The Use of Temporary Fecal Diversion in Colonic and Perianal Crohn's Disease Does Not Improve Outcomes.

AIMS: To determine whether temporary fecal diversion for refractory colonic and/or perianal Crohn's disease can lead to clinical remission and restoration of intestinal continuity after optimization of medical therapy. METHODS: We retrospectively reviewed our prospectively maintained database of patients treated at the University of Maryland for Crohn's disease between May 2004 and July 2014. Patients with colonic, perianal, or colonic and perianal Crohn's disease, who had fecal diversion for control of medically refractory and/or severe disease, were included. Outcomes, including disease activity and rate of ileostomy reversal, were evaluated up to 24 months from stoma formation. RESULTS: Thirty patients were identified. Fecal diversion was performed for perianal disease in 37%, colonic disease in 33%, and both in 30% of patients. Twelve (40%) patients underwent ileostomy reversal. Twenty-five percent of patients with perianal disease had their ostomies reversed compared to 70% of patients with colonic disease alone. More patients with complex compared to simple perianal disease remained diverted (p = 0.02). Six (20%) patients required colectomy. Of these, 50% had complex perianal disease, all had received two or more biologics, and two-thirds were on combination therapy pre-diversion. CONCLUSIONS: Our study found that nearly two-thirds of patients with medically refractory colonic and/or severe perianal Crohn's disease treated with fecal diversion and optimization of postoperative medical therapy remain diverted or require colectomy within two years after ileostomy formation. In patients with severe, refractory perianal disease and those treated with combination therapy and >1 biologic exposure pre-diversion, colectomy rather than temporary fecal diversion should be considered.

Psoriasiform Skin Lesions Are Caused by Anti-TNF Agents Used for the Treatment of Inflammatory Bowel Disease.

BACKGROUND: Tumor necrosis factor (TNF) antagonists used for the treatment of inflammatory bowel disease (IBD) have been associated with the development of psoriasiform skin lesions. We assessed the demographic and clinical characteristics associated with and outcomes of patients with anti-TNF-induced psoriasiform lesions. METHODS: Patients with Crohn's disease (CD) and ulcerative colitis (UC) receiving treatment with anti-TNF therapy (infliximab, adalimumab, or certolizumab pegol) at a tertiary referral center were identified using an IRB-approved clinical data repository. Patients that developed psoriasiform skin lesions after initiation of anti-TNF therapy were included as cases. A group of anti-TNF-treated patients without drug-related psoriasiform lesions were identified as controls. The association between demographic and clinical variables and psoriasiform lesions was assessed using Chi-square analyses and multivariable logistic regression. RESULTS: Five hundred twenty-one patients with IBD undergoing treatment with anti-TNF therapy were identified; of these, 18 (3.5%) had psoriasiform lesions (16 CD and 2 UC). Seventy-two patients were identified as controls. Lesions developed a mean of 58 weeks (range 4-240 weeks) after starting anti-TNF therapy. The majority of patients were female and Caucasian (63 and 78%, respectively). Thirty-nine percent of patients had upper tract disease location. Forty-five patients (50%) were current or former smokers. Location of psoriasiform lesions included palmo-plantar (53%), trunk (47%), and scalp (53%), with 88% reporting involvement of ≥2 locations. Treatment of psoriasiform lesions was instituted with topical therapy in eight patients and systemic therapy (± phototherapy) in five patients. Discontinuation of anti-TNF therapy was recommended in nine patients (50%); of those, three were retreated with a second anti-TNF agent and all had recurrence of psoriasiform lesions. When adjusted for multiple variables, upper GI tract disease was significantly associated with psoriasiform lesions. CONCLUSIONS: Anti-TNF-induced psoriasiform lesions developed in 3.5% of patients with IBD at a tertiary referral center. Similar to prior published studies, most patients were female, had involvement of the palmo-plantar and scalp regions, and did not have severe IBD activity. The presence of upper tract disease was associated with the development of psoriasiform lesions. Skin lesions led to discontinuation of anti-TNF therapy in 50% of patients. Based upon these results, IBD providers should educate patients about this adverse effect, refer to dermatology for treatment, and discuss alternative IBD therapeutic options early if a severe psoriasiform rash develops.

Magnetic resonance enterography: state of the art.

