METHODS: A total of 111 PsA patients and 32 healthy controls were recruited. PBMCs were co-cultured in presence of the biologics. T cell activation and proliferation were analysed by flow cytometry and cytokines in supernatants were measured by ELISA. The effect of biologics on lymphocyte proliferation was determined in response to phytohemagglutinin (PHA). RESULTS: Activated CD4+CD25+ T cells were significantly reduced by adalimumab (ADA) in PsA patients as compared to medium, ixekizumab (IXE), and tocilizumab (TCZ), while in healthy controls, ADA reduced the activated CD4+CD25+ T cells non-significantly. Elevated TNFα and IL-1ß levels were produced in supernatants of PsA patients as compared to healthy controls. TNFα, IL-17A, IL-1ß, and MMP-3 levels were reduced by ADA compared to medium (p<0.0001, p<0.0004, p<0.04, p<0.04, respectively). IXE reduced IL-17A (p<0.0001) but not the other cytokines. ADA had higher susceptibility to inhibit PHA-induced proliferation in both PsA patients and healthy controls (p<0.03) as compared to IXE and TCZ. CONCLUSIONS: Both TNF and IL-17A blockers are suitable for PsA treatment, but exhibit different activity on T cells. Moreover, the study reveals part of the mechanism exerted by ADA and provides a possible explanation for TCZ inefficacy in PsA.

Ultrasound, magnetic resonance imaging and radiography of the finger joints in psoriatic arthritis patients.

OBJECTIVES: To report the discrepancies and agreements between US, MRI and radiography of the hand in PsA, and to compare the sensitivity and specificity of US and radiography to MRI as the gold standard imaging study in PsA. METHODS: All of the 100 prospectively recruited consecutive PsA patients underwent clinical assessment and concomitant radiographic, US and MRI studies of the MCP, PIP and DIP joints of one hand. Synovitis, flexor tenosynovitis, extensor paratenonitis, erosions and bone proliferations were identified and scored. All readers were blinded to clinical data, and agreement was calculated based on prevalence-adjusted bias-adjusted kappa (PABAK). RESULTS: The prevalence of synovitis, flexor tenosynovitis, extensor paratenonitis and erosions was similar for US and MRI, while that of bone proliferation was significantly increased in US and radiography compared with MRI (P < 0.001). The absolute agreement between US and MRI was good-to-very good for synovitis (85-96%, PABAK = 0.70-0.92), flexor tenosynovitis (93-98%, PABAK = 0.87-0.96) and extensor paratenonitis (95-98%, PABAK = 0.90-0.97). Agreement between US, MRI and radiography was 96-98% (PABAK = 0.92-0.97) for erosions and 71-93% (PABAK = 0.47-0.87) for bone proliferations. Sensitivity of US with MRI as gold standard was higher for synovitis (0.5-0.86) and extensor paratenonitis (0.63-0.85) than for flexor tenosynovitis (0.1-0.75), while the specificity was high for each pathology (0.89-0.98). CONCLUSION: There is very good agreement between US and MRI for the detection of inflammatory changes in finger joints in PsA. US, radiography and MRI have a good-to-very good agreement for destructive changes.

Role of ultrasound for assessment of psoriatic arthritis patients with fibromyalgia.

