Search

BACKGROUND AND AIMS: Extra-intestinal manifestations (EIMs) are a common complication of inflammatory bowel diseases (IBD), affecting up to half of the patients. Despite their high prevalence, information on standardised definitions, diagnostic strategies, and treatment targets is limited. METHODS: As a starting point for a national EIM study network, an interdisciplinary expert panel of 12 gastroenterologists, 4 rheumatologists, 3 ophthalmologists, 6 dermatologists, and 4 patient representatives was assembled. Modified Delphi consensus methodology was used. Fifty-four candidate items were derived from the literature review and expert opinion focusing on five major EIMs (erythema nodosum, pyoderma gangrenosum, uveitis, peripheral arthritis, and axial arthritis) were rated in three voting rounds. RESULTS: For use in a clinical practice setting and as part of the creation of a prospective registry of patients with EIMs, the panel developed definitions for erythema nodosum, pyoderma gangrenosum, uveitis, peripheral arthritis, and axial arthritis; identified the appropriate and optimal subspecialists to diagnose and manage each; provided methods to monitor disease course; offered guidance regarding monitoring intervals; and defined resolution and recurrence. CONCLUSIONS: Consensus criteria for appropriate and optimal means of diagnosing and monitoring five EIMs have been developed as a starting point to inform clinical practice and future trial design. Key findings include straightforward diagnostic criteria, guidance regarding who can appropriately and optimally diagnose each, and monitoring options that include patient and physician-reported outcomes. These findings will be used in a national multicenter study network to optimise the management of EIMs.

BACKGROUND Although immune-mediated diseases (IMDs) including inflammatory bowel diseases (IBDs) are known to cluster, to what extent this is due to common environmental influences is unknown. AIM To examine the incidence of IBD in individuals with another IMD. METHODS We used data from the prospective Nurses' Health Study II cohort (1995-2017) to examine the effect of diagnoses of several common IMDs on subsequent risk of Crohn's disease (CD) or ulcerative colitis (UC) using Cox proportional hazards models, adjusting for detailed diet and lifestyle confounders. RESULTS We documented 132 cases of CD and 186 cases of UC over 2 016 163 person-years of follow-up (median age at IBD diagnosis 50 years). Compared to participants with no history of IMD, the HRs of CD for those with 1 and ≥ 2 IMDs were 2.57 (95% CI 1.77-3.74) and 2.74 (95% CI 1.36 to 5.49), respectively (Ptrend

BACKGROUND: The older patient with inflammatory bowel diseases (IBD) is particularly vulnerable to consequences of disease and therapy-related side effects but little is known about the best treatment options in this population. AIM: To compare safety and efficacy of tumor necrosis factor α antagonist (anti-TNF) or vedolizumab (VDZ) in patients with IBD ≥ 60 years of age. METHODS: This retrospective study included patients with Crohn’s disease (CD) or ulcerative (UC) initiating anti-TNF or VDZ therapy at ≥ 60 years of age at 3 study sites. We examined occurrence of infection or malignancy within 1 year after therapy as our primary outcome. Our efficacy outcomes included clinical remission at 3, 6, and 12 months. Multivariable logistic regression models adjusting for relevant confounders estimated odds ratios (OR) and 95% confidence intervals. RESULTS: The study included 131 anti-TNF and 103 VDZ initiated patients (age range 60 – 88 years). Approximately half had CD. At 1 year, there were no significant differences in safety profile between the two therapeutic classes. Infections were observed in 20% of anti-TNF treated and 17% of VDZ treated patients (p=0.54). Pneumonia was the most common infection in both groups. While more anti-TNF treated CD patients were in remission at 3 months compared to VDZ (OR 2.82, 95% CI 1.18 – 6.76), this difference was not maintained at 6 and 12 months suggesting similar efficacy of both classes. CONCLUSIONS: Both anti-TNF and VDZ therapy were similarly effective and safe in elderly IBD patients.

