Bilateral asymptomatic fibrous-ankylosis of the temporomandibular joint associated with rheumatoid arthritis: a case report

The American Academy of Orofacial Pain (AAOP) defines ankylosis of the temporomandibular joint (TMJ) as a restriction of movements due to intracapsular fibrous adhesions, fibrous changes in capsular ligaments (fibrous-ankylosis) and osseous mass formation resulting in the fusion of the articular components (osseous-ankylosis). The clinical features of the fibrous-ankylosis are severely limited mouth-opening capacity (limited range of motion during the opening), usually no pain and no joint sounds, marked deflection to the affected side and marked limitation of movement to the contralateral side. A variety of factors may cause TMJ ankylosis, such as trauma, local and systemic inflammatory conditions, neoplasms and TMJ infection. Rheumatoid arthritis (RA) is one of the systemic inflammatory conditions that affect the TMJ and can cause ankylosis. The aim of this study is to present a case of a female patient diagnosed with bilateral asymptomatic fibrous-ankylosis of the TMJ associated with asymptomatic rheumatoid arthritis. This case illustrates the importance of a comprehensive clinical examination and correct diagnosis of an unusual condition causing severe mouth opening limitation.

PReS-FINAL-2177: Safety and lack of autoantibody production following influenza H1N1 vaccination in patients with juvenile idiopathic arthritis (JIA)

Introduction Vaccination is an effective tool against several infectious agents including influenza. In 2010, the Advisory Committee on Immunization Practices (ACIP) recommended influenza A H1N1/2009 immunization for high risk groups, including juvenile idiopathic arthritis (JIA) patients and more recently the EULAR task force reinforced the importance of vaccination in immunosuppressed pediatric rheumatologic patients. We have recently shown that Influenza A H1N1/2009 vaccination generated protective antibody production with short-term safety profile among 93 JIA patients, but the possible impact of the vaccine in autoimmune response in JIA have not been studied. Therefore, we aimed to assess the production of some autoantibodies generated following influenza H1N1 vaccination in JIA patients. Objectives To assess the autoimmune response and H1N1 serology following influenza H1N1 vaccination in patients with JIA. Methods Cepa A/California/7/2009 (NYMC X-179A) anti-H1N1 was used to vaccinate JIA patients: 1 dose of immunization was given to all participants and those <9yrs of age received a second booster 3 weeks apart. Sera were analyzed before and 3 weeks following complete vaccination. Serology against H1N1 virus was performed by hemagglutination inhibition antibody assay, rheumatoid factor (RF) by latex fixation test, antinuclear antibodies (ANA) by IIF, IgM and IgG anticardiolipin (aCL) by ELISA.Results Among 98 JIA patients that were vaccinated, 58 sera were available for this study. Mean age of 58 JIA patients was 23.9 ± 9.5 yrs, 38 were females and 20 males with mean disease duration of 14.7 ± 10.1 yrs. JIA subtypes were: 33 (57%) poliarticular, 10 (17%) oligoarticular, 6 (10%) systemic and 9 (16%) other. Sixteen patients were off drugs while 42 (72%) were under different pharmacotherapy: 32 (55%) were on 1 DMARD/IS, 10 (17%) on 2 DMARDs/IS, 19 (33%) antimalarials, 29 (50%) MTX, 8(14%) sulfasalazine, 6 (10%) anti-TNFs, 4 (7%) abatacept; no patient was using prednisone >0.5 mg/kg/d. Seroprotection rates against H1N1 influenza increased from 23 to 83% and seroconversion rates were achieved in 78% JIA. Prior to vaccination, 31(53.4%) JIA patients were ANA+, 6(10.3%) RF+, and 4 (7%) IgM + IgG aCL+. After complete H1N1 vaccination, positivity for ANA remained the same whereas 1 patient became negative for IgG aCL, and another for RF, IgM and IgG aCL. One (1.7%) patient turned low titer IgG aCL+. Conclusion Vaccination of JIA patients against pandemic influenza A (H1N1) generated successful protective antibody production without the induction of autoantibody production, except for 1 patient that became positive for low titer IgG aCL, supporting its safety.

