Inhibin B and antiMüllerian hormone as surrogate markers of fertility in male and female Crohn's disease patients: a case-control study.

Background: Several studies suggest that women with Crohn disease (CD) have reduced fertility due to decreased ovarian reserve, among other causes. On the other hand, male CD patients could have difficulties conceiving. The present study aimed to test the effect of CD on both male and female fertility potential, Sertoli cell function and ovarian reserve, assessed by inhibin-B (IB) plus IB:FSH ratio (IFR) and antiMüllerian hormone (AMH), respectively. Sexual dysfunction (SD) was studied as secondary endpoint. Methods: We performed a cross-sectional, case-control study. Serum IB levels plus IFR were measured in 58 men with CD and compared to 25 age-matched healthy controls (HC). Serum AMH levels were measured in 50 women with CD and in 30 HC matched by age. SD was assessed by means of the International Index of Erectile Function (IIFE-15) in males and the Index of Female Sexual Function (IFSF) in women. Results: A total of 108 CD patients and 55 HC were included. IB serum levels were significantly lower in CD men than in HC (177 ± 58 vs. 234 ± 75 pg./mL, p = 0.001). IFR was also decreased in CD patients compared to HC (58.27 ± 59.5 vs. 91.35 ± 60.04, p = 0.014). Women with CD > 30 years had lower serum AMH levels compared to HC (1.15 ± 0.74 vs. 2.14 ± 1.68 ng/mL, p = 0.033). In addition, CD women >30 years presented a serum AMH < 2 ng/mL more frequently than HC (90% vs. 40%, p = 0.004). The prevalence of SD was significantly higher among both male and female CD patients compared to HC, without association to fertility potential. Age was the only predictor of low ovarian reserve. Conclusion: Testicular Sertoli cell function assessed through serum IB levels and IFR is decreased in CD male patients compared to HC, regardless of age. Age > 30 years is the single independent predictor of reduced ovarian reserve in women with CD. These results should be confirmed in further studies in order to properly counsel patients with CD and desire for offspring.

Psychological burden and quality of life in newly diagnosed inflammatory bowel disease patients.

Objective: Psychological factors, such as stress, anxiety, and depression, are frequently related to inflammatory bowel disease (IBD). However, few studies have examined these factors in patients newly diagnosed with IBD. The aim of the present study was to test the psychological burden in patients with a recent diagnosis of IBD and the factors related to this psychological burden. Methods: We performed a prospective, multi-center, observational study in patients with a new diagnosis of IBD (≤6 months). The patients were recruited from four different Spanish hospitals. Clinical and demographic characteristics were collected. Patients were evaluated using the Hospital Anxiety and Depression Scale and quality of life questionnaire for patients with inflammatory bowel disease (IBDQ-32). The Scale of Stress Perceived by the Disease was used to assess stressful life events. Results: We included 156 patients newly diagnosed with IBD [69 women; 80 Crohn's disease (CD) and 76 ulcerative colitis (UC)], with a mean age of 42.3 (SD 16.21) years. A total of 37.2% of patients had symptoms of anxiety and 17.3% had symptoms of depression. Quality of life was affected in 30.1% of patients. Factors related to anxiety in early IBD were being a woman and having CD. The only factor related to depression was the presence of comorbidity. Being a woman and having suffered previous stressful life events were factors related to impaired quality of life. Conclusion: Anxiety, depression, and impaired quality of life are frequent in patients with a recent diagnosis of IBD. This psychological burden is greater in women.

Gender Biases and Diagnostic Delay in Inflammatory Bowel Disease: Multicenter Observational Study.

