Parameniscal cyst: an important differential diagnosis in slow growing masses of the knee.

INTRODUCTION: Parameniscal cysts are small cystic lesions, near the meniscus, involving medial and lateral compartments at equal frequency. Frequently, parameniscal cysts are so small that patients do not notice them, being asymptomatic. However, they can grow and exceed 2 centimeters in diameter, causing pain and alarm due to the slow growing mass. Magnetic Resonance Imaging (MRI) is the gold standard for diagnosis. METHODS: Case report of a patient admitted to rheumatology department in the Centro Hospitalar e Universitário de Coimbra. RESULTS: We report a case of a 47-year-old male with idiopathic juvenile arthritis, who presented with a slow-growing mass over the medial aspect of the right knee. MRI revealed a conspicuous cystic ovoid lesion, compatible with a parameniscal cyst, associated with structural heterogeneity of the posterior edge of the internal meniscus with a longitudinal fracture at this level. CONCLUSION: This is the first case of parameniscal cyst reported in patients with inflammatory rheumatic disease and the differential diagnosis with synovial cyst, baker cyst, ganglion cyst, bursitis, hematoma and neoplasms is of utmost importance.

Clinical spectrum time course in non-Asian patients positive for anti-MDA5 antibodies.

OBJECTIVES: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. METHODS: We conducted a multicentre, international, retrospective cohort study. RESULTS: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. CONCLUSIONS: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

Human Bone Marrow Mesenchymal Stromal/Stem Cells Regulate the Proinflammatory Response of Monocytes and Myeloid Dendritic Cells from Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a disabling autoimmune disease whose treatment is ineffective for one-third of patients. Thus, the immunomodulatory potential of mesenchymal stromal/stem cells (MSCs) makes MSC-based therapy a promising approach to RA. This study aimed to explore the immunomodulatory action of human bone marrow (BM)-MSCs on myeloid dendritic cells (mDCs) and monocytes, especially on cytokines/chemokines involved in RA physiopathology. For that, LPS plus IFNγ-stimulated peripheral blood mononuclear cells from RA patients (n = 12) and healthy individuals (n = 6) were co-cultured with allogeneic BM-MSCs. TNF-α, CD83, CCR7 and MIP-1ß protein levels were assessed in mDCs, classical, intermediate, and non-classical monocytes. mRNA expression of other cytokines/chemokines was also evaluated. BM-MSCs effectively reduced TNF-α, CD83, CCR7 and MIP-1ß protein levels in mDCs and all monocyte subsets, in RA patients. The inhibition of TNF-α production was mainly achieved by the reduction of the percentage of cellsproducing this cytokine. BM-MSCs exhibited a remarkable suppressive action over antigen-presenting cells from RA patients, potentially affecting their ability to stimulate the immune adaptive response at different levels, by hampering their migration to the lymph node and the production of proinflammatory cytokines and chemokines. Accordingly, MSC-based therapies can be a valuable approach for RA treatment, especially for non-responder patients.

Prevalence of vitamin D deficiency and its predictors in the Portuguese population: a nationwide population-based study.