PReS-FINAL-2170: Work disability in adult patients with juvenile idiopathic arthritis (JIA)

Introduction Approximately 20% JIA patients enters adulthood with clinically active disease and disabled, therefore work condition may be affected. Objectives To assess the prevalence of work disability among adult patients with JIA regularly attending a tertiary heumatology center and to determine possible associated risk factors. Methods This was a cross-sectional study that enrolled 43 JIA patients according to 2004 revised ILAR criteria. A questionnaire was developed in order to evaluate working status and labor activity: occupation, current/previous work, employment status and withdrawal rate were actively searched. Demographic data, JIA characteristics, clinical activity (DAS28>2.6), therapeutic intervention, comorbidities, physical activity, sedentarism (WHO definitions), functional class (1991 ACR criteria), HAQ and SF-36 were recorded. The prevalence of work disability was calculated using 95% confidence interval, and compared to all parameters; qualitative variables were analyzed using tests of association (chi-square test) and quantitative variables by Mann-Whitney or student test. Results Patients' mean age was 29+7.4 yrs (range 19-41) with mean JIA duration = 17.2+12.3 yrs (range 3-33); 63% were males and 37% females. JIA subtypes were 64% polyarticular, 11% oligoarticular, 9% systemic, 9% ERA, 2% extended oligoarticular, 2% psoriatic arthritis; 7% had uveitis. Serum RF was positive in 21% and ANA in 21%. The majority (72%, n = 31) of JIA patients were employed, whereas 28% (n = 12) were currently not working. In the latter group, 83% (10/12) were retired due to JIA related disability. Further analysis comparing those currently working vs. Those not working revealed similar age (25,3 yrs vs.29,5 yrs, p = 0,09). Although not significantly, most patients currently working had Poly onset JIA (22 vs. 6 p = 0,37), higher frequencies of good education level >12 yrs of school (31 vs.9, p = 0,38), functional class I (p = 0,96), practiced regular physical activity (9 vs. 0, p = 0,89), were singles (26 vs. 8, p = 0,15). Both groups had comparable HAQ and DAS 28 scores (0,62 vs. 0.59, p = 0,47 and 2,51 vs.2,07, p = 0,64) and similar arthroplasty rate (8 vs. 4, p = 0,427). Frequencies of hypertension (3 vs.1, p = 0,999), dyslipidemia (1 vs. 1, p = 0,125), diabetes (1 vs. 0 p = 0,999), depression (1 vs. 0, p = 0,999) and smokers (3 vs. 1, p = 0,99) were alike in both groups. Remarkably, employed patients had higher SF 36 mental health component (84.0 vs. 70.42, P = 0.01). Conclusion High prevalence of almost 1/3 work disability and of retirement due to disease related incapacity remain major problems for adult JIA individuals. We also identified worse mental health in employed patients indicating that further research is needed, in addition to intense affirmative disability actions in order to remove possible disabling barriers and to adapt restrictive environments for these patients. Moreover, enhanced strategies and policy for inclusion of JIA patients in the job market is urged.

Comparative study by computed radiography, histology, and scanning electron microscopy of the articular cartilage of normal goats and in chronic infection with caprine arthritis-encephalitis virus

In the northeast of Brazil, caprine arthritis-encephalitis (CAE) is one of the key reasons for herd productivity decreasing that result in considerable economic losses. A comparative study was carried out using computed radiography (CR), histological analysis (HA), and scanning electronic microscopy (SEM) of the joints of CAE infected and normal goats. Humerus head surface of positive animals presented reduced joint space, increased bone density, and signs of degenerative joint disease (DJD). The carpal joint presented no morphological alterations in CR in any of the animals studied. Tarsus joint was the most affected, characterized by severe DJD, absence of joint space, increased periarticular soft tissue density, edema, and bone sclerosis. Histological analysis showed chronic tissue lesions, complete loss of the surface zone, absence of proteoglycans in the transition and radial zones and destruction of the cartilage surface in the CAE positive animals. Analysis by SEM showed ulcerated lesions with irregular and folded patterns on the joint surface that distinguished the limits between areas of normal and affected cartilage. The morphological study of the joints of normal and CAE positive goats deepened understanding of the alteration in the tissue bioarchitecture of the most affected joints. The SEM finding sustained previous histological reports, similar to those found for rheumatoid arthritis, suggesting that the goat infected with CAE can be considered as a potential model for research in this area.

