A. Cañas-Ventura

Smoking does influence disease behaviour and impacts the need for therapy in Crohn′s disease in the biologic era

Recently, the notion that smoking may adversely affect Crohn′s disease (CD) outcomes has been challenged by the suggestion that the widespread use of immunosuppressants and anti‐TNF drugs might offset the adverse effects of tobacco.

Observational study on the efficacy of adalimumab for the treatment of ulcerative colitis and predictors of outcome.

BACKGROUND Information on efficacy and predictors of response to adalimumab in ulcerative colitis (UC) clinical practice is limited. AIM Assessment of response to adalimumab and its predictors in an observational cohort study. METHODS Retrospective cohort study based on data obtained from ENEIDA registry. All patients diagnosed with UC treated with adalimumab were included. Response to adalimumab was evaluated at weeks 12, 28, and 54 according to the partial Mayo score, and requirement of colectomy until end of follow-up. RESULTS 48 patients with UC treated with adalimumab were included; 39 (81.3%) had previously received infliximab. Response rates at weeks 12, 28 and 54 were 70.8%, 43.2% and 35% respectively. Response to prior treatment with infliximab was the only predictive factor of response to adalimumab at week 12, which was obtained in 90% of infliximab remitters, 53.8% of responders and 33.3% of primary non-responders (p=0.01). Colectomy was required in 11 patients (22.9%), after a mean time of 205 days. The only clinical independent predictor of colectomy was non-response to adalimumab at week 12: colectomy rates were 5/34 (14.7%) in responders and 6/14 (42.9%) in non-responders (p=0.035), time free of colectomy was significantly reduced in non-responders (p=0.01). Adalimumab withdrawal due to adverse events occurred in 4.2% of patients. CONCLUSION This study shows that adalimumab is an effective treatment in patients with UC. If used as a second anti-TNF, previous achievement of remission with the first anti-TNF predicts response, and failure to achieve response at week 12 predicts colectomy.

Risk of colectomy in patients with ulcerative colitis under thiopurine treatment

BACKGROUND AND AIMS Little is known about the risk factors of colectomy in patients with ulcerative colitis (UC) under thiopurine treatment. The aim of the study was to determine the prevalence and the predictive risk factors of colectomy in an extensive cohort of patients with UC treated with thiopurines in Spain. METHODS Among 5753 UC patients, we identified those diagnosed between 1980 and 2009 and treated with azathioprine or mercaptopurine (AZA/MP). We analyzed the age at diagnosis, familial history of IBD, extraintestinal manifestations (EIMs), disease extent, smoking status and treatment requirements (AZA/MP, cyclosporine (CsA) or anti-TNFα). Colectomies for dysplasia or cancer were excluded. Survival analysis and Cox proportional hazard regression were performed. Results were reported as hazard ratios (HR) with 95% CI. RESULTS Among the 1334 cases included, 119 patients (8.9%) required colectomy after a median time of 26 months (IQR 12-42) after AZA/MP initiation. Independent predictors of colectomy were: Extensive UC (HR 1.7, 95% CI: 1.1-2.6), EIMs (HR 1.5, 95% CI: 1.0-2.4), need for antiTNFα (HR 2.3, 95% CI: 1.5-3.4) and need for CsA (HR 2.4, 95% CI: 1.6-3.7). Patients requiring early introduction of AZA/MP had an increased risk of colectomy with a HR of 4.9 (95% CI: 3.2-7.8) when AZA/MP started in the first 33 months after UC diagnosis. CONCLUSIONS Nearly one-tenth of patients with UC under thiopurines require colectomy. Extensive UC, EIMs, need for CsA or anti-TNFα ever and an early need for AZA/MP treatment were associated with a higher risk of colectomy. These risk factors of colectomy could help to stratify risk in further controlled studies in UC.