Vitamin D deficiency is prevalent worldwide, but its prevalence is unknown in adult Portuguese population. In Portugal, 66% of adults present Vitamin D insufficiency/deficiency. Winter, living in Azores, older age, and obesity were the most important risk factors. It highlights the need of strategies to prevent vitamin D deficiency in Portugal. OBJECTIVE: To estimate the prevalence and risk factors of vitamin D deficiency in the adult Portuguese population. METHODS: Adults (≥ 18 years old) from the EpiReumaPt Study (2011-2013) were included. Standardized questionnaires on socio-demographic and lifestyle features were obtained. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were evaluated using ADVIA Centaur VitD competitive immunoassay (Siemens Healthineers) in 2015-2017 as 25 (OH)D Level 0: ≤ 10 ng/mL; Level 1: 11-19 ng/mL; Level 2: 20-29 ng/mL, and Level 3: ≥ 30 ng/mL. Weighted multinomial regression analysis was conducted to evaluate the association between socio-demographic and lifestyle variables and vitamin D status. RESULTS: Based on weighted analysis, the estimated prevalence of levels of 25(OH)D ≤ 10, < 20, and < 30 ng/mL was 21.2, 66.6, and 96.4%, respectively. The strongest independent predictors of serum 25 (OH)D ≤ 10 ng/mL were living in the Azores archipelagos (OR 9.39; 95%CI 1.27-69.6) and having the blood sample collection in winter (OR 18.53; 95%CI 7.83-43.87) or spring (11.55; 95%CI 5.18-25.74). Other significant predictors included older age (OR 5.65, 95%CI 2.08-15.35), obesity (OR 2.61; 95%CI 1.35-5.08), current smoking (OR 2.33; 95%CI 1.23-4.43), and female gender (OR 1.9, 95%CI 1.1-3.28). Conversely, physical exercise (OR 0.48, 95%CI 0.28-0.81) and occasional alcohol intake (OR 0.48, 95%CI 0.29-0.81) were associated with a lower risk of 25(OH)D ≤ 10 ng/mL. CONCLUSION: Vitamin D deficiency/insufficiency [25(OH)D < 20 ng/ml] is highly prevalent in Portugal, affecting > 60% of all Portuguese adults, with strong geographical and seasonal variation. This study highlights the need to critically assess the relevance of vitamin D deficiency as a public health problem and the urgent need for a wide and scientifically robust debate about the most appropriate interventions at the individual and societal levels.

Educational needs in people with ankylosing spondylitis and psoriatic arthritis: a cross-sectional study.

OBJECTIVES: To assess the educational needs of people with ankylosing spondylitis (AS) and psoriatic arthritis (PsA), test differences across patient subgroups and identify factors independently associated with their educational needs. METHODS: This was a cross-sectional analytic study. Patients with AS and PsA completed the Portuguese version of the Educational Needs Assessment Tool (PortENAT). Data were Rasch-transformed before descriptive and inferential analyses were undertaken. Univariable and multivariable analyses were used to determine differences between patient subgroups and factors independently associated with their educational needs. RESULTS: The study included 121 patients with AS and 132 with PsA. The level of educational needs varied by diagnostic group, but higher needs for both subgroups were reported regarding the "Disease process", "Feelings" and "Managing pain" domains. Overall, patients with AS had a higher level of educational needs than those with PsA. In both diagnostic groups, female gender was independently associated with higher educational needs. In the PsA group, a shorter disease duration was independently associated with higher educational needs in the following domains: "Managing pain", "Movement" and "Feelings". CONCLUSIONS: Educational needs vary by diagnostic group, gender and disease duration. These differences merit consideration in the design of patient education interventions.

Recent Patents on Impact of Lipopeptide on the Biofilm Formation onto Titanium and Stainless Steel Surfaces.

BACKGROUND: Numerous causes of infection in arthroplasties are related to biofilm formation on implant surfaces. In order to circumvent this problem, new alternatives to prevent bacterial adhesion biosurfactants-based are emerging due to low toxicity, biodegradability and antimicrobial activity of several biosurfactants. We revised all patents relating to biosurfactants of applicability in orthopedic implants. METHODS: This work aims to evaluate the capability of a lipopeptide produced by Bacillus subtilis ATCC 19659 isolates acting as inhibitors of the adhesion of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213 onto titanium and stainless steel surfaces and its antimicrobial activity. RESULTS: The adhesion of the strains to the stainless-steel surface was higher than that of titanium. Preconditioning of titanium and stainless-steel surfaces with 10 mg mL-1 lipopeptide reduced the adhesion of E. coli by up to 93% and the adhesion of S. aureus by up to 99.9%, suggesting the strong potential of lipopeptides in the control of orthopedic infections. The minimal inhibitory concentration and minimum bactericidal concentration were 10 and 240 µg mL-1 for E. coli and S. aureus, respectively. CONCLUSION: The lipopeptide produced by Bacillus subtilis ATCC 19659 presented high biotechnological application in human health against orthopedic implants infections.

