PARADOXICAL RESPONSE IN THE TREATMENT OF TUBERCULOSIS AFTER DISCONTINUATION OF ANTI TNF IN PATIENTS WITH INFLAMMATORY DISEASES: A CASE-SERIES

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Abstracts from 10th Congress of the European Federation of Internal Medicine/European Journal of Internal Medicine 22S (2011) S1–S112

Patient II A fifty-nine years old Caucasian man with mild diabetes, hypertension and chronic renal insufficiency had overnight fasting hypertriglyceridemia of 7.12 mmol/L (630 mg/dL). Bezafibrate 400 mg/day was started. Triglycerides decreased to 4.23mmol/L (374mg/dL). Serum creatinine increased from 189 Pmol/l (2.14 mg/dL) to 261 Pmol/L (2.95mg/dL) after treatment with benzafibrate. This also was reversible after stopping Bezafibrate. Discussion: Pathofysiology of renal insufficiency due to fibrates remains to be illuminated. Rhabdomyolysis was excluded by normal plasma creatine kinase levels in both cases. Another explanation could be a change in renal hemodynamics with a decrease in glomerular filtration due to a critical balance in afferent glomerulus. Another pathway could be an increased creatinine production in combination with a decline in tubular secretion of creatinine. Conclusion: Fibrate induced renal insufficiency is important to prevent. In patients with chronic renal insufficiency with a glomerular filtration rate below 60ml/min or serum creatinine level above 135 Pmol/l fibrate therapy is contraindicated. CREATININE-BASED FORMULA (MDRD) VERSUS CISTATIN C-BASED FORMULA (SIMPLE CYSTATIN C FORMULA) FOR ESTIMATION OF GFR IN PATIENTS WITH CHRONIC KIDNEY DISEASE Sebastjan Bevc, Radovan Hojs, Robert Ekart. Clinic of Internal Medicine, Dept. of Nephrology, University Medical Center, Maribor, Slovenia Introduction: Serum creatinine (Screa) and Screa-based formulas are the most commonly used markers to estimate glomerular filtration rate (GFR). Recently, serum cystatin C (Scys)-based formula was proposed as new GFR marker. The aim of our study was to compare Modification of Diet in renal Disease Study (MDRD) formula and simple Scys formula (100/ Scys) against 51CrEDTA clearance in patients with chronic kidney disease (CKD). Methods: 617 adult Caucasians patients (266 women, 351 men; mean age 57.6 years) were included. In each patient 51CrEDTA clearance, Screa (IDMS traceable method) and Scys (immunonephelometric method) were determined. GFR was calculated using MDRD and simple Scys formulas. Results: The mean 51CrEDTA clearance was 47.9±34.7 ml/min/1.73m2, mean Screa 265.1±195 mcg/l, mean Scys 2.65±1.6 mg/l. Statistically significant correlations between 51CrEDTA clearance and both formulas were found (P<0.0001). In the ROC curve analysis (cut-off for GFR 60 ml/min/1.73m2) no significant difference of diagnostic accuracy between MDRD formula and simple Scys formula was found (P=0.478). Bland and Altman analysis for the same cut-off value showed that MDRD formula (bias: -29 ml/min/1.73m2) underestimated and simple Scys formula (bias: 2.7 ml/min/1.73m2) overestimated measured GFR. Analysis of ability to correctly predict GFR below and above 60 ml/min/1.73m2 showed higher prediction for simple Scys formula (91.6%) compare to MDRD formula (84.3%) (P<0.0005). Conclusions: Our results indicate that simple Scys formula is reliable marker of GFR in patients with CKD and comparable to MDRD formula. NODULAR PULMONARY AMYLOIDOSIS Charalampos Birbilis, Basilis Basilopoulos, Emanouil Passas, Christos Papadas, Ioanna Stavraka, Dimitris Katrinis, Spyros Kloudas, Periklis Aggelis, Aggelos Pefanis. Department Of Internal Medicine, “Sotiria” General Hospital Background: Localized pulmonary amyloidosis is defined as amyloid deposition isolated to the respiratory tract, without evidence of systemic amyloidosis. It is uncommon and occurs in three types: tracheobronchial, parenchymal (single or multiple nodules), and diffuse (senile). Nodular pulmonary amyloidosis is usually found incidentally on chest radiographs in asymptomatic adults and has a benign course. Case Report: A 66-year-old woman underwent chest CT scan after a car accident she had had. The CT showed a 3-cm calcified nodule at the left upper lobe and a smaller 1-cm at the right middle lobe. She was asymptomatic and her physical exam, laboratory workup and past medical history were unremarkable. Bronchoscopy showed no abnormalities, and brushings were negative for malignancy. A CT-guided needle biopsy of the left upper lobe lesion revealed necrotic material and the suspicion of granulomatous disease. PET scan also, raised the possibility of granulomatous disease. Thereafter, thoracotomy and resection of the left nodule were performed. The histo-