Studien zur Immunregulation am Beispiel der Kollagen-Typ-II-induzierten Arthritis

Die Immunisierung von Mäusen bestimmter Stämme (z.B. DBA/1) mit Kollagen-Typ-II (CII) führt zu Gelenkentzündungen, die in ihrem Verlauf der Rheumatoiden Arthritis beim Menschen ähnlich sind. Viele Untersuchungen deuten darauf hin, daß vor allem TH1-Zellen entscheidend an der Entstehung einer CIA beteiligt sind. In diesem Zusammenhang ist IL-12, das an der Induktion der TH1-Zellantwort beteiligt ist, von herausragender Bedeutung. Zur Klärung der Funktion von IL-12 wurde ein IL-12-Antagonist, (IL-12(p40)2), der aus einem Homodimer der IL-12p40-Kette besteht, in vivo eingesetzt. DBA/1-Mäuse, die transgen für die T-Zellrezeptor ß-Kette eines CII-spezifischen, arthritogenen T-Zellklons sind und infolge dessen eine CIA mit 100%-iger Inzidenz, frühem Auftreten und einem schweren chronischen Verlauf entwickeln, wurden mit IL-12(p40)2 behandelt. Die Behandlung von TCR-ßtg-Mäusen mit IL-12(p40)2 verzögerte die Entwicklung einer CIA und führte zu deutlich abgeschwächten Krankheitssymptomen, konnte aber nicht die Induktion einer CIA verhindern. Darüber hinaus produzierten die Milzzellen der IL-12(p40)2-behandelten Gruppe nach einer Stimulation mit CII geringere Menge an IFN-g, verglichen mit Kontrollgruppe. Somit resultiert aus einer in vivo Neutralisation von IL-12 eine supprimierte Entwicklung von CII-spezifischen TH1-Zellen. Diese Ergebnisse lassen darauf schließen, daß endogen gebildetes IL-12 bei der Induktion einer CIA eine wichtige Rolle spielt, indem es die Differenzierung von TH1-Zellen fördert und die Produktion von IFN-g steigert. Hinsichtlich der Funktion von IFN-g bei der CIA gibt es allerdings widersprüchliche Befunde. Zur Klärung der Funktion von IFN-g wurden die TCR-ßtg-Mäuse mit Mäusen gekreuzt, die defizient für die Produktion von IFN-g (IFN-g KO) sind. Es zeigte sich, daß keine der verwendeten F2 (IFN-g KO, TCR-ßtg)-Mäuse nach Immunisierung Symptome einer CIA entwickelten. Somit scheint IFN-g essentiell für die Entstehung einer CIA zu sein. Unerwarteterweise führte aber auch die Behandlung mit IL-12 von F2 (IFN-g KO,TCR-ßtg)-Mäusen in 50% der Tiere zur Entwicklung einer CIA. Da solche Mäuse kein IFN-g bilden können, kann IL-12 auch unabhängig von IFN-g die Induktion einer CIA vermitteln. IL-12 scheint somit eine zweifache Bedeutung bei der Entstehung einer CIA zuzukommen, zum einen als direkter Induktor, wie am Beispiel der F2 (IFN-g KO, TCR-ßtg)-Mäuse nachgewiesen wurde, und zum anderen als starker Promoter der IFN-g-Bildung in normalen Mäusen.

