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In Germany community-acquired Legionnaires' disease is usually caused by the species Legionella pneumophila. Recurrent cases of Legionnaires' disease are rarely reported and are due either to a second infection (reinfection) or a relapse of a previous case. We report a case of recurrent Legionnaires' disease in an 86-year-old female patient infected with Legionella pneumophila serogroup 1, monoclonal antibody-subtype Knoxville, sequence type unknown. Between the two disease incidents the patient had completely recovered. Legionella pneumophila was detected with the monoclonal antibody-subtype Knoxville, sequence type 182, in the drinking water of the patient's apartment. Exposure to contaminated drinking water was interrupted after the first incident exposure through the application of point-of-use water filters. The filters were later removed due to low water pressure, and the second illness occurred thereafter. It is unclear if immunological predisposition has contributed to this case of probable reinfection of Legionnaires' disease. Clinical, microbiological and epidemiological information combined suggest this is a case of reinfection of Legionnaires' disease. In cases of recurrent Legionnaires' disease complete collection of patient and water samples is necessary to differentiate relapse from reinfection cases, to implicate the source of infection and to gain more evidence for the role of immunological predisposition.

Introduction Sources of infection of most cases of community-acquired Legionnaires’ disease (CALD) are unknown. Objective Identification of sources of infection of CALD. Setting Berlin; December 2016–May 2019. Participants Adult cases of CALD reported to district health authorities and consenting to the study; age and hospital matched controls. Main outcome measure Percentage of cases of CALD with attributed source of infection. Methods Analysis of secondary patient samples for monoclonal antibody (MAb) type (and sequence type); questionnaire-based interviews, analysis of standard household water samples for Legionella concentration followed by MAb (and sequence) typing of Legionella pneumophila serogroup 1 (Lp1) isolates; among cases taking of additional water samples to identify the infectious source as appropriate; recruitment of control persons for comparison of exposure history and Legionella in standard household water samples. For each case an appraisal matrix was filled in to attribute any of three source types (external (non-residence) source, residential non-drinking water (RnDW) source (not directly from drinking water outlet), residential drinking water (RDW) as source) using three evidence types (microbiological results, cluster evidence, analytical-comparative evidence (using added information from controls)). Results Inclusion of 111 study cases and 202 controls. Median age of cases was 67 years (range 25–93 years), 74 (67%) were male. Among 65 patients with urine typable for MAb type we found a MAb 3/1-positive strain in all of them. Compared to controls being a case was not associated with a higher Legionella concentration in standard household water samples, however, the presence of a MAb 3/1-positive strain was significantly associated (odds ratio (OR) = 4.9, 95% confidence interval (CI) 1.7 to 11). Thus, a source was attributed by microbiological evidence if it contained a MAb 3/1-positive strain. A source was attributed by cluster evidence if at least two cases were exposed to the same source. Statistically significant general source types were attributed by calculating the population attributable risk (analytical-comparative evidence). We identified an external source in 16 (14%) cases, and RDW as source in 28 (25%). Wearing inadequately disinfected dentures was the only RnDW source significantly associated with cases (OR = 3.2, 95% CI 1.3 to 7.8) and led to an additional 8% of cases with source attribution, for a total of 48% of cases attributed. Conclusion Using the appraisal matrix we attributed almost half of all cases of CALD to an infectious source, predominantly RDW. Risk for LD seems to be conferred primarily by the type of Legionella rather than the amount. Dentures as a new infectious source needs further, in particular, integrated microbiological, molecular and epidemiological confirmation.

Objective: To characterize the specific structural properties of the erosion-prone bare area of the human joint and to search for early microstructural changes in this region during rheumatoid arthritis Methods: An initial cadaveric study was used for exact localization of the bare area of the metacarpal heads, detection of cortical micro-channels (CoMiCs) in this region by high-resolution peripheral computed tomography (HR-pQCT) and, after anatomical dissection, their validation by micro-computed tomography (μCT). In the second part, number and distribution of CoMiCs were analyzed in 105 healthy individuals and 107 RA patients with similar sex and age distribution. Results: HR-pQCT investigation combined with adaptive thresholding allowed detection of CoMiCs in the bare area of cadaveric joints. Their existence in the bare area was additionally validated by μCT. In healthy individuals, the number of CoMiCs increased with age. RA patients showed significantly (p