pathological examination revealed multinucleated giant cells and amorphous eosinophilic material. Congo red stain exhibited apple-green birefringence under polarized microscopy, consistent with amyloidosis. Tests for multiple myeloma were performed and proved negative (i.e. negative immunoelectrophoresis, absence of Bence-Jones proteins in urine). Therefore, a final diagnosis of nodular pulmonary amyloidosis was made. Six months later she remains well, without evidence of recurrence or systematic disease. Conclusion: There are no disease-specific radiographic characteristics for nodular pulmonary amyloidosis. The differential diagnosis includes but is not limited to bronchogenic carcinoma. Diagnosis relies on biopsy. Treatment is by surgical excision. A CHALLENGE TO AN INTERNIST: TWO PREGNANCIES IN A NONCOMPLIANT PATIENT WITH A MILD MENTAL RETARDATION DUE TO PHENYLKETONURIA Lenka Bosanska1, Karin Loschen1, Nikolaus Tiling1, Elke Windt2, Eberhard Moench1, Ursula Ploeckinger1. 1Centre of Excellence for Rare Metabolic Diseases, Interdisziplinäres Stoffwechsel Centrum; 2Department of Pediatrics, both Charité Universitaetsmedizin Berlin, Berlin, Germany We report on a 29-ys old woman with classic phenylketonuria (IVS12-1G>A homozygosity), an inborn error in aminoacid metabolism. In spite of early treatment with dietary phenylalanine restriction and tyrosine supplementation, the patient developed mild mental retardation due to non-compliance with the prescribed diet. At our Centre all female patients receive routine and repeated counselling concerning possible conception and pregnancy. Her first unplanned pregnancy (at 21-ys) occurred in a situation of insufficient metabolic control, and thus posed a high risk of phenylalanine embryopathy (microcephaly, congenital heart defect, low birth weight). During the first trimester her phenylalanine blood concentrations were raised (range 6,9-12,2 mg/dl; recommended 0,7-4,0 mg/dl) resulting in psychomotoric retardation and behavioural problems in the child. During the second unplanned pregnancy (at 29-ys) her phenylalanin blood concentrations were raised due to dietary non-compliance almost throughout the whole pregnancy (range 2,6-10,8 mg/dl, median 6,9 mg/dl). Unfortunately all efforts to improve adherence to therapy as intensive dietary counselling, hospitalisation, frequent communication with the patient, her legal guardian, gynaecologist, social worker and lawyers were ineffective. The full-term male newborn had a low birth weight (2730 g) indicating phenylalanin embryopathy. In addition, classical phenylketonuria was diagnosed in the child. More and more women with phenylketonuria and early onset of therapy reach the childbearing age. With tight metabolic control, at conception and during pregnancy, pregnancy-loss or severe phenylalanine embryopathy can be avoided. However, pregnancy in non-compliant patients with mild mental retardation may, despite all efforts, fail to achieve a save outcome for the child. PARADOXICAL RESPONSE IN THE TREATMENT OF TUBERCULOSIS AFTER DISCONTINUATION OF ANTI TNF IN PATIENTS WITH INFLAMMATORY DISEASES: A CASE-SERIES Claire Rivoisy1, Nathalie Nicolas2, D. Salmon3, D. Sereni4, G. Carcelain5, X. Mariette6, F. Tubach2, Anne Bourgarit7. 1Infectious disease Department, Necker Hospital, APHP, Paris, France; 2Clinical Research Unit, Bichat Hospital, APHP, Paris, France; 3Infectious Disease, Cochin Hospital, APHP, Paris, France; 4 Internal Medicine, Saint-Louis hospital, Paris, APHP, Université Paris 7, France; 5Immunology, Pitié-Salpétrière Hopital, Paris, APHP, UPMC , France; 6 Rheumatology, Bicetre hospital, Paris APHP, Paris 11, France; 7Internal Medicine, Hautepierre Hospital, HUS Strasbourg, UDS, France Background: Paradoxical worsening of tuberculosis is known since the use of efficient antibiotics and well describe under HAART in HIV-infected-patients as the Immune Reconstitution Syndrome. Methods: We report cases of paradoxical reaction (PR) of tuberculosis in patients treated with anti-TNFD from the French national register RATIO and a national case call. Results: Fourteen patients presented a PR of their anti-TNF-induced tuberculosis after antibiotic initiation. Median age of 55,5 years old (27-87), they received adalimumab (5), infliximab (7), certolizumab (1), etanercept (1) for rheumatoid arthritis (4), psoriasis (2), ankylosing spondylarthritis (5) and horton’s disease (1). Mean duration of the inflammatory disease and anti-TNF treatment before tuberculosis diagnosis was respectively 8 years (4 months-