BACKGROUND: Female gender could be a cause of diagnostic delay in inflammatory bowel disease (IBD). The aim of this study was to investigate the diagnostic delay in women vs men and potential causes. METHODS: This multicenter cohort study included 190 patients with recent diagnosis of IBD (disease duration <7 months). Reconstruction of the clinical presentation and diagnostic process was carried out in conjunction with the semistructured patient interview, review, and electronic medical records. RESULTS: The median time from symptom onset to IBD diagnosis was longer in women than in men: 12.6 (interquartile range, 3.7-31) vs 4.5 (2.2-9.8) months for Crohn's disease (CD; P = .008) and 6.1 (3-11.2) vs 2.7 (1.5-5.6) months for ulcerative colitis (UC; P = .008). Sex was an independent variable related to the time to IBD diagnosis in Cox regression analysis. The clinical presentation of IBD was similar in both sexes. Women had a higher percentage of misdiagnosis than men (CD, odds ratio [OR], 3.9; 95% confidence [CI], 1.5-9.9; UC, OR 3.0; 95% CI, 1.2-7.4). Gender inequities in misdiagnosis were found at all levels of the health system (emergency department, OR 2.4; 95% CI, 1.1-5.1; primary care, OR 2.5; 95% CI, 1.3-4.7; gastroenterology secondary care, OR 3.2; 95% CI, 1.2-8.4; and hospital admission, OR 4.3; 95% CI, 1.1-16.9). CONCLUSIONS: There is a longer diagnostic delay in women than in men for both CD and UC due to a drawn-out evaluation of women, with a higher number of misdiagnoses at all levels of the health care system.

This paper shows a longer delay in the diagnosis of inflammatory bowel disease in women compared with men for both Crohn's disease and ulcerative colitis. These differences are present at all levels of the health care system, and misdiagnosis is also more common in women.

Food Protein-Induced Enterocolitis Syndrome in Adulthood: Clinical Characteristics, Prognosis, and Risk Factors.

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) in adults is being increasingly recognized; however, little is known about its characteristics. OBJECTIVE: To describe the clinical characteristics, prognosis, and associated factors in adult FPIES. METHODS: A 10-year prospective study was conducted in the Allergy Section of Alicante General Hospital in adults diagnosed with FPIES. Detailed interviews with patients and oral food challenges (OFCs) were performed to confirm diagnosis or evaluate for tolerance. Comorbidities and possible risk factors were analyzed retrospectively through electronic medical records to assess their association with the disease. RESULTS: One hundred and seven adults with FPIES (93.5% female) were followed for a median of 6.2 years. Abdominal pain was the most common manifestation (96.3%), followed by diarrhea (72%) and vomiting (60.7%). Seafood (59.8%), egg (14%), and milk (10.3%) were the most common triggers, whereas 43.9% reacted to more than 1 food group. We performed 49 OFCs: 9 to confirm diagnosis and 40 to evaluate for tolerance. After a median 3.5 years, 16.8% achieved tolerance. Resolution was correlated inversely with duration of the disease (P = .04) and seafood (P = .023) but not with age of onset. The prevalence of gastrointestinal pathologies such as irritable bowel syndrome (IBS), eosinophilic esophagitis, inflammatory bowel disease, and celiac disease was higher than in the general population. A higher number of FPIES triggers were correlated with also having a diagnosis of IBS (P = .02). CONCLUSIONS: Although adult FPIES normally persists, some patients achieve tolerance. Adults with FPIES have a relatively high prevalence of gastrointestinal pathologies. The predominance of women may be related to hormonal factors. The clinical differences with pediatric FPIES warrant a revision of diagnostic criteria in adults.

Evolution of the emotional impact in patients with early inflammatory bowel disease during and after Covid-19 lockdown / Evolución del impacto emocional en pacientes con enfermedad inflamatoria intestinal temprana durante y después del bloqueo de COVID-19

