Treatment and outcome of ulcerative colitis during the first 10 years after diagnosis in a prospectively followed population-based cohort.

BACKGROUND AND AIMS: There is a shortage of studies evaluating the effect of prevalent use of immunomodulators (IMMs) and biologicals on the clinical course of ulcerative colitis (UC) during 10 years. The aim of the present study is to report the use of drugs and surgery as well as mortality in a population based setting. METHODS: Between 2005 and 2009, we identified 330 patients in all ages (3-86 years) with an incident diagnosis of UC in the County of Uppsala, Sweden. They were followed prospectively and the medical notes were retrospectively analysed with special reference to the use of drugs, surgery and mortality. RESULTS: Median follow-up was 11.2 years (inter-quartile range 10.2-12.7). Out of the 330 patients, 298 (90.3%) could be followed for at least 10 years or until death. The cumulative exposure to different drugs was as follows: 5-ASA 96.6%, steroids 73.3%, IMMs 35.4% and biologicals 11.4%. Fourteen patients (4.6%) needed a colectomy during the observation time. Overall mortality in 10 years was 7% (23/330) whereof three patients died as a consequence of the disease or its treatment. Three patients (0.9%) were diagnosed with colonic cancer of whom two also had sclerosing cholangitis. CONCLUSIONS: A frequent use of IMMs and biologicals during 10 years, can result in a low need for colectomy without increased mortality compared to previous reports.

Complications and adverse effects related to surgical and medical treatment in patients with inflammatory bowel disease in a prospectively recruited population-based cohort.

BACKGROUND: Medical adverse effects and surgical complications have been reported during treatment of patients with inflammatory bowel diseases (IBDs). There is however a shortage of studies describing these in the same cohort of patients. AIM: To describe medical adverse effects and surgical complications in a prospectively followed population-based cohort of patients followed for at least 10 years. METHODS: All newly diagnosed patients with ulcerative colitis (UC) and Crohn's disease (CD) in the county of Uppsala between 2005 and 2009 were prospectively followed. At the end of 2019, the medical notes were scrutinised and all medical adverse effects and postoperative surgical complications were registered. RESULTS: A total of 330 patients with UC and 153 patients with CD in all age groups were included in the cohort. Four hundred and forty-two of these (91.5%) could be followed for 10 years or until death. One hundred and twenty-two patients (26.9%) experienced one or more adverse effects during the pharmacological treatment, and 25 of these could be classified as serious. Fifty-seven malignancies were diagnosed during the observation time. Surgery was performed in 16/330 UC and 33/153 CD patients. Frequency of early postoperative complications was 31% for UC patients and 36% for CD patients. Most complications were minor but two patients were re-operated, two needed intensive care and one patient died postoperatively. CONCLUSIONS: Adverse effects related to medical therapy were experienced by approximately every fourth patient, and by every third patient that was operated.

Clinical course of Crohn's disease in a population-based cohort in Uppsala County followed for 10 years.

BACKGROUND AND AIMS: There is a shortage of studies describing the outcome of patients with Crohn's disease (CD) where both biological therapy and immunomodulators (IMMs) have been available. The aim of the present study was to describe the clinical course of the disease, the use of drugs, the need for surgery and mortality in a prospectively recruited population-based cohort of patients followed for 10 years. METHODS: All patients diagnosed with CD in the County of Uppsala in Sweden 2005-2009 were prospectively recruited and followed until the end of 2019. The medical notes were scrutinised and relevant information collected. RESULTS: One hundred and fifty-four patients covering all age groups were diagnosed with CD and 145 (94.2%) could be followed for 10 years or until death. Nine patients were lost to follow up. The following drugs were used: 5-ASA 83%, steroids 84%, IMMs 69% and biologicals 23%. The proportion of penetrating disease increased from 9.7 to 14.5%. Primary bowel resections were performed in 22% of the patients, and none of these had any secondary surgery because of recurrent or progressive disease during the observation time. Twelve patients (7.8%) died during the follow up, and one of these because of a small bowel carcinoma. CONCLUSIONS: In the present study, the clinical course of CD was similar to previous reports during the first year after diagnosis, but the following years were considerably more stable with moderate increase of intestinal damage and totally a low frequency of surgery and no repeated surgery.