Analyse des anti-inflammatorischen Pilzmetaboliten S-Curvularin in verschiedenen Modellen der rheumatoiden Arthritis

An der Entwicklung und Aufrechterhaltung chronisch-inflammatorischer Erkrankungen wie der rheumatoiden Arthritis (RA) ist die Fehlregulation verschiedener pro-inflammatorischer Gene von entscheidender Bedeutung. Bei der RA führt unter anderem eine erhöhte Expression der induzierbaren NO-Synthase (iNOS) zu einer gesteigerten NO-Produktion, was schließlich zum Knochenabbau beiträgt. Für eine Therapie der RA werden häufig Glukokortikoide eingesetzt, die jedoch viele Nebenwirkungen zeigen. Um eine mögliche Therapiealternative zu identifizieren, sollten die Effekte des anti-inflammatorisch wirksamen Pilzmetaboliten S-Curvularin in verschiedenen Modellen der RA analysiert werden.rnIn humanen C-28/I2-Chondrozyten als in vitro-Modell der RA führte die Inkubation mit einem Zytokingemisch zu einer Induktion der iNOS-Expression, die vom chondrogenen Differenzierungsgrad der Zellen abhängig war. Entscheidend für die iNOS-Induktion in C-28/I2-Zellen ist hauptsächlich der p38-MAPK-, der JAK-STAT- und der NF-kappa B-Signaltransduktionsweg. Eine Inkubation der Zellen mit S-Curvularin führte zu einer deutlichen Hemmung der iNOS-Expression. Dexamethason hatte hingegen keinen Effekt auf die iNOS-Expression, was vermutlich auf die fehlende Expression der Glukokortikoidrezeptor-mRNA zurückgeführt werden kann. Daher können von S-Curvularin abgeleitete Pharmaka möglicherweise auch in Fällen einer Steroidresistenz zur Therapie von RA-Patienten zum Einsatz kommen.rnIm Tiermodell der Kollagen-induzierten Arthritis konnte die anti-inflammatorische Wirkung von S-Curvularin auf mehreren Ebenen bestätigt werden. Die Pilzsubstanz reduzierte sowohl die Schwellung der Pfoten als auch die Expression CII-induzierter pro-inflammatorischer Gene, wie z.B. S100A8, Defb6, Camp und Mpo. Dabei waren die Effekte von S-Curvularin meist deutlicher als in Dexamethason-behandelten Mäusen. Die Analyse von Zytokinen (z.B. TNF-alpha, IL-1beta) und Chemokinen (z.B. MCP-1, MIP-1alpha) zeigte, dass die CII-induzierte Expression dieser pro-inflammatorischen Mediatoren in den Pfoten der Mäuse durch eine Therapie mit S-Curvularin und Dexamethason wieder reduziert werden konnte, wobei Unterschiede zwischen den Behandlungen beobachtet werden konnte.rnAuch im Tiermodell der LPS-induzierten akuten Entzündung wurde die iNOS- und die S100A8-Expression in verschiedenen Geweben S-Curvularin reduziert. rnrnS-Curvularin ist also in der Lage, in verschiedenen Modellen der RA und im akuten Entzündungsmodell die pro-inflammatorische Genexpression effizient zu hemmen und könnte somit in Zukunft eine Rolle in der Therapie der RA einnehmen.rn

Rheumatoide Arthritis und Arteriosklerose : Bedeutung der zu Grunde liegenden chronisch entzündlichen Prozesse für die endotheliale Dysfunktion ; Wirkung der antiinflammatorischen Substanz Galiellalacton in murinen Arteriosklerosemodellen