Introduction Smoking has been linked with adverse outcomes in Crohn's disease(CD), however it is not known whether oral tobacco use affects disease outcomes in these patients. The study aimed to assess the association between smoking or oral tobacco(OT) and outcomes in CD. Methods Retrospective analysis was performed on prospectively maintained records of CD patients from 2004-2016. The parameters assessed included disease characteristics at baseline(location, behavior, age at onset, perianal disease, extra-intestinal manifestations), course pattern and outcomes (surgery, hospitalizations, immunomodulator or biologics use, and steroid requirement). Results 426 patients were included(mean age:39.9 years; 60% males; median follow up: 71 months). 40 patients were ever-OT users and 59 were ever-smokers, ever-use being defined as daily use for atleast 2 years. OT use was associated with male sex and smoking. Both OT use and smoking had no effect on baseline characteristics, but upper GI disease was less common in ever-smokers. Both OT use and smoking did not have any effect on surgery, hospitalizations, immunomodulator and biologic use. Similarly, no association was found between these outcomes and duration, daily and cumulative exposure to tobacco. Current but not former tobacco use in both smoked (aOR = 2.59[1.22-5.49]), and OT(aOR = 2.97[1.03-8.6]) forms increased risk of hospitalizations. Conclusion Oral tobacco use and smoking had no significant detrimental effect on disease phenotype or medical and surgical requirements in CD in Indian patients, affirming other non-caucasian studies that found lack of effect of smoking. However, current tobacco use in any form was associated with hospitalization during follow up.

SummaryBackground Mucosal healing is an important therapeutic endpoint in the management of Crohn's disease (CD) and ulcerative colitis (UC). Limited data exist regarding the comparative efficacy of various therapies in achieving this outcome. Aim To perform a systematic review and meta-analysis of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis. Methods We performed a systematic review and meta-analysis of randomised controlled trials (RCT) examining mucosal healing as an endpoint of immunosuppressives, anti-tumour necrosis factor α (anti-TNF) or anti-integrin monoclonal antibody therapy for moderate-to-severe CD or UC. Pooled effect sizes for induction and maintenance of mucosal healing were calculated and pairwise treatment comparisons evaluated using a Bayesian network meta-analysis. Results A total of 12 RCTs were included in the meta-analysis (CD – 2 induction, 4 maintenance; UC – 8 induction, 5 maintenance). Duration of follow-up was 6–12 weeks for induction and 32-54 weeks for maintenance trials. In CD, anti-TNFs were more effective than placebo for maintaining mucosal healing [28% vs. 1%, Odds ratio (OR) 19.71, 95% confidence interval (CI) 3.51–110.84]. In UC, anti-TNFs and anti-integrins were more effective than placebo for inducing (45% vs. 30%) and maintaining mucosal healing (33% vs. 18%). In network analysis, adalimumab therapy was inferior to infliximab [OR 0.45, 95% credible interval (CrI) 0.25–0.82] and combination infliximab-azathioprine (OR 0.32, 95% CrI 0.12–0.84) for inducing mucosal healing in UC. There was no statistically significant pairwise difference between vedolizumab and anti-TNF agents in UC. Conclusions Anti-TNF and anti-integrin biological agents are effective in inducing mucosal healing in UC, with adalimumab being inferior to infliximab or combination therapy. Infliximab and adalimumab were similar in CD.

SummaryBackground Differentiation between intestinal tuberculosis and Crohn's disease is difficult and may require therapeutic trial with anti-tubercular therapy in tuberculosis-endemic regions. Aim To evaluate the role of therapeutic trial with anti-tubercular therapy in patients with diagnostic confusion between intestinal tuberculosis and Crohn's disease. Methods We performed retrospective-comparative (n = 288: 131 patients who received anti-tubercular therapy before being diagnosed as Crohn's disease and 157 intestinal tuberculosis patients) and prospective-validation study (n = 55 patients with diagnostic confusion of intestinal tuberculosis/Crohn's disease). Outcomes assessed were global symptomatic response and endoscopic mucosal healing. Results In the derivation cohort, among those eventually diagnosed as Crohn's disease, global symptomatic response with anti-tubercular therapy was seen in 38% at 3 months and in 37% who completed 6 months of anti-tubercular therapy. Ninety-four per cent of intestinal tuberculosis patients showed global symptomatic response by 3 months. Endoscopic mucosal healing was seen in only 5% of patients with Crohn's disease compared with 100% of intestinal tuberculosis patients. In the validation cohort, all the patients with intestinal tuberculosis had symptomatic response and endoscopic mucosal healing after 6 months of anti-tubercular therapy. Among the patients with an eventual diagnosis of Crohn's disease, symptomatic response was seen in 64% at 2 months and in 31% who completed 6 months of anti-tubercular therapy, none had mucosal healing. Conclusions Disproportionately lower mucosal healing rate despite an overall symptom response with 6 months of anti-tubercular therapy in patients with Crohn's disease suggests a need for repeat colonoscopy for diagnosing Crohn's disease. Patients with intestinal tuberculosis showing significant symptomatic response after 2–3 months of anti-tubercular therapy, suggest that symptom persistence after a therapeutic trial of 3 months of anti-tubercular therapy may indicate the diagnosis of Crohn's disease.

