26 e Internistendagen Abstractboek april 2014 MECC Maastricht

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1 26 e Internistendagen Abstractboek april 2014 MECC Maastricht 26 e Internistendagen Abstractboek (Abstracts submitted to the Annual Meeting of the Netherlands Association of Internal Medicine, April 2014, Maastricht, the Netherlands) april 2014 MECC Maastricht

2 INHOUD 26 e Internistendagen Abstractboek april 2014 MECC, MAASTRICHT Voorwoord 3 Presentations Schop de Heilige Huisjes omver! 4 I Oral Presentations Research en Case reports 10 II Endocrinology Research 33 III Endocrinology Case reports 33 IV Diabetes Mellitus Case reports 39 V Diabetes Mellitus Research 39 VI Haematology Research 41 VII Haematology Case reports 45 VIII Oncology Research 61 IX Oncology Case reports 64 X Vascular Medicine Research 69 XI Vascular Medicine Case reports 73 XII Gastro-Enterology Research 77 XIII Gastro-Enterology Case reports 78 XIV Infectious Diseases Research 79 XV Infectious Diseases Case reports 83 XVI Nephrology Research 97 XVII Nephrology Case reports 100 XVIII Intensive Care Research 106 XIX Intensive Care Case reports 110 XX Rheumatology Research 114 XXI Rheumatology Case reports 114 XXII Immunology/Allergology Research 117 XXIII Immunology/Allergology Case report 118 XXIV Other Research 119 XXV Other Case reports 121 XXVI General Internal Medicine Research 121 XXVII General Internal Medicine Case reports 122 Index 134 1

3 Voorbereidingscommissie An Reyners - voorzitter Paul van Daele Kees Hovingh Harry Koene Robin Peeters Hilde Royen Patricia Stassen Roderick Tummers-de Lind van Wijngaarden (JNIV) Joost Wiersinga Deelnemende verenigingen Nederlandse Internisten Vereniging (NIV) Internistisch Vasculair Genootschap Juniorafdeling Nederlandse Internisten Vereniging Nederlandse Federatie voor Nefrologie Nederlandse Vereniging voor Allergologie Nederlandse Vereniging voor Endocrinologie Nederlandse Vereniging voor Gastro-Enterologie Nederlandse Vereniging voor Haematologie Nederlandse Vereniging voor Immunologie Nederlandse Vereniging voor Klinische Farmacologie en Biofarmacie Nederlandse Vereniging voor Medicale Oncologie Nederlandse Vereniging voor Medical Onderwijs NIV Sectie Acute Interne Geneeskunde NIV Sectie Intensive Care NIV Sectie Ouderengeneeskunde Vereniging voor Infectieziekten Organiserende vereniging Nederlandse Internisten Vereniging (Medicinae Internae B.V.) Postbus LB Utrecht Tel: Fax: Congressecretariaat Congress & Meeting Services Holland Postbus AZ EINDHOVEN Tel Fax internistendagen@congresservice.nl Uitgever Van Zuiden Communications B.V. Postbus CC Alphen aan den Rijn Tel.: Fax: info@vanzuidencommunications.nl Internet: Overname van delen uit dit abstractboek kan alleen plaatsvinden na schriftelijke toestemming van de uitgever. ISBN:

4 VOORWOORD/INTRODUCTION Met genoegen presenteren wij u het Abstractboek van de 26 e Internistendagen, gehouden van april 2014 in het MECC te Maastricht. De abstracts betreffen zowel wetenschappelijk onderzoek als case reports. Uit alle windrichtingen zijn de abstracts in grote getale ingestuurd. Er zijn 232 abstracts ingediend, die zijn opgenomen in dit Abstractboek. Uit deze abstracts werden 40 abstracts geselecteerd voor orale presentatie. Deze worden eerst vermeld (de O -nummers), gevolgd door de overige abstracts (de C -nummers), geclassificeerd per vakgebied. De selectie is gebaseerd op wetenschappelijke inhoud, originaliteit en presentatie. De selectie gebeurt anoniem (auteurs en instituut worden geblindeerd) door drie leden van de commissie. De abstracts met de hoogste scores zijn geselecteerd voor orale presentatie. Dit jaar is er voor gekozen om de abstracts zoveel mogelijk per onderwerp te bundelen met een algemene inleiding door de voorzitters. Het grote aantal ingezonden abstracts onderschrijft dat dit een belangrijk onderdeel is van de Internistendagen. In de eerste plaats voor de arts-assistenten omdat de Internistendagen een uniek podium zijn om resultaten van onderzoek of bijzondere observaties te presenteren aan een enthousiast publiek. In de tweede plaats voor de toehoorders, die kunnen vernemen wat er gebeurt aan het front van de Interne Geneeskunde in Nederland en in de derde plaats om de diverse onderzoeksgebieden binnen de Interne Geneeskunde met elkaar in contact te brengen. Ook dit jaar zal per sessie een winnaar worden aangewezen die een prijs van 500 euro overhandigd zal krijgen! Ook zullen de vier uitgekozen Heilige Huisjes in dit Abstractboek worden vermeld. Tijdens de plenaire sessie op vrijdagochtend 25 april zullen de auteurs proberen hun Heilige Huisje omver geschopt te krijgen. Namens de hele Commissie Internistendagen wens ik u veel plezier toe met het lezen maar vooral aanhoren van de vaak gloednieuwe onderzoeksresultaten en het oplossen van de leerzame puzzels in de case reports uit alle klinieken van Nederland! An Reyners Voorzitter Commissie Internistendagen This abstract book contains all abstracts that have been submitted to the Annual Meeting of the Netherlands Association of Internal Medicine, April 2014 in Maastricht, the Netherlands. Both research abstracts and case reports are included, representing all disciplines of Internal Medicine. 40 abstracts have been selected for oral presentation. These abstracts are printed first, in the order of presentation. The remainder of abstracts is categorized according to discipline. An Reyners Chairman Organizing Committee 3

5 PRESENTATIONS Schop de Heilige Huisjes omver! (Sessie vrijdag 25 april uur Auditorium 1) HH1 The sepsis criteria: blessed but not yet holy! M.G.B. van Onna, P. Stassen, A.E.R.C.H Boonen Maastricht University Medical Center, Department of Internal Medicine, Rheumatology, P. Debyelaan 25, 6229 HX MAASTRICHT, the Netherlands, Sepsis is a systemic inflammatory response syndrome (SIRS), caused by an infection. The condition is associated with a mortality up to 25%, which emphasizes the need for early diagnosis and adequate treatment. 1 Criteria to define sepsis are now part of composite clinical practice guidelines, the Surviving Sepsis Campaign (SSC) 1,2 As a result of the SSC, the sepsis criteria have become an important diagnostic screening tool, also in the Netherlands and fulfilment of the sepsis criteria often leads to the start of a more intensive antibiotic regimen. We want to draw attention to the incorrect use of the sepsis criteria, since these criteria have not been thoroughly validated in the emergency care setting and application of the sepsis criteria in the individual patient might result in misdiagnosis, overexposure to (broad spectrum) antibiotic regimens and a false sense of security. Why do we want to develop criteria sets as physicians? Most diseases or syndromes, like sepsis, lack a single distinguishing feature. Therefore, a combination of clinical, laboratory and radiological manifestations is needed to identify the disease. The most important manifestations of a disease can be merged into a criteria set. 3 Criteria sets can roughly be divided into 2 categories, namely diagnostic and classification criteria. The group of experts that developed the sepsis criteria however state that the criteria should be broadly useful both to clinicians caring for patients at the bedside (diagnosis) and to researchers designing observational studies and clinical trials (classification). 2 There are 3 major concerns regarding this statement. First, there are crucial differences between diagnostic and classification criteria sets. Diagnostic criteria are used to make a diagnosis and the clinical value is therefore highly dependent on the prevalence of the disease. Classification criteria are applied to patients in whom the clinical diagnosis has already been made and aim to create homogeneous groups of patients, which facilitates comparisons of clinical studies. 3 Prevalence of the disease is not important when using classification criteria, because all patients already have the disease, since they have been previously diagnosed as such. Therefore, making a diagnosis because a patient fulfills certain classification criteria runs a high risk of misdiagnosis. 3 Furthermore, patients either fulfill or not fulfill classification criteria. In clinical practice, this yes or no option is not acceptable, since a physician needs a flexible and open mind during the diagnostic process in order to decide on definite, probable or possible presence of a disease. 3 This nuance is not included in the current sepsis criteria and this may again lead to misdiagnosis of sepsis. Also, criteria developed for diagnosis of a disease with high mortality (i.e. sepsis) should have a high sensitivity in order to identify as many patients as possible (low rate of false negative patients). Conversely, classification criteria should have a high specificity in order to prevent that patients without the target disease are classified. Second, it is debatable whether the sepsis criteria are robust enough to even meet the requirements of either diagnostic or classification criteria. After development of a candidate criteria set, the candidate criteria set should be validated in patients suffering from the disease. The expert physician s diagnosis is often used as a gold standard. We could identify only one article that validates the sepsis criteria in the emergency department. In a prospective study of Gille-Johnson et al., 72% of patients in which SIRS was observed at first presentation on the emergency department, had no (severe) sepsis at follow-up. Furthermore, 23% of patients with severe sepsis within 24 hours after admission did not present with SIRS. 4 These results show that the sepsis criteria lack acceptable discriminative ability and that a criteria set that has not been validated before implementation runs an even higher risk of misdiagnosis. Last, applying the sepsis criteria in individual patients can lead to circular reasoning. A patient fulfils the sepsis criteria when there are signs of SIRS in addition to a documented or presumed infection. However, clues that point in the direction of a presumed infection are often the signs of SIRS. For instance, a physician suspects that a patient has pneumonia because of a respiratory rate > 20/ min and a white blood cell count > 12 x 10E9, but these manifestations are also listed signs of SIRS. In conclusion, we underscore the need to have robust sepsis criteria both diagnostic and classification criteriathat will be able to reduce sepsis related mortality and morbidity. However, we were surprised to notice that the sepsis criteria have not been validated in the target population. They should therefore most certainly not be used as diagnostic criteria and not be applied in individual patients, since the current sepsis criteria run a high risk of misdiagnosis. How should we apply the sepsis criteria at this moment? One can use the sepsis criteria for pattern recognition. The physician is the only one that can consider all relevant features in an individual patient, even those features that are not represented in the sepsis criteria. Relying on 4