Disease severity in familial cases of IBD

BACKGROUND Phenotypic traits of familial IBD relative to sporadic cases are controversial, probably related to limited statistical power of published evidence. AIM To know if there are phenotype differences between familial and sporadic IBD, evaluating the prospective Spanish registry (ENEIDA) with 11,983 cases. METHODS 5783 patients (48.3%) had ulcerative colitis (UC) and 6200 (51.7%) Crohns disease (CD). Cases with one or more 1st, 2nd or 3rd degree relatives affected by UC/CD were defined as familial case. RESULTS In UC and CD, familial cases compared with sporadic cases had an earlier disease onset (UC: 33 years [IQR 25-44] vs 37 years [IQR 27-49]; p<0.0001); (CD: 27 years [IQR 21-35] vs 29 years [IQR 22-40]; p<0.0001), higher prevalence of extraintestinal immune-related manifestations (EIMs) (UC: 17.2% vs 14%; p=0.04); (CD: 30.1% vs 23.6%; p<0.0001). Familial CD had higher percentage of ileocolic location (42.7% vs 51.8%; p=0.0001), penetrating behavior (21% vs 17.6%; p=0.01) and perianal disease (32% vs 27.1%; p=0.003). Differences are not influenced by degree of consanguinity. CONCLUSION When a sufficiently powered cohort is evaluated, familial aggregation in IBD is associated to an earlier disease onset, more EIMs and more severe phenotype in CD. This feature should be taken into account at establishing predictors of disease course.

Outcome in obscure gastrointestinal bleeding after capsule endoscopy

AIM To investigate the clinical impact of capsule endoscopy (CE) after an obscure gastrointestinal bleeding (OGIB) episode, focusing on diagnostic work-up, follow-up and predictive factors of rebleeding. METHODS Patients who were referred to Hospital del Mar (Barcelona, Spain) between 2007 and 2009 for OGIB who underwent a CE were retrospectively analyzed. Demographic data, current treatment with non-steroid anti-inflammtory drugs or anticoagulant drugs, hemoglobin levels, transfusion requirements, previous diagnostic tests for the bleeding episode, as well as CE findings (significant or non-significant), work-up and patient outcomes were analyzed from electronic charts. Variables were compared by χ (2) analysis and Student t test. Risk factors of rebleeding were assessed by Log-rank test, Kaplan-Meier curves and Cox regression model. RESULTS There were 105 patients [45.7% women, median age of 72 years old (interquartile range 56-79)] and a median follow-up of 326 d (interquartile range 123-641) included in this study. The overall diagnostic yield of CE was 58.1% (55.2% and 63.2%, for patients with occult OGIB and overt OGIB, respectively). In 73 patients (69.5%), OGIB was resolved. Multivariate analysis showed that hemoglobin levels lower than 8 g/dL at diagnosis [hazard ratios (HR) = 2.7, 95%CI: 1.9-6.3], patients aged 70 years and above (HR = 2.1, 95%CI: 1.2-6.1) and significant findings in CE (HR = 2.4, 95%CI: 1.1-5.8) were independent predictors of rebleeding. CONCLUSION One third of the patients presented with rebleeding after CE; risk factors were hemoglobin levels < 8 g/dL, age ≥ 70 years or the presence of significant lesions.

Tocilizumab in Amyloidosis-Associated Kidney Disease Secondary to Inflammatory Bowel Diseases

We read with interest the article by Sattianayagam et al. [1] about inflammatory bowel diseases (IBD) and AA amyloidosis with amyloidosis-associated kidney disease. The authors concluded that suppression of inflammatory activity may improve systemic amyloidosis prognosis and that patients undergoing renal transplantation have an excellent outcome. There is some evidence of the efficacy of the humanized anti-interleukin-6 receptor antibody tocilizumab (TCZ) on renal failure associated with AA amyloidosis improvement. TCZ has been reported to be effective in secondary AA amyloidosis related to rheumatologic diseases [2], in amyloidosis in the GI tract [3], and in renal amyloidosis [4], despite the scarcity of controlled evidence. In support of the effect of TCZ, we report the case of a 45-year-old patient with ulcerative colitis and grade III sacroileitis (HLA-B27 negative), followed in another center. After an acute flare, refractory to corticosteroids and cyclosporine, the patient underwent a proctocolectomy with an ileoanal pouch. Ten years later he was referred to our unit with elevated inflammatory markers, diarrhea, and abdominal pain. He had suffered from mild to moderate symptoms for at least the two previous years. Endoscopy revealed extensive ulceration of the pouch, jejunum, and ileum. Crohn’s disease was therefore diagnosed, and, because of persistent clinical activity, he was treated sequentially with adalimumab, infliximab, and methotrexate, without clinical response. Concurrently, the patient developed progressive chronic kidney disease with non-nephrotic range proteinuria reaching CKD stage IV (glomerular filtration rate \15 ml/min/m). After exclusion of other potential causes of renal dysfunction in IBD (5-ASA treatment, hypercalcemia renal oxalate stones), AA amyloidosis secondary to chronic inflammation related to IBD was diagnosed on the basis of amyloid A deposits in subcutaneous fat biopsy and duodenum, ileum, and colon biopsies (Congo redstained positive). Because of the clinical activity and the diagnosis of AA amyloidosis, we decided to start TCZ 8 mg/kg monthly. Tolerance of the treatment was excellent and the patient improved progressively and achieved clinical remission at week 52. At week 64, an ileoscopy, through the ileostomy, and a capsule endoscopy were performed; these showed mucosal healing was complete. In addition, renal function improved progressively and remained stable for two years (Cr 2.4 mg/dl, GFR 32 ml/min/1.73 m). Ileal biopsies performed two years after the onset of treatment showed no AA deposits. This clinical case and the literature published so far emphasize the importance of TCZ in controlling inflammatory activity in IBD and in reducing AA deposits, leading to improvement of renal function. It may therefore be considered as an alternative treatment or as bridge therapy before renal replacement therapy.

