Cloé Charpentier

Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study

Data on the natural history of elderly-onset inflammatory bowel disease (IBD) are scarce. Methods In a French population-based cohort we identified 841 IBD patients >60 years of age at diagnosis from 1988 to 2006, including 367 Crohns disease (CD) and 472 ulcerative colitis (UC). Results Median age at diagnosis was similar for CD (70 years (IQR: 65–76)) and UC (69 years (64–74)). Median follow-up was 6 years (2–11) for both diseases. At diagnosis, in CD, pure colonic disease (65%) and inflammatory behaviour (78%) were the most frequent phenotype. At maximal follow-up digestive extension and complicated behaviour occurred in 8% and 9%, respectively. In UC, 29% of patients had proctitis, 45% left-sided and 26% extensive colitis without extension during follow-up in 84%. In CD cumulative probabilities of receiving corticosteroids (CSs), immunosuppressants (ISs) and anti tumor necrosis factor therapy were respectively 47%, 27% and 9% at 10 years. In UC cumulative probabilities of receiving CS and IS were 40% and 15%, respectively at 10 years. Cumulative probabilities of surgery at 1 year and 10 years were 18% and 32%, respectively in CD and 4% and 8%, respectively in UC. In CD complicated behaviour at diagnosis (HR: 2.6; 95% CI 1.5 to 4.6) was associated with an increased risk for surgery while CS was associated with a decreased risk (HR: 0.5; 0.3 to 0.8). In UC CS was associated with an increased risk (HR: 2.2; 1.1 to 4.6) for colectomy. Conclusions Clinical course is mild in elderly-onset IBD patients. This information would need to be taken into account by physicians when therapeutic strategies are established.

Adjunct therapy of n-3 fatty acids to 5-ASA ameliorates inflammatory score and decreases NF-κB in rats with TNBS-induced colitis

5-aminosalicylic acid (5-ASA) is widely used for the treatment of inflammatory bowel disease (IBD). Recent studies have evaluated the potential of nutritional intervention as adjunct therapy to 5-ASA in IBD. N-3 polyunsaturated fatty acids (PUFA) have shown potent anti-inflammatory properties in gut inflammation. Therefore, we aimed to evaluate the efficacy of the dual therapy (n-3 PUFA plus 5-ASA) in rats with 2, 4, 6-trinitrobenzen sulfonic acid (TNBS)-induced colitis. Colitis was induced by intrarectal injection of TNBS while control rats received the vehicle. Rats received by gavage a fish oil-rich formula (n-3 groups) or an isocaloric and isolipidic oil formula supplemented with 5-ASA for 14 days. A dose response of 5-ASA (5-75 mg. suppression mg kg(-1) d(-1)) was tested. Colitis was evaluated and several inflammatory markers were quantified in the colon. COX-2 expression (P<.05) and pro-inflammatory eicosanoids production of prostaglandin E2 (P<.001) and leukotriene B4 (P<.001) were significantly inhibited by n-3 PUFA or 5-ASA therapy. 5-ASA also reduces mRNA levels of tumor necrosis factor α (P<.05). n-3 PUFA or 5-ASA significantly inhibits nuclear factor κB (NF-κB) activation (P<.01 and P<.05, respectively). The dual therapy n-3 PUFA plus 5-ASA also inhibited inflammatory response by lowering NF-κB activation (P<.01) or inducing peroxisome proliferator-activated receptor-γ (PPARγ) expression (P<.05). These results indicate that 5-ASA plus n-3 PUFAs are more effective than a higher dose of 5-ASA alone to reduce NF-κB activation and to induce PPARγ. By contrast, the dual therapy did not improve the effects of individual treatments on eicosanoids or cytokine production. Use of n-3 PUFA in addition to 5-ASA may reduce dose of standard therapy.

Magnetic resonance colonography in rats with TNBS-induced colitis: a feasibility and validation study

Background: Magnetic resonance colonography (MRC) has been recently developed to assess bowel inflammation in inflammatory bowel disease (IBD) patients. Evaluating animal models of inflammation with MRC may be important in new drug‐screening processes. The aim of this study was to assess the feasibility of MRC in colitic rats and confront it with model characteristics. Methods: Colitis was induced by rectal injection of trinitrobenzene‐sulfonic acid (TNBS) in 13 rats while six rats received the vehicle. MRC was performed at day 2. Colon inflammation and production of inflammatory mediators were evaluated. Image quality was assessed by wall and motion artifacts. MRC criteria were bowel wall thickness, wall signal intensity on T2‐weighted (T2w) and T1w images, the appearance of a target sign pattern, and irregular patterns of mucosal surface. Results: MRC quality was good or excellent in 16/21 examinations with no difference between groups. Colitis rats were significantly different from controls in terms of wall thickness (P = 0.004), the appearance of a target sign pattern (P = 0.02), irregular patterns of mucosal surface (P = 0.01), and hyperintensity on T1w images (P = 0.03). All MRC criteria except maximal bowel wall thickness were associated with colon weight:length ratio and inflammatory biomarkers (all P < 0.05). Minimal bowel wall thickness and wall signal intensity on T2w images were associated with histological score (P < 0.05). Conclusions: MRC is feasible and reliable in rats with TNBS‐induced colitis. MRC criteria including colon wall thickness, wall signal intensity on T2w images, hyperintensity in T1w sequence, and the appearance of a target sign pattern may be potential targets for new IBD drugs. (Inflamm Bowel Dis 2012)

