Significance of low ferritin without anaemia in screen-detected, adult coeliac disease patients.

BACKGROUND: Low ferritin without anaemia has been linked to adverse health effects. OBJECTIVES: To investigate the prevalence and clinical significance of low ferritin in screen-detected coeliac disease. METHODS: Seventy-six screen-detected coeliac disease patients were enrolled in the prospective collection of comprehensive clinical, laboratory and histological data at diagnosis and after 1-2 years on a gluten-free diet (GFD). All variables were compared between patients with different ferritin levels. RESULTS: At coeliac disease diagnosis, six patients had anaemia. Of the 70 nonanaemic patients, ferritin levels were <15 µg/L in 21%, 15-29 µg/L in 19%, 30-99 µg/L in 36% and ≥100 µg/L in 24%. Those with lower ferritin were more often females, had lower body mass index, haemoglobin and villous height-crypt depth ratio and also had higher intra-epithelial lymphocyte CD3+ levels in duodenal biopsies. The groups did not differ in neurological or gastrointestinal symptoms, health-related quality of life, bone mineral density, liver values, vitamin, albumin or coeliac autoantibody levels or the prevalence of comorbidities. Median ferritin levels increased from 41.5 µg/L to 86.0 µg/L on GFD (p < 0.001). Ferritin remained <30 µg/L in 21% of patients but was not associated with dietary compliance, nor was any correlation between changes in ferritin and quality of life, gastrointestinal symptoms, autoantibody levels or degree of histological damage detected. CONCLUSION: Decreased ferritin is a frequent finding in screen-detected coeliac disease and may not be fully restored on a GFD. However, low ferritin levels are not associated with more severe symptoms or poorer quality of life.

Clinical Relevance of Anti-Gliadin Seropositivity in the Ageing Population: A Long-term Follow-up Study.

AIMS: To explore if anti-gliadin antibody (AGA) positivity is associated with overall mortality or morbidity and especially with the development of coeliac disease during long-term gluten exposure. METHODS: The study population comprised 130 persistently AGA-positive but transglutaminase-2 (anti- TG2) -negative and 52 persistently AGA- and anti-TG2 -negative subjects aged 64-88 years. HLA-typing for DQ2 and DQ8 (coeliac-type HLA) was performed on the AGA-positives. The medical records of the study population were reviewed to compare mortality and morbidity during a long-term follow-up of 12-13 years since the initial antibody analysis. RESULTS: Mortality or cumulative prevalence of gastroenterological, autoimmune, psychiatric, cardiovascular or any malignant diseases did not differ statistically between the AGA-positives and the AGA-negatives. Neurological diseases were more common in the AGA-negative group (p=0.017), but there was no statistical difference between the prevalence of any particular neurological diseases. Coeliac-type HLA in AGA-positive subjects did not influence mortality or morbidity. However, during the last six to seven years the incidence of immunological diseases was more common in the AGA-positive subjects without coeliac-type HLA than in those with coeliac-type HLA, or in the AGA-negative group (p=0.020). None of the persistently AGA-positive subjects developed clinically diagnosed coeliac disease. CONCLUSIONS: Gliadin antibody positivity without coeliac disease does not predict mortality or morbidity in the ageing population continuing to consume gluten for over ten years.

Safety of alemtuzumab in a nationwide cohort of Finnish multiple sclerosis patients.

BACKGROUND: Alemtuzumab is an effective disease-modifying therapy (DMT) for highly active multiple sclerosis (MS). However, safety concerns limit its use in clinical practice. OBJECTIVES: To evaluate the safety of alemtuzumab in a nationwide cohort of Finnish MS patients. METHODS: In this retrospective case series study, we analyzed the data of all but two MS patients who had received alemtuzumab in Finland until 2019. Data were systematically collected from patient files. RESULTS: Altogether 121 patients were identified, most of whom had received previous DMTs (82.6%). Median follow-up time after treatment initiation was 30.3 months and exceeded 24 months in 78 patients. Infusion-associated reactions (IARs) were observed in 84.3%, 57.3%, and 57.1% of patients during alemtuzumab courses 1-3, respectively. Serious adverse events (SAEs) were observed in 32.2% of patients, serious IARs in 12.4% of patients, and SAEs other than IARs in 23.1% of patients. Autoimmune adverse events were observed in 30.6% of patients. One patient died of hemophagocytic lymphohistiocytosis, and one patient died of pneumonia. A previously unreported case of thrombotic thrombocytopenic purpura was documented. CONCLUSIONS: SAEs were more frequent in the present cohort than in previous studies. Even though alemtuzumab is a highly effective therapy for MS, vigorous monitoring with a long enough follow-up time is advised.