Erhöhte arteriosklerotische und thrombotische Vorfälle sind ein Hauptgrund für die gesteigerten Zahlen kardiovaskulärer Todesfälle von Patienten mit chronisch entzündlichen Erkrankungen wie der rheumatoiden Arthritis (RA). Diese erhöhte Mortalität ist nicht auf die traditionellen Risikofaktoren, wie Alter, Geschlecht, Bluthochdruck oder Diabetes zurückzuführen. Man nimmt an, dass die systemische Entzündung einen nicht-traditionellen Risikofaktor für die erhöhten kardiovaskulären Todesfälle von RA-Patienten darstellt. Da die derzeitige Behandlung der RA zum Teil schwere Nebenwirkungen zur Folge haben kann, war es das Ziel dieser Doktorarbeit, die Zusammenhänge zwischen RA und Arteriosklerose (AS) näher zu untersuchen, sowie die neue antiinflammatorische Substanz Galiellalacton (Gal) für die Behandlung der AS zu charakterisieren.rnIn dem chronisch inflammatorischen Tiermodell der TTP-defizienten Mäuse, dessenrnPhänotyp dem einer humanen RA-Erkrankung ähnelt, konnte eine verschlechterternEndothelfunktion, die als ein erstes Symptom einer erworbenen AS gilt, nachgewiesen werden. Dies konnte auf eine erhöhte Stabilität der Nox2-mRNA zurückgeführt werden, die unabhängig von der erhöhten Expression des Entzündungsmarkers TNFα war. Diese gesteigerte Nox2-Menge führte wiederum zu einer erhöhten Bildung von reaktiven Sauerstoff- und Stickstoffspezies und somit zu einer verringerten Menge an bioaktivem Stickstoffmonoxid, welches die endotheliale Dysfunktion (eDF) bedingte.rnAls ein traditioneller Risikofaktor für das Auftreten von kardiovaskulären Ereignissen gilt unter anderem eine Diabeteserkrankung. Durch die Ausbildung einer Nitrattoleranz bei der Therapie mit organischen Nitraten wie NTG, ISMN oder ISDN kommt es zu der Entwicklung einer eDF. PETN, ein weiteres organisches Nitrat zeigt diese Nebenwirkung nicht. PETN, vermittelt seinen antioxidativen Effekt über die Nrf2-abhängige Induktion der HO-1-Promotoraktivität.rnDie Behandlung von arteriosklerotischen Mäusen (ApoE-/-- und ApoE-/-TFPI+/--Mäuse) mit dem antiinflammatorischen Pilzsekundärmetaboliten Gal zeigte eine verringerte mRNA-Expression von arteriosklerotischen und inflammatorischen Mediatoren, sowie eine reduzierte Thrombenbildung durch eine verringerte Plättchenadhäsion.rnZusammenfassend konnte gezeigt werden, dass inflammationsabhängiger oxidativerrnStress ein Hauptgrund für die entzündungsgetriebene Artheriogenese ist und Galrneine neue Leitsubstanz für die Behandlung dieser Erkrankung ist.

Hepatoprotective effect of tumour necrosis factor alpha blockade in psoriatic arthritis: a cross-sectional study

Objective To evaluate the impact of tumour necrosis factor α (TNFα) blockers on the presence of liver fibrosis in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) treated with methotrexate (MTX). Methods Participants were consecutive patients with RA and PsA who had undergone MTX treatment for at least 1 year ± TNF blockade for over 6 months. Liver fibrosis was assessed using non-invasive transient elastography (FibroScan). Regression models were used to compare FibroScan values of patients with RA and patients with PsA receiving TNFα blockers with those who were not. Results FibroScan assessments were performed on 51 patients with RA and 43 patients with PsA. Compared to patients with RA, those with PsA were predominantly young men, received lower cumulative dosages of MTX and exhibited a higher incidence of liver steatosis and hyperlipidaemia. An abnormal result was observed in 7.1% of the anti-TNFα-naïve and in 13% of the anti-TNFα-treated patients in the RA group and in 30% of the anti-TNFα-naïve and 4.3% of the anti-TNFα-treated patients in the PsA group (OR=0.11, 95% CI 0.02 to 0.98). Results of the PsA group were robust when adjusted for baseline characteristics. Conclusion The results suggest a protective effect of TNFα inhibitors against the development of liver fibrosis in patients with PsA.