Natural History of Crohn's Disease in Elderly Patients Diagnosed Over the Age of 70 Years: A Population-Based Study.

Introduction:Elderly onset (>60 yrs at diagnosis) Crohns disease (CD) seems to be associated with a better outcome than when diagnosed earlier in life. The aim of this study was to compare the natural history of patients with CD older than 70 years at diagnosis with that of elderly patients diagnosed between 60 and 70 years in the EPIMAD population-based registry. Methods:Three hundred seventy patients with elderly onset CD diagnosed between January 1988 and December 2006 were identified. Among them, 188 (63%) were older than 70 years at diagnosis (≥70 yrs). Clinical presentation, disease location, and behavior at diagnosis and also natural history, surgery needs, and drug exposure were recorded, with a median follow-up of 4.5 years (1.1; 8.3) in CD diagnosed after 70 years and of 7.8 years (3.3; 12.1) in CD diagnosed between 60 and 70 years, respectively. Results:CD incidence in elderly patients diagnosed ≥70 years was 2.3/100,000 inhabitants, compared with 2.6/100,000 in elderly patients diagnosed below the age of 70 (60–69 yrs). The proportion of males was lower in patients ≥70 years than in patients aged 60 to 69 (31% versus 45%, P = 0.006). Clinical presentation at diagnosis was similar in both groups. Pure colonic location (L2) was more frequent among patients >70 years both at diagnosis (73% versus 57%, P = 0.004) and maximal follow-up (70% versus 47%, P < 0.0001). Disease extension (from L1 or L2 to L3) was not significantly different among patients >70 years and patients aged 60 to 69 years (hazard ratio [HR] = 2.0 [0.9; 4.5] for 60 to 69 yrs, P = 0.09). The most frequent behavior in the 2 groups was inflammatory, both at diagnosis (75% versus 80%, P = 0.43) and at maximal follow-up (69% versus 70%, P = 0.55). There was no significant difference in patients >70 years compared with patients aged 60 to 69 years regarding treatment with 5-aminosalicylic acid (P = 0.72), oral corticosteroids (P = 0.83), and anti–tumor necrosis factor therapies (P = 0.37). However, the use of immunosuppressants was significantly less frequent in patients >70 years (HR = 2.1 [1.3; 3.5] for 60 to 69 yrs, P = 0.003). Risk of surgery was similar in both groups (P = 0.72). Extraintestinal manifestations at diagnosis were significantly associated with an evolution to complicated behavior (HR = 2.7 [1.0; 7.0], P = 0.045), immunosuppressant treatment (HR = 2.9 [1.4; 6.0], P = 0.006), and corticosteroid use (HR = 3.3 [1.8; 6.1], P < 0.0001). Conclusions:The natural history of CD in elderly patients diagnosed over the age of 70 is mild with low disease extension and complicated behavior. This needs to be taken into account when establishing therapeutic strategies.

Inflammatory Pseudotumor of the Cerebellum in a Patient with Crohn's Disease

BACKGROUND Inflammatory pseudotumors are ubiquitous lesions characterized by a polymorphous inflammatory infiltrate containing plasma cells and lymphocytes. In the central nervous system, this pathological condition is rare and the association with Crohns disease has never been described. CASE DESCRIPTION A 31-year-old woman with a history of Crohns disease was referred to our department for progressive headaches and nausea. Neurological examination was normal. Magnetic resonance imaging showed an irregular heterogeneous enhanced mass infiltrating the left cerebellar hemisphere. Total resection was performed and pathological examination led to the conclusion of an inflammatory pseudotumor. CONCLUSION To our knowledge, this case is the first describing an intra-cerebral inflammatory pseudotumor associated with an inflammatory bowel disease. The diagnosis of an extradigestive location of Crohns disease was excluded by pathological examination. Although the precise cause of this association remains unknown, it could be hypothesized that the intra-cranial lesion could be the result of the immunosuppressive therapy given for Crohns disease, or, more likely, could be a part of a systemic dysimmune process.

