Erythropoietin in patients with anaemia in rheumatoid arthritis.

Iron status and erythropoietin (Ep) level in serum and urine were determined in 30 patients with anaemia in rheumatoid arthritis. The anaemia in these patients was mild and fulfilled the criteria for anaemia of chronic disorders. The iron status of these patients differed from the iron status in patients with sideropenic anaemia. Serum Ep, level, measured indirectly by the polycythaemic mouse bioassay, was either not detected or when detected it did not correspond to the degree of anaemia. The data suggest that the failure to produce sufficient amount of Ep, among other causes, could be important in the pathogenesis of anaemia in rheumatoid arthritis.     

Celiac disease presenting as the Paterson-Brown Kelly (Plummer-Vinson) syndrome

We describe two patients with Paterson-Brown Kelly (Plummer-Vinson) syndrome whose iron deficiency anemia was due to celiac disease. They presented with dysphagia 13 and 9 yr, respectively, before celiac disease was diagnosed. Neither had gastrointestinal symptoms suggestive of malabsorption. Celiac disease is a recognized cause of chronic iron deficiency and should be considered as an etiological factor for sideropenic dysphagia.     

Argon plasma coagulation ablation of Barrett's oesophagus

Helicobacter pylori has been proposed as a major determinant in multiple gastric disorders. We describe the case of a young adult with a long-standing medical history of sideropenic anaemia and of oral iron consumption dependence with a chronic superficial H. pylori-positive gastritis. All other causes of sideropenic anaemia were carefully excluded. Histology showed a peculiar pattern of non-active H. pylori-positive gastritis. The bacterium was a non-VacA-producing strain. The first attempt at eradication caused a reduction in bacterial load and led to a partial normalization of haematologic variables without improving the ferritin level. A successful second course of eradication therapy completely reversed the anaemia and restored the iron deposit, which persisted at the 29-month follow-up. H. pylori infection can be involved in unexplained cases of iron deficiency anaemia in adults, and its cure can normalize the haematologic picture.     

The aetiology of severe anaemia in pregnancy in Ndola, Zambia

The aetiology of severe anaemia (haemoglobin less than 7.0 g dl-1) has been studied in 37 pregnant Zambians. Aetiology was usually multiple; 31 (84%) had Plasmodium falciparum malaria, 23 (62%) were folate deficient, 13 (35%) were iron deficient, one had sickle-cell anaemia and one had the acquired immunodeficiency syndrome (AIDS). Folate deficiency was most often secondary to malarial haemolysis: iron deficiency was nutritional, but hookworm was contributory in about one-third of patients. The anaemia of malaria and folate deficiency was both more common and more severe than anaemia due to iron deficiency; it was seen in younger women although primigravidae were not over-represented, it occurred earlier in pregnancy, and was associated with low birthweight. AIDS must now be included in the differential diagnosis of anaemia in pregnancy. Vigorous antimalarial treatment and prophylaxis are essential in the management and prevention of anaemia in pregnancy. Total dose iron infusion is indicated only when severe iron deficiency anaemia has been proven, and must be accompanied by antimalarial therapy and folic acid supplements. Because of the risk of transmission of human immunodeficiency virus, it is more important than ever to prevent anaemia and malaria in pregnancy, and to give blood transfusion only as a life-saving treatment.     

Disturbed anal sphincter function following vaginal delivery.