Acute severe attacks of ulcerative colitis in a population-based cohort: epidemiology, treatment and outcome.

Background: Although the criteria for acute severe ulcerative colitis have been stable for decades, the epidemiology for this condition has rarely been described in a population-based setting.Aim: To describe the appearance, treatment and outcome of acute severe ulcerative colitis in a population-based cohort of ulcerative colitis diagnosed between 2005 and 2009.Methods: Between 2005 and 2009, all patients diagnosed with ulcerative colitis in the County of Uppsala, a geographical area consisting of an average 318,000 individuals, were included in a cohort that was followed until the end of 2019. Three hundred and thirty patients covering an age interval of 3-86 years, were included. The medical records of the patients were scrutinized with regard to clinical course, drugs prescribed for IBD, hospitalization and surgical interventions. Patients that had left the health care area were contacted through letters except in case of emigration outside the country.Results: Forty-nine patients experienced a first severe attack (14.8%), and six of these were operated (12.2%). Fifteen patients suffered a second or third attack, and one more was operated. One elderly lady died postoperatively from sepsis.Conclusions: Acute severe attacks of ulcerative colitis appeared early after diagnosis and if surgery was escaped, there was no increased need for surgery in case of a new severe attack later.

Collagenous colitis without diarrhoea at diagnosis - a follow up study.

OBJECTIVE: Chronic watery diarrhoea is a classical symptom of collagenous colitis (CC). However, in some cases, the typical histologic findings of CC can be found in patients without this symptom. In this study we have performed a follow up on patients with a confirmed histological diagnosis of CC without the typical symptom watery diarrhoea. PATIENTS AND METHODS: A structured medical record follow-up was performed on the subgroup of patients without watery diarrhoea but diagnosed with the typical CC histologic appearance in a previous study of microscopic colitis. RESULTS: At follow up after a median time of 8 years (range: 0.33-12 years), five of these fifteen patients developed bowel symptoms but only two developed characteristic CC symptoms with watery diarrhoea. CONCLUSION: The majority of patients without chronic watery diarrhoea at diagnosis remained free from this symptom during follow up and only in a few cases symptoms attributed to CC developed.

Clinical course of Crohn's disease during the first 5 years. Results from a population-based cohort in Sweden (ICURE) diagnosed 2005-2009.

OBJECTIVE: The aim of the study was to describe the medical treatment, change in phenotype, need for surgery and IBD-associated mortality during the first 5 years after diagnosis. MATERIAL AND METHODS: Patients diagnosed with Crohn's disease including all age groups in the Uppsala healthcare region in the middle of Sweden 2005-2009 were included in the study. Medical notes were scrutinised and patients contacted. Out of 269 patients, 260 (96.3%) could be followed for 5 full years or until death. RESULTS: The following drugs were used: 5-ASA 66.7%, systemic steroids 76.4%, antimetabolites 56.7% and anti-TNF 20.3%. Described with the Montreal classification, the proportion with inflammatory behaviour decreased from 78.1% to 74.0% from diagnosis to end of the observation, patients with stricturing behaviour increased from 13.0% to 15.4% and patients with penetrating behaviour increased from 8.9% to 10.6%. After the first year, 12.4% had been treated with intestinal resection or colectomy, a figure that increased to 14.8 after 5 years. Two patients suffered an IBD-related death. CONCLUSIONS: Compared to similar patient cohorts, the present study demonstrates that although the course of Crohn's disease seems difficult to change during the first year after diagnosis, the following years up to 5 years shows a more benign course than has usually been described earlier.

Low colectomy rate five years after diagnosis of ulcerative colitis. Results from a prospective population-based cohort in Sweden (ICURE) diagnosed during 2005-2009.

OBJECTIVE: The medical treatment of ulcerative colitis (UC) has seen a change towards a more active attitude during recent years, including both the use of more traditional drugs as well as new biological substances. In this epidemiological study we have evaluated the results of modern treatment of UC in a population-based cohort of patients including all age groups, with regard to relapse rate, colectomy and IBD-associated mortality. MATERIAL AND METHODS: Patients diagnosed with UC in the Uppsala health care region in the middle of Sweden during 2005-2009 were included in the study. Out of 524 patients, 491 (93%) could be followed for five full years or until death. RESULTS: Nineteen patients (3.9%) had died and two of these deaths could be attributed to UC (one postoperative death and one colonic carcinoma). The following drugs were used by the patients during the study period: 5-ASA (91%), systemic steroids (66%), immunomodulators (IMM), mainly thiopurines (26%) and anti-TNF (11%). During the observation period, 74% experienced at least one relapse and 5.3% were subjected to colectomy. Among patients <17 years at diagnosis, colectomy was performed in two (4.8%). CONCLUSIONS: Five years after diagnosis of ulcerative colitis, 5.3% had been subjected to colectomy and two patients (0.38%) had died because of the disease.