Serology-based criteria for adult coeliac disease have excellent accuracy across the range of pre-test probabilities.

BACKGROUND: The revised paediatric criteria for coeliac disease allow omission of duodenal biopsies in symptomatic children who have specific serology and coeliac disease-associated genetics. It remains unclear whether this approach is also applicable for adults with various clinical presentations. AIM: To evaluate the accuracy of serology-based criteria in adults with variable pre-test probabilities for coeliac disease. METHODS: Three study cohorts comprised adults with high-risk clinical coeliac disease suspicion (n = 421), moderate-risk family members of coeliac disease patients (n = 2357), and low-risk subjects from the general population (n = 2722). Serological and clinical data were collected, and "triple criteria" for coeliac disease comprised transglutaminase 2 antibodies >10× the upper limit of normal, positive endomysium antibodies, and appropriate genetics without requirement of symptoms. The diagnosis was based on intestinal biopsy. RESULTS: The diagnosis of coeliac disease was established in 274 subjects. Of these, 59 high-risk subjects, 17 moderate-risk subjects, and 14 low-risk subjects fulfilled the "triple criteria". All had histologically proven coeliac disease, giving the criteria a positive predictive value of 100%. Altogether, 90 (33%) of all 274 newly diagnosed patients could have avoided biopsy, including 37% among high-risk, 20% among moderate-risk, and 48% among low-risk patients. No histological findings other than coeliac disease were found in the biopsies of "triple positive" subjects. CONCLUSIONS: Coeliac disease can reliably and safely be diagnosed without biopsy in adults fulfilling the "triple criteria" regardless of the pre-test probability. Revised criteria would enable the number of endoscopies to be reduced by one-third.

The Use of MoCA and Other Cognitive Tests in Evaluation of Cognitive Impairment in Elderly Patients Undergoing Arthroplasty.

OBJECTIVE: To examine the prevalence and effect of cognitive impairment on treatment outcomes in elderly patients undergoing arthroplasty and to describe the feasibility of cognitive tests. MATERIALS AND METHODS: The participants were 52 patients with a mean age of 78 years 11 months (SD: 3.3), waiting for primary arthroplasty. We translated Montreal Cognitive Assessment (MoCA) into Finnish and compared it with Mini-Mental State Examination (MMSE), Mini-Cog, and clock-drawing tests prior to and 3 months after the surgery. The ability to perform activities of daily living, depression, quality of life, and years of education were evaluated. RESULTS: The mean MoCA score on the first visit was 20.7 (SD: 4.1). The pre- and postoperative cognitive tests implied there were no changes in cognitive functioning. Unambiguous delirium was detected in 6 patients. Delirium was not systematically assessed and consequently hypoactive delirium cases were possibly missed. Both MMSE and Mini-Cog found 3/6 of those and clock drawing and MoCA 6/6. Low preoperative MoCA, MMSE, and Mini-Cog scores predicted follow-up treatment in health-care center hospitals (P = .02, .011, and .044, respectively). During the 5-year follow-up period, 11/52 patients died. Higher education was the only variable associated with survival. The survivors had attained the median of 8 (range: 4-19) years of education compared with 6 (range: 4-8) years among the deceased. CONCLUSION: The prevalence of cognitive impairment among older patients presenting for arthroplasty is high and mostly undiagnosed. It is feasible to use the MoCA to identify cognitive impairment preoperatively in this group. The clock-drawing test was abnormal in all patients with postoperative delirium, which could be used as a screening test. Higher education predicted survival on a 5-year follow-up period.