Iron deficiency anaemia may be due to occult bleeding into the gut. However, although clinical investigations may show a high frequency of gastrointestinal tract disease in these patients, the cause-effect relationship between the lesions detected and anaemia remain uncertain. This study aimed to establish whether lesions detected by endoscopy or imaging of the gastrointestinal tract in patients with unexplained iron deficiency anaemia are bleeding continuously. Routine clinical tests were performed in 42 patients with unexplained iron deficiency anaemia referred to this unit. Whole gut lavage and assay of haemoglobin in the gut perfusate were also performed. The main outcome measures were clinical diagnoses (by imaging and endoscopy of the upper gastrointestinal tract and colon); the concentration of haemoglobin in whole gut lavage fluid; and the calculated gastrointestinal blood loss per day. There were 73 clinical, dietary, or iatrogenic factors of possible aetiological importance in the 42 patients--poor diet (10), gross gastrointestinal abnormality (34 in 28 patients), malabsorption (14), coagulation problems (6), and NSAID use (9). The gut lavage test showed, however, that at the time the test was performed, only eight patients were losing more than 2 ml blood daily into the gut, including all four with colonic cancer, one with diffuse gastric vascular ectasia, and one with severe ulcerative oesophagitis. It is concluded that occult gastrointestinal bleeding sufficient to cause anaemia was evident in only 19% of 42 patients. There was a high frequency of other potential causes of iron deficiency in the remainder, suggesting that most of the gastrointestinal diseases and lesions detected in them were probably coincidental. Factors other than blood loss should be considered and treated in patients referred for anaemia assessment.     

Adult oligosymptomatic coeliac disease

Coeliac disease is a chronic pathology of the small intestine. The pathogenic mechanism is caused by gluten intolerance. This disease present a characteristic and unspecific injury that causes nutrients and vitamins malabsorption. In adults is an underdiagnosed entity due to atypical forms. To make a premature diagnosis is basic because gluten-free diet prevent the complications after long-term like the intestinal T lymphoma and other digestives malignancies, and decrease the mortality of these patients. We present a case of adult oligosymptomatic coeliac disease in a patient with iron deficiency anaemia and vaginal bleeding. We study the clinic-nutrition and the alterations evolution of the patient.     

Clinical evaluation of simultaneously administered58Co labelled vitamin B 12 and57Co labelled vitamin B 12 bound to intrinsic factor in patients with pernicious anaemia

Summary The clinical and laboratory data from 75 patients with altered vitamin B 12 absorption were reviewed. In 36 cases the diagnosis of pernicious anaemia had been established. Of these, 14 patients showed malabsorption of radiolabelled vitamin B 12, but the absorption of vitamin B 12 bound to the intrinsic factor (IF) was normal (Group A). The other 22 patients with pernicious anaemia showed altered free and IF-bound vitamin B 12 absorption (Group B). Laboratory and clinical data and the absorption tests (xylose and fat excretion) were more abnormal in group B than in group A.Finally, 39 patients (Group C) with general malabsorption showed alteration of the absorption of free and IF-bound vitamin B 12 (Group C). The clinical and biological data were different in these patients from that found in groups A and B.It is possible that in patients with pernicious anaemia who are untreated an alteration of the intestinal mucosa may produce a malabsorption of vitamin B 12 even in the presence of intrinsic factor.     

Blue rubber bleb nevus syndrome co-existing with celiac disease

BACKGROUND: Anaemia caused by iron deficiency is one of the most common disorders in the world. We describe a patient with iron deficiency anaemia in whom absorption was limited due to celiac disease, superimposed to chronic blood loss due to the blue rubber bleb nevus syndrome, a rare syndrome characterised by multiple cutaneous venous malformations in association with visceral lesions. CASE REPORT: A 54-year-old patient with severe iron deficiency anaemia showed marked rubbery cutaneous lesions on the body surface, extremities, under and on the left side of the tongue as well as in the stomach and duodenum. The appearance and pathological examination of the lesions were consistent with the diagnosis of blue rubber bleb nevus syndrome (BRBNS). Biopsy of the mucosa of the duodenum showed celiac disease. No association between celiac disease and BRBNS has been previously described. CONCLUSION: Combined loss of iron and malabsorption from the gastrointestinal tract can lead to severe iron deficiency. Early recognition of both diseases can result in early treatment. Patients can recover completely with iron suppletion and a gluten-free diet. Recognising typical BRBNS skin lesions would provide a potential diagnosis and could prevent unnecessary procedures or invasive surgery.     

