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Re: My Approach. An approach to duodenal biopsies
We read with interest the section in this review of duodenal pathology describing AIDS enteropathy. However, the histological description of the lesion by Serra and Jani 1 does not accurately reflect the majority of literature on the subject and the comments regarding pathogenesis are confused.
The pathogenesis of villous at...
The pathogenesis of villous atrophy in the small intestinal mucosa of many patients infected with HIV (HIV enteropathy), and the significance of reduced mucosal absorptive surface area in the aetiology of diarrhoea,
remain controversial in spite of two decades of investigation.2 The bowel is one system which merits further study in AIDS.3 The paper of Serra and Jani describes villous atrophy with crypt hypoproliferation, and yet also details a hyper-regenerative crypt response to villous atrophy mediated by cytokine effects.
Villous atrophy in the small intestine of patients infected with HIV has indeed been associated with both hyperproliferative4-8 and hypoproliferative9-11 activity in crypts. There is also some evidence based on studies of primates infected with Simian Immunodeficiency Virus that a hyperproliferative enteropathy may evolve into a hypoproliferative state later in the course of the disease.12 Furthermore, there is confusion regarding whether changes in crypt cell kinetics are a regenerative response to enterocyte shedding and villous collapse, or whether they cause villous shortening.13 The changes in mucosal structure observed in HIV enteropathy bear some similarities to the lesion of coeliac disease, although severe villous atrophy is seen rarely in HIV-infected patients. Coeliac disease is mediated by a T cell response in the intestinal lamina propria mounted against antigenic gluten peptides.14 A response to damage and loss of villous enterocytes, increased proliferation of crypt epithelial cells induced by local growth factors, mucosal response to luminal nutrients, and increased degradation of the extracellular matrix support of the villous structure all may contribute to the mucosal changes observed in an enteropathy.13 14 It is not clear whether these phenomena are causally linked, and if so, which are primary or secondary events. There is evidence from fetal explant experiments, however, that crypt cell hyperplasia induced by mucosal T cell activation is the primary mucosal response and that this precedes villous atrophy.15 16 More recently we have shown that hyperplasia affects both transit and stem cells of the crypt epithelium in patients infected with HIV.17
A close correlation is present in the small bowel mucosa of patients infected with HIV between crypt hypertrophy and reduced villous surface area. 4 5 This structural relationship in the crypt/villus unit indicates either that crypt elongation encroaches on villous height, or that villous collapse stimulates crypt hyperplasia. Crypt hypertrophy is the mucosal response of human fetal explants to HIV infection, indicating that accelerated crypt kinetics is the driving force in the pathogenesis of
villous atrophy in the intestine of AIDS patients.18 Crypt cell hyperplasia is the primary mucosal lesion in this enteropathy, driving immature enterocytes onto the sides of villi and reducing absorptive villous surface area by shifting the crypt/villus junction in a luminal direction.
The contribution of this pathology to the malabsorption and weight loss these patients suffer is as yet unclear. There is a strong correlation between fat malabsorption and jejunal villous atrophy in HIV positive patients in the absence of enteropathogens. Whilst this tructural-functional relationship in the crypt/villus unit accounts for
diarrhoea and weight loss in some of the patients, it is important to recognise that factors other than enteropathy may be responsible for these symptoms in others, such as exocrine pancreatic insufficiency,19 gut autonomic neuropathy 20 and drug therapy.
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20 Batman P A, Miller A.R.O, Sedgwick M.P, Griffin G.E.G. Autonomic
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P A Batman, MD FRCPath, Consultant Histopathologist, Bradford
Teaching Hospitals Foundation Trust, UK
M S Kapembwa, PhD FRCP, Consultant Physician, Northwick Park Hospital, UK
The authors have no competing interest