6 criteria without evaluating the context of these criteria sends the wrong message to future/young physicians. More efforts should therefore be made to train and educate physicians about the full range of symptoms associated with the concept of sepsis, including the clinical manifestations of infection. In a nutshell, before the sepsis criteria can officially be declared holy, one or two miracles still need to happen. References 1. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, Intensive Care Med. 2013;39: doi: /s Levy MM, Fink MP, Marshall JC, et al SCCM/ESICM/ ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31: Rudwaleit M, Khan MA, Sieper J. The challenge of diagnosis and classification in early ankylosing spondylitis: do we need new criteria? Arthritis Rheum. 2005;52: Gille-Johnson P, Hansson KE, Gårdlund B. Severe sepsis and systemic inflammatory response syndrome in emergency department patients with suspected severe infection. Scand J Infect Dis. 2013;45: HH2 Deep venous thrombosis in the iliac veins: in hospital treatment or ambulatory care? B. de Jong, R. Heijligenberg, E. de Kruijf Gelderse Vallei, Department of Internal Medicine, Willy Brandtlaan 10, 6716 RP EDE, the Netherlands, benjongde@gmail.com To prevent pulmonary embolism (PE) and recurrent thrombosis most patients with deep venous thrombosis (DVT) are treated with low molecular weight heparin (LMWH) and oral anticoagulants on an outpatient basis. However, especially with thrombi in the external iliac or common iliac vein some physicians assume an increased risk for complications such as acute PE and decide to admit the patient for treatment and observation. We critically appraised this topic by defining the following question of the week : will ambulatory treatment of patients with a first iliac DVT lead to more morbidity and mortality compared to in-hospital treatment? PubMed was searched using the query ambulatory care AND deep venous thrombosis. 449 items were found and titles and abstracts were screened for relevance. Four articles were selected prospectively randomizing adult patients to in- or outhospital treatment for a proximal DVT. Levine conducted a RCT in patients with acute proximal DVT confirmed by venography or duplex ultrasonograpy. Exclusion criteria were previous 2 episodes with venous thromboembolism (VTE), active bleeding, active peptic ulcer, familial bleeding disorder, PE, unfractionated heparin (UFH) 18 hours, inability to treat with LMWH, noncompliance, geographic inaccessibility, deficiency of antithrombin III, protein C, protein S or pregnancy. Patients were assigned to ambulatory treatment with 1 mg enoxaparin per kilogram subcutaneously twice daily or in-hospital treatment with UFH with a bolus dose of 5000 units and targeted aptt of seconds. Study medication was discontinued with minimal five days of treatment when targeted INR ( ) was reached, after which warfarin was prescribed for a duration of 3 months. Follow-up was three months and included impedance plethysmography. Principal outcome events were symptomatic recurrent VTE and bleeding during study medication or within 48 hours after discontinuation consecutive patients were screened, 1491 excluded and 239 refused participation remaining 500 participants. Duration of study treatment was comparable (5.8 ± 1.8 LMWH vs 5.5 ± 1.2 days UFH) as was the percentage of time INR in the therapeutic range (63% vs 62%). Both symptomatic recurrent VTE and bleeding events did not differ between the groups (5.3% LMWH vs 6.7% UFH, p = 0.57 and 2.0% vs 1.2%, p = 0.50). 1 Koopman conducted a RCT in patients with acute proximal DVT diagnosed by venography or ultrasonography. Exclusion criteria were VTE within preceding 2 years, suspected PE, treatment with UFH 24 hours, geographic inaccessibility, life expectancy 6 months, post-thrombotic syndrome or pregnancy. Patients were assigned to ambulatory treatment with nadroparin twice daily adjusted for body weight or in-hospital treatment with UFH with a bolus of 5000 units and targeted aptt 1.5 to 2 times the mean value in normal subjects. Study medication was discontinued when targeted INR was > 2.0 two consecutive days with minimal five days of treatment after which oral anticoagulant treatment was started for 3 months. Follow-up was three months and in cases of suspected recurrent DVT venography or ultrasonograpy was performed. Primary analysis involved recurrent VTE during the first six months. Secondary outcome events were incidence of major bleeding in the first three months. From 692 eligible patients, 216 were excluded and 76 refused participation remaining 400 participants. In both groups, 68% of the participants had thrombi of the femoral vein or more proximal veins. Duration of study treatment was comparable as was the percentage of time INR in the therapeutic range. Both recurrent VTE and incidence of major bleeding events did not differ between the groups. 2 Belcaro conducted a RCT in patients with acute proximal DVT diagnosed by color duplex ultrasonography. Exclusion criteria were previous 2 episodes with VTE, active bleeding, ulcers, familial bleeding or coagulation disorder, PE, UFH 48 hours, geographic inaccessibility, patients with malignancy requiring surgery or chemotherapy 5

7 following 3 months, participants with likelihood of low/no compliance, pregnancy and platelet count < 100 x 10 9 /L. Patients were assigned to ambulatory treatment with subcutaneously nadroparin 100 IU per kg or subcutaneous calcium heparin IU twice daily or in-hospital treatment with intravenous UFH with a bolus of 5000 units and targeted aptt seconds or subcutaneously nadroparin. Study medication was (LMWH, UFH) discontinued when targeted INR was > 2.0 for 2 consecutive days after which oral anticoagulant treatment was started for 3 months. Follow-up was 3 months and included ultrasonography. Main outcome events were recurrent DVT, bleeding during study medication or within 48 hours after discontinuation, PE, days of hospitalization and number of patients without admission. 589 patients were screened, 264 excluded and 54 patients refused participation remaining 325 participants (66% were outpatients). Main outcome events did not differ. 3 Finally, Boccalon conducted a RCT in patients with proximal DVT diagnosed by venography or ultrasonography. Exclusion criteria were thrombus in inferior vena cava, floating thrombus, previous PE, DVT within preceding 6 months, necessity for hospitalization, contraindication for anticoagulant treatment, UFH 48 hours, pregnancy, geographic inaccessibility or logistical problems. Patients were assigned to in or outhospital treatment with LMWH and an oral anticoagulant. Follow-up was 6 months and included ultrasonography. Primary endpoints were DVT recurrence, PE or major bleeding. 204 patients were enrolled in the study. 65% had a femoral and 18% an iliac thrombosis. Primary endpoints did not differ between both groups. 4 Several other prospective and retrospective cohort studies and case series confirm the safety and effectivity of ambulatory care of patients with proximal DVT A systematic review recommends outpatient treatment with LMWH in patients with acute DVT(level 1 evidence). 12 A multicenter prospective cohort study selected patients with acute PE for outpatient treatment which was effective and safe irrespective of the presence of iliac vein thrombosis. 13 To assess whether the question to admit a patient with thrombosis in the iliac veins is only an issue in our hospital, we interviewed 20 internists (university medical centers, medium and large (non)teaching hospitals). Nine internists stated that they would treat and observe these patients on an in-patient basis. Conclusion: Proximal DVT confined to the iliac veins often leads to admittance for the patient for observation and treatment. Presumably because the treating internist perceives an increased risk for complications. However, the available evidence advocate outpatient treatment with a level of evidence 1A. 4 HH3 Reassuring patients, internists primary task of the future? Not by ordering (even more) diagnostic tests! B.P.A. Spaetgens, E. Fonseca Wald, P.M. Stassen Maastricht University Medical Center+, Department of Internal Medicine, P. Debyelaan 25, 6229 HX MAASTRICHT, the Netherlands, bpa.spaetgens@gmail.com Introduction: Reassuring patients is one of the essential medical competences (communication) of today s physician. It is also (one of) the main task(s) of the internist, especially in the outpatient clinics, where more than one-third of the patients present theirselves with symptoms for which no apparent organic pathology can be found. 1,2 Limited research on this subject has been performed and therefore the factors that contribute to successful reassurance of patients are largely unknown. This is an interesting finding, because not being able to reassure patients has significant clinical (psychological) and financial consequences. 3 It is therefore even more interesting that physicians tend to reassure patients by using diagnostic tests, even in patients with a low pretest probability of disease. The ordered diagnostic tests vary from simple blood testing to magnetic resonance imaging (MRI), depending on the main complaint. In one study, the number two reason for ordering tests is to reassure patients (the number 1 reason is to exclude other diseases ). 4 After several experiences with patients who were not reassured after unnecessary diagnostic testing ( the doctor just does not know yet what I have! ), we have reasonable doubt about the use of diagnostic testing to reassure patients with low pretest probability of disease. Last, but certainly not least, we express our doubt because unnecessary testing may lead (leads?) to higher costs, to possible complications (e.g. anaphylactic shock after iodine contrast) and to false-positive test results, which make it even harder to reassure patients. 2,3 This led to the following clinical question: Does diagnostic testing, when applied in low pretest probability of disease, reassure patients in case of a negative test result? This question was critically appraised using the following PICO: Patient: Patients at the outpatient clinics internal medicine with a low pretest probability of disease after anamnesis and physical examination Intervention: Perform diagnostic testing Control: Do not perform diagnostic testing OR perform testing, but not revealing results to the patient Outcome: Reassurance as measured by: 1) Health-Related Quality of Life: Illness concern, anxiety and symptom persistence; 2) Health care resource utilization (and costs). Search strategy: A literature search of PubMed was performed. Search terms were: 1) Reassurance AND 6