Immunomodulatory effect of human bone marrow-derived mesenchymal stromal/stem cells on peripheral blood T cells from rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a Th1/Th17-mediated autoimmune disease whose current treatment, consisting in the blockage of inflammatory cytokines by disease-modifying antirheumatic drugs, is not effective for all patients. The therapeutic potential of mesenchymal stromal/stem cells' (MSCs) immunomodulatory properties is being explored in RA. Here, we investigate the effect of human bone marrow (BM)-MSCs on the expression of cytokines involved in RA physiopathology by the distinct functional compartments of CD4+ and CD8+ T cells from RA patients. Peripheral blood mononuclear cells from healthy individuals (n = 6) and RA patients (n = 12) were stimulated with phorbol myristate acetate plus ionomycin and cultured in the presence/absence of BM-MSCs. The expression of (interleukin) IL-2, tumor necrosis factor alpha (TNF-α), and interferon-gamma (IFN-γ) was evaluated in naive, central memory, effector memory, and effector CD4+ and CD8+ T cells, whereas IL-6, IL-9, and IL-17 expression was measured in total CD4+ and CD8+ T cells. mRNA expression of IL-4, IL-10, transforming growth factor beta (TGF-ß), cytotoxic T-lymphocyte-associated antigen 4, and/or forkhead box P3 was quantified in fluorescence-activated cell sorting-purified CD4+ T cells, CD8+ T cells, and CD4+ Treg. BM-MSCs inhibited the production of TNF-α, IL-17, IL-6, IL-2, IFN-γ, and IL-9 by T cells from RA patients, mainly by reducing the percentage of cells producing cytokines. This inhibitory effect was transversal to all T cell subsets analyzed. At mRNA level, BM-MSCs increased expression of IL-10 and TGF-ß by CD4+ and CD8+ T cells. BM-MSCs displayed a striking inhibitory action over T cells from RA patients, reducing the expression of cytokines involved in RA physiopathology. Remarkably, BM-MSC-derived immunomodulation affected either naive, effector, and memory T cells.

Gloeosporiocide, a new antifungal cyclic peptide from Streptomyces morookaense AM25 isolated from the Amazon bulk soil.

Actinobacteria are known by their ability to produce several antimicrobial compounds of biotechnological interest. Thus, in this study, we isolated and identified by partial 16S RNA sequencing ∼100 actinobacteria isolates from guarana (Paullinia cupana) bulk soil. Besides, we isolated from the actinobacteria Streptomyces morookaense AM25 a novel cyclic peptide, named gloeosporiocide, molecular formula C44H48N11O7S3 (calculated 938.2901), and characterized by the presence of cyclized cysteins to form three thiazols. The novel compound had activity against the plant pathogen Colletotrichum gloeosporioides, assayed by the paper disk diffusion method (42.7% inhibition, 0.1 mg disk-1) and by the microdilution assay (1.25 g L-1). Our results reveal the potential of the actinobacteria from the Amazon rhizospheric soils as biocontrol agents as well as producers of new compounds with antifungal activity. Thus, this work constitutes a step forward in the development of the biotechnology of actinobacteria in the production of compounds of agronomic interest.

The many faces of IgG4-related disease: report of a case with inaugural recurrent aortic aneurism ruptures and literature review.

Vascular involvement in IgG4-related disease (IgG4-RD), is a well-recognized feature and large vessel commitment, especially the aorta, can be the only manifestation of the disease. Being a newly recognized disease, its diagnosis and workup still represents a challenge in clinical practice. A 47-year-old-man with two aortic aneurysms ruptures, one at abdominal and the other at thoracic level, was referred to our rheumatology department. The initial analysis of the surgical specimen obtained 3 years earlier revealed a nonspecific aortitis. Re-evaluation of the biopsy with immunohistology now demonstrated the presence of IgG4 deposits. Evidence-based recommendations regarding diagnosis, treatment and follow-up of IgG4-related large-vessel involvement are lacking. In this particular case, histopathology were crucial. The authors review and discuss vascular involvement in IgG4-RD and respective treatment options.