Crohn's disease is a chronic inflammatory bowel disease of the gastrointestinal tract manifested by frequent periods of relapses and remissions of symptoms. The small bowel is most frequently affected. Progression of transmural inflammation can lead to stricturing or penetrating complications. At the time of diagnosis, approximately 10% of patients have disease beyond the reach of the colonoscope. Imaging can aid in clinical evaluation by depicting small bowel involvement and extraenteric disease. Magnetic resonance enterography (MRE) has emerged as a valuable tool and is being used with increasing frequency for the diagnosis and management of Crohn's disease. This article will discuss the current state of the art in MRE. In addition to reviewing the literature reporting its utility, we will present case examples illustrating how MRE best depicts the various findings of Crohn's disease within 4 imaging categories of disease: active inflammatory, fibrostenotic, fistulizing/perforating, and reparative or regenerative. We will present additional important clinical considerations in routine use of MRE, including implications for monitoring disease activity and response to treatment, cost-effectiveness, and appropriate use in the context of the American College of Radiology Appropriateness Criteria.

Sexual dysfunction in inflammatory bowel disease.

Sexual health is a broad term that encompasses a variety of functions including sexual thoughts, desire, arousal, intercourse, orgasm, and the impact of body image. Sexual dysfunction in individuals with inflammatory bowel disease is multifactorial including the impact of psychosocial factors, disease activity, medical therapies, surgical interventions, body image perceptions and changes, hypogonadism, and pelvic floor disorders. Providers caring for patients with inflammatory bowel disease should be cognizant of these concerns and develop management plans and techniques for earlier diagnosis and treatment.

Pseudomembranous Colitis: Not Always Caused by Clostridium difficile.

Although classically pseudomembranous colitis is caused by Clostridium difficile, it can result from several etiologies. Certain medications, chemical injury, collagenous colitis, inflammatory bowel disease, ischemia, and other infectious pathogens can reportedly cause mucosal injury and subsequent pseudomembrane formation. We present the case of a middle-aged woman with vascular disease who was incorrectly diagnosed with refractory C. difficile infection due to the presence of pseudomembranes. Further imaging, endoscopy, and careful histopathology review revealed chronic ischemia as the cause of her pseudomembranous colitis and diarrhea. This case highlights the need for gastroenterologists to consider non-C. difficile etiologies when diagnosing pseudomembranous colitis.

Racial differences in disease activity and quality of life in patients with Crohn's disease.

BACKGROUND: The existing literature on racial differences in Crohn's disease (CD) activity and quality of life (QOL) is limited and extrapolated from surrogate measures. AIM: The aim of our study was to compare objective markers of disease activity and QOL over time by race. STUDY: A clinical data repository of inflammatory bowel disease (IBD) patients at University of Maryland, Baltimore IBD Program, was used. CD patients from 2004 to 2009 were included if they had greater than or equal to two clinic visits with disease activity and QOL scores during the study period. Differences in disease activity and QOL were compared by race over time. RESULTS: A total of 296 patients with CD met inclusion criteria; of these, 19% (56/296) were African Americans (AA) and 81% (240/296) were Caucasian. Baseline disease activity and QOL scores did not differ by race (p > 0.05). Caucasians had a steady decline in disease activity and increase in QOL. AA experienced a similar pattern of change in disease activity and QOL scores over time; however, the declines were not statistically significant between groups. At each time point post-baseline, disease activity and QOL scores were similar between races. CONCLUSION: We found that Caucasian and AA patients with CD had similar disease activity and QOL scores at initial presentation and over time. Thus, AA do not represent a more severe subgroup of CD patients to treat. These findings have important implications for clinicians that care for patients with CD.

Step up versus early biologic therapy for Crohn's disease in clinical practice.

BACKGROUND: Recent studies have demonstrated superior outcomes of early biologic therapy. Our purpose was to evaluate differences in disease course among patients in clinical practice treated with early biologic therapy compared with those receiving conventional Step Up therapy. METHODS: Patients with Crohn's disease evaluated from July 2004 to November 2010 at a tertiary referral center were included. Demographic data were obtained from a prospectively maintained database. Patients were categorized into 1 of 2 groups: Early Bio group (with or without concomitant immune suppressants) or Step Up group (initial immune suppressants with or without escalation to biologic). Disease activity, quality of life, use of steroids, and number of hospitalizations, and surgeries were assessed. RESULTS: Ninety-three patients with Crohn's disease met inclusion criteria: 39 (45%) in the Step Up group and 54 (58%) in the Early Bio group. There was no significant difference in demographic and clinical variables between groups. Mean Harvey-Bradshaw index and Short Inflammatory Bowel Disease Questionnaire scores at 3, 6, and 12 months were not different between groups. Response rates were higher in the Step Up group compared with the Early Bio group only at 3 months. Early Bio patients had a greater number of hospitalizations at 1 year (P = 0.04). CONCLUSIONS: In clinical practice, early biologic therapy did not improve disease activity or quality of life and did not decrease the need for steroids or surgeries 1 year after therapy. Our results suggest that clinical outcomes are not worsened using the conventional approach. Therefore, an accelerated Step Up approach for most patients seems reasonable.