Abstracts from 10th Congress of the European Federation of Internal Medicine/European Journal of Internal Medicine 22S (2011) S1–S112 29 years) and 11 months (7 weeks-64 months). Tuberculosis was disseminated or extrapulmonary for twelve patients. All discontinued anti TNF treatment. A PR was diagnosed in a mean delay of thirteen weeks (0 week-48 weeks) after antibiotics introduction. Manifestations were fever, lymph nodes swelling (7) with fistulas (3), lung cavitations (2), cold abscess (1), pericarditis (1), cerebral vasculitis (1) and cerebral and medullar tuberculoma (2). In eight patients, underlying inflammatory disease reactivates. All recovered but required steroids dose increase (9), rituximab initiation (1), new antituberculous treatment (2) or surgery (4). Steroids and antituberculous treatment were maintained with a mean duration of 11 months (3-14) and 16 months (8-36) respectively. Conclusion: Paradoxical worsening of anti-TNF induced-tuberculosis after biotherapy withdrawal is a an impressive and sometime difficult clinical diagnosis leading to numerous that should be early recognized since therapy requires anti-TB and anti-inflammatory treatment maintain. TOLOSA HUNT SYNDROME Diana Briosa E Gala, Joao Santos, Diana Moura, Pureza Dias, Jose Leite, Celio Fernandes. Internal Medecine Department, Hospital Santo André, Leiria, Portugal Tolosa hunt syndrome consists of retro or unilateral periorbital pain associated with ophtalmoparesis of the III, IV or VI cranial nerves with pain relief after (beginning) corticotherapy. It is a diagnosis of exclusion. The authors present the following clinical case: a 56 year old woman with hypertension, depressive syndrome, right facial nerve paralysis three years ago and left facial nerve paralysis two years ago. The patient was observed in the emergency room due to right periorbital and supracilliar pain associated with ipsilateral diplopia and ptosis with four days of evolution. The neurological exam showed incomplete paralysis of the III right cranial nerve: ptosis, medial rectus palsy, left looking diplopia with pupil constriction and dilation preserved. Magnetic resonance imaging identified asymmetric cavernous sinus, with right cavernous sinus signal enhancement after contrast, traducing an inflammatory process. The blood and CSF tests were normal. Treatment with 1mg/Kg/day of prednisolone was initiated with pain remission after 48 hours. After six months the magnetic resonance imaging showed resolution of the inflammatory process. After analytical and imagiological studies, the excellent response to the beginning of corticotherapy and exclusion of other differential diagnosis, Tolosa Hunt syndrome diagnosis was established. METABOLIC SYNDROME AND CARDIOVASCULAR RISK IN HOSPITALISED PATIENTS Magdalini Bristianou1, Charalambos Panou1, Ioannis Chatzidakis2, Vaina Tsiligrou1, Anna Tsiara1, Panayiotis Tolis1, Aspasia Kouloukoura1, Leonidas Lanaras1. 1Lamia General Hospital; 2Dromokaiteion Psychiatric Hospital Aim: The assessment of the metabolic syndrome (MS) frequency, the characteristics and its relationship to the smoking habit as well as the cardiovascular events in hospitalized patients. Materials & Methods: In this study participated 287 patients (males: 53.56%), aged 21-87 which had been hospitalized in our clinic. The following data were recorded: smoking history, cardiovascular disease history, waist perimeter, arterial blood pressure, fasting blood glucose, triglycerides, total cholesterol and HDL. Results: The MS frequency was 41.5% and the age of the people with MS was >46 years old. There was no difference between sexes. The smoking habit frequency was the same between the MS patients and the no-MS patients. The patients with MS presented with higher fasting glucose, systolic blood pressure and total cholesterol (p=0.0001); the recorded parameters of people with MS were: increased blood pressure (88.4%), increased waist perimeter (68.1%), increased triglycerides (38.1%), decreased HDL (75.8%) and increased fasting blood glucose (81.4%). The coronary heart disease and cerebrovascular accident history were associated to the presence of diabetes mellitus, age, dyslipidemia and elevated blood pressure. An increased frequency of cardiovascular complications was also noted to the smokers without MS. Conclusions: The metabolic syndrome is frequent at hospitalized patients; it depends on the age and is associated to the frequency of cardiovascular com-