The objective of this cross-sectional study was to define normal sex and age-dependent values of intra-articular bone mass and microstructures in the metacarpal heads of healthy individuals by high-resolution peripheral quantitative computed tomography (HR-pQCT) and test the effect of rheumatoid arthritis (RA) on these parameters. Human cadaveric metacarpal heads were used to exactly define intra-articular bone. Healthy individuals of different sex and age categories and RA patients with similar age- and sex-distribution received HR-pQCT scans of the second metacarpal head and the radius. Total, cortical and trabecular bone densities as well as microstructural parameters were compared between (i) the different ages and sexes in healthy individuals, (ii) between metacarpal heads and the radius and (iii) between healthy individuals and RA patients. The cadaveric study allowed exact definition of the intra-articular (=intra-capsular) bone margins. These data were applied in measuring intra-articular and radial bone parameters in 214 women and men (108 healthy individuals, 106 RA patients). Correlations between intra-articular and radial bone parameters were good (r = 0.51 to 0.62, p

Background Although the effects of interleukin-17A (IL-17A) inhibition on the signs and symptoms of psoriatic arthritis (PsA) are well defined, little is known about its impact of local inflammatory and structural changes in the joints. The PSARTROS study was designed to elucidate the effects of IL-17A inhibition on inflammation and bone changes in joints affected by PsA. Methods This was a prospective open-label study in 20 patients with active PsA receiving 24 weeks of treatment with the IL-17A inhibitor secukinumab. Magnetic resonance imaging (MRI), power Doppler ultrasound (PDUS), and high-resolution peripheral quantitative computer tomography (HR-pQCT) of the hands were performed at baseline and after 24 weeks to assess synovitis, periarticular inflammation, bone erosion, enthesiophyte formation, and bone structure. Demographic and clinical measures of joint disease (DAPSA and DAS28-ESR), skin disease (PASI and BSA), and composite measures (minimal disease activity, or MDA) were also recorded. Results Treatment with secukinumab led to significant improvement of signs and symptoms of PsA; 46% reached MDA and 52% DAPSA low disease activity. MRI synovitis (P = 0.034) and signal in PDUS (P = 0.030) significantly decreased after 24 weeks of treatment. Bone erosions in MRI and HR-pQCT and enthesiophytes in the HR-pQCT did not show any progression, and structural integrity and functional bone strength remained stable. Conclusions IL-17 inhibition by secukinumab over 24 weeks led to a significant decrease of synovial inflammation and no progression of catabolic and anabolic bone changes in the joints of patients with PsA. Trial registration ClinicalTrials.gov Identifier: NCT02483234, June 26, 2015; retrospectively registered. Electronic supplementary material The online version of this article (10.1186/s13075-018-1653-5) contains supplementary material, which is available to authorized users.

Background Functional properties of bone in rheumatoid arthritis (RA) are still not well characterised. Objectives This study aimed to define the impact of anti-citrullinated antibodies (ACPA) on biomechanical properties in RA. Methods Based on on high-resolution peripheral quantitative computed tomography (HR-pQCT) data from the distal radius of ACPA-positive RA (RA+), ACPA-negative RA (RA-) and healthy controls (HC) micro-finite element analysis (µFEA) was carried out to measure failure load and stiffness of bone.( 1 Comparisons of µFEA parameters between groups was calculated and multivariate models were used to determine the role of demographic, disease-specific and structural data of bone strength. Results A total of 276 subjects (96 RA+, 84 RA- and 96 HC) were analysed. Age and sex distributions were not significantly different between the three groups. In RA +but not in RA- failure load and stiffness were significantly decreased compared to HC (both p Conclusions In summary, µFEA showed that bone strength is significantly decreased in RA +but not in RA- disease. Reference [1] Macneil JA, Boyd SK. Bone strength at the distal radius can be estimated from high-resolution peripheral quantitative computed tomography and the finite element method. Bone2008;42(6):1203–13. Disclosure of Interest None declared

