Melanosis Coli

Etiology

Chronic laxative use, typically from the anthranoid group, causes Melanosis coli. Senna glycoside (senna) is the main causative laxative. As the laxative travels down the intestinal tract, it remains in its inactive form until it reaches the large intestine. Once in the large intestine, the molecules transform into their active form, leading to cell damage in the lining of the intestine and death, and apoptosis. As these cells undergo apoptosis, they create a dark pigment, lipofuscin, which eventually lines the large bowel. Eventually, these dead cells are taken up by macrophages. Melanosis coli can occur within only a few months of chronic laxative use. 

Epidemiology

Anyone who abuses laxatives using them chronically is at risk of developing melanosis coli. It is typically seen in individuals over the age of 45, but it has been reported in younger individuals. The rate increases with age. It is equally common in both sexes. Melanosis coli has also been seen in patients with chronic colitis (IBD) who do not abuse laxatives.[1]

Pathophysiology

Melanosis coli is caused by chronic laxative use. Anthraquinones in laxatives have a direct toxic effect on the epithelial cells of the colon. When these laxative molecules turn into their active form in the large bowel, they can cause cell damage to the lining of the large bowel, leading to cell death. As the cells die, they create a dark pigment, which is lipofuscin deposition in the macrophages within the lamina propria, that is visible under colonoscopy. Melanosis coli is more common in the proximal bowel and much rarer in the distal colon. This is probably due to the difference in the macrophage distribution in the colonic wall. Once laxative use is halted, the dark pigmentations may resolve.[2]

Histopathology

Under microscopic evaluation, pigment-laden macrophages are typically seen on periodic acid–Schiff stain.

Toxicokinetics

Anthraquinones laxatives work in three ways:

1. It stimulates the active transport of chloride into the gut, which in turn causes an osmotic gradient and pulls water into the gut lumen.
2. It inhibits Na-K ATPase on the enterocytes, which further inhibits the reabsorption of water, sodium, and potassium, ultimately excreting it into the feces.
3. It stimulates local prostaglandins, which stimulate peristalsis and decreases transit time through the bowel.

The adverse effects of Senna and other stimulant laxatives include hypovolemia, leading to dizziness, palpitation, and syncope; miscarriages in women; and decreased absorption of oral medications due to uptake inhibition. 

History and Physical

Typically melanosis coli causes no symptoms and is incidentally found during colonoscopy for other reasons. A detailed history should be focused on chronic laxative use, typically senna or cascara which contain anthraquinone, and a history of inflammatory bowel disease or colitis. These stimulant laxatives also can be found in over-the-counter herbal supplements and teas. Physical findings of melanosis coli are described through colonoscopy as black pigmentations lining the colonic mucosa. 

Evaluation

Evaluation of melanosis coli is through colonoscopy. Biopsies should be taken to rule out true melanosis which may relate to more threatening diseases such as Peutz-Jegher Syndrome. No laboratory or imaging studies will help in making the diagnosis of melanosis coli. Characteristically, melanosis coli is most intense at the cecum and diminishes as it moves down the colon. [3][4]

Treatment / Management

The treatment of melanosis coli is to stop laxative use. Resolution takes up to a year.[4][5][6][2](B3)

Differential Diagnosis

It is important to rule out other causes before making the diagnosis of melanosis coli. Peutz-Jeghers syndrome, an autosomal dominant disorder that leads to numerous hamartomatous polyps in the bowel with distinct findings of melanin deposition in the skin and mucosa, may look like melanosis coli. Patients with this disease are at a 15-fold increase of developing colon cancer and must be ruled out prior to making the diagnosis of melanosis coli. 

Prognosis

The prognosis is extremely positive in these patients. Melanosis coli will typically go away with causative laxative cessation. This can take up to one year. Rebound constipation can occur with laxative cessation. [7][1]

Complications

Some research has found a correlation between melanosis coli and colonic polyps. However, there is no consensus or evidence relating to an increased risk of colon cancer. There has been research supportive of melanosis coli and colorectal adenomas. Increased stimulant laxative use can cause electrolyte derangements due to the rapid transit through the bowel and lack of nutrition and water reabsorption. The most common is potassium imbalance which may be fatal.