Monica Cesarini

Internet use among inflammatory bowel disease patients : an Italian multicenter survey

Background The internet has been increasingly used as a resource for accessing health-related information. A recent US survey found that approximately half of inflammatory bowel disease (IBD) patients in an IBD clinic use the internet to gather IBD-specific information. Aim The aim of this study was to evaluate the use of the internet among Italian IBD patients. Methods The study was performed in seven Italian IBD referral centers by using a 28-item anonymous questionnaire. Results In all, 495 questionnaires were returned for analysis, in which 305 of 495 patients (61.6%) indicated that they are able to access the internet. A large proportion used the internet to gather health-related information (180 of 305, 59.1%) and IBD-related information (226 of 305, 74.2%). The use of the internet increased significantly with level of education (P<0.0001) and household income (P<0.0001). In addition, the use of the internet to gather IBD-related information increased significantly with the increase of disease activity and severity. Conclusion Approximately half of the patients in Italian IBD referral centers used the internet to gather IBD-related information. This use positively correlated with disease activity and severity. The great majority of patients indicated that it was very important for IBD referral centers to have their own IBD-dedicated website.

Dose optimization is effective in ulcerative colitis patients losing response to infliximab: A collaborative multicentre retrospective study

BACKGROUND Subjects maintained on infliximab scheduled therapy for inflammatory bowel disease may require dose optimization due to secondary loss of response. There are limited data on infliximab dose optimization for ulcerative colitis. AIMS To investigate dose optimization in ulcerative colitis patients with secondary loss of response. METHODS This was a retrospective multicentre study. Primary outcome was rapid clinical response assessed at the next administration of infliximab after dose intensification. Secondary outcomes were rapid clinical remission, and clinical response, remission and colectomy rate by week 52. Doubling the dose (10mg/kg q8 weeks) vs. shortening the dose interval (5mg/kg every 6 or 4 weeks) were compared. RESULTS Forty-one patients from eight centres were enrolled (15 for double dose and 26 for interval shortening). Rapid response was achieved in 37/41 patients (90.2%), while 19/41 (46.3%) achieved rapid clinical remission. At week 52, 28/41 patients were maintained in clinical remission, but 4 (9.8%) underwent colectomy. No difference was found between the two optimization strategies. Subjects achieving rapid clinical response had a significantly higher colectomy-free rate at week 52 (p=0.002). CONCLUSION Dose optimization of infliximab was effective to restore clinical response or remission and to prevent colectomy in ulcerative colitis patients with secondary loss of response.

The long journey of salicylates in ulcerative colitis: The past and the future

The advent of salicylates in the treatment of ulcerative colitis started in 1938 with the discovery of Salazopyrin by Nanna Svartz. This drug offered for the first time a therapeutic chance to patients with ulcerative colitis. In this paper we describe the fascinating history of Salazopyrin and salicylates from the first serendipitous observations to the last randomized clinical trials. Attention was paid to the pharmacokinetics and the mechanism of action of 5-aminosalicylates and, in particular, to the issue of the mucosal concentrations of 5-aminosalicylates and its therapeutic efficacy. Moreover a look at the new oral mesalazine formulations that allow the homogenous distribution of 5-aminosalicylate through all the large bowel was taken. Lastly, the possible use of mesalazine in the prevention of colorectal cancer was reviewed.

Guillain-Barrè syndrome after treatment with human anti-tumor necrosis factorα (adalimumab) in a Crohn's disease patient: case report and literature review.

Anti-tumor necrosis factor alpha antibodies have been used with increasing frequency despite the number of reported adverse effects. Further new information is still emerging. Here we report the case of a 71-years-old patient affected by Crohns disease and HCV-positive who developed Guillain-Barrè syndrome after four injections of fully human anti-tumor necrosis factor alpha antibodies (adalimumab). Indication for the treatment was severe clinical recurrence of Crohns disease following intestinal resection. Guillain-Barrè syndrome was treated by intravenous immunoglobulins, and methylprednisolone and plasmapheresis were started with a progressive partial resolution of neurological symptoms. To date, Crohns disease was maintained in clinical remission with low dose steroid therapy.