Chronic inflammatory diseases are associated with bone loss. While the occurrence of systemic bone loss is well described in chronic inflammatory diseases, the impact of these conditions on articular bone has not been systematically investigated. Recent refinements in high-resolution CT assessment of the joints now allow the accurate measure of articular bone composition. In this study 476 subjects comprising healthy individuals and patients with anticitrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA), ACPA-negative RA, Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PsO) and psoriatic arthritis (PsA) were subjected to high-resolution quantitative computed tomography (HR-pQCT) of the hand. Metacarpal heads were assessed for total, trabecular and cortical volumetric bone mineral density (vBMD). Only ACPA+RA, but not the remaining inflammatory diseases (ACPA-RA, CD, UC, PsO, PsA) showed significant (p 0.001) loss of articular bone affecting both the trabecular and the cortical compartments. Age and body mass index were also associated with articular bone changes, the former with lower, the latter with higher articular bone mass. In multivariate models, presence of ACPA+RA was an independent factor for articular bone loss. Among chronic inflammatory diseases ACPA+RA is the most potent precipitator for articular bone loss pointing out the role of autoimmunity in the development of articular bone disease in the context of chronic inflammatory disease.

ObjectivesBone loss is a well-established consequence of rheumatoid arthritis (RA). To date, bone disease in RA is exclusively characterised by bone density measurements, while the functional properties of bone in RA are undefined. This study aimed to define the impact of RA on the functional properties of bone, such as failure load and stiffness.MethodsMicro-finite element analysis (µFEA) was carried out to measure failure load and stiffness of bone based on high-resolution peripheral quantitative CT data from the distal radius of anti-citrullinated protein antibody (ACPA)-positive RA (RA+), ACPA-negative RA (RA−) and healthy controls (HC). In addition, total, trabecular and cortical bone densities as well as microstructural parameters of bone were recorded. Correlations and multivariate models were used to determine the role of demographic, disease-specific and structural data of bone strength as well as its relation to prevalent fractures.Results276 individuals were analysed. Failure load and stiffness (both PConclusionIn summary, µFEA showed that bone strength is significantly decreased in RA+ and associated with fractures.

Background Bone damage in rheumatoid arthritis (RA) typically emerges at certain anatomical hotspots corresponding to the so-called “bare area”, an intra-articular region between the cartilage and the insertion site of the joint capsule (1,2). We hypothesized that this region exhibits certain micro-anatomical properties, which facilitates the emergence of bone erosions. Objectives To find the micro-structural correlate of the origin of bone erosions in the bare area of the human joint Methods Bare areas of human joints were analyzed for early microstructural changes by in-vivo high-resolution peripheral computed tomography (HR-pQCT). First, bare areas were exactly defined by scanning 6 cadaveric hands for localization of the bare area in the human metacarpal head. Bone lesions found in the cadaveric hand by HR-pQCT were additionally by super-resolution ex vivo micro-CT (μCT40). Then, number and distribution of the type of bare area bone lesion found in cadaveric study were analyzed in a cohort of 105 healthy individuals and 107 anti-citrullinated peptide (ACPA) positive RA patients with similar sex and age distribution. Results HR-pQCT combined with adaptive thresholding allowed the definition of a new type of bone lesions in the bare areas of the human joint termed “COMIC” standing for “cortical micro-channel”. Their existence in the bare area was additionally validated by microCT (Figure 1). RA patients showed significantly (p Conclusions CoMiCs represent a new structural feature of the joint, which is characteristic for the bone of the bare area. COMICS at low level are also found in young healthy individuals but they significantly increase with age and particularly with RA. COMICs develop much earlier and much more pronounced in RA patients than in healthy individuals and therefore represent an interesting new early indicator for erosion development in ACPA positive RA patients. References Stach CM, Bauerle M, Englbrecht M, Kronke G, Engelke K, Manger B, et al. Periarticular bone structure in rheumatoid arthritis patients and healthy individuals assessed by high-resolution computed tomography. Arthritis & Rheumatism. 2010;62(2):330–9. Simon D, Kleyer A, Stemmler F, Simon C, Berlin A, Hueber AJ,Haschka J, Renner N, Figueiredo C, Neuhuber W, Buder T, Englbrecht M, Rech J, Engelke K, Schett G. Age- and Sex-Dependent Changes of Intra-articular Cortical and Trabecular Bone Structure and the Effects of Rheumatoid Arthritis. J Bone Miner Res. 2016 Oct 27. doi: 10.1002/jbmr.3025. [Epub ahead of print]. Disclosure of Interest None declared