8 Diagnostic Techniques and Procedures (Mesh-term). 2) Limits: Humans AND Systematic Review OR Meta-Analysis OR Randomized Controlled Trial OR Comparative study. There were 220 hits and after screening titles and abstracts, 2 articles (systematic review and metaanalysis) seemed useful to answer the clinical questions. Results: In 2011, van Ravesteijn et al. performed a wellconducted systematic review of randomised controlled trials (RCT) that studied the efficacy of using diagnostic tests to reassure patients. 5 After an adequate, welldescribed literature search, they included 5 RCTs that met the inclusion criteria. The RCTs studied different diagnostic tests, which were: laboratory tests in patients with fatigue, radiography or MRI lumbar spine in patients with low back pain, MRI brain in patients with headache and ECG and laboratory tests in patients with chest pain. In this systematic review, no differences in level of reassurance were found in the short-term (within 3 months, in 4 of the 5 RCTs) nor in the long-term (after 3 months, in all 5 RCTs), regardless of the diagnostic test that was performed. Another systematic review and meta-analysis by Rolfe et al. studied the effect of diagnostic testing on reassurance as well. 6 After an adequate and well-described search, they included 14 RCTs. In this study, reassurance was measured using questionnaires about worries on illness, anxiety and symptom persistence, both in the short- (within 3 months) and long-term (after 3 months), They also included RCTs on the effect of diagnostic testing on health care resource utilization. In the RCTs, the following diagnostic tests were performed: testing for dyspepsia (endoscopy or Helicobacter Pylori-testing), radiography or MRI in back pain, MRI in headache and lab testing in patients with chest pain and palpitations. They showed that performing diagnostic tests did not reduce worries (short-term Odds Ratio (OR): 0.90; 95% CI ; long-term OR: 0.87;95% CI ) or symptom persistence (short-term OR: 0.92; 95% CI ; long-term OR: 0.99; 95% CI ). On the contrary, there was even more anxiety in the investigation group (vs. control group) as shown by a higher standardized mean difference (SMD) in anxiety score: short-term SMD: 0.06 ( ); long-term SMD: 0.21 ( ). Subsequent health care resource utilization was slightly lower in the investigation group, mainly because of lower number of primary care visits. However, this reduction in health care utilization required several patients (varying from 16 to 26) to undergo further diagnostic testing in order to prevent only one primary care visit. In conclusion, the presented systematic reviews are elegantly performed and of sufficient quality and showed that performing diagnostic tests to reassure patients with a low pretest probability of disease is not useful. In practical terms, this means that the after-testing statement: everything is normal is insufficient to reassure most patients. The postulated mechanism behind this is that patients already develop negative ideas and beliefs about their possible disease and thus reassurance is less effective. 7 This shows/confirms communication is very important and patients should be educated about normal test results in advance, which already had been shown effective in one study. 8 References 1. Hatcher S, Arroll B. Assessment and management of medically unexplained symptoms. BMJ. 2008;336(7653): Bass C, Sharpe M. Medically unexplained symptoms in patients attending medical outpatient clinics. In: Weatherall DA, Ledingham JG, Warrell DA, eds. Oxford textbook of medicine. 4th ed. Oxford: Oxford University Press, 2003: Winterberg D, Krol L. Effectief geruststellen. Medisch Contact. 2005; Boven van K, et al. Defensive testing in Dutch family practice. Is the grass greener on the other side of the ocean? J Fam Pract. 1997;44: Van Ravestijn H, et al. The reassuring value of diagnostic tests: A systematic review. Patient Educ Couns. 2012;86: Rolfe A, Burton C. Reassurance after diagnostic testing with a low pretest probability of serious disease. JAMA Intern Med. 2013;173: Donkin L, et al. Illness perceptions predict reassurance following negative exercise testing result. Psychol Health. 2006;21: Petrie KJ, et al. Effect of providing information about normal test results on patients reassurance: randomised controlled trial. BMJ. 2007;334(7589):352. HH4 Should all immunocompomised patients recieve PJP-prophylaxis? To measure is to know.. J.C.H. van der Hilst 1, S Cuyx 2 1 Jessaziekenhuis, Department of Infectious Diseases and Immunity, Stadsomvaart 11, 3500 HASSELT, Belgium, jeroen.vanderhilst@jessazh.be, 2 Katholieke Universiteit Leuven, LEUVEN, Belgium Introduction: Pneumocystis jirovecii is a fungal organism, primarily known as the cause of pneumonia in HIV-infected patients with CD4+ T-lymphocytopenia. However, in recent years the incidence of Pneumocystis jirovecii pneumonia (PJP) in immunocompromised non-hiv patients is rising (1). The PJP risk in some patient categories can be as high as 5-15% (2). This increased incidence should be seen in context of the expansion of therapeutic options with more aggressive chemotherapies in solid tumors and hematological malignancies, and 7

9 immunosuppressant and immunomodulating medications in inflammatory diseases and transplantation medicine (3-6). The presentation of PJP in non-hiv patients is more severe and mortality is higher than in patients with HIV. Symptoms and signs include a non-productive cough, dyspnea, low-grade fever, tachypnea, tachycardia, and often normal auscultation of the lungs (3-5). CD4+ lymphocytes play a crucial role in the defense against PJP. The AIDS epidemic in the early 80 s has taught us that the risk of developing PJP dramatically increases when CD4 + counts drop < 200 cells/mm 3. In concordance with the guidelines, prophylaxis is started in all HIV-infected patients when CD4 + counts are < 200 cells/mm 3 (7). In contrast, no such guidelines yet exist for other immunocompromised patients. Ideally, and analogous to guidelines for HIV-infected patients, a biomarker with a specific threshold could be used to determine whether to start prophylaxis in these patients, while simultaneously preventing overtreatment and minimizing the occurrence of side effects and development of drug resistance. Considering CD4 + count for this purpose seems evident. Clinical question: Can CD4 + counts select those non-hiv immunocompromised patients that benefit from PJP prophylaxis? Methods: A Pubmed search was performed using the keywords Pneumocystis, non-hiv, AND Prophylaxis. Limits were set to English language, humans and adults. The title and abstract of 26 articles were screened. References and related citations were examined. 29 articles were selected to answer the question. Results: In the 1990 s, several case reports suggested CD4 + lymphocytopenia as the cause of PJP in non-hiv patients (8-11). In a Cochrane review by Green et al., it was shown that the administration of antibiotic prophylaxis with trimethoprim/sulfamethoxazole significantly reduces the occurrence of PJP by 91% and the PJP mortality with 83% in immunocompromised non-hiv patients. Studies demonstrating the potentially beneficial effect of chemoprophylaxis have been performed in patients with inflammatory bowel disease (12), connective tissue disease (13), immunemediated dermatologic conditions (14), hematologic malignancies and solid tumors (15), rheumatic disease (16), in transplant recipients (2, 17), in patients receiving some form of immunosuppressive medication (18-22), and after allogeneic stem cell transplant (23). However, CD4 + count was measured in only one of these studies. In a prospective observational study by Mansharamani et al., CD4 + counts were found to be significantly reduced in patients with active PJP, in high clinical risk groups (< 6 months after organ transplantation, patients receiving chemotherapy) and in a subset of patients with low or undefined risk (namely those on long-term corticosteroid therapy). At the time of PJP diagnosis the mean CD4 + count was 61 cells/mm 3 (median: 118 cells/mm 3 ). 91% of patients had CD4 + counts < 300/mm 3, prompting the suggestion of using this threshold to guide initiation of chemoprophylaxis (24). Several other studies found similar results. A study by Glück showed a mean CD4 + count of 90.6/mm 3 (median 80/mm 3 ) in 7 patients who developed PJP during immunosuppressive treatment for various underlying diseases. Seeing only a minor shift in the CD4 + /CD8 + ratio, the authors conclude that the absolute number of T-helper cells, but not the CD4 + /CD8 + ratio nor the underlying disease determines the risk of PJP (25). In a retrospective descriptive study by Fily et al., CD4 + count was available for 26 PJP cases in non-hiv-infected patients. Here, the mean CD4 + count was 338 cells/ mm 3 (median: 107/mm 3 ). The authors suggest regularly monitoring CD4 + counts in moderate risk patients and acknowledge its role in the decision to start prophylaxis (3). Roblot et al. found a mean of 200 CD4 + cells/mm 3 (median: 100 cells/mm 3 ) in 25 immunocompromised non-hiv patients, suggesting further investigations into the usefulness of this parameter (6). In another study performed by Roblot et al. in non-hiv immunocompromised patients, a mean of 210 CD4 + cells/mm 3 was found in 14 patients. However, 42.9% of patients had counts > 200 cells/mm 3. Therefore, the authors conclude that the critical CD4 + count is different from that in HIV, but assessing the amount of CD4 + cells should still be considered to determine the level of immunodeficiency (5). Martin-Garrido et al. found data on 10 PJP patients treated with Rituximab, showing a median of 25.5 CD4 + cells/mm 3 (26), while De Castro et al. found a median of 131/mm 3 in 8 patients after allogeneic stem cell transplantation (23). In a case report by Kane et al., a patient on weekly methotrexate had a CD4 + count of 150 cells/mm 3, leading the authors to suggest that suppression of CD4 + counts could be the mechanism for development of PJP (8). In the absence of CD4 + counts being measured, low lymphocyte counts have often been reported, being a possible surrogate marker (17, 22, 27-29). Of particular interest is the finding by Godeau et al. in patients being treated for granulomatosis with polyangiitis that the risk of PJP was significantly associated with only the severity of pretreatment lymphocytopenia at a cutoff of 800/mm 3 and the lymphocyte count during the first 3 months of treatment, with 10/12 PJP patients showing counts under the threshold of 600/ml at least once. Lymphocyte subsets were not measured in this study (27). Conclusion: Chemoprophylaxis against PJP in various groups of immunocompromised patients is effective. The available data shows that, similar to in HIV patients, CD4 + counts strongly correlate with the risk of developing PJP. We suggest to measure CD4+ counts in all patients taking immunosuppressive medication and only initiating prophylaxis when CD4+ counts are < 300 CD4 + cells/mm 3. 8

