Filipe Vilas-Boas

High C-reactive protein in Crohn's disease patients predicts nonresponse to infliximab treatment.

BACKGROUND Infliximab (IFX) is effective in treating Crohns disease (CD) and C-reactive protein (CRP) is a useful biomarker in assessing inflammatory activity. AIM Correlate CRP levels before beginning of IFX, at week 14 and CRP delta within the first year of IFX treatment. METHODS Retrospective study of CD patients undergoing treatment with IFX. Primary nonresponse (PNR) was defined as no symptomatic improvement and CRP persistently elevated; sustained response (SR) as symptomatic improvement for at least 1 year without therapeutic adjustment; response after therapeutic adjustment (RTA) as analytic and clinical response but requiring IFX dose/frequency adjustment or association with another drug. RESULTS Baseline CRP levels were higher in PNR compared with SR (26.2mg/L vs 9.6 mg/L, p=0.015) and RTA (26.2mg/L vs 7.6 mg/L, p=0.007). CRP levels greater than 15 mg/L at baseline predict PNR with 67% sensitivity and 65% specificity. Lower CRP levels at week 14 were more likely to predict SR relative to RTA (3.1mg/L vs 7.6 mg/L p=0.019) and PNR (3.1mg/L vs 9.1mg/L; p=0.013). CRP levels greater than 4.6 mg/L at week 14 predict PNR with 67% sensitivity and 62% specificity. A higher CRP delta between beginning of treatment and week 14 is more likely to predict SR relative to RTA (5.2mg/L vs 0.6 mg/L p=0.027). CONCLUSION CRP levels at week 14 were associated with SR in patients treated with IFX, independently of baseline CRP serum levels. High inflammatory burden at beginning of IFX treatment was correlated with a worse response.

Tuberculosis in anti-TNF-α treated patients remains a problem in countries with an intermediate incidence: Analysis of 25 patients matched with a control population

BACKGROUND AND AIMS An increased incidence of tuberculosis (TB) in patients under anti-TNF-α therapy has been reported, but outcome compared with TB in the general population are unknown. METHODS Patients who had active tuberculosis while taking anti-TNF-α drugs were studied and compared with a control group of community-acquired TB matched for sex, age and data of TB. RESULTS Twenty-five cases of TB were reported from a cohort of 765 patients under anti-TNF-α from 2001 to 2012. The incidence of TB per 100,000 patient-years was estimated to be 1337, 792 and 405 respectively for those on infliximab, adalimumab and etanercept. Twelve patients had inflammatory bowel disease, ten had rheumatologic diseases and three had psoriasis. From the 17 patients screened for latent TB before anti-TNF-α, three were treated with isoniazid. TB was diagnosed 1-108 months after starting anti-TNF-α, being the median time six, seven and 89 months respectively for those on infliximab, adalimumab and etanercept. Sixty per cent of the cases had extra-pulmonary TB. No deaths occurred in the case groups, while two died in control TB patients. Patients on anti-TNF-α drugs had more frequent extra-pulmonary TB, fever on presentation, higher mean C-reactive protein and lower positive rate of acid-fast bacilli. CONCLUSIONS TB may still occur in those with negative testing, some of them probably representing new infections instead of reactivations. Three out of 25 patients had TB in spite of previously treated LTB, although, the outcome of TB was not worse than in the general population.

Listeria infection in patients on anti-TNF treatment: Report of two cases and review of the literature

Listeria monocytogenes is an aerobic gram positive intracellular bacillus, predominantly affecting pregnant women, immunocompromised patients and old individuals. Invasive listeriosis, meningitis and meningoencephalitis, bacteraemia with or without joint, eye or heart focalization are clinical manifestations of the disease. Anti-TNF-α drugs blocking the hosts response against various microorganisms, particularly intracellular agents like Listeria monocytogenes, increase the risk of disease. We report two cases of L. monocytogenes meningitis in ulcerative colitis patients under infliximab plus steroids. One patient is HIV-1 infected. A review of reported invasive listeriosis cases under anti-TNF drugs is also showed.

Epstein-Barr virus in inflammatory bowel disease-correlation with different therapeutic regimens.

Background: Inflammatory bowel disease (IBD) is associated with a higher prevalence of opportunistic infections. Epstein–Barr virus (EBV) is a ubiquitous virus related to several malignancies, namely lymphoma; its prevalence in patients with IBD and its relation with different therapeutic regimens are not well studied. Methods: Patients followed in our IBD outpatient clinic were consecutively enrolled for participation in a prospective study, and healthy volunteers were recruited as controls. EBV DNA was measured at least 1 time in each patient. Results: Three hundred and seventy-nine individuals were enrolled in the study (93 treated with 5-aminosalicylates, 91 with azathioprine, 70 with infliximab, 43 with combined treatment with infliximab and azathioprine, and 82 controls). More than 90% of the patients had previous EBV exposure. EBV DNA was found in 132 samples (35%); its prevalence was significantly higher in every group of patients with IBD, comparing to controls. Among patients with IBD, infliximab with or without azathioprine was related to higher prevalence of EBV comparing to azathioprine alone or 5-aminosalicylates (P < 0.05). Age above 60 years was related to EBV DNA positivity with a specificity of 92%. Concerning treated groups, ulcerative colitis was the only risk factor identified for high levels of EBV DNA (>1000 and 2500 copies per milliliter). No relationship was found between EBV and C-reactive protein. Conclusions: IBD is a risk factor for the presence of EBV DNA in blood, particularly in older patients and in those taking infliximab. C-reactive protein was not related to EBV DNA prevalence.