We examined the impact of HBV/HIV co-infection on outcomes in hospitalized patients compared to those with HBV or HIV monoinfection. Using the 2011 US Nationwide Inpatient Sample, we identified patients who had been hospitalized with HBV or HIV mono-infection or HBV/HIV co-infection using ICD-9-CM codes. We compared liver-related admissions between the three groups. Multivariable logistic regression was performed to identify independent predictors of in-hospital mortality, length of stay and total charges. A total of 72,584 discharges with HBV mono-infection, 133,880 discharges with HIV monoinfection and 8,156 discharges with HBV/HIV co-infection were included. HBV/HIV co-infection was associated with higher mortality compared to HBV monoinfection (OR 1.67, 95% CI 1.30-2.15) but not when compared to HIV mono-infection (OR 1.22, 95% CI 0.96-1.54). However, the presence of HBV along with cirrhosis or complications of portal hypertension was associated with 3-times greater in-hospital mortality in patients with HIV compared to those without these complications (OR 3.00, 95%CI 1.80-5.02). Length of stay and total hospitalization charges were greater in the HBV/HIV co-infected group compared to the HBV mono-infection group (+1.53 days, p

Assiduous measures are taken to prevent perinatal transmission of hepatitis B virus (HBV) to infants; it is unclear whether the mothers receive appropriate care for their chronic HBV. We sought to assess the quality of HBV care in hepatitis B surface antigen (HBsAg)-positive mothers following pregnancy. HBsAg-positive women (n = 243) who had sought prenatal care at Massachusetts General Hospital were retrospectively identified and charts reviewed. The primary outcome was adherence to the American Association for the Study of Liver Diseases (AASLD) and American College of Obstetricians and Gynecologists guidelines. Over one-third (37%) of women were first diagnosed with HBV infection at a prenatal visit. One-third (32%) did not undergo timely liver function test measurements. HBV DNA was never measured in 26% and was untimely in 34% of patients. One-third (34%) of the women were at high-risk for HCC based on AASLD criteria, yet only 33% of these women underwent timely imaging. Nearly half (49%) never saw a liver specialist for their HBV care. In multivariate analysis, women were 3.7 times more likely to have a timely ALT and 8.1 times more likely to have a timely HBV DNA if they were followed by a liver specialist (P = 0.001

With a worldwide median prevalence of 16% and an annual direct medical cost in excess of $230 million in the U.S. alone, constipation represents a substantial financial burden to the healthcare system and takes an equally significant toll on health-related quality of life. Constipation-related concerns accounted for almost 8 million ambulatory visits per year in the U.S. in the early 2000s, with more than 1 million patients seeking care for constipation from a gastroenterologist per year during that time period (1). Despite this, little is known about the predictors of healthcare resource utilization among constipated patients. Prior studies evaluating predictors of healthcare seeking in constipation have largely been confined to cross-sectional, observational studies using billing records and survey data to examine the influence of demographics and comorbid disease. Female gender has consistently emerged as the strongest predictor of healthcare utilization in constipation (2, 3). Additionally, comorbid depression(2), higher educational level (3), and severity of constipation symptoms (4) influence likelihood of seeking care. Physiologically, constipation is often multifactorial and may be governed by slow colonic transit, pelvic floor outlet obstruction, visceral hypersensitivity, or indeed a combination of these parameters. Identification of disordered defecation using anorectal manometry (ARM) has emerged as an important subtype of constipation (5) with good treatment response to biofeedback therapy (6-8). Similarly, the treatment options for slow colonic transit has expanded with the introduction of the clinically-efficacious secretagogues, lubiprostone (9) and linaclotide (10), as well as the 5-HT4 receptor agonist prucalopride (11). Traditional laxatives such as polyethylene glycol remain effective options for some patients as well (12, 13). Despite these advances in the understanding and treatment of chronic constipation, treatment failure is a common and costly aspect of the care of this patient population, accounting for significant healthcare utilization (14). Furthermore, as more therapeutic options with different mechanisms of effect become available, it is increasingly important to identify the physiologic parameters that may be the most significant determinants of healthcare utilization and costs in patients with constipation in order to develop appropriate sequential treatment algorithms for these patients. To our knowledge, there is limited data connecting physiologic measurements in constipation with healthcare seeking. Therefore, we sought to delineate the relationship between physiology and healthcare resource utilization in a large cohort of patients with chronic constipation evaluated at two large, tertiary treatment centers using established measures of colonic and anorectal function. We hypothesized that physiologic parameters including colonic transit and outlet dysfunction would be predictors of increased clinical visits among the patients with chronic constipation. Evidence linking physiologic measures with healthcare seeking in chronic constipation could provide a better understanding of which patients have the greatest unmet need with the current standard of care and serve as the impetus for new, targeted treatments in the future.