10 HH5 Is thiamine administration before glucose infusion in patients with suspected thiamine deficiency really necessary? E.M. Assenberg van Eijsden 1, P.H.P. Groeneveld 2 1 Isala klinieken, Zwolle, Department of Internal Medicine, Dokter van Heesweg 2, 8025 AB, 8302 WJ EMMELOORD, the Netherlands, liesbethassenberg@gmail.com, 2 Isala klinieken, ZWOLLE, the Netherlands Introduction: Wernicke encephalopathy is a neurological disorder caused by prolonged thiamine (vitamin B1) deficiency. It is most commonly seen in alcoholics, but can also be found in any malnourished state; patients with hyperemesis gravidarum, intestinal obstruction, acquired immunodeficiency syndrome, gastric bypass, and malignancies are commonly cited. 1 Thiamine acts as a coenzyme for the decarboxylation of pyruvate to acetyl coenzyme A; this bridges anaerobic glycolysis and the Krebs cycle. Thiamine is also a coenzyme within the Krebs cycle and in the hexose monophosphate shunt. 2 A lack of thiamine causes inhibition of anaerobic glycolysis. Besides Wernicke encephalopathy, accumulation of toxic intermediates including lactate occur, which can cause lactate acidosis. 3 Medical school curricula and medical textbooks teach clinicians that it is very important to supplement thiamine before administering glucose in patients with possible thiamine deficiency. 4,5,6 Harrison s 18th edition page 2260; Thiamine should be given prior to treatment with IV glucose solutions. Glucose infusions may precipitate Wernicke s disease in a previously unaffected patient or cause a rapid worsening of an early form of the disease. Clinical question: Is thiamine administration before glucose infusion required in patients with suspected thiamine deficiency to prevent Wernicke encephalopathy and lactate acidosis? This clinical question was critically appraised using the following PICO: - Patient: Patients with suspected thiamine deficiency and infusion of glucose Intervention: Thiamine infusion before glucose infusion Control: No thiamine infusion before glucose infusion Outcome: Wernicke encephalopathy and lactate acidosis Methods: A literature search was performed in different databases; including the National guideline of Clearinghouse, TRIP Database, Cochrane library and PubMed. Search terms were: Thiamine AND glucose AND Wernicke OR Lactate There were 144 hits and after screening abstracts, 1 article seemed useful. A systematic review from 2008 with expert opinions (n = 2), case reports (n = 13) and animal models (n = 4). Results: The case reports were all descriptions of patients which suspected thiamine deficiency. Including alcoholics, anorexia from gastritis, kidney failure, pseudo-obstruction and people on a starvation diet. Most of the cases already showed symptoms of thiamine deficiency before glucose infusion. There was no thiamine given before or after the start of glucose infusion. In the next two to twelve days the symptoms worsened after the glucose infusion. After thiamine infusion the symptoms were less severe or disappeared. 1 Discussion: No evidence above the level of case reports were found. Furthermore there were no case reports about lactate acidosis and the research done in animal models cannot be extrapolated to humans. In reviewing the case reports, there is no sufficient information to ascertain whether patients conditions worsened due to the progression of their underlying disease or due to the supposed effects of glucose on the depletion of thiamine stores that could induce Wernicke s. Mounting evidence from case reports does seem to show that prolonged glucose administration without the addition of thiamine can be a risk factor for the development or worsening of Wernicke encephalopathy. But, there is no research done about thiamine suppletion before compared with thiamine infusion after the glucose infusion. Conclusion: There is no evidence that thiamine supplementation is required before the glucose infusion. Recommendation: Do not delay the glucose infusion. Give patients with a suspected thiamine deficiency thiamine supplementation after or concurrent with the start of glucose infusion References 1. Schabelman E, et al. Glucose before thiamine for wernicke encephalopathy: a literature review. The Journal of Emergency Medicine, Vol. 42, No. 4, pp , Watson AJ, et al. Acute Wernickes encephalopathy precipitated by glucose loading. Ir J Med Sci. 1981;150: Kuo SH, Debnam JM, Fuller GN, de Groot J. Wernicke s encephalopathy: an underrecognized and reversible cause of confusional state in cancer patients. Oncology. 2009;76: Keffer MP. Diabetic emergencies. In: Ma OJ, Cline DM, Tintinalli JE, Kelen GD, Stapczynski SJ, eds. Emergency medicine manual. 6th ed. New York: The McGraw-Hill Companies, Inc. 2004: Harrison s 18th edition; p Van der Meer Interne geneeskunde, 2005; p

11 HH6 Respiratory alkalosis and Gram-negative bacteraemia: is there an unique relationship? A.G. Vos, S.U.C. Sankatsing Diakonessenhuis, Bosboomstraat 1, 3583 KE UTRECHT, the Netherlands, Background: It is generally accepted in current medicine that a bacteraemia with a Gram-negative organism should be considered in case of a respiratory alkalosis. In the Acute boekje of the Nederlandse internisten vereniging an early bacteraemie, especially of Gram-negative organism, is mentioned as a possible cause of a respiratory alkalosis.this suggested relation is based on historical studies. In 1951 a review of 29 cases related Gram-negative bacteraemia to different clinical patterns of shock. 1 Subsequent reviews of patterns and clinical and laboratory findings of shock were performed. Most studies included only patients with a Gram-negative bacteraemia. From the late 50 s it became possible to perform blood gas analysis on a larger scale. Respiratory alkalosis was observed as a frequent concomitant sign of septic shock. It was postulated that stimulation of the central respiratory center and peripheral baroreceptors by bacterial endotoxins, especially or exclusively of Gram-negative microorganisms, could induce hyperventilation. To investigate if there is an unique relation between respiratory alkalosis and Gram-negative bacteraemia, a systematic literature search was performed. Methods: A PubMed and EMBASE search was conducted using the following synonyms in title or abstract: sepsis OR shock OR SIRS OR systemic inflammation AND alkalosis AND Gram negative. Thirteen studies were identified. After screening for relevance and checking the references, six studies 2-7 remained. Results: Al studies were observational, dating from 1960 till 1993, the number of patients ranged from 11 till 50. Study quality was marginal. In all but one inclusion criteria were not clear. 4 out of 6 studies included only patients with a proven Gram-negative bacteraemia. 2-5 Moments of inclusion were heterogeneous, varying from bacteraemia without shock till late, refractory shock. 3 studies 5-7 included patients with early shock or bacteraemia without shock. A respiratory alkalosis was observed in 60-93% of the patients. 2 out of these 3 studies included both patients with a Gram-positive and a Gram-negative bacteraemia. No difference in prevalence of respiratory alkalosis between Gram-positive and Gram-negative bacteraemias was found. Of the remaining 3 studies included patients with late or refractory shock and one with both early and late shock. No correlation with respiratory alkalosis was found. Conclusion: Respiratory alkalosis seems to be related to bacteraemie without shock or with early shock. This phenomenon is not exclusively related to Gram-negative bacteraemia. The assumption of this exclusive relationship is based on historical studies with a bias in inclusion of patients, which can be understood at the background of medical history. References 1. Waisbren BA. Bacteremia due to Gram-negative bacilli other than Salmonella. Archives of Internal Medicine 1951;88: Blair E. Hypocapnia and gram-negative bacteremic shock. Am J Surg. 1970;119: Blair E, Cowley RA, Wise A, Mackay AG. Clinical physiology of late (refractory) gram-negative bacteremic shock. Am J Surg. 1969;117: Elisaf M, Theodorou J, Pappas H, Siamopoulos KC. Acid-base and electrolyte abnormalities in febrile patients with bacteraemia. Eur J Med. 1993;2: Simmons DH. Nicoloff J. Guze LB. Hyperventilation and respiratory alkalosis as signs of gram-negative bacteremia. JAMA 1960:174: MacLean LD, Mulligan GW, et al. Alkalosis in septic shock. Surgery 62:655, Winslow EJ, Loeb HS, Rahimtoola SH, Kamath S, Gunnar RM. Hemodynamic studies and results of therapy in 50 patients with bacteremic shock. Am J Med. 1973;54: I O01 ORAL PRESENTATIONS RESEARCH AND CASE REPORTS Clinical value of serum IgG4 subclass levels in patients with idiopathic retroperitoneal fibrosis L.G. Pelkmans, E. Vermeer, T.R. Hendriksz, E.F.H. van Bommel Albert Schweitzer Hospital, Albert Schweitzerplaats 25, 3318 AT DORDRECHT, the Netherlands, l.g.pelkmans@asz.nl Objective: In patients with idiopathic retroperitoneal fibrosis (irpf), inflammation and fibrosis may be a manifestation of IgG4-related disease. As such, serum IgG4 levels may be of value as parameter of IgG4-related inflammation and in predicting treatment response. Design: Prospective, observational study of 29 consecutive irpf patients who were seen at our tertiary care referral centre from September 2010 through November Measurements: Clinical, laboratory and radiological investigation was performed at presentation and at repeated follow-up. All but 2 patients were treated with tamoxifen. Treatment success was defined as such satisfactory clinical, laboratory and radiological response to tamoxifen during follow-up that there was no need to alter therapy. Treatment outcome analysis included patients who had at least 10

