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Evolution of disease phenotype in adult and pediatric onset Crohn's disease in a population-based cohort

World Journal of Gastroenterology 2013年第14期19卷 2217-2226页

作者： Barbara Dorottya Lovasz Laszlo Lakatos Agnes Horvath Istvan Szita Tunde Pandur Michael Mandel Zsuzsanna Vegh Petra Anna Golovics Gabor Mester Mihaly Balogh Csaba Molnar erzsebet Komaromi Lajos Sandor Kiss Peter Laszlo Lakatos First Department of Medicine Semmelweis University Department of Medicine Csolnoky F Province Hospital Department of Pediatrics Csolnoky F Province Hospital Department of Medicine Grof Eszterhazy Hospital Department of Infectious Diseases Magyar Imre Hospital Department of Gastroenterology Municipal hospital

AIM:To investigate the evolution of disease phenotypein adult and pediatric onset Crohn's disease(CD) populations,diagnosed between 1977 and ***:Data of 506 incident CD patients were analyzed(age at diagnosis:28.5 years,interquartile range:22-38 years).Both in-and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database,which included incident patients diagnosed between January 1,1977 and December 31,2008 in adult and pediatric onset CD *** phenotype according to the Montreal classification and long-term disease course was analysed according to the age at onset in time-dependent univariate and multivariate ***:Among this population-based cohort,seventy-four(12.8%) pediatric-onset CD patients were identified(diagnosed ≤ 17 years of age).There was no significant difference in the distribution of disease behavior between pediatric(B1:62%,B2:15%,B3:23%) and adult-onset CD patients(B1:56%,B2:21%,B3:23%) at diagnosis,or during ***,the probability of developing complicated disease behaviour was 49.7% and 61.3% in the pediatric and 55.1% and 62.4% in the adult onset patients after 5-and 10-years of ***,time to change in disease behaviour from non stricturing,non penetrating(B1) to complicated,stricturing or penetrating(B2/B3) disease was not significantly different between pediatric and adult onset CD in a Kaplan-Meier *** year of diagnosis(P = 0.04),ileal location(P < 0.001),perianal disease(P < 0.001),smoking(P = 0.038) and need for steroids(P < 0.001) were associated with presence of,or progression to,complicated disease behavior at diagnosis and during follow-up.A change in disease location was observed in 8.9% of patients and it was associated with smoking status(P = 0.01),but not with age at ***:Long-term evolution of disease behavior was not different in pediatric-a

关键词： Crohn’s disease Age at diagnosis Disease behavior Disease course

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Is early limited surgery associated with a more benign disease course in Crohn's disease?

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World Journal of Gastroenterology 2013年第43期19卷 7701-7710页

作者： Petra Anna Golovics Laszlo Lakatos Attila Nagy Tunde Pandur Istvan Szita Mihaly Balogh Csaba Molnar erzsebet Komaromi Barbara Dorottya Lovasz Michael Mandel Gabor Veres Lajos S Kiss Zsuzsanna Vegh Peter Laszlo Lakatos First Department of Medicine Semmelweis UniversityH-1083 BudapestHungary Department of Medicine Csolnoky F Province HospitalH-8200 VeszpremHungary Department of Surgery Csolnoky F Province HospitalH-8200 VeszpremHungary Department of Medicine Grof Eszterhazy HospitalH-8500 PapaHungary Department of Infectious Diseases Magyar Imre HospitalH-8400 AjkaHungary Department of Gastroenterology Municipal HospitalH-8100 VarpalotaHungary First Department of Pediatrics Semmelweis UniversityH-1083 BudapestHungary

AIM:To analyze the difference in disease course and need for surgery in patients with Crohn’s disease(CD).METHODS:Data of 506 patients with incident CD were analyzed(age at diagnosis:31.5±13.8 years).Both hospital and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database,which includes incident CD patients diagnosed between January 1,1977 and December 31,***-up data were collected until December 31,*** patients included had at least 1year of follow-up *** with indeterminate colitis at diagnosis were excluded from the ***:Overall,73 patients(14.4%)required resective surgery within 1 year of *** exposure and need for biological therapy were lower in patients with early limited surgery(P<0.001 and P=0.09).In addition,surgery rates during follow-up in patients with and without early surgery differed significantly after matching on propensity scores(P<0.001,HR=0.23).The need for reoperation was also lower in patients with early limited resective surgery(P=0.038,HR=0.42)in a Kaplan-Meier and multivariate Cox regression(P=0.04)***,this advantage was not observed after matching on propensity scores(PLogrank=0.656,PBreslow=0.498).CONCLUSION:Long-term surgery rates and overall exposure to steroids and biological agents were lower in patients with early limited resective surgery,but reoperation rates did not differ.