Causes of malabsorption in the elderly

The pathogenesis of malabsorption has been studied in 70 patients who presented over the age of 65 years and who were referred to a special investigative unit. Often more than one cause was apparent. Fourteen patients had pancreatic insufficiency, most of whom had no history of pain, alcoholism or gallstones. Twenty-three patients had the postgastrectomy syndrome or small-bowel diverticulosis or both. There were eight coeliacs aged 65-72 years at diagnosis. Fifteen patients had an anatomically normal small bowel; eight of these were over 80 years old, and 10 had vitamin B12 deficiency of whom five had confirmed pernicious anaemia. Enterobacterial overgrowth was a feature of all diagnostic groups except pancreatic and coeliac disease. Vitamin B12 deficiency may be an effect of malabsorption, but can also be a cause through impairment of enterocyte function. The association of pernicious anaemia and B12 deficiency with otherwise unexplained malabsorption and bacterial overgrowth suggests that gastric atrophy is a major causal factor in this syndrome, combined in some cases with a 'vicious circle' of B12 malabsorption and deficiency.     

Intestinal Mucosa in Children with Geophagia and Iron-Deficiency Anaemia

Twenty-one patients between the ages of 3 1/2 and 16 years, with geophagia and iron deficiency anaemia were investigated by d-Xylose absorption, glucose tolerance tests and oral intestinal biopsy, in addition to routine haematological studies. Two subjects had flat glucose tolerance curves and one had abnormal d-Xylose absorption whereas 13 showed evident but slight histologic changes compatible with malabsorption. Oral iron treatment and a normal diet corrected both the anaemia and the abnormal mucosal histology.     

Rise and fall of the Plummer-Vinson syndrome

Three hypotheses have been proposed for the decreased incidence of Plummer-Vinson disease: non-existence, identity with inlet gastric mucosa of the oesophagus and disappearance of the predisposing condition(s). We examined these possibilities by reviewing our understanding of the syndrome. The early framers disagreed on the cause, but many thought it was a precursor for upper oesophageal carcinoma. Four explanations arose to account for the pathogenesis: iron deficiency; nutritional deficits; autoimmunity; and gastric lesion. We believe the decline in recognition paralleled the improve of dietary status and the treatment of sideropenic anaemia with inorganic iron salts.     

Does active rheumatoid arthritis affect intestinal iron absorption?

One of the causes of anaemia in rheumatoid arthritis is thought to be defective iron absorption. In this study the 59Fe absorption in patients with active rheumatoid arthritis is measured and correlated with the results for bone marrow iron stores (and in some cases with the iron stores in the terminal duodenum), which were assessed simultaneously with semiquantitative methods, and with the serum ferritin concentration. In 11 patients with rheumatoid arthritis and increased bone marrow iron stores, iron absorption was decreased. In five patients it was normal and in three further patients, whose bone marrow iron stores were depleted, iron absorption was maximally increased. According to the results both intestinal malabsorption and defective iron absorption can be excluded as causes.     

Iron Metabolism and Absorption Studies in the X-linked Anaemia of Mice

S ummary . The X-linked anaemia of mice (gene symbol, sla ) is hypochromic and microcytic, and the stainable iron stores are reduced. Chemical estimates of total body iron content and serum iron concentration show low values and the total serum iron binding capacity is elevated in anaemic mice. Rapid plasma iron clearance and increased iron utilization provide further confirmation of iron deficiency in anaemic animals. Alterations in activity of haem-containing enzymes have been sought in the heart, liver and kidney of anaemic mice, and slightly decreased activity found only in kidney cytochrome oxidase.
The blood volume of mice with X-linked anaemia is increased in spite of decreased red cell mass, and thus the anaemia is in part due to dilution. The cause of the increased blood volume has not been elucidated, but it may be related to splenic enlargement. In contrast to iron depleted humans and experimental animals, mice with X-linked anaemia show impaired rather than increased intestinal iron absorption, indicating that the anaemia is a consequence of iron malabsorption. The defect in iron absorption may be an isolated one, since evidence of impaired retention of orally administered radio-iodinated triolein, radio-zinc, radio-copper and radio-cobalt has not been found. It is suggested that the genetically-determined defect in the intestinal mucosa of mice with X-linked anaemia may be due to deficiency of either an enzyme or a carrier substance necessary for the normal transfer of iron from the intestinal mucosal cell to the plasma.     

Incidence of sideropenia and effects of iron repletion treatment in women with subclinical hypothyroidism.