Sarcoidosis of gastrointestinal tract: a rare disease.

Gastrointestinal (GI) tract sarcoidosis is an uncommon form of sarcoidosis. The GI tract can be involved as an isolated disease as a part of systemic sarcoidosis. Clinical manifestations of esophageal, gastric, small bowel, colon, and appendicular sarcoidosis are discussed in this review. The differential diagnosis of GI sarcoidosis is extensive. Other granulomatous diseases of the GI tract, like tuberculosis, fungal infections, parasitic diseases, inflammatory bowel disease, and Whipple's disease, should be excluded before making the diagnosis of GI sarcoidosis. Corticosteroid therapy is effective in treatment of GI sarcoidosis. Surgical intervention may be necessary in patients with bowel obstruction, perforation, or massive hemorrhage.

MK801 and amantadine exert different effects on subthalamic neuronal activity in a rodent model of Parkinson's disease.

Efforts to develop adjuvant therapies for the treatment of Parkinson's disease (PD) have led to interest in drugs that could mimic the therapeutic effects of lesion or deep brain stimulation of the subthalamic nucleus (STN). Extracellular single unit recordings were conducted to determine whether noncompetitive NMDA receptor blockade, suggested to have potential as an adjuvant treatment in PD, attenuates rate increases and firing pattern changes observed in the STN in a rodent model of PD. Systemic administration of the noncompetitive NMDA antagonist MK801 to rats with unilateral dopamine cell lesions did not significantly alter burstiness or interspike interval coefficient of variation, although mean firing rate decreased by a modest 20% with 50% of neurons showing decreases in rate >15% and spike train power in the 3-8-Hz (theta) range was reduced. MK801, combined with the D1 dopamine agonist SKF 38393 in intact rats or administered alone in lesioned rats, also significantly reduced incidence of multisecond (2-60 s) periodic oscillatory activity. Amantadine, a drug currently used as an adjuvant agent in PD whose beneficial effects are commonly attributed to its noncompetitive NMDA antagonist properties, had effects that contrasted with those of MK801. In both intact and lesioned animals, amantadine significantly increased STN firing rates and total spike train power in the 8-50-Hz range and did not alter spike power in the 3-8-Hz range or multisecond oscillatory activity. These observations show that an effective noncompetitive NMDA antagonist such as MK801 induces modest change in STN activity in 6-hydroxydopamine (6-OHDA)-lesioned rats, with the most notable effect on multisecond periodicities in firing rate and theta frequency total spike power. Amantadine's effects differed from MK801's, raising questions about its primary mechanism of action and the role in PD pharmacotherapy of the STN rate increases induced by this drug.

Multisecond periodicities in basal ganglia firing rates correlate with theta bursts in transcortical and hippocampal EEG.

Multisecond oscillations in firing rate with periods in the range of 2-60 s (mean, 20-35 s) are present in 50-90% of spike trains from basal ganglia neurons recorded from locally anesthetized, immobilized rats. To determine whether these periodic oscillations are associated with similar periodicities in cortical activity, transcortical electroencephalographic (EEG) activity was recorded in conjunction with single- or dual-unit neuronal activity in the subthalamic nucleus (STN) or the globus pallidus (GP), and the data were analyzed with spectral and wavelet analyses. Multisecond oscillations in firing rates of 31% of the STN neurons and 46% of the GP neurons with periodicities significantly correlated with bursts of theta (4-7 Hz) activity in transcortical EEG. Further recordings of localized field potentials in the hippocampus and frontal or parietal cortices simultaneously with GP unit activity showed field potentials from the hippocampus, but not from the frontal or parietal cortices, exhibited bursts of theta rhythm that were correlated with GP firing rate oscillations. These results demonstrate a functional connectivity between basal ganglia neuronal activity and theta band activity in the hippocampus.