Importance of apoptosis in the histopathology of drug related lesions in the large intestine.
OBJECTIVE
To investigate the possibility that the incidence of apoptotic bodies in the cryptal epithelium might help to identify colonic lesions due to drugs, especially non-steroidal anti-inflammatory drugs (NSAIDs).


METHODS
The apoptotic count (AC) the number of apoptotic bodies per 100 crypts was calculated in a series of colorectal biopsy specimens, stained with haematoxylin and eosin from patients with (a) known or suspected drug induced colitis and (b) inflammatory bowel disease before or after treatment with salazopyrine or corticosteroids. These specimens were compared with normal biopsy specimens from a control group of comparable age and sex distribution.


RESULTS
Under normal conditions apoptotic bodies were seldom seen at all and the mean apoptotic count was less than 1.0. In untreated inflammatory bowel disease the mean apoptotic count was marginally increased (2.4), but when there was a partial response to drug treatment the apoptotic count rose to 13.1 (p 0.003). In colonic lesions directly attributable to drugs the apoptotic count was always increased, reaching its highest level (106) with 5-fluorouracil. In colitis related to NSAIDs apoptoses were associated with inflammation, most notably an increase in lymphocytes in both lamina propria and epithelium.


CONCLUSIONS
The presence of crypt apoptoses in substantial numbers (with an apoptotic count in excess of 5) should always raise the possibility of drug effect. The mechanisms involved are not clear but with NSAIDs the changes might well be immunologically mediated.
Lee
F D
FD
Department of Pathology, Glasgow Royal Infirmary.
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D017209:Apoptosis; D002452:Cell Count; D003092:Colitis / Q000139:chemically induced* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005472:Fluorouracil