SummaryBackground Anti-tumour necrosis factor α (anti-TNF) agents have been implicated in drug-induced liver injury. There is minimal data on this occurrence in inflammatory bowel disease (IBD) patients. Aim To identify the characteristics of liver enzyme elevations following anti-TNF therapy initiation in IBD. Methods A retrospective cohort of patients initiating anti-TNF therapy were analysed for new onset alanine transaminase (ALT) elevation (≥60 U/L). We collected data on natural history, outcomes and patient characteristics compared with controls with persistent normal liver enzymes. Likelihood of causal association was assessed using the RUCAM score. Results From 1753 patients initiating an anti-TNF (1170 infliximab, 575 adalimumab, 8 certolizumab), 102 (6%) developed new onset ALT elevation. In 54 (53%), this could be linked to an alternate aetiology. Among those with idiopathic ALT elevations, the median time to ALT elevation from anti-TNF initiation was 18 weeks and median peak ALT was 96 U/L. Six underwent liver biopsy, all demonstrating hepatitis with autoimmune features. Compared to controls, cases were on a lower dose of infliximab (5.7 vs. 6.7 mg/kg, P = 0.02) but were otherwise similar in body mass index, sex and age. On follow-up, 34 continued the anti-TNF, 14 stopped therapy and 4 initiated steroids. Most (85%) normalised their LFTs after a median of 17 weeks including 28 (82%) of those who continued anti-TNF therapy. Ten patients were transitioned to a second anti-TNF without recurrence. Conclusions ALT elevations occurred in 6% of IBD patients initiating anti-TNF therapy. Most idiopathic elevations were mild, transient and resolved despite therapy continuation.

SummaryBackground Vitamin D is traditionally associated with bone metabolism. The immunological effects of vitamin D have increasingly come into focus. Aim To review the evidence supporting a role of vitamin D in inflammatory bowel diseases. Methods A comprehensive search was performed on PubMed using the terms ‘crohn's disease’ ‘ulcerative colitis’ and ‘vitamin D’. Results Vitamin D deficiency is common in patients with inflammatory bowel diseases (IBD) (16–95%) including those with recently diagnosed disease. Evidence supports immunological role of vitamin D in IBD. In animal models, deficiency of vitamin D increases susceptibility to dextran sodium sulphate colitis, while 1,25(OH)2D3 ameliorates such colitis. One prospective cohort study found low predicted vitamin D levels to be associated with an increased risk of Crohn's disease (CD). Limited data also suggest an association between low vitamin D levels and increased disease activity, particularly in CD. In a large cohort, vitamin D deficiency (

Introduction: Emerging evidence supports an immunologic role for 25-hydroxyvitamin D (25(OH)D) in inflammatory bowel disease (IBD). Here we examined if pretreatment vitamin D status influences durability of anti–tumor necrosis factor (TNF)–α therapy in patients with Crohn’s disease (CD) or ulcerative colitis (UC). Methods: All IBD patients who had plasma 25(OH)D level checked

Summary Background Patients with inflammatory bowel disease (IBD) are at higher risk for Clostridium difficile infection (CDI). Disruption of gut microbiome and interaction with the intestinal immune system are essential mechanisms for pathogenesis of both CDI and IBD. Whether genetic polymorphisms associated with susceptibility to IBD are also associated with risk of CDI is unknown. Aims To use a well-characterised and genotyped cohort of patients with UC to (i) identify clinical risk factors for CDI; (ii) examine if any of the IBD genetic risk loci were associated with CDI; and (iii) to compare the performance of predictive models using clinical and genetic risk factors in determining risk of CDI. Methods We used a prospective registry of patients from a tertiary referral hospital. Medical record review was performed to identify all ulcerative colitis (UC) patients within the registry with a history of CDI. All patients were genotyped on the Immunochip. We examined the association between the 163 risk loci for IBD and risk of CDI using a dominant genetic model. Model performance was examined using receiver operating characteristics curves. Results The study included 319 patients of whom 29 developed CDI (9%). Female gender and pancolitis were associated with increased risk, while use of anti-TNF was protective against CDI. Six genetic polymorphisms including those at TNFRSF14 [Odds ratio (OR) 6.0, P-value 0.01] were associated with increased risk while 2 loci were inversely associated. On multivariate analysis, none of the clinical parameters retained significance after adjusting for genetics. Presence of at least one high-risk locus was associated with an increase in risk for CDI (20% vs. 1%) (P = 6 × 10−9). Compared to 11% for a clinical model, the genetic loci explained 28% of the variance in CDI risk and had a greater AUROC. Conclusion Host genetics may influence susceptibility to Clostridium difficile infection in patients with ulcerative colitis.

