Spontaneous regression of disease manifestations can occur in type 1 Gaucher disease; results of a retrospective cohort study

Gaucher disease (GD) is a lysosomal storage disorder, caused by deficient activity of the enzyme glucocerebrosidase. GD is classically divided into three major phenotypes. The most prevailing form is type 1, which presents with variable hepatosplenomegaly, cytopenia, and/or bone disease. In adult patients with mild manifestations, progress of disease might be slow or even absent. As a consequence, treatment with intravenous enzyme replacement or substrate reduction is not always necessary. In the Netherlands, the follow-up of GD patients is centralized, which allows detailed investigation of untreated patients.A retrospective study was conducted in 18 type 1 GD patients, (2 teenagers: 15 and 16 years of age at first visit) who were not treated for at least one year. The chitotriosidase activity, platelet count, hemoglobin level, lumbar bone marrow fat content measured with quantitative chemical shift imaging (QCSI), liver ratio (ml/kg body weight), and spleen volume were recorded. Criteria were developed to score regression, stability or progression of disease.During a mean follow up of 4.5 years (range 1.1–12.2) seven patients (39%) showed spontaneous regression of GD. Eight patients (44%) were stable. Two patients had progressive disease, solely based upon a sustained increase in chitotriosidase activity. A pediatric patient had an increase in splenomegaly but an improvement in bone marrow fat fraction, probably due to aging. Nine patients fulfilled the local criteria to start treatment at first visit, of whom six started treatment within 1.1 to 6.8 years. The other three refused therapy, but nevertheless showed stability or even regression of the disease during a follow up of 4.6, 9.5 and 11.4 years respectively. None of the parameters was predictive of progression or regression of disease.In conclusion, GD in adults can, in some cases, regress spontaneously. No parameters for accurately predicting future disease course exist.     

Oral contraceptive use and the clinical course of Crohn's disease: a prospective cohort study.

BACKGROUND: Women with Crohn's disease are usually advised not to take oral contraceptives, but, unlike smoking, there is no clear association between current oral contraceptive use and more severe disease. AIM: To assess the effect of oral contraceptive use on the clinical course of Crohn's disease. PATIENTS: 331 women, aged 16-50 years, with Crohn's disease and Crohn's disease activity index <200, were enrolled consecutively during a one year period. Patients were classified at inclusion as oral contraceptive users or non-users and smokers or non-smokers. METHODS: A prospective 12-18 month cohort study was used. The main outcome measures were flare up rate and time to flare up. RESULTS: In total, 134 women used oral contraceptives, in most cases low oestrogen formulations. During the study period, 61 oral contraceptive users (46%) developed a flare up, compared with 85 non-users (43%). The hazard ratio for oral contraceptive use was 1.11 (95% confidence interval 0.80 to 1.55). Variables associated with flare up were smoking status, recently active disease, baseline Crohn's disease activity index, and presence of anoperineal lesions. The same results were obtained when the analysis was restricted to patients eligible for a relapse prevention trial. CONCLUSION: Unlike smoking, oral contraceptives have no effect on Crohn's disease activity.     

Clinical course in Crohn's disease: results of a five-year population-based follow-up study (the IBSEN study)

BACKGROUND: There are few population-based, prospective studies on the clinical course in patients with Crohn's disease (CD). AIM: To extend the observation period in a population-based prospective study (the IBSEN study) to find out more about the initial 5-year clinical course in CD patients and to relate the findings to the Vienna classification. METHODS: All patients diagnosed with inflammatory bowel disease (IBD) in southeastern Norway in the 4 years 1990-1993 were followed prospectively. The patients were invited to a systematic follow-up visit at their local hospital 1 and 5 years after inclusion in the study. The visits included a structured interview, a clinical examination and colonoscopy. RESULTS: Out of 843 patients initially diagnosed with IBD, 200 patients with definite CD were alive and had sufficient data for analysis 5 years after diagnosis. Changes in disease localization and behaviour in relation to the Vienna classification were observed in 27 (13.5%) and 35 patients (17.5%), respectively. During the observation period, 56 patients (28%) underwent surgery with intestinal resection, and half of these had disease localized in the terminal ileum. At the time of the 5-year visit, oral sulfasalazin and 5-aminosalicylic acid (5-ASA) were the most frequently used medications (by 54% of the patients), while oral glucocorticosteroids and azathioprine were being used by 25% and 13%, respectively. Seventy-two percent of the patients had taken oral glucocorticosteroids at some time in the course of the 5-year period. The majority of the patients had intestinal symptoms at 5 years, but only 16% had symptoms that interfered with everyday activities. Fourteen percent of the patients had had a relapse-free 5-year course; however, relapse was not related to the initial Vienna classification. When the patients described the clinical course, 44% reported an improvement in symptoms during the follow-up period. CONCLUSIONS: The 5-year clinical course in an unselected cohort of CD patients was mostly mild. The frequency of surgery was lower than that observed in other studies and only a minority of the patients had symptoms that interfered with everyday activities 5 years after the initial diagnosis. The Vienna classification predicted the risk of surgery, but did not predict symptoms at 5 years, relapses during the observation period or the course of disease as described by the patients.     