Invalidation in Patients with Rheumatic Diseases: Clinical and Psychological Framework.

OBJECTIVE: The term "invalidation" refers to the patients' perception that their medical condition is not recognized by the social environment. Invalidation can be a major issue in patients' lives, adding a significant burden to symptoms and limitations while increasing the risk of physical and psychological disability. In this study in patients with rheumatic diseases, we investigated the relationship between invalidation and sociodemographic, clinical, psychological, and personality characteristics. METHODS: This international cross-sectional study included 562 adults with rheumatoid arthritis (n = 124), spondyloarthritis (n = 85), systemic lupus erythematosus (n = 112), or fibromyalgia (FM; n = 241). Assessed were the family and health professionals subscales of the Illness Invalidation Inventory (3*I), happiness (Subjective Happiness Scale), personality (Ten-Item Personality Inventory), pain, and loneliness (numerical rating scales). Univariate and multivariate analyses were used to test different models. RESULTS: Invalidation occurred in all rheumatic diseases, but patients with FM reported the most invalidation. Including all correlated variables in the multivariate model, pain remained as a determinant of invalidation by health professionals, but not by family. Regarding psychological variables, loneliness remained as a determinant of invalidation by family, but not by health professionals. FM and low levels of happiness, agreeableness, and conscientiousness were associated with invalidation while taking account of other variables. CONCLUSION: Invalidation occurs in all rheumatic diseases and patients with FM experience the most invalidation. Psychological factors (happiness, agreeableness, and conscientiousness), loneliness, and pain intensity are associated with invalidation, irrespective of the rheumatic disease and may deserve dedicated interventions.

Analgesic Effect of Photobiomodulation on Bothrops Moojeni Venom-Induced Hyperalgesia: A Mechanism Dependent on Neuronal Inhibition, Cytokines and Kinin Receptors Modulation.

BACKGROUND: Envenoming induced by Bothrops snakebites is characterized by drastic local tissue damage that involves an intense inflammatory reaction and local hyperalgesia which are not neutralized by conventional antivenom treatment. Herein, the effectiveness of photobiomodulation to reduce inflammatory hyperalgesia induced by Bothrops moojeni venom (Bmv), as well as the mechanisms involved was investigated. METHODOLOGY/PRINCIPAL FINDINGS: Bmv (1 µg) was injected through the intraplantar route in the right hind paw of mice. Mechanical hyperalgesia and allodynia were evaluated by von Frey filaments at different time points after venom injection. Low level laser therapy (LLLT) was applied at the site of Bmv injection at wavelength of red 685 nm with energy density of 2.2 J/cm2 at 30 min and 3 h after venom inoculation. Neuronal activation in the dorsal horn spinal cord was determined by immunohistochemistry of Fos protein and the mRNA expression of IL-6, TNF-α, IL-10, B1 and B2 kinin receptors were evaluated by Real time-PCR 6 h after venom injection. Photobiomodulation reversed Bmv-induced mechanical hyperalgesia and allodynia and decreased Fos expression, induced by Bmv as well as the mRNA levels of IL-6, TNF-α and B1 and B2 kinin receptors. Finally, an increase on IL-10, was observed following LLLT. CONCLUSION/SIGNIFICANCE: These data demonstrate that LLLT interferes with mechanisms involved in nociception and hyperalgesia and modulates Bmv-induced nociceptive signal. The use of photobiomodulation in reducing local pain induced by Bothropic venoms should be considered as a novel therapeutic tool for the treatment of local symptoms induced after bothropic snakebites.

Subset-specific alterations in frequencies and functional signatures of γδ T cells in systemic sclerosis patients.

