Why can laxatives turn the colon black?
For this episode, we investigated the phenomenon of melanosis coli, a benign finding of dark pigmentation of the mucosal lining of the colon, classically associated with long-term use of laxatives.
Melanosis coli first appeared in the medical literature in 1830, at which time the French anatomist Jean Cruveilhier wrote about his contemporary Gabriel Andral: “M. Andral has found in an individual affected with chronic diarrhea, the inner surface of the large intestine as black as Chinese ink, from the ileocecal valve right down to the rectum. The color resided in the internal membrane, which showed no other alterations beyond a remarkable development of its follicles.” This phenomenon was further described by several other scientists, and dubbed “melanosis coli” in 1858 by Virchow.
Subsequent studies described a spectrum of findings. As one review of 41 cases, published in 1933, described it, “the color of the mucosa varies from buff to dark brown or black, the deeper shade being broken into small angular, polyhedral designs by fine netlike striae of lighter shade, either yellow or brown. These small fields vary in size between 2 and 10mm in diameter. Small pinhead yellow follicles are frequently seen, being more noticeable in the milder cases of melanosis.” And if you look at case reports or photos of melanosis coli today, you will see a wide range of pigment intensity and extent within the colon. In some cases, the finding is so dramatic that in one case it was almost misdiagnosed as diffuse colonic ischemia! And across this wide range of observations of melanosis coli, an association with laxative use has remained.
Melanosis coli is specifically associated with a group of common stimulant laxatives called the anthranoid group, the most widely-used of which is senna. Senna and the other anthranoid laxatives (e.g., cascara, aloe, and rhubarb) contain anthraquinones, which are organic compounds that function by stimulating intestinal peristalsis and modulating aquaporin expression. In particular, these compounds lead to more water movement out into the colon.
But the peristalsis results when these compounds get into the colon and are degraded into their metabolites by the gut microbiome. The laxatives that lead to this each have metabolites that results in apoptosis. When laxatives are used consistently this can lead to build up and promote apoptosis of the cells in the lamina propria, or cell layer of the gut wall closest to the lumen.
And Why Melanosis?
As it turns out, melanosis coli is not a condition of melanin at all. As early as 1933 scientists studying this condition had an inkling that melanin was not at play. As noted above, metabolites cause apoptosis of the cells in the lamina propria. When these cells die, they create lipofuscin, or what is often described as an “aging” or “wear-and tear” pigment. Lipofuscin builds up in the lysosomes of the macrophages in the lamina propria, causing the dark color that we see on colonoscopy.
In most case reports and studies, it appears that it takes at least 2-4 months to develop. Once present, the timing of resolution isn’t clear. In one study that prospectively followed patients in whom melanosis coli had been detected on routine colonoscopy, macroscopic resolution occurred after approximately 2 years, and microscopic changes lasted longer than that.
Is Apoptosis Benign?
Early data suggested there might be a link between melanosis coli and polyp discovery. Fortuantely, more recent studies do not show a connection between melanosis coli and colon cancer. Interestingly, one reason for the initially described higher polyp detection rate may be the color contrast of the polyps against the background of pseudomelanosis.
Take Home Points
- Melanosis coli is hyperpigmentation of the bowel wall, associated with the use of laxatives like senna, aloe, and rhubarb that contain anthraquinones.
- These anthraquinones cause apoptosis of the cells in the lamina propria of the gut wall, and phagocytosis of those apoptosed cells, and the lipofuscin in those apoptotic bodies, is what causes the color change
- While these findings can be dramatic, they are not associated with an increased risk of colon cancer!
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Credits & Citation
◾️Episode written by Hannah Abrams
◾️Show notes written by Hannah Abrams and Tony Breu
◾️Audio edited by Clair Morgan of nodderly.com
Abrams HR, Cooper AZ, Breu AC. Why do laxatives turn the colon black? The Curious Clinicians Podcast. October 27, 2021
Image credit: https://www.nejm.org/doi/10.1056/NEJMicm020208