Coeliac disease and hereditary haemochromatosis: association and implications

Coeliac disease and hereditary haemochromatosis are genetic disorders paradoxically associated with altered intestinal absorption of iron. Hereditary haemochromatosis is the most common autosomal recessive disease in the Caucasian population and is characterised by an iron overload state. Coeliac disease, or gluten sensitive enteropathy, on the other hand is frequently associated with iron deficiency anaemia. We report the cases of two patients who developed both coeliac disease and hereditary haemochromatosis. We review the literature of this rare association and examine how the clinical presentation is modified by their co-existence and the potential genetic linkage of these two disorders.     

Kawasaki disease and scald injuries: a possible association

The cause of Kawasaki disease (KD) is still unknown. Evidence is available to support both a conventional infection, as well as a superantigen-mediated illness. The cases of two children who were hospitalized with scald injuries are presented. Both patients became febrile without an infectious source and subsequently developed typical KD, that responded to treatment with intravenous immunoglobulin, without cardiac sequelae. The temporal association between the thermal injury and the onset of KD could be explained by the entry of an infectious agent(s), toxin or superantigen through the compromised skin barrier, leading to an inflammatory vasculitis and the clinical manifestations of KD.     

Antiphospholipid syndrome and palindromic rheumatism: a new possible association

Objective The aim of this study was to report six patients with palindromic rheumatism (PR) in whom signs, symptoms, and/or serologic evidence of antiphospholipid syndrome (APS) developed.Methods The medical histories of the patients were reviewed with special emphasis on age, gender, duration of PR, and lapse of time until antiphospholipid antibodies were detected or APS was diagnosed. Three representative cases are described.Results Two patients were women and four were men. Their mean age was 49.3 years (range 36–80), and the mean duration of PR was 5.5 years (range 3–8). In all patients, raised titers of antiphospholipid antibodies were found on two or more occasions. Two patients developed clinical pictures compatible with APS, two showed symptoms which may be attributable for APS, and raised titers of antiphospholipid antibodies were found in only two.Conclusion It seems that the appearance of these two uncommon conditions together is more than coincidental and may point to a previously unreported clinical association.     

Horton's disease and corticosteroid-responsive hearing loss

BACKGROUND: Temporal arteritis (TA) is a inflammatory panarteritis of the elderly, which may diffuse to all large arteries. Five to 10% of the patients present nonclassical signs with respiratory, vascular, cardiologic, neurologic or hepatic manifestations. We reviewed eighteen cases of TA and deafness in the literature and report two new cases. CASE REPORTS: Our two patients developed sudden, bilateral and corticosteroid responsive hearing loss. One patient developed hearing loss before the diagnosis of TA. CONCLUSION: The mechanism of deafness is probably explained by vertebrobasilar or terminal cochleovestibular arteritis. While the diagnosis of TA is usually easy, it may be difficult in other circumstances. Sensorineural hearing loss may be the first symptom of TA. Prompt recognition and treatment may lead to partial or total improvement of hearing loss in 55% of the cases.     

Coeliac disease and autoimmune cholangitis: a case report

Autoimmune cholangitis can be associated with other autoimmune disorders. The case is described of a 58-year-old female who developed severe microcytic anaemia resistant to oral iron treatment. Evaluation of the patient led to the diagnosis of coeliac disease, a rarely described association. Gluten-free diet and treatment with oral haematinics led to reversal of the anaemia.     

Coeliac disease: changing views

A continuing flow of new scientific developments concerning coeliac disease in the last decade asks for the formulation of new concepts of pathophysiology and clinical considerations. Immunogenetic studies have shown a correlation of the disease to the HLA region on the short arm of chromosome 6, immunological research has led to the concept of a T-cell driven immunologic response of the small intestine, with the identification of highly sensitive and specific antibodies. The understanding of the histopathology of coeliac disease has changed dramatically, initiated by the proposition of a spectrum of gluten sensitive enteropathy by Marsh in 1992. Clinical studies report a significant change in patient characteristics and epidemiology. The incidence of the disease has shifted to a majority of adult coeliacs, the disease may present with less severe symptoms of malabsorption and the screening studies suggest an overall prevalence of up to 1 in 200-300. Histopathology has been standardized; lymphocytic enteritis (Marsh I), lymphocytic enteritis with crypthyperplasia (Marsh II), and villous atrophy, subdivided in partial, subtotal and total (Marsh IIIABC). Special attention is given to a subgroup of 'refractory coeliacs', including the identification of pre-malignant T-cells in the intestinal mucosa. The management of coeliacs primarely consists of monitoring for compliance and complications. Dietetic and medical associations need to establish protocols and offer additional training to undergraduetes, internships, general practitioners and other allied health professionals. It might be relevant to have a low threshold for intestinal biopsies. However, screening asymptomatics may be harmful for individuals. Research is needed to assess the benefits of mass-screening in the future. HLA analysis can contribute towards recognising populations at increased risk.     