OBJECTIVE: To investigate whether ultrasonography (US), as an objective imaging modality, can optimise the evaluation of disease activity in psoriatic arthritis (PsA) patients with concomitant fibromyalgia syndrome (FMS). METHODS: The study population included 156 consecutive PsA patients who were recruited prospectively and fulfilled the ClASsification criteria for Psoriatic ARthritis criteria. The patients underwent complete clinical evaluation including assessment of fulfilment of the 2016 fibromyalgia classification criteria. All of the patients underwent US evaluation including 52 joints, 40 tendons and 14 entheses. The US score was based on the summation of a semiquantitative score (including synovitis, tenosynovitis and enthesitis). Scoring was performed by a sonographer blinded to the clinical data. Spearman's correlation coefficient and multivariate linear regression models were used to examine the association of FMS with clinical and the US scores. RESULTS: Forty-two patients (26.9%) with coexisting PsA and FMS were compared with 114 (73.1%) PsA patients without FMS. Patients with PsA and FMS had significantly increased scores for clinical composite indices, including non-Minimal Disease Activity, Composite Psoriatic Disease Activity Index (CPDAI), Disease Activity for Psoriatic Arthritis (DAPSA) and Psoriatic Arthritis Disease Activity Score (PASDAS) (p<0.001). In contrast, the total US score and its subcategories were similar for those with and without FMS. The total US score significantly correlated with CPDAI, DAPSA and PASDAS (p<0.001) in the PsA without FMS but not in the PsA with FMS group. FMS was significantly associated with higher clinical scores (p<0.001) but not with the US score (multivariable linear regression models). CONCLUSIONS: US has significantly greater value than composite clinical scores in the assessment of disease activity in PsA patients with FMS.

Prevalence of Nonradiographic Sacroiliitis in Patients With Psoriatic Arthritis: A Real-life Observational Study.

OBJECTIVE: To establish the prevalence of nonradiographic sacroiliitis within a real-life sample of patients with psoriatic arthritis (PsA), using pelvic radiographs and magnetic resonance imaging (MRI) of sacroiliac joints (SIJs). METHODS: This cross-sectional study included 107 consecutive adults with PsA (Classification Criteria for Psoriatic Arthritis criteria). Participants completed clinical and laboratory evaluation, pelvic radiographs scored for radiographic sacroiliitis according to the modified New York (mNY) criteria, and noncontrast MRI of SIJs, scored by the Berlin score and categorized into active sacroiliitis using the 2016 Assessment of Spondyloarthritis international Society (ASAS) criteria and the presence of structural sacroiliitis. RESULTS: Radiographic sacroiliitis/mNY criteria were detected in 28.7% (n = 29), confirmed by MRI-detected structural lesions in 72.4% (n = 21). Active sacroiliitis was detected by MRI in 26% (n = 28) of patients, with 11% (n = 11) qualifying for nonradiographic sacroiliitis. Patients with radiographic and nonradiographic sacroiliitis had similar clinical characteristics, except for a longer duration of psoriasis (PsO) and PsA in the radiographic subgroup (PsO: 23.8 ± 12.5 vs 14.1 ± 11.7 yrs, P = 0.03; PsA: 12.3 ± 9.8 vs 4.7 ± 4.5 yrs, P = 0.02, respectively). Inflammatory back pain (IBP) was reported in 46.4% (n = 13) with active sacroiliitis and 27% (n = 3) with nonradiographic sacroiliitis. The sensitivity of IBP for detection of nonradiographic sacroiliitis was low (27%) and moderate for radiographic sacroiliitis (52%), whereas specificity ranged from 72% to 79% for radiographic and nonradiographic sacroiliitis, respectively. CONCLUSION: The prevalence of active sacroiliitis among a real-life population of patients with PsA was 26%. However, the prevalence of nonradiographic sacroiliitis was low (11%) compared to the radiographic sacroiliitis (28.7%) seen in patients with longer disease duration. IBP was not a sensitive indicator for the presence of early-stage sacroiliitis that was commonly asymptomatic.

Immunogenicity and safety of vaccination against seasonal influenza vaccine in patients with psoriatic arthritis treated with secukinumab.

