Background Only few studies have investigated evolution of MRI inflammation (infl.) and structural lesions by serial MRI and radiography (CX) in patients with ankylosing spondylitis (AS). Objectives To investigate evolution of infl. and structural lesions over 5 years on MRI and CX during treatment with TNFα inhibitors (TNFα-I) with multiple serial examinations. Methods The study population comprised 34 patients with AS followed for 5 years after initiation of TNFα-I. MRIs of the sacroiliac joints (SIJs) and lower spine (Th9-S1) and spinal CXs were performed 7 and 4 times, respectively. UW and RSN evaluated the MRIs and CXs, respectively, in known time sequence. MRIs were evaluated according to the SPARCC sacroiliac (SIJ) and Spine Infl. Index and Structural Scores (SSS) (1). The Canada-Denmark MRI definitions of infl., fat (2), erosion and new bone formation (3,4) were transformed into scores. The CXs were scored according to the modified Stoke AS Spine Score (mSASSS). Results MRI infl., compared to baseline, decreased significantly in SIJ and spine from week 22 and onwards, while SIJ erosion decreased significantly from week 46 (see table). Conversely, the SIJ and spinal MRI fat and SIJ ankylosis scores increased significantly from week 22. Only minor changes for SIJ backfill and spine erosion score were observed. These findings indicate that reduction of infl. during TNF-I is followed by structural progression. During the 5 years of TNF-I, mSASSS and the structural MRI spine score SASSS had, compared to baseline, increased significantly from year 1 and 2, respectively, and onwards. Conclusions Shortly after initiation of TNF-I spine and SIJ MRI infl. decreased and structural scores changed indicating new bone formation. Thereafter the MRI scores remained unchanged. In constrast, mSASSS continuously increased. References Maksymowych et al. J Rheum 2014; Pedersen et al. Arthritis Res Ther 2014; Lambert et al. J Rheum 2009; Østergaard et al. J Rheum 2009 Disclosure of Interest None declared

Background Connective tissue diseases (CTD) are a heterogeneous group of autoimmune systemic diseases characterized by circulating autoantibodies and varying degrees of organ involvement including interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH).1–2 PAH in CTD is known to be associated with increased mortality. Whether ILD alone is associated with increased mortality is uncertain, but lung infections have been suggested to accelerate the development of ILD and impair the prognosis. Objectives To investigate a cohort of CTD patients with biopsy verified ILD and examine whether histopathologic ILD patterns, PAH and/or lung infections requiring hospital admission are independent predictors of mortality. Methods A retrospective cohort study of CTD patients with lung biopsy verified ILD. Data regarding ILD patterns were obtained from lung biopsies, PAH was evaluated with transthoracic echocardiography (TTE) using tricuspidal regurgitation ≥36 mmHg as a parameter for PAH. Data regarding lung infections requiring hospital admission and death were obtained from medical records. Survival was analyzed by age and gender adjusted multiple cox-regression analysis using SPSS version 22. Results Fifty-six CTD patients had ILD verified CTD, 21 (37%) with systemic sclerosis, 14 (25%) with polymyositis, 14 (25%) with undifferentiated connective tissue disease and 7 (13%) with mixed connective tissue disease. At the time of lung biopsy, the 56 CTD patients (50% females) had a mean (SD) age of 53.5 (11.3) years and disease duration of 4.4 (9.1) years. The follow-up after biopsy consisted of 203 person-years. Eight patients (14%) died during follow-up translating to a mortality rate of 39.4 per 1000 person years. Non-specific interstitial pneumonia (NSIP) histopathological pattern was observed in 15 (27%), fibrosis in 16 (29%), while 25 (44%) had other histopathological patterns. Thirteen (23%) patients had PAH which was associated with increased mortality with a HR=5.3 [95% CI 1.2–24.2], p=0.03. The patients with histopathological NSIP and fibrosis patterns had a higher mortality than other types of ILD, nevertheless the histopathologic pattern of ILD and hospital admission requiring infections did not predict increased mortality. Conclusions PAH predicts poor outcome in CTD patients with ILD, irrespective of the histopathological ILD pattern. In CTD with interstitial lung disease early PAH screening and initiation of treatment is paramount for optimizing survival among patients with CTD and ILD. References Khanna D. et al. Arthritis Rheum. 2013 December; 65 (12): doi: 10.1002/art.38172 Solomon J.J. and Fisher A. Journal of Intensive Care Medicine 2015, vol. 30 (7) 392–400: doi: 10.1177/0885066613516579 Galié N. et al. European Heart Journal (2016) 37, 67–119. doi: 10.1093/eurheartj/ehv3172) Yoshida S. Allergology International. 2011;60:405–409. Disclosure of Interest None declared