The comparison between different techniques to quantify the 3-dimensional size of inflammatory bone erosions in rheumatoid arthritis(RA) patients.Anti-cyclic citrullinated peptide antibody(ACPA) positive RA patients received high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the metacarpophalangeal joints (MCP). Erosions were measured by three different segmentation techniques: (1) manual method with calculation by half-ellipsoid formula, (2) semi-automated modified Evaluation Script for Erosions (mESE), and (3) semi-automated Medical Image Analysis Framework (MIAF) software. BlandAltman plots were used to describe agreement between methods. Furthermore, shape of erosions was classified as regular or irregular and then compared to the sphericity obtained by MIAF.A total of 76 erosions from 65 RA patients (46 females/19 males), median age 57 years, median disease duration 6.1 years and median disease activity score 28 of 2.8 units were analyzed. While mESE and MIAF showed good agreement in the measurement of erosion size, the manual method with calculation by half-ellipsoid formula underestimated erosions size, particularly with larger erosions. Accurate segmentation is particularly important in larger erosions, which are irregularly shaped. In all three segmentation techniques irregular erosions were larger in size than regular erosions (MIAF: 19.7 vs. 3.4mmMIAF and mESE allow segmentation of inflammatory bone erosions in RA patients with excellent inter reader reliability. They allow calculating erosion volume independent of erosion shape and therefore provide an attractive tool to quantify structural damage in individual joints of RA patients.

Background Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) result in severe joint destruction and functional disability if left untreated. We aim to develop tools that help patients with RA and PsA to understand and experience the impact of inflammatory joint disease on the integrity of their (juxta-articular) bone and increase adherence to medical treatment. In this study, we used high-resolution peripheral quantitative computed tomography (HR-pQCT) to develop 3D prototypes of patients’ finger joints. Methods HR-pQCT (XtremeCT, Scanco) measurements were performed in healthy individuals and patients with inflammatory joint disease, followed by a 3D print using the objet30 printer. Healthy participants (n = 10), and patients (n = 15 with RA and 15 with PsA) underwent a detailed, standardized interview with demonstration of printed joints. Results Utilizing HR-pQCT images of metacarpophalangeal (MCP) heads, high quality and exact 3D prints as prototypes were created. Erosions in different sizes and the trabecular network printed in detail were visualized, demonstrating structural reduction in arthritic vs. healthy bone. After demonstration of 3D prints (healthy vs. erosive joint, visual and haptic) 26/39 (66%) participants (including healthy volunteers) were deeply affected, often quoting “shock”. Of the patients with RA and PsA, 13/15 (86%) and 11/15 (73%), respectively, stated that they would rethink their attitude to medication adherence. More importantly, 21/24 patients with RA or PsA (87.5%) expressed that they would have wished to see such 3D prints during their first disease-specific conversations. Conclusion Using arthro-haptic 3D printed prototypes of joints may help to better understand the impact of inflammatory arthritides on bone integrity and long-term damage. Electronic supplementary material The online version of this article (doi:10.1186/s13075-017-1234-z) contains supplementary material, which is available to authorized users.

