Background: Myotonic dystrophy type 1 (DM1) is a monogenetic disease affecting many organs. Gastrointestinal symptoms are prevalent and of considerable consequences for affected individuals. The life expectancy is shortened and the objective of the study is to evaluate if gastrointestinal symptoms can predict the outcome of the disease. Method: Fifty-one patients with DM1 were interviewed regarding symptoms from the gastrointestinal tract in the mid-1990s. Survival of all patients was evaluated in 2023 and the impact of symptoms on survival was assessed. Results: At the beginning of the study, the mean age was 35.9 years, (median 37.0, 9–63). At the end of the study 47 out of the 51 patients were deceased at a mean age of 53.7 years (median 55.7, 32.5–79.0). Patients with the congenital form of DM1 (n = 6) died at an age of 46.0 years (median 45.2, 40.0–53.6). There was no correlation between the gastrointestinal symptoms and survival. Conclusion: Albeit prevalent and of considerable clinical consequence, gastrointestinal symptoms are not correlated to survival in myotonic dystrophy type 1.

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. (Oral Surg Oral Med Oral Pathol Oral Radiol 2023;136:691-702)

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.

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.

Abstract is missing (Short communication)

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.

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.

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.

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.

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.

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.

Regulatory T (Treg) cells play a key role in immune system homeostasis by suppressing detrimental immune responses against self-proteins, in particular in the intestine.1 Patients with mutations in the gene FOXP3 display a severe defect of Treg-cell function that results in IPEX syndrome (OMIM 304790) characterized by impaired immune tolerance and multiorgan autoimmunity. Dermatitis, type 1 diabetes, and in particular autoimmune enteropathy are hallmarks of the syndrome. Intestinal Treg cells normally suppress immune responses against harmless dietary antigens and commensal microorganisms, but the intestinal self-proteins that are guarded by Treg cells have not yet been fully identified.

Background and Aims: Acute severe colitis [ASC] is associated with major morbidity. We aimed to develop and externally validate an index that predicted ASC within 3 years of diagnosis.Methods: The development cohort included patients aged 16-89 years, diagnosed with ulcerative colitis [UC] in Oxford and followed for 3 years. Primary outcome was hospitalization for ASC, excluding patients admitted within 1 month of diagnosis. Multivariable logistic regression examined the adjusted association of seven risk factors with ASC. Backwards elimination produced a parsimonious model that was simplified to create an easy-to-use index. External validation occurred in separate cohorts from Cambridge, UK, and Uppsala, Sweden.Results: The development cohort [Oxford] included 34/111 patients who developed ASC within a median 14 months [range 1-29]. The final model applied the sum of 1 point each for extensive disease, C-reactive protein [CRP] >10 mg/l, or haemoglobin < 12 g/dl F or < 14 g/dl M at diagnosis, to give a score from 0/3 to 3/3. This predicted a 70% risk of developing ASC within 3 years [score 3/3]. Validation cohorts included different proportions with ASC [Cambridge = 25/96; Uppsala = 18/298]. Of those scoring 3/3 at diagnosis, 18/18 [Cambridge] and 12/13 [Uppsala] subsequently developed ASC. Discriminant ability [c-index, where 1.0 = perfect discrimination] was 0.81 [Oxford], 0.95 [Cambridge], 0.97 [Uppsala]. Internal validation using bootstrapping showed good calibration, with similar predicted risk across all cohorts. A nomogram predicted individual risk.Conclusions: An index applied at diagnosis reliably predicts the risk of ASC within 3 years in different populations. Patients with a score 3/3 at diagnosis may merit early immunomodulator therapy.

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.

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.

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.

To prospectively follow the evolution of hepatobiliary diseases in a population‐based cohort of patients with inflammatory bowel diseases.

The overall aims of this thesis were to investigate the incidence of inflammatory bowel disease in the Uppsala Region of Sweden, to study the clinical course and the impact of the disease with regards to complications.Patients in Uppsala County were included in the study from the 1st of January 2005 and patients in Falun, Eskilstuna and Aland counties from the 1st of January 2007. The study was closed for all centres on the 31st of December 2009. Mean population in the study region was 305,381 in 2005–2006 and 642,117 in 2007–2009.The mean incidence for ulcerative colitis (UC) during the time period 2005-2009 was 20.0 /100,000/year (95% CI: 16.1-23.9) and for Crohn’s disease (CD) it was 9.9/100,000/year (95% CI: 7.1-12.6). The combined incidence for UC or CD in the area was thus 29.9/100,000/year (95% CI: 25.1-34.7).Half of the UC patients relapsed during the first year. Risk factors for relapse were female gender and young age. Colectomy during the first year was uncommon (2.5%). CD patients with complicated disease had longer symptom duration before diagnosis and less often diarrhoea and blood in stools compared to patients with non-complicated disease. The risk for surgery during the first year was 12%.The prevalence of anaemia at the time of diagnosis was 30% and after one year 18%. Anaemia was more common among newly diagnosed patients with CD compared with UC. 13% of the UC patients developed an acute severe episode. During the first 90 days 22% of these patients were subjected to colectomy. There was a significant difference between University and County hospitals in colectomy frequency (7.5% vs. 41%). The cumulative prevalence of treatment complications was 12% at the hospital with low colectomy rate versus 41% at the hospitals with high colectomy rate.In conclusion, the incidence of UC and CD in Sweden was high compared to international studies. Colectomy frequency for UC during the first year was low. Patients with complicated CD at the time of diagnosis had longer symptom duration and less alarming symptoms compared to uncomplicated disease. Anaemia was a common trait among patients with newly diagnosed IBD and more effort is needed to treat anaemia in these patients. Severe UC can be treated safely with prolonged medical therapy instead of colectomy.