ObjectiveCardiac events are a major cause of death in patients with idiopathic inflammatory myopathies. The study objective was in a controlled setting to describe cardiac abnormalities by noninvasive methods in a cohort of patients with polymyositis (PM) or dermatomyositis (DM) and to identify predictors for cardiac dysfunction.MethodsIn a cross‐sectional study, 76 patients with PM/DM and 48 matched healthy controls (HCs) were assessed by serum levels of cardiac troponin I, electrocardiography, Holter monitoring, echocardiography with tissue Doppler imaging, and quantitative cardiac 99mTc‐pyrophosphate (99mTc‐PYP) scintigraphy.ResultsCompared to HCs, patients with PM/DM more frequently had left ventricular diastolic dysfunction (LVDD) (12% versus 0%; P = 0.02) and longer QRS and QT intervals (P = 0.007 and P < 0.0001, respectively). In multivariate analysis, factors associated with LVDD were age (P = 0.001), disease duration (P = 0.004), presence of myositis‐specific or ‐associated autoantibodies (P = 0.05), and high cardiac 99mTc‐PYP uptake (P = 0.006). In multivariate analysis of the pooled data for patients and HCs, a diagnosis of PM/DM (P < 0.0001) was associated with LVDD.ConclusionPatients with PM or DM had an increased prevalence of cardiac abnormalities compared to HCs. LVDD was a common occurrence in PM/DM patients and correlated to disease duration. In addition, the association of LVDD with myositis‐specific or ‐associated autoantibodies and high cardiac 99mTc‐PYP uptake supports the notion of underlying autoimmunity and myocardial inflammation in patients with PM/DM.

Journal of the European Academy of Dermatology and VenereologyVolume 28, Issue 2 p. 259-260 Letter to the Editor Low prevalence of positive skin pathergy testing in Danish patients with Behçet's disease M. Gyldenløve, Corresponding Author M. Gyldenløve Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, Hellerup, DenmarkCorrespondence: M. Gyldenløve. E-mail: mette.gyldenloeve@regionh.dkSearch for more papers by this authorN. Tvede, N. Tvede Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, DenmarkSearch for more papers by this authorJ.L. Larsen, J.L. Larsen Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, DenmarkSearch for more papers by this authorS. Jacobsen, S. Jacobsen Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, DenmarkSearch for more papers by this authorJ.P. Thyssen, J.P. Thyssen Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, Hellerup, Denmark Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, DenmarkSearch for more papers by this author M. Gyldenløve, Corresponding Author M. Gyldenløve Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, Hellerup, DenmarkCorrespondence: M. Gyldenløve. E-mail: mette.gyldenloeve@regionh.dkSearch for more papers by this authorN. Tvede, N. Tvede Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, DenmarkSearch for more papers by this authorJ.L. Larsen, J.L. Larsen Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, DenmarkSearch for more papers by this authorS. Jacobsen, S. Jacobsen Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, DenmarkSearch for more papers by this authorJ.P. Thyssen, J.P. Thyssen Department of Dermato-Allergology, Copenhagen University Hospital Gentofte, Hellerup, Denmark Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, DenmarkSearch for more papers by this author First published: 16 May 2013 https://doi.org/10.1111/jdv.12189Citations: 3Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume28, Issue2February 2014Pages 259-260 RelatedInformation

Background CVD is a major cause of death among patients with PM or DM. Still, data on prevalence and types of cardiovascular involvement and corresponding risk factors are limited and no systematic studies of subclinical coronary atherosclerosis have been performed in adults with PM or DM. Objectives Our purpose was to determine the distribution of traditional CVD risk factors and to assess CAC in adults with PM or DM. Methods In a cross-sectional, observational study of 76 prevalent patients with PM (n=51) or DM (n=25) clinical and immunological variables and the following traditional CVD risk factors were assessed: age, sex, CVD family history, smoking (current, former or never), body mass index (BMI), blood pressure (BP), total cholesterol (TC), LDL cholesterol (LDL-C), and mean blood glucose (mBG) calculated from HbA1c. Further, CAC were quantified by means of non-contrast enhanced cardiac CT scan and reported as a CAC score with the following ranges; no calcifications (CAC score =0 U); low CAC score (1-399 U); or high CAC score (≥400 U). High CAC score is consistent with severe coronary atherosclerosis. Results The mean age of the patients was 60 years (range 33-85) and 65% were women. A CVD family history was reported in 20% of the patients and 25% were current smokers; 28% were former smokers. Overweight (25≤BMI<30) was observed in 23 (30%) whereas 33 (43%) were obese (BMI>30). High systolic blood pressure (>140 mmHg) was observed in 35 (47%); 54 (74%) had high TC (>4.95 mmol/L), and 41 (59%) high LDL-C as well. mBG was increased (>6.95 mmol/L) in 16 (21%) patients. A CAC score >0 was noticed in 46 (61%) of whom 15 (20%) had a high score. Conclusions We report that a significant proportion of patients with PM or DM have a high burden of CVD risk factors and evidence of clinically significant calcium deposits in their coronary arteries. Several chronic inflammatory rheumatic diseases are associated with accelerated atherosclerosis, which may also apply to PM/DM. To what extent the increased CAC score is related to disease severity, the burden of CVD risk factors, prednisolone treatment or combinations hereof cannot be decided from this cross-sectional study. However, these preliminary data indicate that a prospective assessment of the CV system is warranted in PM and DM. Disclosure of Interest None Declared