OBJECTIVE AND DESIGN: Here, we evaluated the distribution and functional profile of circulating CD27+ and CD27- γδ T-cell subsets in systemic sclerosis (SSc) patients to assess their potential role in this disorder. MATERIALS AND METHODS: Peripheral blood from 39 SSc patients and 20 healthy individuals was used in this study. The TCR-γδ repertoire, cytokine production and cytotoxic signatures of circulating γδ T-cell subsets were assessed by flow cytometry. Gene expression of EOMES, NKG2D and GZMA was evaluated by quantitative RT-PCR in both purified γδ T-cell subsets. RESULTS: Absolute numbers of γδ T-cell subsets were significantly decreased in SSc groups, likely reflecting their mobilization to the inflamed skin. Both γδ T-cell subsets preserved their relative proportions and Th1-type cytokine responses. However, cytotoxic properties showed significant disease-associated and subset-specific changes. SSc patients exhibited increased percentages of CD27+ γδ T cells expressing granzyme B or perforin and upregulated GZMA expression in diffuse cutaneous SSc. Conversely, EOMES and NKG2D were downregulated in both SSc γδ T-cell subsets vs. normal controls. Interestingly, patients with pulmonary fibrosis showed a biased TCR repertoire, with a selected expansion of effector Vγ9+ γδ T cells associated with increased frequency of cells expressing granzyme B, but decreased IFN-γ production. CONCLUSIONS: Significant alterations on circulating γδ T-cell subsets suggest a deregulated (increased) cytotoxic activity and thus enhanced pathogenic potential of CD27+ γδ T cells in SSc.

CD38, CD81 and BAFFR combined expression by transitional B cells distinguishes active from inactive systemic lupus erythematosus.

In view of its heterogeneous presentation and unpredictable course, clinical management of systemic lupus erythematosus (SLE) is difficult. There is a need for biomarkers and diagnostic aids to monitor SLE disease activity and severity prior to, during and after treatment. We undertook this study to search for unique phenotypic patterns in each peripheral blood (PB) B cell subset, capable of distinguishing SLE patients with inactive disease versus SLE patients with active disease versus controls by using an automated population separator (APS) visualization strategy. PB was collected from 41 SLE patients and 28 age- and gender-matched controls. We analyzed the cell surface markers (in a tube CD20/CD27/CD19/CD45/CD38/CD81/BAFFR combination) expression on PB B cell subsets using principal component analysis, implemented in the APS software tool. Overall, our analysis indicates that active SLE can be distinguished from inactive SLE on the basis of a single tube analysis, focused on the decreased expression of CD38, CD81 and BAFFR in transitional B cells. The cluster analysis of immunophenotypic profiles of B cell subsets highlighted disease-specific abnormalities on transitional B cells that emerge as promising surrogate markers for disease activity. Further validation is needed with larger samples and prospective follow-up of patients.

Comparative Effectiveness of Tocilizumab and TNF Inhibitors in Rheumatoid Arthritis Patients: Data from the Rheumatic Diseases Portuguese Register, Reuma.pt.

OBJECTIVES: To compare the effectiveness of TNF inhibitors (TNFi) and tocilizumab in rheumatoid arthritis (RA) treatment, according to different response criteria. METHODS: We included RA patients registered in the Rheumatic Diseases Portuguese Register treated with TNFi or tocilizumab for at least 6 months, between January 2008 and July 2013. We assessed remission/low disease activity (LDA) at 6 months according to DAS28, CDAI, and SDAI, as well as Boolean ACR/EULAR remission and EULAR response rate, adjusting for measured confounders. RESULTS: Tocilizumab-treated patients (n = 95) presented higher baseline disease activity and were less frequently naïve to biologics compared to TNFi users (n = 429). Multivariate logistic regression analysis including the propensity score for receiving tocilizumab showed that patients treated with tocilizumab were more likely to achieve remission or LDA according to DAS28 (OR = 11.0/6.2, 95% CI 5.6-21.6/3.2-12.0), CDAI (OR = 2.8/2.6, 95% CI 1.2-6.5/1.3-5.5), or SDAI (OR = 3.6/2.5, 95% CI 1.5-8.7/1.1-5.5), as well as a good EULAR response (OR = 6.4, 95% CI 3.4-12.0). However, both groups did not differ in Boolean remission (OR = 1.9, 95% CI 0.8-4.8) or good/moderate EULAR response (OR = 1.8, 95% CI 0.8-4.5). CONCLUSIONS: Compared with TNFi, tocilizumab was associated with greater likelihood of achieving DAS28, CDAI, and SDAI remission/LDA and EULAR good response. Boolean remission and EULAR good/moderate response did not differ significantly between groups.