OBJECTIVE: To assess the immunogenicity and safety of vaccination against seasonal influenza in psoriatic arthritis (PsA) patients treated with secukinumab versus healthy controls (HC). METHODS: PsA patients administered secukinumab for ≥3 months and HC received the Sanofi Pasteur vaccine composed of 3 antigens (H3N3, H1N1, and B) and underwent clinical and laboratory assessments on the day of vaccination and 4-6 weeks later. Immunogenicity of the vaccine was evaluated by hemagglutination inhibition assay against those 3 antigens. Responders to each antigen were defined by a 4-fold increase in the antigen titer or by seroconversion in patients whose baseline level was <1/40. RESULTS: Thirty-two consecutive PsA patients treated with secukinumab for ≥3 months comprised the study group, 10 of whom received concomitant conventional synthetic disease-modifying drugs, mostly methotrexate. There were 17 age- and gender-matched HC (median age 48.5 years, 6 females). The geometric mean titers of each antigen increased significantly in both groups. The number of responders in each group was similar for H3N2 and H1N1, and significantly higher for B/Brisbane in the PsA group. The proportion of patients with a seroprotective level (a titer >1/40) was high and similar in both groups. There was no correlation between the response rate and age, gender, or selected parameters of disease activity (tender/swollen joint counts, Leeds enthesitis index, physician and patient global assessment, psoriasis area severity index, and C-reactive protein). No disease exacerbation was observed following the vaccination. No serious adverse effects were observed in both groups during the study period. CONCLUSION: Secukinumab treatment does not affect the humoral response to influenza vaccine of patients with PsA.

Prevalence of high-sensitivity cardiac troponin T in real-life cohorts of psoriatic arthritis and general population: a cross-sectional study.

Patients with psoriatic arthritis (PsA) are at increased risk of cardiovascular disease (CVD). High-sensitivity cardiac troponin T (hs-cTnT) is a novel biomarker of CVD. The objective of this study is to determine the prevalence of circulating hs-cTnT in patients with PsA compared to the general population and to characterize a PsA subset with detectable hs-cTnT. A cross-sectional analysis of serum hs-cTnT levels was performed in 116 consecutive patients with PsA and the Tel-Aviv Medical Center Inflammatory Survey cohort of the general population (n = 6052) as a control group. The level and prevalence of hs-cTnT (ng/L) were similar in the entire study population: 4.94 ± 4.4, 30.2% in PsA, 5.17 ± 6.7, 34.2% and 5.38 ± 4.3, 37.9% in unmatched and matched control groups according to age, gender and cardiovascular risk factors, respectively. Factors associated with detectable hs-cTnT in PsA included male gender (p = 0.002), age (p = 0.007), hypertension (p < 0.001), diabetes mellitus (p < 0.001), and smoking (p = 0.001). Axial disease, present in 25% of patients with PsA, was significantly associated with detectable hs-cTnT (p = 0.004). This association remained significant after adjusting for age, gender and traditional cardiovascular risk factors. No correlation between hs-cTnT levels and disease characteristics, PsA activity indices, C-reactive protein levels, or treatments for PsA was found. In summary, serum hs-cTnT was detectable in about the third of the PsA and control cohorts. In PsA, axial disease was significantly associated with detectable hs-TnT, warranting a particular attention to cardiovascular risk assessment in this sub-group. The role of hs-cTnT as a biomarker for CVD in PsA should be further investigated in prospective studies.

[RITUXIMAB IN RHEUMATOID ARTHRITIS - THERAPEUTIC ASPECTS BASED ON 18 YEARS OF GLOBAL EXPERIENCE].

INTRODUCTION: Rituximab, a monoclonal antibody against CD20 positive B cell, depletes these cells peripherally, and is a successful treatment in rheumatoid arthritis (RA). It is the second efficacious biologic to be established in the treatment of RA after TNFα blockers. Eighteen years of global experience from diverse clinical trials and from "real world" data, have demonstrated clinical efficacy in various disease scenarios and patient populations - short and long disease duration, methotrexate naïve patients and those with incomplete response to methotrexate, biologic naïve patients and those with incomplete response to previous biologics. Moreover, it has demonstrated the inhibition of radiographic progression. It seems to be most efficacious in seropositive patients. Despite vast experience, the need for concomitant traditional disease-modifying anti rheumatic drugs (DMARD), the optimal retreatment dose, and the favored retreatment interval remain somewhat uncertain. The recommended dosage is 1000 mg, administered twice, with a 2 weeks interval, although in some cases, a reduced dosage of 500 mg, administered twice may be considered. The safety profile of rituximab includes mainly infusion-related reactions, which are usually mild. A small risk of major infections has remained stable over time and repeated courses. Opportunistic infections are infrequent. Nevertheless, reactivation of hepatitis B is still a concern. Tuberculosis, malignancies, cardiovascular events and deterioration of interstitial lung disease do not appear to be increased. Since rituximab severely impairs the humoral response to vaccinations, they should be administered prior to treatment whenever possible. Rituximab has been a powerful addition to the large armamentarium for the treatment of RA. Rituximab is indicated in Israel as a second line biologic treatment for active RA.