OBJECTIVE:To describe the incidence of malignancies in a cohort of Danish patients with Wegener's granulomatosis (WG) and to investigate the cancer risk associated with cyclophosphamide (CYC) -therapy in WG. METHODS:In total, 293 patients diagnosed with WG between 1973 and 1999 were studied. Cancer incidence in the cohort was assessed through 2003 by linkage to the Danish Cancer Registry and compared to that of the general population by calculation of standardized incidence ratios (SIR). Analyses were stratified according to treatment with low cumulative CYC doses (< or = 36 g) and high doses (> 36 g, corresponding to treatment with 100 mg CYC/day for > 1 year). RESULTS:Fifty cancers occurred during 2121 person-years of followup (SIR of cancer of 2.1, 95% CI 1.5-2.7). Significantly increased SIR were observed for acute myeloid leukemia (AML; SIR 19.6, 95% CI 4.0-57), bladder cancer (SIR 3.6, 95% CI 1.2-8.3), and non-melanoma skin cancers (SIR 4.7, 95% CI 2.8-7.3). Leukemias and bladder cancers were diagnosed 6.9-18.5 years after initiation of CYC therapy. The risk of these malignancies was not increased for patients who never received CYC or for patients treated with cumulative CYC doses < or = 36 g. In contrast, high risks of AML (SIR 59.0, 95% CI 12-172) and bladder cancer (SIR 9.5, 95% CI 2.6-24) were observed for patients treated with cumulative CYC doses > 36 g. CONCLUSION:Treatment with high cumulative CYC doses implies a substantial risk of late-occurring, serious malignancies in WG. Patients with WG should be monitored for development of cancer for several decades after cessation of CYC therapy. These findings emphasize the need for development of new treatment regimens in WG.

AIM:The safety and potential efficacy of a chimaeric anti-tumour necrosis factor alpha monoclonal antibody (infliximab) were examined in diffuse cutaneous systemic sclerosis (dcSSc). METHODS:A 26-week open-label pilot study in which 16 cases of dcSSc received five infusions of infliximab (5 mg/kg). Clinical assessment included skin sclerosis score, scleroderma health assessment questionnaire, self-reported functional score and physician global visual analogue scale. Collagen turnover, skin biopsy analysis and full safety evaluation were performed. RESULTS:There was no significant change in skin score at 26 weeks but a trend for lower modified Rodnan skin score at 22 weeks (OR 17, 95% CI 6 to 46) compared with peak value (OR 29, 95% CI 11 to 44; p = 0.10). Serum aminoterminal propeptide of type III collagen level was significantly lower at week 26 compared with baseline (p = 0.03). Secretion of type I collagen by dermal fibroblasts was reduced at 26 weeks compared with baseline (p = 0.02). There were no deaths during the study and no suspected unexpected serious adverse reactions. 21 serious adverse events (AE) occurred in seven subjects, mostly attributable to dcSSc. 127 distinct AE occurred in 16 subjects. Of these, 19 AE (15%) were probably or definitely related to infliximab treatment. Eight (50%) patients prematurely discontinued infliximab. Anti-infliximab antibodies developed during the study in five subjects and were significantly associated with suspected infusion reactions (p = 0.025). CONCLUSION:In dcSSc infliximab did not show clear benefit at 26 weeks but was associated with clinical stabilisation and a fall in two laboratory markers of collagen synthesis. The frequency of suspected infusion reactions may warrant additional immunosuppression in any future studies in systemic sclerosis.