Active cytomegalovirus infection diagnosed by real-time PCR in patients with inflammatory bowel disease: a prospective, controlled observational study (.).

OBJECTIVE: It is assumed that cytomegaloviral (CMV) infection in inflammatory bowel disease (IBD) is caused by reactivation due to the immunosuppressive therapy, but the role of CMV as a pathophysiological factor and prognostic marker in IBD is unclear. The aim of this study was to investigate CMV infection in IBD, with real-time polymerase chain reaction (PCR) and immunohistochemistry, with emphasis on newly diagnosed disease. MATERIALS AND METHODS: In this prospective, controlled study, 67 patients with IBD and 34 control patients with irritable bowel syndrome (IBS) or rectal bleeding were included. Serology for CMV was analysed along with CMV DNA in plasma, mucosal biopsies, and faeces. Mucosal biopsies were further analysed with histopathology and CMV immunohistochemistry. RESULTS: Detection of CMV IgM was more common in patients with IBD, compared to controls, 21% versus 3%. CMV DNA was found in 16% of patients with newly diagnosed, untreated IBD and in 38% of steroid-treated patients. Four of the five patients that needed urgent surgery were CMV-DNA positive in at least one of three sample types. None of the controls had detectable CMV DNA. CONCLUSIONS: Active CMV infection was found in high proportions of newly diagnosed untreated patients with IBD, in patients on immunosuppression and in patients in the need of surgery. Low CMV-DNA levels in non-immunosuppressed patients were not a risk factor for the development of more severe IBD, while the detection of CMV DNA in patients on immunosuppressive therapy may foresee disease progression.

Celiac disease, collagenous sprue and microscopic colitis in IBD. Observations from a population-based cohort of IBD (ICURE).

OBJECTIVE: Inflammatory bowel disease (IBD), microscopic colitis and celiac disease are all diseases with worldwide distribution and increased incidence has been reported from many areas. There is a shortage of studies investigating the occurrence of these diseases in the same individual and whether those affected demonstrate any particular phenotype. The aim of the study was to describe the concomitant incidence of microscopic colitis and celiac disease in a population-based IBD cohort. METHODS: All 790 individuals in a prospective population-based cohort included 2005-09 from Uppsala region, Sweden, were reviewed regarding the appearance of microscopic or celiac disease before or after IBD diagnosis. RESULTS: Fifty percent (396/790) of the patients had been examined for the possibility of celiac disease. Seventeen patients with celiac disease were found, representing 2.2% of the cohort. Patients with celiac disease were younger compared to the non-celiac patients and those with colitis had more often an extensive inflammation of the colon. Seventy-one percent (12/17) were women. The majority of the patients were diagnosed with celiac disease before IBD. Five patients with IBD had an earlier diagnosis of microscopic colitis or developed it after the IBD diagnosis. One teenager developed collagenous sprue, misinterpreted as a severe relapse of ulcerative colitis (UC) resulting in colectomy. CONCLUSIONS: The risk for celiac disease seems not to be increased in IBD, but those affected by both diseases seem to be predominantly women with extensive UC. There is a potential association between microscopic colitis and IBD.

Appearance of hepatobiliary diseases in a population-based cohort with inflammatory bowel diseases (Inflammatory Bowel Disease Cohort of the Uppsala Region).