Objective To examine the impact of pregnancy on health-related quality of life (HRQoL) of women with inflammatory bowel disease (IBD). Methods This was a retrospective study in a tertiary referral center and included women with ≥2 short inflammatory bowel disease questionnaire (SIBDQ) scores obtained during their pregnancy. Regression models were used to identify independent factors influencing SIBDQ scores and changes of SIBDQ scores at different time points. Results A total of 32 women (23 CD, 9 UC) with a mean age at pregnancy of 29.4 years and a mean disease duration of 7.8 years were included in the study. The mean pre-pregnancy SIBDQ score in our cohort was 49, which was significantly lower than the values during (55, P

Summary Background A significant proportion of patients with IBD lose response to anti-TNF therapies. There is limited knowledge of the long-term outcomes of those who have failed two anti-TNF agents and commenced a third. Aim To examine the safety and efficacy of third anti-TNF treatment after failure of two prior anti-TNF agents in patients with inflammatory bowel disease. Methods This was a retrospective study of all IBD patients [Crohn's disease (CD), ulcerative colitis (UC)] treated with a third anti-TNF agent after loss of response or intolerance to two prior anti-TNF agents at a single tertiary North American centre. Disease activity, drug therapy and Montreal phenotypes were noted at disease onset and commencement of the third anti-TNF agent. Kaplan–Meier estimates were used to calculate the probability of remaining on the third anti-TNF agent and to identify predictors of long-term clinical response. Results A total of 63 patients (64% women, 57 CD and 6 UC) were included in the analysis. The mean disease duration at initiation of third anti-TNF was 12 years. Thirty-five (55.6%) patients discontinued the third anti-TNF after a mean of 13.2 months. Probability of remaining on the third anti-TNF was 0.69, 0.55, 0.37 and 0.25 at 6, 12, 24 and 36 months respectively. Prior primary nonresponders to the first anti-TNF agent [hazard ratio (HR) 6.4, 95% CI 2.5–16.1] and persistent disease activity at 3 months after commencement of a third anti-TNF (HR 3.2, 95% CI 1.3–7.8) predicted poorer response. Conclusions Over half of patients with inflammatory bowel disease, initiated on a third anti-TNF agent after failure of two prior anti-TNF drugs, are able to remain on the third anti-TNF at 1 year.

SUMMARY Background Recent data suggest that acid suppressive medications may alter factors central to the pathophysiology of inflammatory bowel diseases (IBD), whether through shifts in the intestinal microbiome due to acid suppression or effects on immune function. Aim To assess the relationship between the use of proton pump inhibitors (PPIs) or histamine2-receptor antagonists (H2Ra) and incidence of ‘flares’ (hospitalisation/surgery and change in medication). Methods We conducted a new user cohort study including individuals diagnosed with IBD in British Columbia using linked healthcare utilisation databases (available from July 1996 through April 2006). Propensity-score matched incidence rates during a 6-month follow-up period and rate ratios (RR) and 95% CI were calculated. Results Among 16 151 IBD patients, 1307 Crohn’s disease (CD) and 996 ulcerative colitis (UC) patients experienced a new use of PPIs, whereas 741 CD and 738 UC used H2Ra. All IBD subgroups were matched separately to an equal number of unexposed IBD patients. H2Ra use in CD doubled the risk of hospitalisation/surgery (RR = 1.94; 95%CI 1.24–3.10) and numerically less so in UC patients (RR = 1.11) with widely overlapping CIs (0.61–2.03). Proton pump inhibitors use was associated with medication change in UC (RR = 1.39; 95%CI 1.20–1.62), but without meaningfully, increased risk of hospitalisation/surgery for UC or CD patients. Extending follow-up showed persistence, but attenuation, of all effects. Conclusions Initiation of PPIs or H2Ra may be associated with short-term changes in the course of IBD. Although confounding by indication was adjusted using propensity score matching, residual confounding may persist and findings need to be interpreted cautiously.