Coeliac disease and diabetes

Coeliac disease is associated with type 1 diabetes mellitus more than ten times more frequently than it is present in nondiabetic population. It often exists with minimal signs or without them. It may cause different complications if it would remain without treatment. Active screening of coeliac disease and similarly of autoimmune thyreopathy is therefore an integral part of examination in type 1 diabetic patients.     

Coeliac disease and malignancy

The development of malignancy, particularly lymphoma, is the most serious complication to affect patients with coeliac disease. Although the association has been known for about 40 years, there are still gaps in our understanding. The prevalence of lymphoma and why only some coeliac patients develop this are not clear but environmental and genetic factors must be at work. Based on data from a large coeliac clinic in Derby, about 55 lymphomas per year would arise in the coeliac population of the United Kingdom, of which half would affect the small bowel. Whether patients with coeliac disease who have atypical or no symptoms at diagnosis, are at the same risk as those who are diagnosed as a result of classical symptoms as was more the case in the past, is not known. Some patients, however do have coeliac disease and lymphoma diagnosed at the same presentation. This consideration has implications for initiating screening programmes to detect coeliac disease and thus offer patients a gluten-free diet early that would help to reduce the risk of lymphoma from developing. In this context, case-finding rather than blanket population screening is to be recommended on present evidence. Research into the role of intraepithelial lymphocytes in the genesis of lymphoma has indicated that non-responsive coeliac disease (refractory sprue) and ulcerative jejunoileitis (ulcerative jejunitis) are part of the lymphoma spectrum. The diagnosis of lymphoma can be difficult and the prognosis, in general, is poor, although with modern chemotherapeutic regimes and surgery in selected cases, long-term survival is possible. The best option is to try and prevent lymphoma from arising by advising all patients to adhere to a strict gluten-free diet. Malignant complications of coeliac disease are uncommon but will continue to challenge clinicians and clinical scientists. Unravelling the mechanisms that contribute to the development of lymphoma and other tumours in coeliac disease may well contribute to a wider understanding of oncogenesis.     

Coeliac disease: changing views on gluten-sensitive enteropathy

BACKGROUND: The continuing flow of scientific development in coeliac disease in the past decade points to the need for the formulation of a new concept of pathophysiology and clinical approach to the coeliac condition. Immunogenetic studies have shown a correlation of the disease to the HLA region on the short arm of chromosome 6; immunological research has led to the concept of a T-cell-driven immunologic response of the small intestine, with the identification of highly sensitive and specific antibodies; and our understanding of the histopathology of coeliac disease has changed dramatically, initiated by the proposition of a spectrum of gluten-sensitive enteropathy by Marsh in 1992. Clinical studies report a significant change in patient characteristics and epidemiology. The incidence of the disease has shifted to a majority of adult coeliacs, and it may present with less severe symptoms of malabsorption. Screening studies suggest an overall prevalence of up to 1 in 200-300. METHODS: Update on histopathology concentrating on the work of our research group. RESULTS: We specifically describe the work of our group in Arnhem concerning the identification and validation of the spectrum of intestinal histopathology in gluten-sensitive enteropathy, i.e. lymphocytic enteritis (Marsh I lesion), lymphocytic enteritis with crypt hyperplasia (Marsh II lesion), and villous atrophy, subdivided into partial villous atrophy (Marsh IIIA), subtotal villous atrophy (Marsh IIIB) and total villous atrophy (Marsh IIIC). Special attention is given to a subgroup of 'refractory coeliacs', including the identification of (pre-)malignant aberrant T cells in the intestinal mucosa of these patients. CONCLUSION: New data on immunogenetics, epidemiology, histopathology and patient characteristics point to a significant change of view on coeliac disease.