Systemic Bartonella henselae infection and Crohn's disease treatment with infliximab.

Bartonella henselae infection is well recognized as the responsible agent of cat-scratch disease (CSD), but also prolonged fever of unknown origin (FUO), endocarditis, hepatosplenic disease, encephalopathy, dermatological lesion, hemolytic anemia, and ocular diseases. Immunocompetent individuals infected by B. henselae start an interferon-c-mediated T-helper 1 cell response, resulting in macrophage recruitment and stimulation, producing a decrease of bacterial load but also a subsequent granuloma formation. In these patients, infection remains within lymphatics with a symptomatic immune response characterized by fever, generalized aches, anorexia, and nausea that lasts 2–4 months. Host immune status is determinant for clinical manifestations and response to infection. Immunodeficient patients are at higher risk of systemic bartonellosis characterized by neoangiogenic lesions or febrile bacteriemia. These have been described most commonly in HIV-infected, chemotherapy patients, and in transplant recipients. Currently, a newer group of high-risk patients should be taken into account: those undergoing tumor necrosis factor a (TNF-a) antagonists therapy for immune-related diseases. We report the case of a 74-yearold woman, allergic to penicillin. Spondyloarthropathy was diagnosed in 1995 when she was taking prednisone 5 mg daily. In 2000, Crohn’s disease (CD) was diagnosed and she had been in clinical remission for the last 8 years with azathioprine (2.5 mg/kg/day) and infliximab (5 mg/kg every 8 weeks). In March 2010 she was admitted to our hospital with abdominal pain, bloody diarrhea, and septic shock due to Campylobacter jejuni. A computed tomography (CT) scan showed no signs of CD activity and no lymphadenopathies. Empirical ciprofloxacin and metronidazole were started with a successful clinical outcome. Seven months later she was readmitted with fever (38.5 C) and headache. Blood tests showed C-reactive protein 18 mg/dL (0–0.8). Urine, stool, and blood cultures were negative and respiratory infection was discounted. A CT scan showed signs of mesenteric panniculitis, mediastinic and periceliac borderline lymphadenopathies, and homogenous splenomegaly without signs of CD activity or complications (Fig. 1). Symptomatic treatment was started and her fever disappeared. Two weeks later the fever reappeared with inflammatory signs in the blood test. We studied the FUO by means of mycobacteria cultures, Cytomegalovirus, Epstein Barr virus, and Treponema pallidum tests. Other serologic tests were added: Borrelia burgdorferi, Brucella, Rickettsia conorii, and Rickettsia typhi, Chlamydia psittaci, Coxiella burnetii, and Bordetella pertussis. An exhaustive anamnesis revealed that the patient had cats at home; therefore, B. henselae was tested. Because of the persistence of fever with important and concerning clinical upset, a wide-spectrum antibiotic suitable for penicillin allergics (tigecyclin 50 mg/12 hours) was started. Fever disappeared within 48 hours. Serology B. henselae immunoglobulin G was positive (1/1600). Treatment with tigecycline with subsequent rapid fever remission reinforced the diagnosis of systemic bartonellosis. Biological infection markers tended to normalization and the patient remained afebrile several months after the end of oral antibiotics. There is an increasing concern about opportunistic infections in patients with TNF-a antagonists, especially when these are combined with other immunomodulators. A systematic report showed a granulomatous infections rate (cases per 100,000 patients) of 239 with infliximab and 74 with etanercept. Tuberculosis was the most frequent. Other infections were histoplasmosis, candidiasis, listeriosis, coccidioidomycosis, and nocardiosis. There was one report of a case of Bartonella spp. infection in the infliximab group. B. henselae infections have been described related to etanercept: a cervical lymphadenopathy and a CSD