Biological Therapy for Ulcerative Colitis: What is after Anti-TNF

Ulcerative Colitis (UC) is an idiopathic chronic inflammation. Its etiology is still largely unknown. Environmental and genetic factors in combination with the microbial flora or specific microorganisms are thought to trigger the gut inflammation, leading to the activation of the intestinal immune response. Immune and non-immune cells create a cross talk via the secretion of soluble mediators and expression of cell adhesion molecules, resulting in further cell activation. Mediators such as cytokines and chemokines play a key role in cell recruitment and polarization, intercellular signal amplification or activation and differentiation. Lack of balance between pro-inflammatory and anti-inflammatory cytokines is crucial in the pathogenesis of IBD. Conventional therapy of UC quite commonly fails to avoid complications or colectomy and the therapeutic armamentarium remains still limited. New therapeutic options, such as, biological therapy, gene therapy, hematopoietic stem cell transplantation, and leucoapheresis, have been investigated recently. Biological therapy is focused on different targets involved in the inflammatory process. Several new biological drugs have been introduced in the last decade or are under investigation for the treatment of IBD. They include anti TNF-α agents, anti adhesion molecules, anti IL-12/23, anti IL-6R and more. We review the recent advances in biological therapy for UC treatment beyond the anti-TNFs.

Mucosal Healing in Ulcerative Colitis: Where do we Stand?

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by chronic inflammation affecting the colonic mucosa, that can extend to the whole large bowel. The severity of mucosal lesions directly reflects the disease activity and severity and may be prognostic for an aggressive behavior of the pathology. Remission, is usually defined as resolution of symptoms. Recently, mucosal healing (MH) has emerged as an important end point of any short-term medical therapy for IBD. It may predict long-term remission and may impact on the natural history of the disease in Crohns disease (CD), while data in UC patients are still limited. This review of the literature is focused on the recent evidence on the impact of medications on MH in UC and on the impact of MH on the natural course of UC.

Monthly and Seasonal Birth Patterns and the Occurrence of Crohn's Disease

The American Journal of GASTROENTEROLOGY VOLUME 104 | JUNE 2009 www.amjgastro.com oral use of FPS as a bowel preparation agent for endoscopy, surgery, and radiologic procedures (3 – 5) . It is mentioned that even in patients with normal serum creatinine levels, signi3 cant changes in serum electrolytes can occur (6) . Under normal conditions, 60 – 65 % of dietary phosphorus is absorbed from the intestinal lumen; therea er, it is transferred intracellularly or excreted in the urine. In elderly patients, especially, electrolyte disorders occur more o en and are severe because of inadequate renal potassium conservation, a more sedentary lifestyle, altered gut motility, and the use of some medications, such as diuretics (7) . However, in our case, none of these problems were present. Moreover, serum electrolyte values of our patient were proved to be within normal limits before the administration of oral FPS. 0 erefore, the hypocalcemia in our patient cannot be attributed to her malabsorption syndrome. To the best of our knowledge, this paper is the 3 rst presentation of symptomatic hypocalcemia secondary to the oral administration of FPS in a patient with celiac disease.

Acute lymphoid leukemia in a Crohn's disease patient during treatment with adalimumab after a prolonged treatment with azathioprine and steroids