BACKGROUND AND AIM: To prospectively follow the evolution of hepatobiliary diseases in a population-based cohort of patients with inflammatory bowel diseases. METHODS: Between 2005 and 2009, 790 incident cases of ulcerative colitis and Crohn's disease were registered in the Uppsala Health Region, corresponding to an average incidence of 20.0 and 9.9 new cases/100 000 inhabitants/year, respectively. Liver function tests were analyzed in 97.1% and the results of ensuing investigations were summarized. RESULTS: Seventeen patients with primary sclerosing cholangitis were diagnosed corresponding to an overall prevalence of 2.2% (ulcerative colitis 1.7% and Crohn's disease 3.0%, respectively). The median age at diagnosis was 25 years (interquartile range: 17.0-34.0). Among the 92 patients below 17 years of age, three had autoimmune hepatitis and three primary sclerosing cholangitis, summing up to a prevalence of 6.5% immune-mediated hepatobiliary diseases among the pediatric patients. Three patients have undergone liver transplantation and one died of colonic carcinoma. Ten patients have demonstrated persistent elevation of alkaline phosphatases but had a normal magnetic resonance cholangiopancreatography (two patients) or refused further investigation (one patient). CONCLUSION: In this first large prospective population-based cohort of 526 patients with ulcerative colitis (UC) and 264 with Crohn's disease, 17 cases of primary sclerosing cholangitis were found, among whom three (17%) so far have been liver transplanted and one has died of colon carcinoma. The average age of those affected by primary sclerosing cholangitis is considerably lower than usually reported. Ten patients had or have had elevated alkaline phosphatase without confirmed liver or biliary disease.

Physiological and structural anorectal abnormalities in patients with systemic sclerosis and fecal incontinence.

OBJECTIVE: Fecal incontinence is common in systemic sclerosis (SSc), but the underlying mechanisms are not fully understood. The objectives of this study were to characterize anorectal physiological and morphological defects in SSc patients and to correlate the results with incontinence symptoms. MATERIALS AND METHODS: Twenty-five SSc patients underwent anorectal neurophysiological investigations, anal manometry, and ultrasound. RESULTS: Eleven patients (44%) reported incontinence to solid or liquid feces, but no patient reported diarrhea. Increased fiber density (FD) was recorded in 78% of patients with and in 86% of patients without fecal incontinence not significant (NS). Incontinent patients had lower squeeze pressure (SP; median 49.5 mm Hg) in the high-pressure zone (HPZ) than continent patients (median 72 mm Hg; p = 0.01). In two of the incontinent patients, sonographic abnormalities of the internal anal sphincter (IAS) and the external anal sphincter (EAS) were present, whereas in another two patients isolated IAS abnormalities were seen. These four individuals had lower resting pressure at 1 cm and in the HPZ, and lower SP at 2 cm than patients with normal anorectal sonographic findings (p < 0.05). CONCLUSION: Lower voluntary SP in incontinent patients and EAS sonographic abnormalities only in patients with incontinence suggest that the EAS is more important in maintaining fecal continence in SSc patients than has previously been reported. The finding of increased FD in most patients further supports involvement of the EAS function in SSc and could indicate previous nerve injury with consequent incomplete reinnervation.

Microscopic colitis in Uppsala health region, a population-based prospective study 2005-2009.

OBJECTIVE: The aim of this study is to report on the incidence of microscopic colitis (MC), any possible relation with inflammatory bowel disease (IBD), concomitant drug consumption, related diseases and the clinical course of the diseases. METHODS: Both new cases of IBD and MC were registered at the same time in the same geographical area. The study started in the county of Uppsala 2005-2006, and other parts of the surrounding health region were included 2007-2009. Established morphological criteria were used, i.e. a layer of subepithelial collagen band ≥ 10 µm in collagenous colitis (CC) with concomitant inflammation and at least 20 lymphocytes per 100 epithelial cells in lymphocytic colitis (LC). RESULTS: The authors found 272 new cases of MC, 154 with CC and 118 with LC. The mean age-adjusted incidence was 7.0/1,000,000 for CC and 4.8/100,000 for LC. The clinical course was dominated by single episodes with diarrhea or intermittent symptoms, but 14% suffered from chronic diarrhea. In 10% of the cases, diagnosis was made in individuals without chronic watery diarrhea. Although not systematically tested, concomitant celiac disease was found in approximately 5% of the patients. CONCLUSIONS: The incidence of MC in Uppsala health region is similar to other studied areas. The majority of patients had a self-limiting or easily treated condition, but 14% need a more or less continuous medication. Ten percent of the patients demonstrate other symptoms than chronic watery diarrhea. The possibility of concomitant celiac disease should be considered in new cases of MC.