Inter- and intraobserver reliability of the COFAS end-stage ankle arthritis classification system

End-stage ankle arthritis should have an appropriate classification to assist surgeons in the management of end-stage ankle arthritis. Outcomes research also requires a classification system to stratify patients appropriately.

Metacarpophalangeal joints in rheumatoid arthritis: delayed gadolinium-enhanced MR imaging of cartilage - a feasibility study

To evaluate the feasibility of delayed gadolinium-enhanced magnetic resonance (MR) imaging of the cartilage of metacarpophalangeal (MCP) joints in patients with rheumatoid arthritis (RA) compared with that in control subjects.

Current approach to the haemodynamic management of septic shock patients in European intensive care units: a cross-sectional, self-reported questionnaire-based survey

The aim of this survey was to investigate clinicians' current approach to the haemodynamic management and resuscitation endpoints in septic shock.

Role of selective V2-receptor-antagonism in septic shock: a randomized, controlled, experimental study

ABSTRACT : INTRODUCTION : V2-receptor (V2R) stimulation potentially aggravates sepsis-induced vasodilation, fluid accumulation and microvascular thrombosis. Therefore, the present study was performed to determine the effects of a first-line therapy with the selective V2R-antagonist (Propionyl1-D-Tyr(Et)2-Val4-Abu6-Arg8,9)-Vasopressin on cardiopulmonary hemodynamics and organ function vs. the mixed V1aR/V2R-agonist arginine vasopressin (AVP) or placebo in an established ovine model of septic shock. METHODS : After the onset of septic shock, chronically instrumented sheep were randomly assigned to receive first-line treatment with the selective V2R-antagonist (1 g/kg per hour), AVP (0.05 g/kg per hour), or normal saline (placebo, each n = 7). In all groups, open-label norepinephrine was additionally titrated up to 1 g/kg per minute to maintain mean arterial pressure at 70 ± 5 mmHg, if necessary. RESULTS : Compared to AVP- and placebo-treated animals, the selective V2R-antagonist stabilized cardiopulmonary hemodynamics (mean arterial and pulmonary artery pressure, cardiac index) as effectively and increased intravascular volume as suggested by higher cardiac filling pressures. Furthermore, left ventricular stroke work index was higher in the V2R-antagonist group than in the AVP group. Notably, metabolic (pH, base excess, lactate concentrations), liver (transaminases, bilirubin) and renal (creatinine and blood urea nitrogen plasma levels, urinary output, creatinine clearance) dysfunctions were attenuated by the V2R-antagonist when compared with AVP and placebo. The onset of septic shock was associated with an increase in AVP plasma levels as compared to baseline in all groups. Whereas AVP plasma levels remained constant in the placebo group, infusion of AVP increased AVP plasma levels up to 149 ± 21 pg/mL. Notably, treatment with the selective V2R-antagonist led to a significant decrease of AVP plasma levels as compared to shock time (P < 0.001) and to both other groups (P < 0.05 vs. placebo; P < 0.001 vs. AVP). Immunohistochemical analyses of lung tissue revealed higher hemeoxygenase-1 (vs. placebo) and lower 3-nitrotyrosine concentrations (vs. AVP) in the V2R-antagonist group. In addition, the selective V2R-antagonist slightly prolonged survival (14 ± 1 hour) when compared to AVP (11 ± 1 hour, P = 0.007) and placebo (11 ± 1 hour, P = 0.025). CONCLUSIONS : Selective V2R-antagonism may represent an innovative therapeutic approach to attenuate multiple organ dysfunction in early septic shock.

Early fish oil supplementation and organ failure in patients with septic shock from abdominal infections: a propensity-matched cohort study

Fish oil (FO) has immunomodulating effects and may improve organ function and outcome in critically ill patients. This retrospective, propensity-matched cohort study investigates the effects of early intravenous FO supplementation on organ failure in patients with septic shock from abdominal infection.

The association between body-mass index and patient outcome in septic shock: a retrospective cohort study

It is unknown whether body-mass index (BMI) and commonly defined BMI categories are associated with mortality in patients with septic shock.