12 4 months of follow-up and who underwent at least the first CT scan follow-up. Second-line treatment consisted of corticosteroids, either alone or combined with other immunosuppressants. Results: Overall, 13 patients (44.8%) had IgG4 levels above the normal range of 1.4 g/l. In patients with elevated IgG4 levels, locoregional lymphadenopathy (53.8% vs. 18.8%; p < 0.01) and to lesser extent atypical mass localisation (30.7% vs. 6.3%; p = 0.14) was observed more frequently compared to that in patients with normal range levels. Fibrotic mass thickness did not differ between patients with normal range or elevated IgG4 levels (median 28.0 [IQR ] mm vs [IQR ] mm; p = 0.72). Males tended to have higher IgG4 levels compared to females (1.66 [ ] g/l vs [ ] g/l; p = 0.09). Eleven of 24 patients (45.8%) who received tamoxifen eventually switched to second-line treatment. Success rate in tamoxifen-treated patients with normal range or elevated baseline IgG4 levels did not differ. However, non-responders to tamoxifen had higher baseline IgG4 levels compared to patients who responded satisfactorily to tamoxifen (1.31 g/l [ ] g/l vs [ ] g/l, p = 0.05). All patients (100%) who had treatment failure were men, compared to 57% of patients with treatment success (p = 0.02). In patients who had treatment failure with tamoxifen, IgG4 levels did not decrease until after switch to second-line treatment ( IgG [ ] before switch vs [ ] after switch, p = 0.01). Eleven of 13 patients had success of second-line therapy. Conclusions: irpf patients with elevated IgG4 levels may present more often with atypical mass localisation and particularly locoregional lymphadenopathy. Non-responders to tamoxifen had higher IgG4 levels than responders. Females seem to respond better to tamoxifen therapy, which might be explained by their lower IgG4 levels. O02 Low haptoglobin, reflex: hemolysis! H.F. Dresselaars, K.G. van der Hem Zaans Medical Centre, Department of Internal Medicine, Koningin Julianaplein 58, 1506 DV ZAANDAM, the Netherlands, lenadresselaars@gmail.com A 56 year-old female Creole patient was referred by her general practitioner because of a mild normocytic anemia. Her medical history consisted of recurrent urinary tract infections in the past. She did not use any medications. Anamnesis and physical examination were unremarkable. Laboratory results showed Hb 7.1 mmol/l, MCV 87 fl, leukocytes 4.2 x 10E9/L with normal differentiation, platelets 315 x 10E9/L, ESR 20 mm after 1 hour, reticulocytes x 10^9/L, creatinin 77 micromol/l, albumin 42 g/l, ASAT 23 U/L, ALAT 18 U/L, total bilirubin 6 umol/l, GGT 19 U/L, alkaline phosphatase 88 U/L, lactate dehydrogenase (LDH) 181 U/L, CRP 3.9 mg/l, iron 15.3 umol/l, total iron binding capacity 40.2 umol/l, transferrin saturation 38%, ferritin 109 ug/l, haptoglobin < 0.10 g/l and TSH 2.0 m U/L. The direct agglutination test (Coombs) was negative twice. HIV serology was negative, cerulosplasmin levels were normal and no thalassemia could be found. There was no evidence of paroxysmal nocturnal hemoglobinuria, erythrocytic enzymes were present in normal levels and no splenic abnormalities were seen by echography. While haptoglobin remained undetectably low with normal LDH and bilirubin and Hb remained stable at 7.5 mmol/l, it was concluded there was no hemolysis. Subsequent determination of hemopexin showed a normal value of 1010 mg/l ( mg/l), indicating absence of severe or chronic hemolysis. The diagnosis congenital anhaptoglobinemia was made. An- or hypohaptoglobinemia can both be acquired or congenital. The acquired condition is due to increased consumption in hemolysis or decreased synthesis in liver dysfunction. Congenitally allelic deletion in the Hp-gene cluster leads to decrease or absence of haptoglobin. Hemopexin levels can differentiate between the two forms: since hemopexin binds free heme its level decreases after saturation of the hemoglobin-binding capacity of haptoglobin. When haptoglobin is low in absence of hemolysis hemopexin levels are normal. Different fenotypes of congenital haptoglobin deficiency exist. In true anhaptoglobinemia a silent allele with no gene product is inherited (Hp 0). Hp 0-0 phenotype is present in approximately 1 in 1000 Caucasians. In black people (especially from West Africa) anhaptoglobinemia is more frequent (> 30%). Diagnosing hypohaptoglobinemia has important clinical consequences since it is associated with heme accumulation resulting in iron-driven oxidative stress and vitamin C depletion. In addition, it predisposes for allergic transfusion reactions containing traces of haptoglobin when haptoglobin antibodies are present. O03 Multi-organ toxicity due to chronic occupational heavy metal exposure D.J.L. van Twist, C.V. Hoge, G.H. Koek, H. ten Cate Maastricht University Medical Centre, Department of Internal Medicine, P. Debyelaan 25, 6229 HX MAASTRICHT, the Netherlands, daan.van.twist@mumc.nl Case: A 59-year-old man without relevant medical history was referred to our hospital because of recently diagnosed type 2 diabetes mellitus and thrombocyto- 11

13 penia. The patient complained of recurrent episodes of general weakness, myalgia, feverishness, and dry cough. Physical examination revealed purpura of the lower legs and decreased sensibility of both feet. Routine blood count showed thrombocytopenia (100*10 9 /L), elevated erythrocyte sedimentation rate (100 mm/hour), and normochromic anemia. As we suspected a systemic vasculitis, a biopsy from the purpura was taken. This demonstrated leukocytoclastic vasculitis with perivascular C3 depositions. Chest CT-scan showed mediastinal lymphadenopathy and abdominal ultrasound revealed livercirrhosis and splenomegaly with extensive collaterals, suggesting portal hypertension. Auto-immune serology and viral hepatitis tests were negative. Levels of ceruloplasmin, serum copper and iron were normal, and no nodular abnormalities or iron depositions were found on MRI of the liver. As the patient used no medication, drugs, or alcohol and liver biopsy was not possible due to the thrombocytopenia and presence of extensive collaterals, the etiology of the Child- Pugh-A liver cirrhosis remained unclear. Propranolol was initiated because of esophageal varices, but this resulted in substantial edema and weight gain. Echocardiography indeed revealed decreased left ventricular ejection fraction (30%). When asked, he mentioned running a galvanizing and enameling company for art production for over thirty years. Under suspicion of a heavy metal intoxication we performed blood tests. Indeed, high levels of metals were found: aluminium 0.58 (normal < 0.3) mmol/l, lead 2.02 (< 0.14) mmol/l, cadmium 8.0 (< 6.5) nmol/l, manganese (< 11.3) nmol/l, nickel 86.5 (< 13) nmol/l, and cobalt 33.7 < 7) nmol/l. The patient interrupted the galvanizing and enameling activities, resulting in a significant decrease in metal levels within a few months, but also in a spectacular improvement of his general performance: skin abnormalities, mediastinal lymphadenopathy, and anemia disappeared and ESR normalized. Interestingly, behavioral and cognitive changes were noted: Whereas we formerly saw an apathetic and lethargic patient with memory difficulties, he now made jokes, had good memory, and took initiative to undertake activities. Discussion: We describe a unique case of multi-organ involvement of chronic intoxication with several heavy metals due to chronic occupational exposure. This induced an inflammatory reaction (leukocytoclastic vasculitis, mediastinal lympheadenopathy and so-called metal fume fever ) and chronic damage to liver, nervous system (behavioral and cognitive changes and polyneuropathy), and (probably) heart. This case illustrates the risks of chronic heavy metal exposure and the importance of obtaining a thorough occupational history in each patient. O04 Microbial Strangulation After a Chinese Dinner? J. Vergragt 1, T.J. Blokhuis 2, D.W. Lange, de 2 1 Ikazia Hospital, Department of Intensive Care, Coornhertstraat 1, 3521 XE UTRECHT, the Netherlands, lejoris@gmail.com, 2 University Medical Centre Utrecht, UTRECHT, the Netherlands A 55 year old male presented to the Emergency department with headache, swelling of the upper lip and tachycardia. Initially he was treated for an alleged allergic reaction to the Chinese meal he consumed the evening before. Absence of improvement led to consultation of the neurologist and ENT specialist. After CT-scanning a cerebral sinus thrombosis could not be ruled out, so he received therapeutic dose of low molecular weight heparin. Despite feeling relatively well, the swelling worsened. With a modest fever as the only sign of infection, antibiotics were added. As any diagnosis was still lacking, he was observed on a medium care unit. About 15 hours post admission, things started to go downhill. He was feeling dyspnoeic, the swelling prevented normal speech and saturation dropped. He was put on 100% oxygen and taken to the operating theatre to perform urgent fiberoptic nasal intubation. With exceptional skill and a sheer dose of luck the anesthesiologist could secure the airway without adverse events. Still clueless we strongly observed the clinical course on the ICU. Then, at first daylight, we noticed a spreading reddish discoloration of the left thorax. Meanwhile his need for hemodynamic support also increased. The, at that time, spot-diagnosis was necrotizing fasciitis. Within minutes, he was back in the operating theatre to undergo extensive debridement of the thoracic fasciae. Remarkably, the face and neck remained totally unaffected by the necrotic process. After 41 days in the hospital, our patient recovered quite well. Necrotizing fasciitis is very well known for its destructive power, although the incidence is very low. The typical presentation is excruciating pain, oedema and rapidly spreading erythema. Later, the affected area becomes anaesthetic, due to thrombosis. However, less then 50% of cases presents classically, and the average time to reach diagnosis is hours. Why then, the impressive airway obstruction without infection of the neck? Older literature describes oedema outside the affected area, but the underlying pathophysiological mechanisms still need to be elucidated. Although it almost killed him, the airway obstruction served as an early warning something was seriously wrong. Should we have done better and reach the diagnosis at an earlier stage? Most authors agree having a high degree of suspicion or trusting your gut feeling is superior to any 12