Occurrence of uveitis in a population-based cohort of inflammatory bowel diseases followed for 10 years: an observational study.

OBJECTIVE: The coexistence of inflammatory bowel diseases (IBDs) and uveitis has been known for 100 years. The reported frequency by which these conditions appear in the same patient has varied considerably. The aim of this study was to investigate the occurrence of uveitis in a well-defined population-based cohort of patients with IBD including all age groups and followed for at least 10 years. METHOD AND ANALYSIS: All newly diagnosed patients with ulcerative colitis and Crohn's disease in the county of Uppsala between 2005 and 2009 were prospectively followed. At the end of 2022, the medical notes were checked and all contacts with the healthcare system regarding ocular symptoms were scrutinised. RESULTS: A total of 330 patients with ulcerative colitis and 153 patients with Crohn's disease were included in the cohort. Four hundred and forty-two of these (91.5%) could be followed for 10 years or until death. Thirteen patients with ulcerative colitis were affected by uveitis (3.9%), and one of the patients with Crohn's disease (0.7%). Most often the uveitis was diagnosed after the bowel disease (median 8.9 years, 7.7 years SD). CONCLUSION: Low occurrence of uveitis was identified in the IBD population. All affected individuals except one were diagnosed with ulcerative colitis. Most of the patients had their eye disease around 10 years later than their IBD diagnosis. It is suggested that systemic anti-inflammatory treatment for the IBD protects against intraocular inflammation in this cohort.

Oral manifestations and dental considerations of patients with hereditary hemorrhagic telangiectasia: a scoping review.

OBJECTIVE: We examined the range, nature, and extent of research conducted regarding the oral and dental implications of hereditary hemorrhagic telangiectasia (HHT) to identify gaps in the research and knowledge of the field. STUDY DESIGN: We performed a scoping review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews and 2017 Guidance for the Conduct of Joanna Briggs Institute Scoping Reviews. We searched the MEDLINE and Web of Science databases for all full-text articles published in English from December 1946 to October 2022. RESULTS: We identified 103 articles describing oral and dental considerations of patients with HHT, primarily case reports. Most reported oral telangiectasias of the tongue, lips, and palate. Many reported management of bleeding and the use or recommendation of prophylactic antibiotics before dental procedures. CONCLUSIONS: Oral telangiectasias are commonly found in patients with hereditary hemorrhagic telangiectasia, and dental professionals may be the first to diagnose it in their patients. Early detection and diagnosis are important to prevent potentially fatal outcomes, and prophylactic antibiotics before procedures may be warranted.

Fecal Biomarkers of Neutrophil and Eosinophil Origin Reflect the Response to Biological Therapy and Corticosteroids in Patients With Inflammatory Bowel Disease.

INTRODUCTION: Fecal calprotectin (FC) is a noninvasive tool for examining response to biologics in inflammatory bowel disease (IBD), but its performance in relation to other novel fecal markers of various cellular origins is unknown. METHODS: We performed a prospective multicenter cohort study and included patients with active IBD who provided a fecal sample at initiation of biological therapy. Levels of FC, myeloperoxidase (MPO), human neutrophil lipocalin (HNL), and eosinophil-derived neurotoxin (EDN) were analyzed and related to clinical remission status at 3 months. Changes in levels of markers at 3 months were calculated, and the impact of concomitant use of corticosteroids at baseline was estimated. RESULTS: In patients achieving clinical remission (n = 27), a decrease in levels of FC ( P = 0.005), MPO ( P < 0.001), HNL ( P < 0.001), and EDN ( P < 0.001) was observed, whereas no significant decrease was seen in patients not achieving remission (n = 39). There was a significant difference in the change in the level of MPO ( P = 0.01) and HNL ( P = 0.02) between patients achieving clinical remission and those who did not, but changes in FC and EDN could not differentiate between these groups. Patients with concomitant systemic corticosteroids at inclusion had lower levels of HNL ( P = 0.01) and EDN ( P < 0.001) at baseline, compared with patients without corticosteroids. DISCUSSION: Fecal MPO, HNL, and EDN are all promising biomarkers for assessing the treatment outcome of biologics in patients with IBD. Fecal levels of EDN and HNL are significantly affected by corticosteroids indicating a greater sensitivity to the effects of corticosteroids compared with levels of FC and MPO.