Vitamin D deficiency is common in inflammatory bowel disease (IBD). The aim of the study was to determine the prevalence and predictors of vitamin D deficiency in an IBD cohort. It was hypothesized that vitamin D deficiency is associated with increased disease activity and lower health-related quality of life (HRQOL).This was a retrospective cohort study. Harvey-Bradshaw index and ulcerative colitis disease activity index were used to assess disease activity. Short Inflammatory Bowel Disease Questionnaire scores were used to assess HRQOL. Multivariate logistic regression was used to identify independent predictors of vitamin D deficiency and its association with disease activity and HRQOL.The study included 504 IBD patients (403 Crohn's disease [CD] and 101 ulcerative colitis [UC]) who had a mean disease duration of 15.5 years in CD patients and 10.9 years in UC patients; 49.8% were vitamin D deficient, with 10.9% having severe deficiency. Vitamin D deficiency was associated with older age (P = .004) and older age at diagnosis (P = .03). Vitamin D deficiency was associated with lower HRQOL (regression coefficient -2.21, 95% confidence interval [CI], -4.10 to -0.33) in CD but not UC (regression coefficient 0.41, 95% CI, -2.91 to 3.73). Vitamin D deficiency was also associated with increased disease activity in CD (regression coefficient 1.07, 95% CI, 0.43 to 1.71).Vitamin D deficiency is common in IBD and is independently associated with lower HRQOL and greater disease activity in CD. There is a need for prospective studies to assess this correlation and examine the impact of vitamin D supplementation on disease course.

Up to 10% of all patients with Hepatitis C virus (HCV) infection are co-infected with human immunodeficiency virus (HIV); 25-30% of HIV patients are co-infected with HCV. The aim of this study was to examine the association of HCV/HIV co-infection with outcomes of hospitalized patients compared to those with HCV or HIV monoinfection. Using the 2006 Nationwide Inpatient Sample, patients with HCV or HIV monoinfection or HCV/HIV co-infection were identified using ICD-9-CM codes. We compared liver-related and infection-related admission between the three groups of patients. Multivariate logistic regression was performed to identify independent predictors of in-hospital mortality. A total of 474,843 discharges with HCV monoinfection, 206,758 with HIV monoinfection and 56,304 with HCV/HIV co-infection were included. Liver-related admissions were more common in co-infected patients (15.4%) compared to those with HIV monoinfection (3.3%, P < 0.001). Primary infectious hospitalizations were more common in HIV monoinfection (33.9%) compared to co-infected patients (26%, P < 0.001). HCV/HIV co-infection was associated with higher mortality compared to HCV monoinfection (OR 1.41, 95% CI 1.20-1.65) but not when compared to monoinfected-HIV patients. HCV-associated cirrhosis or complications thereof conferred four times greater mortality risk in patients with HIV (OR 3.96, 95% CI 3.29-4.79). The rate of hospitalization for HCV/HIV co-infected patients (23.5%) was significantly higher than those with HCV (14.8%) or HIV (19.9%) (P < 0.001). HCV/HIV co-infection is associated with significantly higher rates of hospitalization and is a risk factor for in-hospital mortality compared to patients with isolated HCV.

Background Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder that is characterized by recurrent episodes of intense vomiting. There are several postulated mechanisms involved in its pathogenesis and one potential explanation for this disorder may be linked to autonomic dysfunction. The aim of our study was to evaluate autonomic nerve function in patients with CVS prospectively. Methods We tested the sympathetic nervous system through postural changes in heart rate (HR) and blood pressure and the thermoregulatory sweat test. The parasympathetic nervous system was tested through the HR response to deep breathing (R-R variability on EKG). Key Results A total of 20 patients who met Rome III criteria for CVS, 14 (70%) women and 6 (30%) men, and 20 controls were enrolled in the study. A total of 17 (85%) CVS subjects and 2 (10%) controls had abnormalities on thermoregulatory sweat testing (P 30 on standing. Of the subjects, 18 (90%) had either abnormal sudomotor function or postural tachycardia or both. The HR response to deep breathing was normal in 19 (95%) subjects with CVS and 18 (95%) controls. Conclusions & Inferences The results of this study suggest that the majority of subjects (90%) with CVS have impairment of the sympathetic nervous system with postural tachycardia and/or sudomotor dysfunction while parasympathetic nerve function appears to be intact. These findings of dysautonomia in CVS have implications in both the diagnosis and treatment of these patients.