Does active smoking really influence the course of Crohn's disease? A retrospective observational study

BackgroundActive smoking has been associated with a higher risk of developing Crohn's disease (CD). However, its impact on clinical outcomes has been controversial among studies.AimsTo evaluate the influence of active smoking on initial manifestations of CD, the development of disease-related complications, and therapeutic requirements.MethodsPatients diagnosed with CD within a ten-year period (1994–2003) were identified. Clinical and therapeutic features until October 2008 or loss of follow-up were recorded. Smoking status was assessed at each major disease-related event (e.g. penetrating and stricturing complications, perianal disease, intestinal resection, introduction of immunomodulators or biological agents).ResultsA total of 259 patients were included in the study with a median follow-up period of 91 months. At diagnosis, 50.5% were active smokers and only 12% of them quit smoking during follow-up, mostly after a major disease-related event occurred. Smoking at diagnosis was not associated with a particular CD presentation. Active smoking did not influence the development of strictures, intraabdominal and perianal penetrating complications, or increased resectional surgery, biological therapy or immunomodulators requirements.ConclusionsPatients who develop CD while smoking seem to have a similar disease course to those who never smoked.     

Epidemiology and clinical course of Crohn's disease: results from observational studies

The authors review the clinical outcome in patients with Crohn's disease (CD) based on studies describing the natural course of the disease. Population-based studies have demonstrated that the incidence rates and prevalence rates for CD have increased since the mid-1970s. The authors search for English language articles from 1980 until 2011. Geographical variations, incidence, prevalence, smoking habits, sex, mortality and medications are investigated. An increasing incidence and prevalence of CD have been found over the last three decades. The disease seems to be most common in northern Europe and North America, but is probably increasing also in Asia and Africa. Smoking is associated with an increased risk of developing CD. Age < 40 at diagnosis, penetrating/stricturing complications, need for systemic steroids, and disease location in terminal ileum are factors associated with higher relapse rates. A slight predominance of women diagnosed with CD has been found. Ileocecal resection is the most commonly performed surgical procedure, and within the first five years after the diagnosis about one third of the patients have had intestinal surgery. Smoking is associated with a worse clinical course and with increased risk of flare-ups. In most studies the overall mortality is comparable to the background population. To date, the most effective treatment options in acute flares are glucocorticosteroids and tumor necrosis factor (TNF)-α-blockers. Azathioprine/methotrexate and TNF-α-blockers are effective in maintaining remission.     

A prospective study of the course of Crohn's disease

To better define the course of Crohn's disease, certain clinical, laboratory, and radiological features were studied prospectively in a representative group of 25 patients at intervals of up to 77 months. Eleven variables of potential use in assessing the course were analyzed for clinician preference, and the statistical relationship of one variable, the Crohn's disease activity index, to the other 10 was determined. Modest improvement was documented in three clinical variables, as well as in anemia, serum albumin, intestinal protein loss, and radiological extent of disease. Variables most frequently ranked high as reflections of the course of Crohn's disease were hematocrit and extent of disease, followed by body weight, stools per day, B₁₂ absorption, serum albumin, and intestinal protein loss. The highest intervariable correlation was between improvement in protein loss and decrease in radiological extent (r=0.75).Supported by the John A. Hartford Foundation Inc., and General Clinical Research Centers Grant RR109.     

Phenotype of histologically suspected drug-induced colitis; results of a comparative,retrospective cohort study

Abstract

Background/aims: Drug-induced colitis (DiC) is a rarely reported form of colonopathy and data about the clinical and endoscopic characteristics are scarce. The aim was to investigate the phenotype of DiC.