OBJECTIVE:To determine whether variant alleles of the mannose-binding lectin (MBL) gene causing low serum concentrations of MBL and/or polymorphisms of HLA-DRB1 are associated with increased susceptibility to polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) or particular clinical phenotypes of PMR/GCA.METHODS:MBL and HLA-DRB1 alleles were determined by polymerase chain reaction in 102 Danish patients with PMR (n = 37) or GCA (n = 65). Two hundred fifty and 193 healthy individuals served as controls for MBL and HLA genotyping, respectively.RESULTS:The prevalence of MBL variant alleles in controls, patients with PMR only, and patients with GCA was 37, 32, and 53% (p = 0.01), respectively. HLA-DRB1*04 was found in 47% of patients with PMR only and in 54% of patients with GCA, which differed significantly from the 35% found in controls (p = 0.01). HLA-DR4 alleles were not associated with any clinical phenotypes of PMR/GCA, whereas MBL variant alleles were associated with cranial arteritis, high erythrocyte sedimentation rate, and low B-hemoglobin.CONCLUSION:We found MBL variant alleles and HLA-DR4 alleles to be weak susceptibility markers for GCA. In patients with PMR/GCA, MBL variant alleles were associated with signs of increased inflammatory activity and clinical signs of arteritic manifestations. This was not found for HLA-DR4 alleles. These findings indicate that HLA-DR4 and MBL are contributing to the pathophysiology of GCA at different levels in the disease process.

OBJECTIVE To test the usefulness of the Chapel Hill nomenclature, supplemented with surrogate parameters, as diagnostic criteria for primary vasculitides. METHODS To prospectively evaluate vasculitis patients according to a standardised clinical and para-clinical programme. In accordance with the Chapel Hill publication surrogate parameters were used: proteinuria, haematuria and red blood cell casts (glomerulonephritis), angiographic or ultrasonic demonstration of aneurysms or stenoses (arteritis), radiological lung infiltrates or cavitations of more than one month's duration (granuloma in the lungs), bloody nasal discharge or crusts, chronic sinusitis, otitis and/or mastoiditis, bone and/or cartilage destruction, and acute hearing loss (granuloma in upper airways). RESULTS The following entities were diagnosed: giant cell arteritis (n=14), Takayasu arteritis (n=1), polyarteritis nodosa (n=2), Wegener's granulomatosis (n=27), Churg-Strauss syndrome (n=2), microscopic polyangiitis (n=12), Henoch-Schönlein purpura (n=2), cutaneous leucocytoclastic angiitis (n=37), and secondary vasculitis (n=21). Giant cell arteritis and cutaneous leucocytoclastic angiitis were in all cases diagnosed by biopsy. Using the Chapel Hill nomenclature supplemented with surrogate parameters, only 8 of 27 patients were diagnosed with Wegener's granulomatosis, and 3 of 12 cases with microscopic polyangiitis. The number of patients in the remaining diagnostic entities were considered to few to evaluate. CONCLUSIONS The Chapel Hill nomenclature, supplemented with surrogate parameters, failed to act as diagnostic criteria in Wegener's granulomatosis and microscopic polyangiitis. The following diagnostic criteria are proposed for Wegener's granulomatosis: (1) Biopsy or surrogate parameter for granulomatous inflammation in the respiratory system and (2) Biopsy verified necrotising vasculitis in small to medium sized vessels or biopsy/surrogate parameter for glomerulonephritis or positive PR3-ANCA test and (3) Lack of eosinophilia in blood and biopsy samples. The following diagnostic criteria are proposed for microscopic polyangiitis: (1) Biopsy verified necrotising vasculitis in small vessels and/or glomerulonephritis with few or no immune deposits and (2) Involvement of more than one organ system as indicated by biopsy verified vasculitis in small to medium sized vessels or surrogate parameter for glomerulonephritis and (3) Lack of biopsy and surrogate parameter for granulomatous inflammation in the respiratory system. Using these criteria all Wegener's patients and 9 of 12 patients with microscopic polyangiitis could be diagnosed.

This study was designed to examine the effects of hyperthermia in humans on the production of interleukin (IL)-1 alpha, IL-1 beta, tumour necrosis factor (TNF)beta and interferon (IFN)gamma, determined in supernatants from in vitro lipopolysaccharide or phytohemagglutinin stimulated blood mononuclear cells (BMNC), including the effect of indomethacin in the assays on these cytokines. Eight healthy volunteers were immersed into a hot water bath (water temperature 39.5 degrees C) for 2 h, during which their rectal temperature rose to 39.5 degrees C. On a later day they served as their own controls, being immersed into thermoneutral water (34.5 degrees C) for 2 h. Blood samples were collected before, at body temperatures of 38, 39 and 39.5 degrees C, and 2 h after water immersion and at corresponding time points in the control experiment. Hyperthermia did not influence the production of cytokines from stimulated BMNC. Indomethacin in the assays significantly enhanced the ex vivo production of TNF beta at hyperthermic and thermoneutral conditions; this indomethacin enhanced production of TNF beta declined from pre-value in the hyperthermia experiment compared to the control experiment. Furthermore, indomethacin augmented the production of IFN gamma from stimulated BMNC both in the hyperthermic and the control experiments; the indomethacin effect was, however, not different at the two conditions. It is suggested that hyperthermia alters the sensitivity of BMNC to prostaglandins.