Magnetic resonance imaging may predict deep remission in patients with perianal fistulizing Crohn's disease

AIM To evaluate the imaging course of Crohn’s disease (CD) patients with perianal fistulas on long-term maintenance anti-tumor necrosis factor (TNF)-α therapy and identify predictors of deep remission. METHODS All patients with perianal CD treated with anti-TNF-α therapy at our tertiary care center were evaluated by magnetic resonance imaging (MRI) and clinical assessment. Two MR examinations were performed: at initiation of anti-TNF-α treatment and then at least 2 years after. Clinical assessment (remission, response and non-response) was based on Present’s criteria. Rectoscopic patterns, MRI Van Assche score, and MRI fistula activity signs (T2 signal and contrast enhancement) were collected for the two MR examinations. Fistula healing was defined as the absence of T2 hyperintensity and contrast enhancement on MRI. Deep remission was defined as the association of both clinical remission, absence of anal canal ulcers and healing on MRI. Characteristics and imaging patterns of patients with and without deep remission were compared by univariate and multivariate analyses. RESULTS Forty-nine consecutive patients (31 females and 18 males) were included. They ranged in age from 14-70 years (mean, 33 years). MRI and clinical assessment were performed after a mean period of exposure to anti-TNF-α therapy of 40 ± 3.7 mo. Clinical remission, response and non-response were observed in 53.1%, 20.4%, and 26.5% of patients, respectively. Deep remission was observed in 32.7% of patients. Among the 26 patients in clinical remission, 10 had persisting inflammation of fistulas on MRI (T2 hyperintensity, n = 7; contrast enhancement, n = 10). Univariate analysis showed that deep remission was associated with the absence of rectal involvement and the absence of switch of anti-TNF-α treatment or surgery requirement. Multivariate analysis demonstrated that only the absence of rectal involvement (OR = 4.6; 95%CI: 1.03-20.5) was associated with deep remission. CONCLUSION Deep remission is achieved in approximately one third of patients on maintenance anti-TNF-α therapy. Absence of rectal involvement is predictive of deep remission.

Impact of age at diagnosis on natural history of patients with elderly-onset ulcerative colitis: A French population-based study

BACKGROUND Recent population-based study of elderly-onset Crohns disease patients reported age-related differences in disease phenotype and outcome. AIMS The aim was to assess the impact of age at diagnosis on natural history of elderly-onset ulcerative colitis patients with emphasis on disease presentation, phenotype and treatment. METHODS Elderly-onset patients with ulcerative colitis (≥60 years at diagnosis) registered in a French population-based Registry EPIMAD (1988-2006) were included. Demographic and clinical data at diagnosis and at maximal follow-up were collected using predefined questionnaire. RESULTS Four-hundred and sixty-five elderly-onset ulcerative colitis patients were included (median follow-up 6.2 years); 276 (59%) were <70 and 189 (41%) ≥70 years at diagnosis. Patients aged <70 years presented with more rectal bleeding (86% vs. 79%, p = .06) and abdominal pain (44% vs. 34%, p = .04) while those ≥70 years had higher rate of left-sided colitis (62% vs. 49%; p = .02). Cumulative exposure to 5-ASA, corticosteroids and immunosuppressants was similar between the groups as well as surgery rate. However, patients <70 years were significantly more steroid-resistant than older individuals (12% vs. 3%, p < .05) while no significant difference in steroid-dependency was observed. CONCLUSION Patients with elderly-onset ulcerative colitis differed in presentation, disease phenotype and response to medication with respect to age at diagnosis.

Les MICI du sujet âgé

La prevalence des MICI (maladie de Crohn et rectocolite hemorragique) augmente regulierement et le vieillissement de la population va faire de la MICI du sujet âge une situation clinique de plus en plus frequente. Ces maladies du sujet âge posent de nombreux problemes qui vont du diagnostic differentiel initial avec les complications de la diverticulose, les colites ischemiques, infectieuses ou encore iatrogenes aux difficultes therapeutiques specifiques. Ainsi, les traitements les plus efficaces des MICI, les immunosuppresseurs comme les anti-TNF alpha, sont d’emploi plus delicat chez ces patients âges, qu’il s’agisse de risques âge-dependants comme avec les thiopurines ou de comorbidites. Des travaux recents sont venus apporter des donnees solides sur la presentation clinique initiale et l’histoire naturelle de ces formes particulieres en soulignant que ces maladies sont souvent moins bruyantes cliniquement, plus souvent localisees au colon, notamment pour la maladie de Crohn, et exposent a des risques d’extension ou de changement de phenotype moins frequemment que chez les sujets diagnostiques tres tot dans la vie. Ces donnees sont importantes car elles plaident en faveur d’une attitude therapeutique prudente chez le sujet âge ou les enjeux de changer l’histoire naturelle semblent moins pregnants que chez les sujets plus jeunes.