To characterize the specific structural properties of the erosion-prone bare area of the human joint, and to search for early microstructural changes in this region during rheumatoid arthritis (RA).In the initial part of the study, human cadaveric hand joints were examined for exact localization of the bare area of the metacarpal heads, followed by detection of cortical micro-channels (CoMiCs) in this region by high-resolution peripheral quantitative computed tomography (HR-pQCT) and, after anatomic dissection, validation of the presence of CoMiCs by micro-computed tomography (micro-CT). In the second part of the study, the number and distribution of CoMiCs were analyzed in 107 RA patients compared to 105 healthy individuals of similar age and sex distribution.Investigation by HR-pQCT combined with adaptive thresholding allowed the detection of CoMiCs in the bare area of human cadaveric joints. The existence of CoMiCs in the bare area was additionally validated by micro-CT. In healthy individuals, the number of CoMiCs increased with age. RA patients showed significantly more CoMiCs compared to healthy individuals (mean ± SD 112.9 ± 54.7/joint versus 75.2 ± 41.9/joint; P 0.001), with 20-49-year-old RA patients exhibiting similar numbers of CoMiCs as observed in healthy individuals older than age 65 years. Importantly, CoMiCs were already found in RA patients very early in their disease course, with enrichment in the erosion-prone radial side of the joint.CoMiCs represent a new form of structural change in the joints of patients with RA. Although the number of CoMiCs increases with age, RA patients develop CoMiCs much earlier in life, and such changes can even occur at the onset of the disease. CoMiCs therefore represent an interesting new opportunity to assess structural changes in RA.

The objective of this cross-sectional study was to define normal sex- and age-dependent values of intra-articular bone mass and microstructures in the metacarpal heads of healthy individuals by high-resolution peripheral quantitative computed tomography (HR-pQCT) and test the effect of rheumatoid arthritis (RA) on these parameters. Human cadaveric metacarpal heads were used to exactly define intra-articular bone. Healthy individuals of different sex and age categories and RA patients with similar age and sex distribution received HR-pQCT scans of the second metacarpal head and the radius. Total, cortical, and trabecular bone densities as well as microstructural parameters were compared between 1) the different ages and sexes in healthy individuals; 2) between metacarpal heads and the radius; and 3) between healthy individuals and RA patients. The cadaveric study allowed exact definition of the intra-articular (intracapsular) bone margins. These data were applied in measuring intra-articular and radial bone parameters in 214 women and men (108 healthy individuals, 106 RA patients). Correlations between intra-articular and radial bone parameters were good (r = 0.51 to 0.62, p 0.001). In contrast to radial bone, intra-articular bone remained stable until age 60 years (between 297 and 312 mg HA/cm

Background Periarticular bone loss is a typical finding in rheumatoid arthritis (RA) patients. However, this structural bone change is yet insufficiently characterized. Larger studies assessing periarticular bone composition in healthy controls (HC) and RA patients by high-resolution imaging have not been undertaken and have not been validated against standard measurement at the distal radius. Objectives To assess periarticular bone by high-resolution peripheral quantitative computed tomography (HR-pQCT) in the metacarpal heads and compare it with standard measurement in the distal radius in HC and anti-citrullinated peptide antibodies-positive (ACPA+) RA patients. Methods HR-pQCT (XtremeCT, Scanco, Switzerland) scans of the distal radius and of the metacarpal head 2 joints of HC and RA patients were performed. In contrast to previous studies the entire metacarpal head was assessed. After motion grading of the images by two independent readers, images with a motion grade more than 3 were excluded. A graphical objet (GOBJ) was generated and evaluated using the standard evaluation protocol for the radius provided by the manufacturer for both, the metacarpal head and the distal radius. In the last step, bone density values such as average bone density (D100 [mg HA/cm3]), bone volume/total volume (BV/TV), number of trabeculae (Tb N [1/mm])) were determined and compared between (i) the metacarpal head and the radius and (ii) between HC and RA patients. Results 222 subjects (110 HC and 112 RA) were analyzed. Sex and age distribution were balanced between HC (f/m: 58/52; 50.1±16.1 years) and RA patients (f/m: 53/59; 53.2±12.4 years; disease duration 9.2±8.7 years). Bone density in HC was 288.3±54.7 mg HA/cm3 in the distal radius and 294.4±43.3 mg HA/cm3 in the metacarpal head with significant correlation (ρ=0.583 (p Conclusions In this large study, we show that the assessment of periarticular bone structure in metacarpal heads is feasible and correlates well with standard measurement in the distal radius. Furthermore, we show significant bone loss in RA patients as compared to HC in both anatomical sites. Disclosure of Interest None declared