Background: Patients with inflammatory bowel disease (IBD) are vulnerable to some psychological disorders. Here we describe the psychological impact of a COVID-19 pandemic lockdown in patients with IBD.Methods: This multicenter prospective cohort study included 145 patients recently diagnosed with IBD. Data on clinical and demographic characteristics, anxiety and depression scales, and IBD activity were collected in two telephone surveys, during and after the first COVID-19 lockdown in Spain. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.Results: During lockdown, 33.1% and 24.1% scored high on the anxiety and depression scales, respectively. Independent factors related to anxiety (all values ORs; 95% CIs) during lockdown were female sex (2; 1.2–5.4) and IBD activity (4.3; 1.8–10.4). Factors related to depression were comorbidity (3.3; 1.1–9.8), IBD activity (6; 1.9–18.1), use of biologics (2.9; 1.1–7.6), and living alone or with one person (3.1; 1.2–8.2). After lockdown, anxiety and depression symptoms showed significant improvement, with 24.8% and 15.2% having high scores for anxiety and depression, respectively. Factors related to post-lockdown anxiety were female sex (2.5; 1.01–6.3), Crohn's disease (3.3; 1.3–8.5), and active IBD (4.1; 1.2–13.7). Factors associated with depression were previous history of mood and/or anxiety disorders (6.3; 1.6–24.9), active IBD (7.5; 2.1–26.8), and steroid use (6.4; 1.4–29).Conclusions: Lockdown during the COVID-19 pandemic had a significant psychological impact in patients with IBD. Disease activity was related to the presence of anxiety and depression symptoms during and after lockdown.

Antecedentes: Los pacientes con enfermedad inflamatoria intestinal (EII) son vulnerables a sufrir trastornos psicológicos. En este estudio describimos el impacto psicológico que ha supuesto el confinamiento durante el COVID-19 en pacientes con EII.Métodos: Este estudio de cohorte prospectivo multicéntrico se incluyeron 145 pacientes con diagnóstico de EII reciente. Los datos sobre las características clínicas y demográficas, las escalas de ansiedad y depresión y la actividad de la EII se recogieron en dos encuestas telefónicas, durante y después del primer confinamiento por COVID-19 en España. Se calcularon las odds ratios (OR) y los intervalos de confianza (IC) al 95%.Resultados: Durante el confinamiento, el 33,1% y el 24,1% puntuaron alto en las escalas de ansiedad y depresión respectivamente. Los factores independientes relacionados con la ansiedad (todos los valores OR; IC del 95%) durante el confinamiento fueron el sexo femenino (2; 1,2-5,4) y la actividad de la EII (4,3; 1,8-10,4). Los factores relacionados con la depresión fueron la comorbilidad (3,3; 1,1-9,8), la actividad de la EII (6; 1,9-18,1), el uso de biológicos (2,9; 1,1-7,6) y el vivir solo o con una persona (3,1; 1,2-8,2). Tras el confinamiento, los síntomas de ansiedad y depresión mostraron una mejoría significativa, ya que el 24,8% y el 15,2% tenían puntuaciones altas en ansiedad y depresión, respectivamente. Los factores relacionados con la ansiedad tras el confinamiento fueron el sexo femenino (2,5; 1,01-6,3), enfermedad de Crohn (3,3; 1,3-8,5) y EII activa (4,1; 1,2-13,7). Los factores asociados con la depresión fueron los antecedentes de trastornos del estado de ánimo y/o de ansiedad (6,3; 1,6-24,9), EII activa (7,5; 2,1-26,8), y el uso de esteroides (6,4; 1,4-29).

Evolution of the emotional impact in patients with early inflammatory bowel disease during and after Covid-19 lockdown.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are vulnerable to some psychological disorders. Here we describe the psychological impact of a COVID-19 pandemic lockdown in patients with IBD. METHODS: This multicenter prospective cohort study included 145 patients recently diagnosed with IBD. Data on clinical and demographic characteristics, anxiety and depression scales, and IBD activity were collected in two telephone surveys, during and after the first COVID-19 lockdown in Spain. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: During lockdown, 33.1% and 24.1% scored high on the anxiety and depression scales, respectively. Independent factors related to anxiety (all values ORs; 95% CIs) during lockdown were female sex (2; 1.2-5.4) and IBD activity (4.3; 1.8-10.4). Factors related to depression were comorbidity (3.3; 1.1-9.8), IBD activity (6; 1.9-18.1), use of biologics (2.9; 1.1-7.6), and living alone or with one person (3.1; 1.2-8.2). After lockdown, anxiety and depression symptoms showed significant improvement, with 24.8% and 15.2% having high scores for anxiety and depression, respectively. Factors related to post-lockdown anxiety were female sex (2.5; 1.01-6.3), Crohn's disease (3.3; 1.3-8.5), and active IBD (4.1; 1.2-13.7). Factors associated with depression were previous history of mood and/or anxiety disorders (6.3; 1.6-24.9), active IBD (7.5; 2.1-26.8), and steroid use (6.4; 1.4-29). CONCLUSIONS: Lockdown during the COVID-19 pandemic had a significant psychological impact in patients with IBD. Disease activity was related to the presence of anxiety and depression symptoms during and after lockdown.