The Effect of Pregnancy on Disease Activity in Patients with Psoriatic Arthritis.

OBJECTIVE: To evaluate the effect of pregnancy on disease activity in psoriatic arthritis (PsA). METHODS: This is a retrospective case series. Review of the medical files of all female patients followed at the PsA clinic of 2 medical centers identified those with at least 1 pregnancy during followup and 1 visit during or soon after pregnancy. RESULTS: Twenty-five women with PsA (out of 107 women of reproductive age followed up in our PsA clinics) and 35 pregnancies were enrolled. Thirty-three pregnancies resulted in live healthy babies. In the whole group, there was no significant change in disease activity throughout pregnancy, while in 16 (48%) of pregnancies, patients worsened during the first postpartum year. In 15 out of 21 pregnancies, in which the women had been treated before conception with biologics, treatment was discontinued close to pregnancy or during the first trimester. Five of those 15 patients had been classified as having mild to severe PsA activity prior to pregnancy. That number increased to 8, 9, and 14 during the first and second trimesters and postpartum period, respectively. There was no significant change in degree of disease activity in 6 patients whose biologics were continued beyond the first trimester. Improvement in disease activity was observed during pregnancy among the nonbiologics-treated patients. Corticosteroids were initiated or the dosage was increased during 6 pregnancies, all involving patients whose biologics were stopped before pregnancy. CONCLUSION: Continuation of biologics therapy was associated with a low level of disease activity and a low probability of flare during pregnancy. Stopping treatment with biologics before pregnancy is associated with flare during pregnancy and the postpartum period.

Expression levels of selected genes can predict individual rheumatoid arthritis patient response to tumor necrosis factor alpha blocker treatment.

OBJECTIVES: Rheumatoid arthritis (RA) patients have many therapeutic options; however, tools to predict individual patient response are limited. The Genefron personal diagnostic kit, developed by analyzing large datasets, utilizes selected interferon stimulated gene expressions to predict treatment response. This study evaluates the kit's prediction accuracy of individual RA patients' response to tumor necrosis alpha (TNFα) blockers. METHODS: A retrospective analysis was performed on RA patients reported in published datasets. A prospective analysis assessed RA patients, before and 3 months after starting a TNFα blocker. Clinical response was evaluated according to EULAR response criteria. Blood samples were obtained before starting treatment and were analyzed utilizing the kit which measures expression levels of selected genes by quantitative real time polymerase chain reaction (PCR). ROC analysis was applied to the published datasets and the prospective data. RESULTS: The Genefron kit analysis of retrospective data predicted the response to a TNFα blocker in 53 of 61 RA patients (86.8% accuracy). In the prospective analysis, the kit predicted the response in 16 of 18 patients (89% accuracy) achieving a EULAR moderate response, and in 15 of 18 patients achieving a EULAR good response (83.3% accuracy). ROC analysis applied to the two published datasets yielded an AUC of 0.89. ROC analysis applied to the prospective data yielded an AUC of 0.83 (sensitivity - 100%, specificity - 75%) The statistical power obtained in the prospective study was .9. CONCLUSION: The diagnostic kit predicted the response to TNFα blockers in a high percentage of patients assessed retrospectively or prospectively. This personal kit may guide selection of a suitable biological drug for the individual RA patient.

Sputum Anticitrullinated Protein Antibodies in Patients With Long-standing Rheumatoid Arthritis.