TRAF1/C5 but not PTPRC variants are potential predictors of rheumatoid arthritis response to anti-tumor necrosis factor therapy.

BACKGROUND: The aim of our work was to replicate, in a Southern European population, the association reported in Northern populations between PTPRC locus and response to anti-tumor necrosis factor (anti-TNF) treatment in rheumatoid arthritis (RA). We also looked at associations between five RA risk alleles and treatment response. METHODS: We evaluated associations between anti-TNF treatment responses assessed by DAS28 change and by EULAR response at six months in 383 Portuguese patients. Univariate and multivariate linear and logistic regression analyses were performed. In a second step to confirm our findings, we pooled our population with 265 Spanish patients. RESULTS: No association was found between PTPRC rs10919563 allele and anti-TNF treatment response, neither in Portuguese modeling for several clinical variables nor in the overall population combining Portuguese and Spanish patients. The minor allele for RA susceptibility, rs3761847 SNP in TRAF1/C5 region, was associated with a poor response in linear and logistic univariate and multivariate regression analyses. No association was observed with the other allellic variants. Results were confirmed in the pooled analysis. CONCLUSION: This study did not replicate the association between PTPRC and the response to anti-TNF treatment in our Southern European population. We found that TRAF1/C5 risk RA variants potentially influence anti-TNF treatment response.

EVALUATION OF ETHICAL IN INSTRUCTIONS TO AUTHORS OF BRAZILIAN SURGICAL JOURNALS.

BACKGROUND: The instructions to authors are the only means of communication between researchers and the editorial standards of a scientific journal. One of the mandatory items to be contained therein is about the ethical part, to prevent new research to carry out abuses with the enrolled on the research are published and stimulated. AIM: To verify the ethical questions on the guidelines of Brazilian surgical journals Method: Thirteen selected journals were divided into two groups: general surgery (n=3), and surgical specialty (n=10). The instructions to authors were analyzed by the quote of ethical requirements based on a specific research protocol, ranging from zero to six points. RESULTS: The average score of the general surgery group was similar than that of the surgical specialty group (3.66±0.57 vs 3.30±1.15, p=0.6154). When each ethical requirement was compared between the groups, there was no significant difference between the ethical requirements (p<0.05). CONCLUSION: There was respect for most ethical questions evaluated, with no difference between the journals of general or specialty surgery.

Paraneoplastic sclerodermiform syndrome--case report.

Occasionally, auto-immune diseases may emerge as paraneoplastic syndromes. This is especially recognized in the case of polymyositis/dermatomyostis, but it is an extremely rare event in systemic sclerosis (SSc). The authors report the case of a sixty-year-old woman who presented with Raynaud's phenomenon and rapidly progressing skin thickness of the forearms, hands and lower limbs. Patient evaluation revealed a colorectal carcinoma. The patient was referred to the oncology department. This concomitance of cancer and SSc with rapid progression of the latter, suggests that the scleroderma might have a paraneoplastic origin. Such an hypothesis deserves consideration in every case as early diagnosis may be decisive to control the progression of either disease.

Hypermobility syndromes from the clinician's perspective: an overview.