14 scoring system. Our case illustrates that, when in doubt, the best way is to stick with your patient until things have become clear. O05 Constipation and coloured urine: the diagnostic challenge of acute intermittent porphyria C.H.M. Leenen, M. Westerman, C.E.H. Siegert, J. Veenstra St Lucas Andreas Hospital, Department of Internal Medicine, Jan Tooropstraat 164, 1061 AE AMSTERDAM, the Netherlands, Introduction: acute intermittent porphyria (AIP) is one of a cluster of rare metabolic disorders. It is an autosomal dominant condition, characterized by a reduced activity of one of the enzymes in the heme biosynthetic pathway resulting into an array of symptoms characterized by autonomous dysfunction. Case: a 23-year old woman with an unremarkable medical history was admitted to our hospital with complaints of two weeks duration of abdominal pain and constipation. Prior to admission she visited four medical doctors, including three general practitioners and the emergency department. However, the initiated treatment consisting of laxatives and analgesics was ineffective. Upon admission vital signs and temperature were normal. On abdominal examination normal bowel sounds were heard and palpation was not painful. Laboratory tests revealed an acute kidney injury (creatinine 111 mmol/l, GFR using MDRD 53 ml/min), low sodium (sodium 131 mmol/l), increased creatinine kinase (CK 1200 U/L) and a microcytic anemia (hemoglobin 6,5 mmol/l). Abdominal ultrasound was normal. During admission the striking discovery was done that her urine was dark-red coloured. Additional urine analysis showed increased levels of porphyrines, especially a high delta-aminolevulinic acid level (336,3 umol/l) and porphobilinogen level (500,0 umol/l), suggestive for AIP. Furthermore, it appeared she had a positive family history for AIP. In two affected sisters of her father a mutation in the HMBS gene was detected. Her father had never experienced any attacks and had therefore never been tested. Treatment with glucose (10%) intravenously and morphine was immediately started after which the patient fully recovered. This first episode of AIP was probably initiated by an urinary tract infection for which she received intravenously ceftriaxone. In literature, five other cases of rhabdomyolisis and AIP have been reported. Conclusion: In case of unexplained abdominal pain with constipation and unexpected biochemical changes including low sodium levels, rhabdomyolysis and/or microcytic anemia, AIP should be considered.family history is of great importance. O06 Drug induced fatal hepatic toxicity after 1 week nitrofurantoin N.C.W. Laurenssen 1, M. Kramer 1, R. Aydinli 2, J. Gisolf 1, J. Verhave 1 1 Rijnstate Hospital, Department of Internal Medicine, Wagnerlaan 55, 6815 AD ARNHEM, the Netherlands, nicky_laurenssen@hotmail.com, 2 Health Centre Velperweg, ARNHEM, the Netherlands Introduction: Nitrofurantoin is commonly used in urinary tract infections(uti). Hepatotoxicity associated with nitrofurantoin is rare. We report the case of a 64 year old male, presenting with fatigue and jaundice beginning 1 week after treatment with nitrofurantoin for a UTI. Severe hepatotoxicity secondary to nitrofurantoin was diagnosed. This made us question the indication of nitrofurantoin for UTI in elderly men. Case: A 64 year old man with a history of type 2 diabetes and gastric ulcer, was treated with nitrofurantoin for a UTI. After 1 week he suffered from fatigue, nausea and jaundice. Laboratory tests showed elevated cholestatic liver enzymes and decreased liver functions. The diagnosis nitrofurantoin associated cholestatic hepatotoxicity was made by exclusion of other causes of liver disease. During admission the patients clinical condition deteriorated rapidly and he developed multi-organ failure. He died 2 months after hospital admission of severe sepsis. Discussion: In this case nitrofurantoin was prescribed by the general practitioner who followed the Guideline for Urinary Tract Infections of the DutchCollege of General Practitioners (NHG-guideline). This guideline advises a 7 day treatment with nitrofurantoin in men with UTI without systemic symptoms. The NHG state in case of no signs of tissue invasion, pyelonephritis or prostatitis, there is no reason to use different antibiotics in men compared to women. The SWAB suggests that only in young men below 40, a UTI may be considered as uncomplicated. UTI in young men is rare and data from trials are lacking. An epidemiological study from Norway, reported 6 to 8 uncomplicated UTIs per year in men in the age range years.there are several arguments to consider UTI in men as complicated. In men with a UTI there is often a concurrent prostatitis. Prostate involvement occurres in more than 90% of men with febrile UTI, even without clinical signs of acute pyelonephritis. Prostatitis is not easy to diagnose since patients don t always have a fever or pain during rectal examination. Also most UTI s occurring in men are associated with urological abnormalities, bladder outlet obstruction or instrumentation. Finally men with UTIs are more at risk to develop a bacteremia. Conclusion: In our patient nitrofurantoin had a severe adverse effect and led to fatal cholestatic hepatotoxicity. We argue that nitrofurantoin is not the first choice for 13

15 treating a UTI in elderly men. There is often a concurrent prostatitis or urological abnormality and nitrofurantoin has insufficient tissue penetration. O07 A nice CATCH! S. Indhirajanti, J. Alsma, P.L.A. van Daele Erasmus Medical Centre, Department of Internal Medicine Vascular diseases, s-gravendijkwal 230, 3015 CE ROTTERDAM, the Netherlands, s.indhirajanti@erasmusmc.nl Case report: A 42-year old Caucasian man presented at the emergency department with a painful shoulder with restricted movement. His complaints had started spontaneously and traumatic injury was absent. His medical history revealed mental retardation and cardiac anomalies; a ventricular septal defect corrected at the age of two, an aortic coarctation and an aorta valve stenosis. Despite previous testing no specific syndrome had been found. Physical examination not only revealed signs of a fractured shoulder, but also subtle facial dysmorphisms (hypertelorism and hyperplastic gingivae) and prominent pulsations on the right side of the neck. Auscultation of the heart revealed a systolic murmur in accordance to the aortic valve stenosis. Laboratory results included a severe serum hypocalcaemia of 1.41 mmol/l (normal range mmol/l). Ionized calcium was 0.67 mmol/l ( mmol/l). Serum albumin level was normal. Serum phosphate was high at 1.91 mmol/l ( mmol/l). There were a mild thrombocytopenia and anemia. His white blood cell count was slightly elevated with a normal differentiation. Renal function was normal. Both urinary calcium and parathyroid hormone (PTH) concentration were low (0.10 mmol/l ( mmol/l) respectively 1.2 pmol/l ( pmol/l)). Furthermore 25-OH-D was low. A shoulder X-ray revealed a fractured humerus. The diagnosis of hypoparathyroidism was made. The combination of hypoparathyroidism, facial dysmorphisms and cardiac anomalies were highly suggestive for 22q11.2 deletion syndrome. Calcium and vitamin D suppletion were initiated and the patient underwent surgery for the humerus fracture without any complications. The result of the chromosomal analysis to confirm the diagnosis is awaited. Discussion: The 22q11.2 deletion syndrome affects between 1 in 2000 and 1 in 4000 live births. The microdeletion leads to a defective development of the pharyngeal pouch system. The acronym CATCH-22 summarizes the clinical features Cardiac Abnormality, Abnormal facies, Thymic aplasia, Cleft palate and Hypocalcemia/ Hypoparathyroidism, where 22 represents the affected chromosome. However, there is a great variety in clinical presentation. The classic combination of hypoparathyroidism, thymic hypoplasia and facial dysmorphism is also called digeorge syndrome. Although 22q11.2 deletion syndrome is fairly common the diagnosis is often missed as physicians are unaware of the syndrome or see only one part of the cardinal features. Conclusion: The finding of hypocalcaemia in a patient with a considerable medical history should trigger one to think of a 22q11.2 deletion syndrome, even at the age of 42. O08 From endocrine to cardiac storm: ventricular fibrillation in a young patient with thyrotoxicosis and Brugada syndrome L. Both, J.P.H. van Wijk Gelderse Vallei Hospital, Department of Internal Medicine, Willy Brandtlaan 10, 6716 RP EDE, the Netherlands, interneaabothl@zgv.nl Background: Graves disease is the most common cause of thyrotoxicosis. Thyroid storm is a rare but life-threatening complication of Graves disease. We present a case of a 19-year-old male who was hospitalized for ventricular fibrillation due to thyrotoxic storm Case: A 19-year-old man was admitted to the emergency room due to an out-of-hospital cardiac arrest. Ventricular fibrillation was noted on electrocardiographic monitoring and reverted to sinus rhythm after repeated defibrillation and basic life support. He had a history of Graves hyperthyroidism for 3 years and was treated with radioactive iodine 4 months before admission. Block-and-replacement therapy (strumazol 30 mg and levothyroxine 100 mcg) resulting in euthyroidism was given until 2 weeks before admission when it was stopped on our advice.. On admission, laboratory examinations revealed elevated free thyroxine (62 pmol/l, normal pmol/l) and suppressed thyroid-stimulating hormone (< 0,01 miu/l, normal 0,3-4,5 miu/l). Thyroid storm due to recurrent Graves disease, presenting with ventricular fibrillation was diagnosed. He was treated with propylthiouracil 200 mg every 4 hours, propranolol 40 mg every 8 hours, hydrocortisone 100 mg IV every 6 hours, acetaminophen 500 mg every 6 hours and, after propylthiouracil was given, Lugol solution 20 drops every 8 hours. Free thyroxine levels normalized within a few days. Initial post resuscitation echocardiography revealed generalized ventricular failure which complete recovered after reaching euthyroidism. Coronary angiography revealed no abnormalities. Cardiac MRI suggested left ventricular hypertrophy, normal RV and no signs of fibrosis. Post resuscitation electrocardiography showed an incomplete right bundle branch block and upsloping 14