关键词： Crohn’s disease Early surgery Disease course Disease behavior Treatment strategy

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Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn's disease: Phenotype-genotype correlations

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World Journal of Gastroenterology 2005年第10期11卷 1489-1495页

作者： Peter Laszlo Lakatos Laszlo Lakatos Ferenc Szalay Claudia Willheim-Polli Christoph (O|¨)sterreicher Zsolt Tulassay Tamas Molnar Walter Reinisch Janos Papp Gyula Mozsik Hungarian IBD Study Group Peter Ferenci 1st Department of Medicine Laszlo Lakatos Department of Internal Medicine 4 2nd Department of Medicine Semmelweis University 2nd Department of MedicineSemmelweis UniversityBudapest:Laszlo PronaiAnnamaria NemethPal Miheller erzsebet hospital 1st Department of MedicineBudapest: Agota KovacsLaszlo Bene Szent Janos hospital 1st Department of Medicine:Gyorgy Szekely University of Pecs 1st Department of MedicinePecs:Beata Gasztonyi University of Szeged 1st Department of MedicineSzeged:Ferenc NagyJanos Lonovics Semmelweis hospital 1st Department of MedicineMiskolc:Laszlo Ujszaszy University of Debrecen 2nd Department of MedicineDebrecen:Istvan AltorjaiKaroly Palatka Kenezi Gy. County hospital 2nd Department of MedicineDebrecen: Gyula G. Kiss County hospital 2nd Department of MedicineZalaegerszeg Ferenc Tarnok Markusovszky Hospital2nd Department of MedicineSzombathely:Zoltan Dobronte Csolnoky F. County hospital 1st Department of MedicineVeszprem:Zsuzsanna ErdelyiTunde PandurGabor Mester

AIM: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD. METHODS: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 healthy subjects were included. DNA was screened for possible NOD2/CARD15 mutations by denaturing high-performance liquid chromatography (confirmed by direct sequencing). TLR4 D299G was tested by PCR-RFLP. RESULTS: NOD2/CARD15 mutations were found in 185 patients (35.1%) and in 33 controls (16.5%,P<0.0001). SNP8/R702W (10.8% vs 6%, P= 0.02), SNP13/3020insC (19.4% vs 5%, P<0.0001) and exon4 R703C (2.1% vs 0%, P= 0.02) mutations were more frequent in CD, while the frequency of SNP12/G908R was not increased. The frequency of TLR4 D299G was not different (CD: 9.9% vs controls: 12.0%). Variant NOD2/CARD15 allele was associated with an increased risk for CD (ORhet=1.71, 95%CI=1.12-2.6, P= 0.0001, ORtwo-risk alleles = 25.2, 95%CI =4.37- ,P<0.0001), early disease onset (carrier: 26.4 years vs non-carrier: 29.8 years, P=0.0006), ileal disease (81.9% (?) 69.5%, OR = 1.99, 95%CI = 1.29-3.08, P= 0.02, presence of NOD2/CARD15 and TLR4: 86.7% vs 64.8%), stricturing behavior (OR = 1.69,95%CI = 1.13-2.55, P= 0.026) and increased need for resection (OR=1.71, 95%CI: 1.13-2.62, P= 0.01), but not with duration, extra-intestinal manifestations, familial disease or smoking. TLR4 exhibited a modifier effect: age of onset in wt/TLR4 D299G carriers: 27.4 years vs NOD2mut/TLR D299G: 23 years (P = 0.06), in NOD2mut/wt: 26.7 years. CONCLUSION: These results confirm that variant NOD2/ CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease, stricturing disease behavior in Hungarian CD patients. In contrast, although the frequency of TLR4 D299G polymorphism was not different from controls, NOD2/TLR4 mutation carriers tended to present at earlier age.

关键词： Crohn's disease NOD2 CARD15 TLR4 Extraintestinal manifestation Phenotype

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