To the Editor: Antitumor necrosis factor alpha (anti-TNF-a) antibodies are biological agents used worldwide in the treatment of inflammatory bowel disease (IBD). Fully human anti-TNF-a antibodies (adalimumab) have been shown to induce and maintain remission in naı̈ve Crohn’s disease (CD) patients and in those intolerant or losing response to infliximab. The less immunogenicity due to a fully human nature makes adalimumab a welltolerated drug. Long-term safety and the risk for malignancies and infections are still to be fully assessed. Herewith we report the case of a 63-year-old woman with stricturing ileal CD complicated by perianal disease, classified as A2-L1-B2p according to the Montreal Classification. Diagnosis of CD was first made in 1985 on the basis of ileocolonoscopy and histological findings. The disease showed a subsequently chronically active course, requiring surgery twice (ileal resection with right hemicolectomy in 1986, and anastomotic resection in 1993). Despite prolonged and repeated courses of steroids a stable remission or a Crohn’s Disease Activity Index (CDAI) less than 150 points was never reached. Considering that steroid-dependence progressively changed into steroid-refractoriness, the repeated need for surgery and, last but not least, the development of perianal disease besides anastomotic recurrence, in 1994 an immunosuppressive treatment with azathioprine (2.5 mg/kg/day) was started. The disease was then reasonably well controlled for over 10 years. In October 2008, due to the frequent relapse of the disease despite immunosuppressive treatment and the presence of (sub)obstructive symptoms, azathioprine was stopped and adalimumab was started with standard induction treatment (80 mg at week 0 and 40 mg at week 2) followed by maintenance treatment (40 mg every other week). After 10 injections clinical remission was reached (CDAI <150 points), erythrocyte sedimentation rate and Creactive protein were normal, as well as white blood cells and platelets count. However, endoscopic and ultrasonographic findings did not show regression or improvement of ileal lesions. Following the 10th injection the patient complained of chest pain and productive cough. An empirical antibiotic therapy was started with a macrolyd for 1 week with some clinical improvement. The white blood cell count as well as a chest x-ray were normal. Due to persistent mild respiratory symptoms associated with marked asthenia and nausea, new blood tests were performed showing pancytopenia with a marked decrease in platelets (20,000/mmc) and white blood cells, especially neutrophils (350/mmc). A hematologic work-up, including bone marrow aspiration and its microscopic examination, led to the diagnosis of acute lymphoid leukemia (ALL), B common immunophenotype, Philadelphia chromosome-positive (Phþ ALL). All treatments for CD were stopped and an experimental protocol for the treatment of ALL instituted, consisting of steroids for 6 days: 20 mg/m first day; 30 mg/m the second; 40 mg the third and the other 3 days plus Glivec, a tyrosine-kinase inhibitor, 400 mg/ day. A favorable initial response with marked cytolysis ensued. The occurrence of hematologic malignancies in patients with IBD has been previously reported, with 264 hematopoietic cancers found during follow-up on a total of 47,679 Swedish patients with IBD. This number corresponds to a borderline significant 20% increased risk as compared to the general population. In our institution 5 more cases of hematologic malignancies in IBD patients were previously reported. Therapy-related leukemias have been described following immunosuppressive treatment with azathioprine, fluorouracil, methotrexate, 6-mercaptopurine, and fludarabine less frequently than after radiotherapy or treatment with alkylating agents. As far as antiTNF-a agents, in an Italian multicenter matched-pair study, 404 CD patients treated with infliximab were matched with 404 CD patients who had never received infliximab and only 1 case of leukemia was reported in the infliximab-treated group of patients and 1 non-Hodgkin’s lymphoma in a patient in the control group. This study suggested that the occurrence of neoplasia in infliximab-treated CD patients was comparable to that of controls. Moreover, a meta-analysis in rheumatological patients receiving anti-TNF-a agents reported 9 cases of lymphomas and 1 leukemia (this 1 in a patient receiving infliximab). Thus, the pooled odds ratio (OR) for all malignancies in patients with rheumatoid arthritis using anti-TNF drugs versus placebo patients was 3.3 (95% confidence interval [CI], 1.2–9.1). A case of acute myelogenic leukemia in a rheumatological patient receiving adalimumab has also been recently described. Our patient was treated with azathioprine (for 14 years) and steroids (more than 3 cycles per year from the diagnosis) for many years. It is thus Copyright VC 2009 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1002/ibd.21005 Published online 27 July 2009 inWiley InterScience (www.interscience.wiley.com).

Inadvertent Conception During Concomitant Treatment with Infliximab and Methotrexate in a Patient with Crohn's Disease: Is the Game Worth the Candle?