16 ST-segment in V2 and V3. Family history was negative for sudden death or cardiac arrhythmias. With Ajmaline the right precordial leads changed to a type 2 Brugada repolarization pattern. Brugada syndrome is a hereditary arrhythmia characterized by specific electrogardiographic changes due to mutations in sodium channels of the heart (SCN5A) and increased risk of sudden cardiac death. The patient fully recovered. An implantable defibrillator was implanted to treat eventual further cardiac arrhythmias before discharge. The patient was referred for genetic linkage analysis. In the future, total thyroidectomy will be performed. Conclusion: Thyroid storm is a rare, but treatable, potential fatal emergency. In rare cases, ventricular fibrillation is the presenting symptom of a thyroid storm. In our case, the presence of Brugada syndrome probably predisposed to the near-fatal ventricular arrhythmia. O09 Secondary causes for osteoporosis significantly contribute to fracture risk in patients with osteopenia and a recent fracture F. Malgo, N.A.T. Hamdy, N.M. Appelman-Dijkstra Leiden University Medical Centre, Department of Endocrinology & Metabolic Diseases, Albinusdreef 2, 2333 ZA LEIDEN, the Netherlands, f.malgo@lumc.nl In de gedrukte versie van dit abstractboek is een onjuiste inhoud vermeld. De juiste versie treft u als aparte bijlage aan. O10 Olmesartan causing prominent diarrhea and malabsorption J.J.B. Janssen 1, P. Nijeboer 2, C.J.J. Mulder 2 1 St. Elisabeth Hospital, Department of Internal Medicine, Hilvarenbeekse weg 60, 5022 GC TILBURG, the Netherlands, johanjanssen9@hotmail.com, 2 VU University Medical Centre, AMSTERDAM, the Netherlands Introduction: Diarrhea is a frequently reported complaint and has a broad differential diagnosis. The differential diagnosis of diarrhea in combination with villous atrophy is much narrower and mainly includes coeliac disease. Here we present an olmesartan induced enteropathy. Case description: A 63-year-old man, with a history of hypertension and paroxysmal atrial fibrillation presented with recurring symptoms of severe diarrhea (7,5-10 liters a day), acute renal failure (creatinine 692 umol/l and a GFR 7 ml/min/1) and a metabolic acidosis (ph 7.19, PCO2 1,9kpa, PO2 14kpa, Bic 5,1mmol/L) which required several hospitalizations. Psychical examination showed no diagnostic clues, only signs of dehydration. Differential diagnosis included infectious diseases (viral, bacterial and parasitic) and inflammatory diseases (M. Crohn, colitis ulcerosa and coeliac disease). Stool cultures were repeatedly negative, ultrasound showed no thickened bowel wall and coloscopy only atypical redness of the flexura lienanis, with a chronic aspecific inflammation, without signs of an inflammatory bowel disease after pathological examination. Gastroscopy showed a radially antrumgastritis and a mild duodenitis. Pathological work-up revealed a total villous atrophy (Marsh IIIC), but no other deviations (no tropheryma whipplei, giardia lamblia, collagenic enteritis or TBC). Coeliac serology was repeatedly negative, with a HLA-DQ2 haplotype. MRI-enteroclyse showed no deviations, especially no signs of lymphoma. Because of the possibility of seronegative coeliac disease, a gluten free diet was started. This did not have any effect on the episodes of severe diarrhea. Antihypertensive medications were temporarily discontinued at every admission, and restarted at discharge because of ascending blood pressures. This in combination 15

17 met recent literature eventually raised the suspicion of an association between the severe enteropathy and the anti-hypertensivum olmesartan. And indeed, permanent withdrawal of olmesartan resulted in a total and persistent clinical response. Discussion: Olmesartan is a selective type I angiotensin- II-receptor-antagonist and procurable in the Netherlands since Recent American and German literature describes case series of similar patients with olmesartanassociated enteropathy, even after months to years of usage. Since this side effect is reported more often, other causes of villous atrophy were excluded and the symptoms disappeared after discontinuation and reappeared after restarting olmesartan, we consider this, according to the Naranjo causality scale, as a probable adverse drug event. The pathophysiological mechanism underlying olmesartan-associated enteropathy is still unknown, although cell-mediated immunity is suspected to play a role. Since olmesartan is increasingly prescribed in the Netherlands, it should be considered as a cause for diarrhea. Treatment consists of discontinuation of the olmestartan. both phases, and after 3 and 6 months. Steatorrhea-related symptoms were assessed with a scoring system, consisting of questions regarding stool frequency, consistency, stickiness, and abdominal cramps and/or flatulence. The scale ranged from 0-8, with higher scores indicating more severe symptoms. Results: Ten patients were included (50% male; median age 53). With flexible dosing, the CFA went up from 87% to 90%. The mean enzyme dose increased from 3 to 10 capsules per day (p-value < 0.001) and the mean steatorrhea score improved from 5 to 3 (p-value 0.004). Both effects remained present after 3 and 6 months. The BMI did not change during the first 9 weeks of the study (23.5 and 23.7 respectively), but increased significantly after 3 and 6 months (24.5 and 25.0 respectively), compared to phase I (p-values and < 0.001, respectively). Fat-soluble vitamin deficiencies, however, had not yet resolved after 6 months. Conclusion: In exocrine insufficiency, patient-education and flexible enzyme dosing improved steatorrhea related complaints and bodyweight, and should therefore be routinely applied. O11 Exocrine insufficiency in chronic pancreatitis; flexible dosing of pancreatic enzymes improves treatment outcome E.C.M. Sikkens 1, D.L. Cahen 2, J. de Wit 2, C.W.N. Looman 2, F. Kubben 3, M.J. Bruno 2 1 St Lucas Andreas Hospital, Department of Internal Medicine, Jan Tooropstraat 164, 1061 AE AMSTERDAM, the Netherlands, e.sikkens@slaz.nl, 2 Erasmus Medical Centre, ROTTERDAM, the Netherlands, 3 Maasstad Hospital, ROTTERDAM, the Netherlands O12 Juvenile haemochromatosis in a 30-year old patient with heterozygous beta-thalassemia J.E. Tijmensen, H. van Houten Haga Hospital, Department of Internal Medicine, Sportlaan 600, 2566 MJ THE HAGUE, the Netherlands, j.e.tijmensen@hagaziekenhuis.nl In de gedrukte versie van dit abstractboek is een onjuiste inhoud vermeld. De juiste versie treft u als aparte bijlage aan. Introduction: In exocrine insufficiency, pancreatic enzyme supplementation can prevent steatorrhea-related symptoms and malnutrition. The optimal dose varies, according to individual patient characteristics and dietary fat content. However, many patients use a fixed dose regimen. We prospectively evaluated if patient-education and flexible dosing improves treatment efficacy in exocrine insufficiency. Methods: Between August 2010 and October 2012, chronic pancreatitis patients were included if they were treated with a fixed dose of 25,000 to 150,000 units of lipase per day. During the first 4 weeks of the trial, this fixed dose was continued (phase I). In week 5, patients were educated on flexible dosing, which was applied in the last 4 weeks of the trial (phase II). The faecal fat absorption (CFA) was measured at the end of each phase. The enzyme dose, steatorrhea-related symptoms, BMI, and presence of fat-soluble vitamin deficiencies were assessed at the end of 16

18 O13 Case Report: A Turkish family with congenital dyserytropoietic anaemia type II S. Wiebers, T.M. van Maanen, W.G. Meijer Westfries Gasthuis, Department of Internal Medicine/Oncology, Maelsonstraat 3, 1624 NP HOORN, the Netherlands, S.wiebers@outlook.com Introduction: Congenital hemolytic anemias are classified by causative mechanism. The most common types are genetic conditions of the red bloodcell (RBC) membrane (heriditairy spherocytosis, heriditairy elliptocytosis, heriditairy pyropoikilocytosis, heriditairy stomatocytosis), enzyme defects of the RBC (glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency) or hemoglobinopathies (sickle cell anemia, thalassemia). We report on a family with a rare heriditary hemolytic anemia due to congenital dyserythropoietic anemia (CDA) type II. Case report: A 37-year old man was admitted for right upper quadrant abdominal pain, dark urine and discolored stools. His medical history reported M. Bechterew and a mild congenital hemolytic anaemia, not further specified. The patients family is of Turkish background. Two of his sisters (eight siblings) were also diagnosed with hemolytic anaemia. On physical examination there was jaundice and upper abdominal tenderness, vital signs were normal. Laboratory results showed hemoglobin 8.0 mmol/l, mean corpuscular volume 87 fl, platelets 148*10 9 /L, leukocytes 6.5*10 9 /L, blood smear showed no abnormalities, C-reactive protein 2 mg/l, reticulocytes 13 promille, haptoglobin < 0.10 g/l, alkaline phosphatase 142 U/L, gamma-glutamyltransferase 326 U/L, bilirubine conjugated 253 mmol/l, billirubin unconjugated 176 mmol/l, aspartate transaminase 185 U/L, alanine transaminase 279 U/L, lactate dehydrogenase 195 U/L, ferritin 1196 mg/l. Ultrasound showed choledocholithiasis and splenomegaly. On endoscopic retrograde cholangiopancreatography bile ducts were not dilated and no concrements were visualized. A transient gallstone seemed the most probable cause. Further tests were performed to investigate the cause of the hemolytic anemia. Enzymedeficiencies were absent. Hb-electrophoresis showed no evidence for a hemoglobinopathy. Hereditary spherocytosis (HS) was not ruled out: BAND 3 expression was just below the cut-off value, however spectrine percentage was normal. A bone marrow biopsy showed dyserythropoiesis with multinucleated erytroblasts and chromatin bridges. There was a homozygote SEC23B mutation. Conclusion: This patient was admitted for choledocholithiasis due to hemolysis caused by CDA type II based on homozygote SEC23B mutation. Two sisters of our patient are probably affected as well. CDA type II is a rare disorder with autosomale recessive inheritance, leading to ineffective erytropoiesis. Chromatin bridges are in most cases described in CDA type I. A SEC23B mutation is associated with hypoglycosylation of BAND3 in vivo. CDA is often misdiagnosed as hemolytic anemia, thalassemia or hereditary spherocytosis. Iron overload is a common problem in CDA, this explains the high ferritin level in our patient. O14 Iron inflammation, and early death in adults with sickle cell disease E.J. van Beers 1, Y. Yang 2, N. Raghavachari 2, D. Allen 2, J. Nichols 2, L. Mendelsohn 2, S. Nekhai 3, V.R. Gordeuk 3, J.G. Taylor Vi 2, G.J. Kato 2 1 Academic Medical Centre, Department of Clinical Hematology, Meibergdreef 9, 1105 AZ AMSTERDAM, the Netherlands, e.j.vanbeers@amc.uva.nl, 2 National Heart, Lung and Blood Institute, BETHESDA, MD, USA, 3 Howard University, WASHINGTON, DC, USA Introduction: Patients with sickle cell disease are marked by a state of chronic inflammation but the cause of this inflammation and the relevance to patient survival are unknown. Aim od the study: To assess the relationship between iron, inflammation and early death in sickle cell disease. Materials and methods: Registry study of sickle cell disease patients that were followed from February 1, 2001, through January 2011 at the NIH Campus, Bethesda, with a nested case control genetics substudy, supplemented with a hypothesis generating gene expression study. (ClinicalTrials.gov identifier NCT and NCT ) Results: Using peripheral blood mononuclear cell transcriptome profile hierarchical clustering we classified 24 patients and 11 controls in clusters with significantly different expression of genes known to be regulated by iron. Subsequent gene set enrichment analysis showed that many genes associated with the high iron cluster were involved in the toll like receptor system (TLR4, TLR7 and TLR8) and inflammasome complex pathway (NLRP3, 17