Sideropenia affects ca. 20% of the world population, and iron dependent anemia is the most frequent type of anemia worldwide. The aim of the study was to investigate the incidence of sideropenia and dependent anemia in patients with subtle changes of the thyroid function, such as subclinical hypothyroidism (SH). 57 women with SH and 61 euthyroid controls (CG) were studied. Serum concentrations of T4, T3, TSH, anti-TPO, anti-Tg, ferrum (Fe), ferritin (Frt) total iron binding capacity (TIBC) and blood count were determined. In SH 17 patients (29.8%) presented low Fe levels (<50 microg/dl). 9 (15.7%) also had decreased Frt, confirming iron deficiency, whereas 8 patients presented additionally diminished hematocrit and hemoglobin levels, suggesting manifested sideropenic anemia. In CG, 10 persons (16%) had sideropenia, 6 (9.8%) had low Fe and Frt and only 3 (4.9%) had blood count alterations suggesting manifested sideropenic anemia. In SH, anti-TPO were positive in 39 patients (68%), whereas, in CG only 2 (3.2%) were positive. 8 patients with SH and manifested sideropenic anemia were treated with ironproteinsuccinylate (I-PSL), (80 mg Fe /day, for three months), a new iron compound. The repletion treatment safely led to the clinical and laboratory correction of sideropenia and showed a good tolerability. Furthermore, iron treatment provoked a minor increase of T4 and a mild decline of TSH, but the levels were not significant. These results suggest that sideropenia is a common finding in patients with slightly decreased thyroid activity, and that determination of Frt should be routinely advised. Finally, in the assessment of sideropenia and dependent anemia, evaluation of the thyroid function must be taken into account.     

Iron deficiency anaemia: a review of diagnosis, investigation and management

Iron deficiency anaemia (IDA) is the most common form of anaemia worldwide. In men and postmenopausal women the commonest cause of IDA is blood loss from lesions in the gastrointestinal tract, making it a common cause of referral to gastroenterologists. Causes of IDA relate either to blood loss or iron malabsorption. After confirmation with laboratory tests, gastrointestinal evaluation is almost always indicated to exclude gastrointestinal malignancy. Specific patient groups such as premenopausal women, patients with low-normal ferritin and iron-deficient patients without anaemia may need an individualized approach. A small proportion of patients have recurrent or persistent IDA despite negative standard endoscopies. These patients with obscure gastrointestinal bleeding usually require evaluation of the small bowel with capsule endoscopy or double balloon enteroscopy. Treatment should involve prompt iron replacement plus diagnostic steps directed towards correcting the underlying cause of IDA. Oral iron replacement is cheap and effective, but parenteral (intravenous) therapy may be required due to intolerance, noncompliance or treatment failure with oral therapy.     

Congenital dyserythropoietic anaemia type II (HEMPAS) and haemochromatosis: a report of two cases

We describe two patients with severe iron overload in the context of congenital dyserythropoietic anaemia (CDA) type II, which is characterized by a protein glycosylation defect with impairment of N-glycan synthesis. In both patients a corpuscular, haemolytic anaemia had been diagnosed in early childhood and both patients underwent splenectomy before the age of 9 years. They developed clinical manifestations of haemochromatosis and only re-evaluation during adulthood led to the correct diagnosis. Abnormal glycosylation of proteins involved in iron homeostasis is likely to contribute to the massive hepatic iron accumulation characteristic for CDA type II. Both patients required chelation therapy. This report points out the need to consider CDA in patients presenting with haemochromatosis and anaemia.     

Celiac disease in adults: clinical aspects--role of endoscopy]

Adult coeliac disease has a broad clinical spectrum and remains undetected for years. Among subclinical deficiency states, attributable to coeliac enteropathy, combined iron and folic acid malabsorption is predominant. An unexplained recurrent iron anaemia is an indication for small intestinal biopsy. Gastro-intestinal disorders are present in only 50% of the cases. Coeliac disease is frequently associated with other major histocompatibility complex (MMC)-linked diseases which are mediated by immunological mechanisms: dermatitis herpetiformis, oral ulcerations, IgA nephropathy, rheumatoid arthritis, sarcoidosis. Dermatitis herpetiformis is a useful model for examination of the spectrum of mucosal changes that typify gluten sensitivity and subliminal lesions without villous atrophy. An increased interest is devoted to the intra-epithelial T-lymphocyte population, not only in the small intestine, but at the level of the stomach and the colon. A "rectal challenge" test has been proposed for detecting gluten sensitivity in coeliac patients. Such a test could be an original method of screening, reducing so the need of small intestinal biopsy. The preliminary results are to be confirmed. Until now, jejunoscopy remains mandatory for the diagnosis and the survey of intestinal lesions related to coeliac disease.     