Background Bone erosion is a central feature of rheumatoid arthritis (RA). While the detection and semi-qualtitiative evaluation of erosion size is well established, the quantitative assessment of erosion size is less developed, but essential for precisely determining potential longitudinal changes in erosions Objectives To develop a new method to precisely calculate the volume of erosions using High Resolution-peripheral Quantitative Computed Tomography (HR-pQCT) Methods HR-pQCT (XtremeCT, Scanco, Switzerland) scans of ACPA positive RA patients were assessed. Erosions were defined as previously described. [1] Additionally we distinguished between regular shaped erosions, defined as having an uninterrupted surface (Fig 1a) and irregular erosions, those with multiple excrescences creating different sections (Fig 1b). After identification, erosions were contoured automatically using the XtremeCT evaluation program (Fig 1c). This allows a segmentation of the erosion, which means 3D reconstruction and volume calculation (Fig 2a-c). This method was applied by two, blinded, independent assessors. To validate the volume erosion measurement, 125 mm3 cubes were printed using a high resolution 3D printer (Stratasys Objet30) and the same segmentation technique was applied in this geometric printed figure. The statistical analysis was performed with IBM SPSS V.21.0. Categorical variables were presented as numbers and percentages, continuous variables are provided as mean ± standard deviation. Cohen9s kappa coefficient was used to determine the image reading agreement of the two independent and blinded readers. Results A total of 65 RA patients (45 female; 20 male), all ACPA positive, were included and 101 erosions were analyzed. The mean age of all patients was 54.46±12.56 years and the disease duration was 8.4±8.3 years.Inter-reader reliability for the method was 0.997 (CI: 0.996-0.998). The mean erosion volume of all erosions was 30.7±59.6 mm3. Irregular shape of erosions was found in 61.39% of all evaluated erosions. When erosions were separated by their shape (regular/irregular) the mean volume for regular erosions was different compared to the irregular with regular erosions being smaller (5.99±7.00 vs. 46.29±71.89mm3, p Conclusions This method allows to measure the exact erosion volume in a feasible way. We achieved high inter-reader reliability and good agreement with the gold-standard, which was the direct measurement of erosion in a 3D print of the erosion. References Stach, C.M., et al., Periarticular bone structure in rheumatoid arthritis patients and healthy individuals assessed by high-resolution computed tomography. Arthritis Rheum, 2010. 62(2): p. 330-9. Disclosure of Interest None declared

Background Three dimensional (3D) Prototyping allows the creation of individual 3D objects with almost any material. It is a rapid emerging technology, easy to use and quickly accessible. Objectives In this experimental study we tested the feasibility to generate exact models of joints of patients suffering from rheumatoid arthritis and healthy controls. Methods Using a high resolution CT (Xtreme CT, Scanco) we can generate images of metacarpal heads with a resolution as exact as 81 microns voxel size. Two dimensional images were transformed into 3D images, which were visualized by the DICOM viewer Osirix (Open Source software for MacBook). In the following step 3D images were transformed in a printable format called STL (Standard triangulation language), a common file format for 3D printers. Using a ZPrinter (3D Systems/Zcorp), core material (cement-like pouder) was spread in thin layers over the building platform. After each layer, binder is jetted from print heads over the core layer, which causes the core to solidify. Results We generated two 3D prints of a metacarpal head, one from a patient (age 67, male) with long standing Rheumatoid Arthritis (RA) and one from a healthy individual of the same age and sex without clinical signs of arthritis. Notably, this approach allowed creating a high quality and exact 3D model of the metacarpal head (Fig. 1A). The printed model reached a resolution as low as 100 micrometers. Cortical bone breaks resembling bone erosions as well as cortical proliferation can be exactly localized and measured. Particularly this technique also allows an enlargement of 3:1 to visualize the trabecular network of the periarticular bone which is massively reduced in the RA patient (Fig. 1B). Conclusions Herein we show that it is technically possible to print 3D models of arthritic joints and exactly localize and measure bone erosions and loss of trabecular bone network in patients with inflammatory arthritis. To our knowledge this is the first 3D printing approach in the context of clinical rheumatology. We demonstrate that the production of models reflecting exact copies of the joint surface in brilliant quality is feasible. These findings open multiple new possibilities in rheumatology and management of arthritis such as improved patient education, validation of imaging modalities, monitoring of damage as well as improved site-directed injection Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1856