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A CHALLENGE TO AN INTERNIST: TWO PREGNANCIES IN A NONCOMPLIANT PATIENT WITH A MILD MENTAL RETARDATION DUE TO PHENYLKETONURIA
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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
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-