Clinical benefit of gluten-free diet in screen-detected older celiac disease patients.

BACKGROUND: The utility of serologic screening for celiac disease is still debatable. Evidence suggests that the disorder remains undetected even in the older population. It remains obscure whether screening makes good or harm in subjects with long-standing gluten ingestion. We evaluated whether older subjects benefit from active detection and subsequent gluten free dietary treatment of celiac disease. METHODS: Thirty-five biopsy-proven patients aged over 50 years had been detected by serologic mass screening. We examined the disease history, dietary compliance, symptoms, quality of life and bone mineral density at baseline and 1-2 years after the commencement of a gluten-free diet. Symptoms were evaluated by gastrointestinal symptom rating scale and quality of life by psychological general well-being questionnaires. Small bowel biopsy, serology, laboratory parameters assessing malabsorption, and bone mineral density were investigated. RESULTS: Dietary compliance was good. The patients had initially low mean serum ferritin values indicating subclinical iron deficiency, which was restored by a gluten-free diet. Vitamin B12, vitamin D and erythrocyte folic acid levels increased significantly on diet. Celiac patients had a history of low-energy fractures more often than the background population, and the diet had a beneficial effect on bone mineral density. Alleviation in gastrointestinal symptoms was observed, even though the patients reported no or only subtle symptoms at diagnosis. Quality of life remained unchanged. Of all the cases, two thirds would have been diagnosed even without screening if the family history, fractures or concomitant autoimmune diseases had been taken carefully into account. CONCLUSIONS: Screen-detected patients benefited from a gluten-free diet. We encourage a high index of suspicion and active case-finding in celiac disease as an alternative to mass screening in older patients.

Persistently positive gliadin antibodies without transglutaminase antibodies in the elderly: gluten intolerance beyond coeliac disease.

BACKGROUND: The specificity of the conventional gliadin antibody test is considered low. AIMS: We explored whether gliadin antibody(AGA)-positivity without tissue transglutaminase antibodies (tTGA) is persistent in the elderly population and whether such positivity indicates overt or potential coeliac disease in genetically predisposed individuals. METHODS: AGA and tissue transglutaminase antibody were measured in 2089 elderly individuals twice with a three-year interval. AGA-positive but tissue transglutaminase antibody-negative subjects with coeliac-type human leucocyte antigen (HLA) were examined and underwent gastroduodenal endoscopy (cases). Small-bowel mucosal villous morphology and densities of CD3+ and γδ+ intraepithelial lymphocytes and the occurrence of tissue transglutaminase-specific IgA deposits were analysed. Randomly selected persistently AGA-negative age- and sex-matched subjects served as controls. RESULTS: AGA-positivity was persistent in 81% of those initially positive. Amongst the 49 clinically studied and 36 endoscopied cases only one (2.8%) had coeliac disease. Many (54%) showed signs of inflammation in the biopsy, without villous atrophy. Coeliac-type HLA was not over-represented in the persistently AGA-positive compared to the general population. Persistently AGA-positive coeliac-type HLA-positive subjects had more gastrointestinal symptoms than AGA-negative controls. CONCLUSIONS: AGA-positivity is often persistent. Overt coeliac disease is seldom found behind persistent AGA-positivity, but this characteristic is associated with mucosal inflammation and gastrointestinal symptoms at least in HLA-positive individuals.

Late-onset Rasmussen's encephalitis and long-term remission.

We describe an adult man with biopsy-proven Rasmussen's encephalitis and intractable epilepsy, who underwent excellent recovery. To our knowledge, this is the first report of a patient with Rasmussen's encephalitis who has become completely symptomless, at least for three years, on enhanced antiepileptic and immunological medication.

Positive serum antigliadin antibodies without celiac disease in the elderly population: does it matter?