19 NLRC4, and CASP1). Quantitative PCR confirmed the microarray based classification and showed that PBMC ferritin light chain, TLR4 and interleukin-6 expression was more than 100-fold higher in patients than in controls (p < 0.001) and highly correlated to each other (p < 0.001). In a cohort of sickle cell disease patients (n = 161), plasma levels of interleukin-6 were most strongly correlated with the inflammatory C-reactive protein (rho = 0.496, p < 0.001). In a Mendelian randomization experiment 14 sickle cell disease patients with a ferroportin variant that causes intracellular iron accumulation, had significantly higher levels of interleukin-6 and C-reactive protein compared to 14 patients with the wildtype allele, implying a causal effect.(p < 0.05) Finally, in a cohort of 412 patients with sickle cell disease followed for a median period of 47 months, (IQR 24-82, range 2-132), C-reactive protein was strongly and independently associated with early death (hazard ratio 3.0, 95% CI , p < 0.001). Conclusion and relevance: Gene expression markers of high intracellular iron in patients with SCD are associated with markers of steady state inflammation and mortality. The results support a hypothetical model in which intracellular iron promotes clinically significant inflammatory pathways such as TLR system and the inflammasome, identifying important new pathways for therapeutic intervention. O15 Macrocytic anaemia in patients with newly diagnosed anaemia: factors influencing diagnosis and prognosis M.D. Levin 1, K. Stouten 1, P. Sonneveld 2, J. Riedl 1 1 Albert Schweitzer Hospital, Department of Internal Medicine, Albert schweitzerplaats 25, 3018 AT DORDRECHT, the Netherlands, m-d.levin@asz.nl, 2 Erasmus Medical Centre, ROTTERDAM, the Netherlands Introduction: The frequency of underlying causes of macrocytic anaemia is unclear in medical literature. In addition, the prognosis of underlying causes of macrocytic anemia still have to be established. Aim of the study: To clarify causes and prognosis of macrocytic anemia in a prospectively studied cohort of patients with newly discovered anemia. Materials and methods: Patients with a newly discovered anemia from 63 general practitioners were prospectively studied from the 1 st of February 2007 to the 1 st of February 2013, with the follow-up period ending on the 1 st of July Patients with macrocytic anemia (i.e. MCV 100 fl) were included in the study. For each patient a standardised laboratory work-up was performed, which included: haemoglobin, MCV, erythrocytes, erythrocyte sedimentation rate, reticulocytes, thrombocytes, leukocytes, ferritin, transferrin, serum iron, serum vitamin B12, serum folic acid, gamma GT, LDH, creatinin and CRP. Furthermore, a complete hospital chart review (e.g. report on alcohol abuse and medication) was conducted and any additional examinations (e.g. bone marrow examination) were analysed. Results: A total of 2738 patients with a newly diagnosed anaemia were included. Of these patients 190 (6.9%) displayed macrocytic anaemia (MCV 100 fl). In 159 of these 190 patients (83.7%) underlying causes could be established. Seven of these 159 patients (4.4%) displayed two causes for their macrocytic anaemia. Classic causes of macrocytic anaemia (haemolysis, possible bone marrow disease, vitamin B12 deficiency, folic acid deficiency and documented alcohol abuse) were found in 85 patients (44.7%). Alternative causes (anaemia of chronic disease, iron deficiency, renal anaemia and other) were found in 77 patients (40.5%). [ML1] Overall survival of the macrocytic population was 57 months (95% CI ) after entry into the study. Patients diagnosed with nutrient deficiency displayed a shorter survival (41.8 months, 95% CI , p = 0.024) and patients with an unknown cause displayed a longer survival (68.6 months, 95% CI, , p = 0.042) than the residual cohort. Conclusion: The causes of macrocytic anaemia are diverse and include both classic and alternative causes. Therefore we consider a broad diagnostic work-up necessary to elucidate the underlying cause. O16 Cardiac involvement in eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss syndrome) and granulomatosis with polyangiitis (GPA; Wegener s granulomatosis) patients M.R. Hazebroek, M.J. Kemna, S. Schalla, S. Sanders-van Wijk, S.C. Gerretsen, R. Dennert, H.P. Brunner-la Rocca, P. van Paassen, J.W. Cohen Tervaert, S. Heymans Maastricht University Medical Centre, Department of Cardiology, P. Debyelaan 25, 6229 HX MAASTRICHT, the Netherlands, mark.hazebroek@mumc.nl Introduction: Cardiac involvement in ANCA-associated vasculitides (AAV), i.e. eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss syndrome) and granulomatosis with polyangiitis (GPA; Wegener s granulomatosis) patients is an important predictor of mortality, but its prevalence remains unclear. Aim of the study: To investigate the prevalence of cardiac involvement in a large population of ambulatory EGPA and GPA patients in sustained remission. Material and Methods: To address the cardiac involvement in a phenotypical well characterized and large prospective cohort study of EGPA and GPA patients, we included 18

20 50 consecutive EGPA patients (aged 59 ± 11 years) and 41 consecutive GPA patients (aged 60 ± 11 years) in sustained remission and without previous in-depth cardiac screening. The latter comprised clinical evaluation, electrocardiography (ECG), 24-hour Holter registration, echocardiography and cardiac magnetic resonance imaging (CMR). Control subjects included fifty age- and sex-matched subjects, randomly selected from a population study undergoing ECG and echocardiography. Cardiac involvement characterized by major ECG abnormalities, pericardial effusion, (peri)myocarditis, focal or diffuse myocardial fibrosis and/or edema, wall motion abnormalities, valvular regurgitation grade 3, pulmonary hypertension (spap > 45 mmhg), diastolic dysfunction grade 2, or significant coronary stenosi(e)s 70%. Results: Age, sex and cardiovascular risk factors were similar between the EGPA, GPA and control group. ECG and echocardiography demonstrated cardiac involvement in 54% EGPA and 34% GPA patients as compared to 8% in controls (both p < 0.002). Adding CMR as diagnostic modality increased the prevalence of cardiac involvement to 66% in EGPA and 61% in GPA patients. CMR detected cardiac involvement in all AAV patients demonstrating ECG and/or echocardiographic involvement. In patients without such abnormalities, CMR additionally demonstrated cardiac involvement in over 30% of EGPA and 41% of GPA. In 52% EGPA and 44% GPA patients without cardiac symptoms and with normal ECG, cardiac involvement was present. With respect to ANCA detection, cardiac involvement was equally frequent in ANCA negative versus ANCA positive patients (71% (24/34) ANCA- versus 56% (9/16) ANCA+ EGPA patients, p = 0.53; 0% (0/1) ANCA- versus 63% (25/40) ANCA+ GPA patients). Endomyocardial biopsy performed in 11 EGPA and 2 GPA patients demonstrated chronic or acute myocarditis in all but one patient. Conclusion: This large prospective and well characterized cohort reveals an up to 66% cardiac involvement in AAV patients in remission, even in the absence of cardiac symptoms or ECG abnormalities. Therefore, the use of imaging techniques, especially CMR, is recommended for cardiac evaluation of EGPA and GPA patients. x O17 Persisting arthralgias after a stay in Brazil: an unfamiliar infectious risk for visitors to the 2014 FIFA World Cup C.A.D. Slegers,M.Keuter,A.V.vanderVen,Q.deMast Radboud University Medical Centre, Department of Internal Medicine, Postbus 9101, 6500 HB NIJMEGEN, the Netherlands, claire.slegers@radboudumc.nl In de gedrukte versie van dit abstractboek is een onjuiste inhoud vermeld. De juiste versie treft u als aparte bijlage aan. O18 A comparison of the diagnostic value of MRI and FDG-PET/CT in suspected spondylodiscitis I.J.E. Kouijzer 1, C. Smids 2, F.J. Vos 3, T. Sprong 4, A.J.F. Hosman 2, W.J.G. Oyen 2, C.P. Bleeker-Rovers 2 1 Jeroen Bosch Hospital, Department of Internal Medicine, Henri Dunantstraat 1, 5223 GZ DEN BOSCH, the Netherlands, ilsekouijzer@gmail.com, 2 Radboud University Medical Centre, NIJMEGEN, the Netherlands, 3 St Maartens Clinic, NIJMEGEN, the Netherlands, 4 Canisius- Wilhelmina Hospital, NIJMEGEN, the Netherlands 19