Relevance of the barium follow-through examination in the diagnosis of adult celiac disease

Significant changes on a standard barium follow-through examination in celiac disease have been determined by comparison with functional changes (irritable bowel syndrome), malabsorption without a villous lesion (chronic pancreatitis), and a villous abnormality without malabsorption (dermatitis herpetiformis). Patients with iron deficiency anemia formed the control group. Slight jejunal dilatation (26-30 mm) was found in 15% of the celiacs and 17% of the irritable bowel patients. Dilatation in excess of 30 mm and/or effacement of jejunal fold pattern occurred only with an abnormal jejunal biopsy, in 54% of the celiacs and 33% of the dermatitis herpetiformis patients. Patients with malabsorption by itself and 46% of the celiacs could not be distinguished from those with irritable bowel syndrome. The concept of a malabsorption pattern is considered invalid, and the diagnosis of celiac disease can be reliably established only by peroral jejunal biopsy.     

Course and characteristics of anaemia in patients with rheumatoid arthritis of recent onset.

OBJECTIVE: To describe the incidence, cause, and course of anaemia in rheumatoid arthritis (RA). METHODS: Medical records of 225 patients who received a diagnosis of RA between 1990 and 1992 were reviewed longitudinally for mention of anaemia. Anaemia was classified as anaemia of chronic disease if ferritin concentrations reflected adequate body iron stores. Among iron depleted anaemic patients, iron deficiency anaemia was identified using the response to iron supplementation. RESULTS: Anaemia developed in 64% of the patients, mostly within 18 months of follow up, but disappeared again in 54% of those patients. The prevalence of anaemia varied from 39% to 53% throughout follow up. Iron depletion was found in 38% of anaemic patients; 40% of them did not recover from their anaemia after iron supplementation and were classified as having anaemia of chronic disease. Anaemia of chronic disease thus caused 77% and iron deficiency anaemia 23% of observed anaemia. Recovery from anaemia occurred in 42% of the patients with anaemia of chronic disease and in 72% of iron depleted patients after iron supplementation. Anaemic patients, particularly those with anaemia of chronic disease, had a significantly greater number of the American College of Rheumatism criteria for RA, significantly more erosive joint damage, and significantly increased concentrations of serum rheumatoid factor than patients without anaemia. CONCLUSION: Anaemia appeared as a frequent and dynamic manifestation. Recovery and recurrence of anaemia was observed throughout follow up, leading to a longstanding and relatively high prevalence of the condition. Iron deficiency was diagnosed frequently and follow up revealed a considerable overlap with anaemia of chronic disease, making this the most important cause of anaemia in RA. Recovery from anaemia occurred more frequently in iron depleted anaemic patients than in those with anaemia of chronic disease. Anaemic patients, particularly those with anaemia of chronic disease, seemed to have a more serious course of their RA compared with non-anaemic patients.     

Adult Coeliac Disease with Renal Carcinoma

Summary: A 47-year-old female presented with severe iron deficiency anaemia. Investigation demonstrated malabsorption and jejunal subtotal villous atrophy. The malabsorption responded to a gluten free diet but general deterioration in health occurred several months later. Further investigation revealed a left renal carcinoma which was removed by operation. Her progress since nephrectomy has been satisfactory, with significant improvement in jejunal mucosal changes.
Serial immunological studies have revealed a progressive rise in serum IgA levels. This raises the possibility of milk sensitivity or a developing small bowel lymphoma, but there has been no other evidence to support this.
An association between coeliac disease and renal carcinoma has been reported only once before. The possible significance of this association is discussed.