OBJECTIVE: Antigliadin antibodies (AGA) show good sensitivity but low specificity for celiac disease and can also be found in healthy individuals. However, data suggest that AGA positivity might be related to distinct disease entities such as allergy and gluten ataxia. Our aim here is to explore the clinical relevance of positive AGA in the elderly population. MATERIAL AND METHODS: Serum IgA- and IgG-class AGA and IgA-class tissue transglutaminase antibodies (tTGA) were determined in 2815 individuals aged 52-74 years. Equal numbers of AGA- and tTGA-negative participants of similar age and gender, but without known celiac disease, were randomly selected as controls. Information on clinical history was obtained from hospital records in all groups. RESULTS: Altogether 381 persons were positive for IgA/IgG-class AGA; 38 (14%) of them were also positive for tTGA. Out of the biopsied subjects, 34 (100%) in the AGA+ tTGA+ group and five (9%) in AGA+ tTGA- group had celiac disease. Rheumatoid arthritis and depression were found significantly more often in AGA-positives than controls. The significance remained even when tTGA-positive and known celiac disease cases were excluded. No statistical differences were found in the occurrence of neurological diseases, diabetes, allergic and cardiovascular diseases or malignancies. CONCLUSIONS: Although AGA positivity is of clinical relevance only in a subset of elderly people, it seems to be related to rheumatoid arthritis and depression, both conditions linked to celiac disease. Further studies are needed to reveal the mechanisms underlying this. The poor specificity of AGA for celiac disease was here once more in evidence.

Increasing prevalence and high incidence of celiac disease in elderly people: a population-based study.

BACKGROUND: Celiac disease may emerge at any age, but little is known of its appearance in elderly people. We evaluated the prevalence of the condition in individuals over 55 years of age, and determined the incidence of biopsy-proven celiac disease (CDb) and celiac disease including seropositive subjects for anti-tissue transglutaminase antibodies (CDb+s). METHODS: The study based on prevalence figures in 2815 randomly selected subjects who had undergone a clinical examination and serologic screening for celiac disease in 2002. A second screening in the same population was carried out in 2005, comprising now 2216 individuals. Positive tissue transglutaminase antibodies were confirmed with small bowel biopsy. RESULTS: Within three years the prevalence of CDb increased from 2.13 to 2.34%, and that of CDb+s from 2.45 to 2.70%. Five new cases were found among patients previously seronegative; two had minor abdominal symptoms and three were asymptomatic. The incidence of celiac disease in 2002-2005 was 0.23%, giving an annual incidence of 0.08% in this population. CONCLUSION: The prevalence of celiac disease was high in elderly people, but the symptoms were subtle. Repeated screening detected five biopsy-proven cases in three years, indicating that the disorder may develop even in the elderly. Increased alertness to the disorder is therefore warranted.

Diagnostic lumbar puncture. Comparative study between 22-gauge pencil point and sharp bevel needle.

Post-lumbar puncture headache is a frequent clinical problem. Needle design is expected to reduce post-puncture headache. In this study, we compared two different lumbar puncture needle designs in diagnostic lumbar puncture and analysed post-dural puncture headache (PDPH) and social and economical harm associated with the diagnostic lumbar puncture procedure. This prospective, controlled study consisted of 80 consecutive adult patients requiring elective diagnostic lumbar puncture due to various neurological symptoms. Lumbar puncture was completed either with Spinocan 22 G sharp bevel needle or Whitacre 22G pencil point needle. Patients were asked about previous headache symptoms and pain provoked by puncture. One week after the lumbar puncture all patients were interviewed by telephone and occurrence and type of headache, headache intensity, medication and frequency of impairment in activities of daily living were asked. Need for epidural blood patch was also recorded. Thirty-three of 78 (42%) patients experienced headache after diagnostic lumbar puncture and in 26 (33%) the headache could be classified as PDPH. There were no statistically significant differences between needle types in the frequency of common headache, PDPH, puncture pain intensity, need for epidural blood patch or sick leave. Also, there were no other complications except local back pain or headache. In this study, the needle design did not affect the frequency of PDPH. Also, PDPH was common, occurring in 33% cases and caused a considerable amount of disturbance in daily activities. Seeking help for this condition was insufficient and only part of these PDPH patients were treated with epidural blood patch.