OBJECTIVE: The aim of this study was to evaluate the presence of autoantibodies to cyclic citrullinated synthetic peptides (ACPAs) in the sputum of patients with long-standing rheumatoid arthritis (RA). METHODS: Nineteen consecutive RA patients and 16 age- and sex-matched control subjects participated in this cross-sectional study. All underwent complete lung function tests and provided induced sputum. Antibodies to citrullinated (CitP) and the corresponding norleucine-containing (NorP) peptides in the sputum of the RA patients and control subjects, as well as in the serum of the RA patients, were determined by enzyme-linked immunosorbent assay. RESULTS: Patients with RA had the following characteristics: mean disease duration of 12 years, Disease Activity Score for 28 joints of 3.44, and Sharp-van der Heijde score of 57.5. Ten of the 19 RA patients showed high titers of ACPAs in their sera. Four of the seropositive (40%), none of the seronegative RA patients, and only 1 of the control subjects showed detectable levels of ACPAs in their sputum. The ratio between the reactivity with CitP and NorP peptides in the sputum was significantly higher in RA sputum than in control sputum (1.33 ± 1.2 vs. 0.64 ± 0.14, P = 0.02). A positive correlation was found between sputum ACPAs and age, serum ACPAs, sputum anti-NorP, serum anti-CitP/NorP reactivity ratio, and the proportion of neutrophils and lymphocytes in the sputum. No significant correlation was found between sputum ACPAs and disease severity, history of smoking, lung function tests, or treatment for RA. CONCLUSIONS: Anticitrullinated protein/peptide antibodies can be detected in the sputum of RA patients and are correlated with the presence in the serum.

Prevalence of Axial Spondyloarthritis Among Patients With Fibromyalgia: A Magnetic Resonance Imaging Study With Application of the Assessment of SpondyloArthritis International Society Classification Criteria.

OBJECTIVE: To evaluate the prevalence of sacroiliitis, the radiographic hallmark of inflammatory spondyloarthropathy, among patients diagnosed with fibromyalgia syndrome (FMS), using the current Assessment of SpondyloArthritis International Society (ASAS) criteria and magnetic resonance imaging. METHODS: Patients experiencing FMS (American College of Rheumatology 1990 criteria) were interviewed regarding the presence of spondyloarthritis (SpA) features and underwent HLA-B27 testing, C-reactive protein (CRP) level measurement, and magnetic resonance imaging examinations of the sacroiliac joints. FMS severity was assessed by the Fibromyalgia Impact Questionnaire and the Short Form 36 health survey. SpA severity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index. RESULTS: Sacroiliitis was demonstrated among 8 patients (8.1%) and ASAS criteria for diagnosis of axial SpA were met in 10 patients (10.2%). Imaging changes suggestive of inflammatory involvement (e.g., erosions and subchondral sclerosis) were demonstrated in 15 patients (17%) and 22 patients (25%), respectively. The diagnosis of axial SpA was positively correlated with increased CRP level and with physical role limitation at recruitment. CONCLUSION: Imaging changes suggestive of axial SpA were common among patients with a diagnosis of FMS. These findings suggest that FMS may mask an underlying axial SpA, a diagnosis with important therapeutic implications. Physicians involved in the management of FMS should remain vigilant to the possibility of underlying inflammatory disorders and actively search for such comorbidities.

Cocaine-Induced Vasculitis.

The use of cocaine continues to grow worldwide. One of the possible side-effects of cocaine is vasculitis. Two distinct vasculitic syndromes have been described due to cocaine. One is cocaine-induced midline destructive lesion, secondary to a direct vasoconstrictor effect of cocaine, inducing ischemic necrosis of the septal cartilage and perforation of the nasal septum, mimicking findings of granulomatosis with polyangiitis in the upper airways. The other is ANCA-associated vasculitis, attributed to the levamisole component that contaminates about 70% of the cocaine. This type of vasculitis may be myeloperoxidase (MPO) and proteinase 3 (PR3) positive, and its main manifestations are typical cutaneous findings, arthralgia, otolaryngologic involvement, and agranulocytosis. A high degree of suspicion and awareness is needed in order properly to diagnose and treat these patients.