To the Editor: Women with Crohn’s disease (CD) presenting a persistent high activity seem to have a poorer pregnancy outcome with respect to healthy women. To date there is no evidence from toxicity studies that tumor necrosis factor alpha (TNF-a) antagonists are associated with embryotoxicity or teratogenicity. However, according to the Food and Drug Administration (FDA) classification, infliximab (IFX) is considered a pregnancy category B drug (‘‘no documented human toxicity’’). According to European Crohn’s and Colitis Organization (ECCO) guidelines this drug should be avoided in the last trimester of pregnancy. Methotrexate (MTX), on the other hand, is considered by the same FDA classification as a pregnancy category X drug (‘‘contraindicated’’) and therapeutic abortion should be discussed if conception should accidentally occur during treatment due to the teratogenic and embryotoxic effects. We have reported the case of a 31-year-old female with colonic CD who became pregnant during concomitant treatment with azathioprine (AZA) and IFX whose pregnancy showed a good outcome. Here we report the case of a 30year-old woman with ileocecal luminal CD who showed persistent high disease activity despite concomitant treatment with MTX (15 mg/week) and prednisone (40 mg/day). When she was 18 years old the patient was referred to our Gastrointestinal Unit for the appearance of diarrhea, weight loss, fever, sideropenic anemia, vomiting, and axial and peripheral arthritis. At diagnosis the disease was classifiable as A2 L2 B1 according to the Montreal Classification. For recurrent relapses of intestinal and extraintestinal symptoms requiring steroids (2–3 cycles/year), azathioprine (2 mg/kg/ day) was started, CD reached remission, and steroids were stopped. In August 2005, due to AZA treatment failure, consisting of a severe relapse of intestinal and extraintestinal symptoms (sacroileitis and peripheral arthritis with functio lesa and erythema nodosum) with anemia (hemoglobin 9.8 g/ dL) and raised values of erythrocyte sedimentation rate (ESR) (64 mm/h), C-reactive protein (CRP) (7.42 mg/ dL), fibrinogen (414 UI/L), platelets (488 000/mmc), the drug was withdrawn. The patient received IFX with a classical induction regimen (5 mg/kg at weeks 0, 2, 6) followed by scheduled maintenance treatment every 8 weeks. She also received MTX 10 mg/ wk orally. The patient was informed about the risk of an accidental conception during the treatment and contraception methods were recommended. At the beginning of IFX treatment the Crohn’s Disease Activity Index (CDAI) was 250. After 5 infusions of IFX in combination with MTX the patient reached a steroid-free remission (CDAI 42). After the 16th infusion of IFX and despite physician recommendation, the patient was found to be pregnant. Every treatment for CD was stopped. The risks of fetal exposure to MTX were discussed again jointly by the patient, gastroenterologists, and gynecologists. Despite the risk the patient decided to allow the pregnancy. During the pregnancy intestinal symptoms reappeared requiring systemic steroids (prednisone 40 mg/day). The patient developed hypertension requiring a calcium channel blocker. At the 30th week of pregnancy the patient required cesarean section, resulting in a live female birth. Due to prematurity, the baby’s weight at birth was low (1.255 kg). No congenital malformations, intrauterine growth retardation, or neonatal illnesses were reported. Breast feeding was first allowed, but stopped due to a moderate-severe relapse of CD (CDAI 220) characterized by bloody diarrhea, fever, weight loss, and abdominal and articular pain requiring steroid therapy (prednisone 40 mg/day). The patient reached remission but relapsed less than 1 month after steroid withdrawal. Hematological tests showed neutrophil leukocytosis, microcytic anemia, and abnormal values of CRP and ESR. An ileocolonoscopy showed ulcers in the entire colon. Magnetic resonance imaging showed the presence of a severe colonic and perivisceral fat inflammation, as well as the development of sigmoid-ovaric and sigmoid-uterine fistulas. Steroid and antibiotic therapy was started again, with partial response. IFX thereby was initiated again and after 2 infusions the patient showed a marked decrease in ESR and CRP values and disappearance of diarrhea. The available data do not indicate a significantly increased risk for mother and child following inadvertent or intentional use of IFX during pregnancy. The case we reported is in line with data from the literature. Nonetheless, as experience in humans is still limited, the use of IFX during pregnancy should be limited to cases in which uncontrolled activity of intestinal disease represents a severe risk for mother and child.

Successful resolution of pneumonia developed in a patient affected by Crohn’s disease, rheumatoid arthritis, myasthenia gravis and recurrent uveitis during concomitant treatment with tumour necrosis factor α inhibitors and conventional immunosuppressive drugs

Tumour necrosis factor alpha inhibitors, both infliximab and adalimumab, have been approved for the treatment of both rheumatoid arthritis and Crohn’s disease. A slight increase in the risk of infections in patients receiving immunosuppressants and/or biological agents has been reported. Here, we present the case of a 68-year-old woman affected by Crohn’s disease, myasthenia gravis, recurrent uveitis and rheumatoid arthritis who developed pneumonia during concomitant treatment with biological agents and conventional immunosuppressive drugs.