Symptomatic generalized hypermobility is a frequent occurring condition among patients referred to the rheumatologist or other medical specialist. In a subset of patients, a further classifying diagnosis of a specific syndrome can (and should) be made, based on pattern recognition and knowledge of the spectrum of hypermobility syndromes. Diagnostic clues are the patient's and family history and signs at physical examination, including skin abnormalities. It is especially important to recognize hypermobility syndromes with potentially life threatening complications. Genetic testing is only available for some syndromes; is only indicated if there is a reasonable pretest probability regarding a specific syndrome, especially if this syndrome can have life-threatening complications. The therapy is for the major part of syndromes only symptomatic; key features of management are education and physical exercises; joint surgery is to be avoided.

Identification of clinical predictors of flare in systemic lupus erythematosus patients: a 24-month prospective cohort study.

OBJECTIVE: SLE has a relapsing-remitting course with disease activity flares over time. This study aims to identify clinical predictors of SLE flares. METHODS: This prospective cohort study over 24 months included all SLE patients on follow-up at one academic lupus clinic. Flare was defined as an increase in SLEDAI-2K score ≥4 points. Baseline clinical and demographic parameters were compared using survival analysis for time-to-flare outcome with univariate log-rank tests. Variables with significant differences were further evaluated as predictors with multivariate Cox regression models adjusting for potential confounding or contributing factors and hazard ratio (HR) calculation. RESULTS: A total of 202 SLE patients were included. Over the follow-up period, 1083 visits were documented and 16.8% of patients presented with flares. In multivariate analysis, the following parameters emerged as flare predictors: SLE diagnosis up to 25 years of age (HR = 2.14, P = 0.03), lupus nephritis previous to baseline visit (HR = 4.78, P < 0.0001) and immunosuppressor treatment for severe SLE (HR = 3.22, P < 0.001). Baseline disease activity, disease duration and treatment with prednisone or HCQ were not predictive factors. CONCLUSION: Patients with an SLE diagnosis before age 25 years, lupus nephritis or immunosuppressor treatment for severe SLE present greater HRs for flares, suggesting the need for tighter clinical monitoring. Current immunosuppressive strategies seem to be inefficient in providing flare prevention.

A case of infliximab-induced lupus in a patient with ankylosing spondylitis: is it safe switch to another anti-TNF-α agent?

Anti-TNF-α therapies are the latest class of medications found to be associated with drug-induced lupus, a distinctive entity known as anti-TNF-α-induced lupus (ATIL) (Williams et al., Rheumatology (Oxford) 48:716-20, 2009; De Rycke et al., Lupus 14:931-7, 2005; De Bandt et al., Clin Rheumatol 22:56-61, 2003). With the widespread use of these agents, it is likely that the incidence of ATIL will increase. The onset of ATIL in patients with rheumatoid arthritis and Crohn's disease has been described, but the literature regarding the occurrence of this entity in patients with ankylosing spondylitis (AS) is scarce (De Bandt et al., Clin Rheumatol 22:56-61, 2003; Ramos-Casals et al., Autoimmun Rev 9:188-93, 2010; Perez-Garcia et al., Rheumatology 45:114-116, 2006). To our knowledge, few reports of switching anti-TNF-α therapy after ATIL in AS have been reported (Akgül et al., Rheumatol Int, 2012). Therefore, it is not clear whether the development of ATIL should prohibit switch to another therapy, since patients may respond to another anti-TNF-α agent (Akgül et al., Rheumatol Int, 2012; Bodur et al., Rheumatol Int 29:451-454, 2009; Mounach et al., Clin Exp Rheumatol 26:1116-8, 2008; Williams and Cohen, Int J Dermatol 50:619-625, 2011; Ye et al., J Rheumatol 38:1216, 2011; Wetter and Davis, Mayo Clin Proc 84:979-984, 2009; Cush, Clin Exp Rheumatol 22:S141-147, 2004; Kocharla and Mongey, Lupus 18:169-7, 2009). A lack of published experience of successful anti-TNF-α switching is a cause of concern for rheumatologists faced with this challenging clinical scenario. We report the case of a 69-year-old woman with AS who developed infliximab-induced lupus, which did not recur despite the subsequent institution of etanercept. The authors review and discuss ATIL and the possible implications for subsequent treatment with alternative anti-TNF-α agents.