[Osler's disease - a disease with a wide variety of clinical manifestations deserving multidisciplinary competence]. / Mångfasetterade morbus Osler kräver multidisciplinär kunskap.

Hereditary haemorrhagic telangiectasia (HHT, Osler disease) is an autosomal dominant disease with a prevalence of about 1 in 5 000. The most common symptom is epistaxis in 90 percent of patients, with an average onset at the age of 12 years. Pulmonary arteriovenous malformations are present in 15-35 percent of patients and are associated with embolic complications, such as stroke and cerebral abscesses.  No causative treatment for HHT exists. Iron deficiency anaemia is a common complication. It is treated with oral or intravenous iron replacement depending on the response to tranexamic acid and local treatments. Bevacizumab has been reported to be effective in reducing bleeding complications as well as hepatic and cardiac failure. A multidisciplinary center for the treatment of HHT was established at the University Hospital in Uppsala in 2009.

Type I interferon system activation and association with disease manifestations in systemic sclerosis.

OBJECTIVES: To study the presence of interferogenic autoantibodies in systemic sclerosis (SSc) and their correlation with clinical manifestations, serum levels of interferon alpha (IFNalpha) and chemokines of importance in the disease process. METHODS: Peripheral blood mononuclear cells (PBMCs) or purified plasmacytoid dendritic cells (pDCs) from healthy donors were stimulated with sera from patients with SSc (n=70) or healthy individuals (n=30), together with necrotic or apoptotic cell material. The IFNalpha produced and serum levels of IFNalpha, IFN-inducible protein-10 (IP-10)/chemokine (C-X-C motif) ligand 10, monocyte chemoattractant protein-1 (MCP-1)/(C-C motif) ligand-2 (CCL-2), macrophage inflammatory protein-1alpha (MIP-1alpha)/CCL-3 and RANTES/CCL-5 were measured and correlated with the presence of autoantibodies and clinical manifestations in the patients with SSc. RESULTS: Sera from both diffuse SSc and limited SSc contained interferogenic antibodies, which correlated with the presence of anti-ribonucleoprotein and anti-Sjögren syndrome antigen autoantibodies. The pDCs were responsible for the IFNalpha production which required interaction with FcgammaRII and endocytosis. Increased serum levels of IP-10 were associated with vascular manifestations such as cardiac involvement (p=0.027) and pulmonary arterial hypertension (p=0.036). Increased MCP-1 or IFNalpha serum levels were associated with lung fibrosis (p=0.019 and 0.048, respectively). Digital ulcers including digital loss were associated with increased serum levels of IFNalpha (p=0.029). CONCLUSION: An activated type I IFN system previously seen in several other systemic autoimmune diseases is also present in SSc and may contribute to the vascular pathology and affect the profibrotic process.

Different regulation of eosinophil activity in Crohn's disease compared with ulcerative colitis.

The aim of this investigation was to study the involvement of eosinophil and neutrophil granulocytes in different stages of Crohn's disease (CD) and ulcerative colitis (UC). Biopsy samples were taken from the right flexure of the colon and from the rectum in patients with active (n=12) and inactive colonic CD (n=7), patients with active (n=33) and inactive UC (n=24), and from control subjects (n=11). Cell suspensions from biopsies and blood were analyzed by flow cytometry with regards to activation markers and viability. Immunohistochemistry was used to evaluate cell number and degranulation. Blood eosinophils were cultured with Th1 and Th2 cytokines, and the expression of activity markers was assessed by flow cytometry. Eosinophil number, viability, and activity were increased during active CD and UC compared with controls. The activity, assessed as CD44 expression, tended to diminish during inactive CD but was increased further in quiescent UC. Neutrophil number and activity were increased only during inflammation in both diseases. Culture of blood eosinophils with IL-5 and IL-13 caused increased CD44 expression, whereas IL-5 and IFN-gamma induced elevated CD69 expression. We observed different patterns of eosinophil activation in CD and UC, with the highest CD44 expression during quiescent UC. Our in vitro experiments with recombinant cytokines suggest that the diverse mechanisms of eosinophil activation in CD and UC are a result of different cytokine milieus (Th1 vs. Th2). In contrast, neutrophil activation reflects the disease activity in CD and UC, irrespective of Th cell skewing.