Oral squamous cell carcinoma in a Crohn's disease patient taking azathioprine: Case report and review of the literature

Thiopurines are widely used for remission maintenance and post-operative recurrence prevention in Crohns disease. The increased risk of cancer in transplant recipients on azathioprine is well recognized and there are concerns that this may also be true for inflammatory bowel disease patients. We report a case of a 33-year-old Caucasian woman with Crohns disease treated with azathioprine for 9 years who developed an ulcerated lesion at the right superior retromolar trigone. Biopsy specimen revealed a squamous cell carcinoma.

Disseminated cutaneous herpes simplex infection in a patient with Crohn's disease under azathioprine and steroids: First case report and literature review

Immunosuppressive treatments used in the management of Inflammatory Bowel Disease, namely steroids, thiopurines and anti-TNF drugs, raise the risk of acquiring opportunistic infections. However, most of these infections are mild and self-limited, not requiring specific therapy or suspension of the immunosuppressors. We report a case of disseminated cutaneous herpes simplex infection in a patient with Crohns disease under steroids and azathioprine.

Crohn's disease outcome in patients under azathioprine: A tertiary referral center experience

BACKGROUND AND AIMS Azathioprine is of major importance in the treatment of Crohns disease; its efficacy has been showed in several works, but real-life data regarding its use is scarce. Our aim was to address the outcome of patients with Crohns disease under azathioprine in the real-life setting. METHODS Crohns disease patients followed at an Inflammatory Bowel Disease Outpatient Clinic under azathioprine were consecutively enrolled, being allocated in one of four groups. Two groups included patients on treatment with this drug, regarding its two major indications - prevention of post-operative recurrence and steroid-dependent disease; a third group included patients who needed infliximab in addition to azathioprine and a fourth group comprised patients who did not tolerate azathioprine. RESULTS A total of 221 patients were enrolled, 180 on azathioprine due to steroid-dependency (64 needing additional treatment with infliximab) and 41 for prevention of post-operative recurrence. Steroid-free remission was obtained in 48%. Immunosuppression decreased the number of hospitalized patients (64% vs 36%; p<0.001), but not the surgery rates per person per year. Azathioprine as a post-operative drug was effective in decreasing hospitalizations. The addition of infliximab decreased the number of patients hospitalized (p=0.009) and hospitalization rates per person per year (p<0.001), but had no effect in the surgery rates per person per year. Sixty patients (23%) experienced adverse effects with AZA, 39 requiring discontinuation of the drug. CONCLUSIONS In this real-life study, azathioprine had a long-term steroid sparing effect and reduced hospitalizations. Combination with infliximab reduced hospitalizations but did not decrease the surgery rate.

Thalidomide-induced acute cholestatic hepatitis: Case report and review of the literature

Drug-induced liver injury (DILI) is a leading cause of liver failure and an important safety issue in drug development. Thalidomide is nowadays used for the treatment of several conditions including multiple myeloma (MM). Several adverse effects have been described but liver toxicity was seldom reported. We describe a case of thalidomide-induced hepatitis in a man treated for MM. The clinical setting and temporal association between the start of the drug and liver injury allowed the assumption of the causative role of thalidomide. As its clinical indications expand we wish to increase awareness of a new potential side effect of thalidomide. A short review on thalidomide-induced liver injury is also presented.

CA 19-9 as a Marker of Survival and a Predictor of Metastization in Cholangiocarcinoma

Background: Cholangiocarcinoma is the second most frequent primitive liver malignancy and is responsible for 3% of the malignant gastrointestinal neoplasms. The aims of this study were to determine the association of serum levels of CA 19-9 at diagnosis with other clinical data and serum liver function tests and to identify possible factors that influence the survival rates during follow-up. Methods: Retrospective observational study of 89 patients with a diagnosis of cholangiocarcinoma followed at the Department of Gastroenterology during 5 years. Statistical analyses were performed using SPSS version 20.0. Results: Patients were followed up for a median time of 127 days (IQR: 48-564), and the median age at diagnosis was 71.0 years (IQR: 62.0-77.5). The median survival rate was 14.0 months (IQR: 4.3-23.7), and the mortality rate was 79%. Patients with CA 19-9 levels ≥103 U/L had lower albumin levels and higher levels of alanine aminotransferase and γ-glutamyltransferase. CA 19-9 levels ≥103 U/L were associated with a higher probability of metastization (p = 0.001) and lower rates of treatment with curative intent (p = 0.024). In a multivariate analysis, CA 19-9 levels <103 U/L and surgery were independent predictors of survival. Conclusion: Predictive factors for overall survival were identified, namely presence of metastasis, surgery, and chemotherapy. CA 19-9 levels ≥103 U/L were predictive factors for survival and metastization.

Case Description of Cap Retention in the Submucosal Tunnel During Peroral Endoscopic Myotomy

Case Description of Cap Retention in the Submucosal Tunnel During Peroral Endoscopic Myotomy