The Effect of the Presence of Fibromyalgia on Common Clinical Disease Activity Indices in Patients with Psoriatic Arthritis: A Cross-sectional Study.

OBJECTIVE: To study the effect of the presence of fibromyalgia (FM) on common clinical disease activity indices in patients with psoriatic arthritis (PsA). METHODS: Seventy-three consecutive outpatients with PsA (mean age 51.7 yrs; 42 females, 57.5%) were enrolled in a prospective cross-sectional study. FM was determined according to American College of Rheumatism criteria (2010 and 1990). All patients underwent clinical evaluation of disease activity and completed the Health Assessment Questionnaire (HAQ), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Dermatology Life Quality Index, and the Leeds Enthesitis Index (LEI). Disease activity was evaluated using the Composite Psoriatic Disease Activity Index (CPDAI), minimal disease activity (MDA), and the Disease Activity Index for Psoriatic Arthritis (DAPSA) scores. RESULTS: The overall prevalence of FM was 17.8% (13 patients), and all but 1 were women (12 patients, 92.3%, p = 0.005). CPDAI and DAPSA scores were significantly higher in patients with coexisting PsA and FM (9.23 ± 1.92 and 27.53 ± 19.23, respectively) than in patients with PsA only (4.25 ± 3.14 and 12.82 ± 12.71, respectively; p < 0.001 and p = 0.003). None of the patients with FM + PsA met the criteria for MDA, whereas 26 PsA-only patients did (43.3%, p = 0.003). HAQ, BASDAI, and LEI scores were significantly worse in patients with PsA and associated FM. CONCLUSION: Coexisting FM is related to worse scores on all tested measures in patients with PsA. Its influence should be taken into consideration in the treatment algorithm to avoid unnecessary upgrading of treatment.

Induced Sputum Analysis in Subjects With Systemic Sclerosis.

BACKGROUND: Induced sputum is a noninvasive tool, aimed at collecting cellular and soluble materials from lung airways. Induced sputum sampling analysis has been validated in chronic obstructive lung diseases as well as in various diffuse interstitial lung disorders. Our objective was to evaluate the utility of induced sputum speciments of cellular and soluble materials noninvasively sampled from the lung airways of subjects with systemic sclerosis compared with healthy controls and determine possible correlation with disease manifestations. METHODS: The study population included 20 consecutive subjects with systemic sclerosis and 16 healthy volunteers (controls). All of the participants underwent pulmonary function testing (PFT), single-breath diffusion capacity of carbon monoxide, and induced sputum cytology analysis. RESULTS: The systemic sclerosis subjects' induced sputum samples contained a higher neutrophil count (P = .09) and lower lymphocyte count (P = .045) compared with the controls. Within the systemic sclerosis population, several clinical, PFT, and induced sputum findings were positively correlated: the modified Rodnan skin score score and CD3 (P = .044), modified Rodnan skin score and CD4 (P = .04), modified Rodnan skin score and percentage neutrophils (P = .059), and total lung capacity (TLC) and percentage lymphocytes (P = .02). Induced sputum neutrophil counts were inversely associated with TLC (P = .02) and FVC (P = .02). Induced sputum samples from the subgroup of systemic sclerosis subjects with PFT restrictive pattern contained a significantly lower percentage of lymphocytes (P = .004) and lower CD4/CD8 ratio (P = .03) compared with controls. In this subgroup, TLC also was negatively correlated with the neutrophil count (P = .043), and positive correlations were found between TLC and CD3 (P = .053), disease duration and CD4/CD8 ratio (P = .033), TLC and FVC and percentage macrophages (P = .033 and P = .052, respectively), diffusion per unit of alveolar volume, and percentage macrophages (P = .032), and C-reactive protein and percentage lymphocytes, percentage macrophages, and neutrophil count (P = .02, P = .008, and P = .006, respectively). CONCLUSIONS: Induced sputum analysis of subjects with systemic sclerosis, including those with restrictive lung disease, shows changes in cellular pattern and correlation with several highly relevant clinical and PFT parameters.