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plications. The smoking cessation and the immediate management of the MS risk factors may contribute to the decrease of cardiovascular complications. TUBERCULOUS HEPATIC ABSCESS – CLINICAL CASE Clara Brito, Miriam Magalhães, Ana Araújo, Pedro Soares, Diana Fernandes, Luísa Teixeira, Marta Gôja, Nuno Sousa, Alcina Ponte, Renato Saraiva. Santo André Hospital E.P.E. - Medicine 1 department Background: Tuberculosis is an infection caused by Mycobacterium tuberculosis that frequently affects lungs, although any other organ can be stricken. About 20% to 30% of world wide population is infected by mycobacterium, of witch prevalence is much high in developing countries. The incidence of extra pulmonary infection is being raised especially with the increase of cases of human immunodeficiency virus (VIH). The most frequent affected, locations are lymph node, pleura, gastrointestinal tract, osteo-articular system, meninges, peritoneum and pericardium. Methods: The authors propose to present a case of a 73 years old patient with no relevant background, who went to the emergency department with complaints of malaise, high fever and abdominal pain located on the right hypochondrium. The patient referred as well significant weight loss in the last month. Physical exam revealed icteric sclerotic and painful hepatomegalia. The abdominal ultrasound revealed an hepatic heterogeneity lesion and abdominal tomography confirmed an abscess in the left lobe. It was made abscess drainage and parenquima biopsies were taken. The direct appreciation of the exudates did not revealed bacteria and anatomopathological study suggested an inflammatory pseudotumor. Results: For abscess relapse, a new drainage was made and culture was positive for Mycobacterium tuberculosis. Conclusion: The authors intend to present this case to be an infrequent form of extra pulmonary tuberculosis, especially in negative VIH patients. THE SIGNIFICANCE OF INSULIN SECRETION AND RESISTANCE ON THE OCCURRENCE OF CHD IN PREDIABETES TYPE 2 Milena Brkic. Clinic for endocrinology, diabetes and metabolism, Banja Luka Objectives: It has been proven that the occurrence of type 2 DM is associated with abnormalities in insulin secretion and the relationship of sensitivity to the development of coronary heart disease(CHD ). In type 2 DM have an important role of metabolic risk factors: elevated insulinemia, IR, dyslipidemia, obesity. This risk is already present in patients with prediabetes. Goal: Evaluation of insulin secretion and resistance in type 2 prediabetes (IGT) and significance levels insulin the occurrence and intensity of CD. Methods: The study included 120 participants: a) IGT with CHD (n = 30), b) IGT without CHD (n = 30), c) CHD without IGT (n = 30), healthy (n = 30). In each group we performed 75 gr glucose tolerance test (OGTT), we measured glucose level and insulin level to calculate parameters IR (HOMA index) and insulin secretion (insulin index), lipid status, glycogen regulation, obesity and blood pressure parameters.For statistic analysis we used student T and X2 test, correlation coefficient and uni and multivariant logistic regression analysis. Results: The group with IGT with and without IBS, the highest insulin level and calculated HOMA-IR was after 120 minutes, however the lowest insulin index. In subjects with IGT associated with CHD, the most pronounced was insulinemia 120 min after, even 7x more, as calculated by HOMA-IR, while the lowest insulin index. Applying logistic regression analysis, we found that glucose has a significant effect on the expression of CHD in patients with IGT. There was a significant correlation HgbA1C and IR. Conclusion: Significantly decreased sensitivity of peripheral tissue to insulin and significant IR in patients with IGT with IBS points that IR has an important role in appearance of IBS in pre-diabetes. Keywords: insulin resistance, prediabetes, ischemic heart disease FUNGAL PROSTHETIC VALVE ENDOCARDITIS AS A CAUSE OF ISCHEMIC STROKE Ana Luísa Broa, Elisabete Gavancho, Rita Nortadas, Henrique Santos. Garcia de Orta Hospital, Almada, Portugal Background: Fungi are a rare cause of endocarditis representing 1,3-6% of all cases but associated with a high mortality rate. The most associated species