Idiopathic acute pancreatitis in patients with inflammatory bowel disease: A multicenter cohort study.

BACKGROUND: Idiopathic acute pancreatitis (IAP) in patients with inflammatory bowel disease (IBD) is not well characterized. Our purpose was to better understand this condition and its natural history. METHODS: Retrospective cohort study conducted at nine Spanish IBD referral centers. Patients with IBD and a first episode of acute pancreatitis (AP) between 1998 and 2018 were included. Patients with a previous episode of AP or a diagnosis of chronic pancreatitis were excluded. IAP and non-IAP were compared by multivariate logistic regression and survival analysis. RESULTS: We identified 185 patients with IBD (68.7% Crohn's disease) and a first episode of AP. Thirty-eight of those 185 (20.6%) fulfilled criteria for IAP. There were no severe cases of IAP. On multivariate analysis, AP before IBD diagnosis (21.1% vs. 3.4%, p = 0.04) and ulcerative colitis (52.6% vs. 23.1%, p = 0.002) were significantly more common in IAP. Further work-up was performed in 16/38 (42%) IAP patients, and a cause was identified in 6/16 (37.5%). Median time from AP to the end of follow-up was 6.3 years (3.1-10). Five-year risk of AP recurrence was significantly higher in IAP group (28% vs. 5.1%, log-rank p = 0.001), with a median time to first recurrence of 4.4 months (2.9-12.2). CONCLUSIONS: IAP represents the second cause of AP in patients with IBD. It is more frequent in ulcerative colitis, and presents a high risk of recurrence. Additional imaging work-up after a first episode of IAP in IBD patients is highly advisable, as it identifies a cause in more than one-third of cases.

Actual Anti-TNF Trough Levels Relate to Serum IL-10 in Drug-Responding Patients With Crohn's Disease.

BACKGROUND: Patients with Crohn's disease (CD) responding to anti-tumor necrosis factor (anti-TNF) show great variability in serum drug levels, even within the therapeutic range. We aimed at exploring the role of inflammatory, genetic, and bacterial variables in relation to anti-TNF through levels in CD patients. METHODS: Consecutive CD patients receiving stable doses of infliximab or adalimumab were included. Clinical and analytical parameters were recorded. Cytokine response, bacterial DNA translocation, and several immune-related genes' genotypes were evaluated, along with serum through anti-TNF drug levels. A linear regression analysis controlled by weight and drug regimen was performed. RESULTS: One hundred nineteen patients were initially considered. Five patients on infliximab and 2 on adalimumab showed antidrug antibodies in serum and were excluded. One hundred twelve patients were finally included (62 on infliximab, 50 on adalimumab). Fourteen patients on infliximab and 15 on adalimumab (22.6% vs 30%, P = 0.37) were receiving an intensified drug regimen. C-reactive protein (CRP), fecal calprotectin, Crohn's Disease Activity Index, leukocyte count, and albumin levels in plasma were not significantly associated with infliximab or adalimumab levels in the multivariate analysis. Serum interleukin-10 (IL-10) levels were directly related to infliximab (Beta = 0.097, P < 0.0001) and adalimumab levels (Beta = 0.069, P = 0.0241). The best multivariate regression model explaining the variability of serum infliximab and adalimumab levels included IL-10. Predicted drug levels by this model robustly fitted with actual drug levels (R2 = 0.841 for infliximab, R2 = 0.733 for adalimumab). CONCLUSION: Serum IL-10 is significantly related to serum anti-TNF levels in CD patients, showing how the disposition of anti-TNF drugs is significantly influenced by the degree of immunological activation.