Methods: Patients in a retrospective case control study were assigned to either DiC or one of two age- and gender-matched control groups (non-inflammatory controls and inflammatory colitis from other causes) based on histopathological findings. Patients’ basic characteristics, symptoms, biochemical results and endoscopic appearance were collected. Statistical analysis included ANOVA, the chi-squared test and two-tailed t-test.

Results: A total of 211 patients with DiC were included (97 males, age 62.1?±?16.1 years, BMI 25.9?±?6.1?kg m^?2). In comparison to both control groups, DiC patients presented higher ASA and ECOG-scores and more particularly atherosclerotic comorbidities. The most abundant symptoms were abdominal pain (51.8%), diarrhoea (50.7%) and haematochezia (24.3%). The red blood cell count demarcated anaemia (12.7?±?2.3?mg/dl) and C-reactive protein was slightly elevated (2.7?±?5.2?mg/dl). The endoscopic features included erythema (46.9%), oedema (29.9%), erosions (29.9%) and ulcers (14.7%). The inflammation affected the rectum rarely (2.4%) but affected the rest of the colon without predilection in a segmental manner (p<.05). The severity of DiC was mostly mild (85.7%).

Conclusions: The phenotype of DiC differs slightly from that of colitis from other causes. Taking the clinical features into account might help to confirm drug-induced aetiology once the pathologist has raised the suspicion.     

Feasibility and safety of granulocytapheresis in Crohn's disease: a prospective cohort study

Background and objective

This study evaluated the feasibility and safety of granulocytapheresis (GCAP) in inducing and maintaining remission in refractory Crohn's disease. The relationship between the clinical outcomes and the location (ileal or ileocolonic) of disease was also assessed.

Patients

We evaluated 16 patients with ileal location (group A), 14 with ileocolonic location (group B). The patients underwent five sessions (1 session/wk) of GCAP (Adacolumn^TM). CDAI was measured at the end of the GCAP, at 6, 9 and 12 months.

Results and conclusions

No major complications were observed. At the end of GCAP, 19 (63.3%) patients showed a clinical remission: 10 (62.5%) in group A versus 9 (64.2%) in group B. At 6 months, 16 (53.3%) of the cases had maintained remission: 9 (56.2%) in group A versus 7 (50.0%) in group B. At 9 months, 13 (43.3%) patients had maintained remission: 7 (43.7%) in group A versus 6 (42.8%) in group B. At 12 months, 12 (40%) patients were still in clinical remission: 7 (43.7%) in group A versus 5 (35.7%) in group B. Risk of relapse was not related to disease location. The procedure was well tolerated and feasible in an important percentage of Crohn's disease patients.     

Childhood adversities and mid-late depressive symptoms over the life course: evidence from a retrospective cohort study in China

Background

The cumulative effect of childhood adversities on depressive symptoms in later life is well documented in many countries. However, there is a dearth of accurate information about this effect in the Chinese population. We aimed to examine the cumulative effect of childhood adversities on depressive symptoms in mid-to-late life, using data from the Chinese population.

Treatment of Crohn's disease with anti-TNF alpha antibodies (infliximab): results of a multicentric and retrospective study

OBJECTIVE: To evaluate the results of infliximab therapy, an anti-TNF-alpha antibody, in patients with severe and refractory Crohn's disease or with fistulas, treated outside the setting of a therapeutic trial. METHODS: All Crohn's disease patients treated at the Departments of Gastroenterology of the University Hospitals of Bordeaux, Nantes, Poitiers, Rennes and Tours were retrospectively analyzed. RESULTS: Sixty-nine patients were treated with a total of 170 infusions of infliximab, 32 patients being treated for refractory Crohn's disease and 37 for fistulas. The median follow-up was 8 months (extremes 1-20). An objective response was observed in 79% of refractory Crohn's disease patients and 78% of fistulazing patients. A remission was observed in 72% and 70% of the patients respectively. Forty-five percent of patients had relapsed within 4 months (extremes 2-7). Immunosuppressive therapy was associated with a lower relapse rate (18% with versus 56% without, P=0.004). Infliximab resulted in a steroid-sparing effect in 73% of patients. Forty adverse events, none of severe grade, were observed in 22% of the patients, without any influence of steroids or immunosuppressive therapy. CONCLUSION: This study confirms that infliximab is very effective in steroid-dependent and fistulazing Crohn's disease. Infliximab has a steroid-sparing effect and immunosuppressive therapy is associated with a reduced relapse rate. Although the tolerance is good in the short term, long term safety remains to be established by further studies.