Pellagra  is a disease caused by a lack of the vitamin niacin (vitamin B3). Symptoms include inflamed skin, diarrhea, dementia, and sores in the mouth. Areas of the skin exposed to either sunlight or friction are typically affected first. Over time affected skin may become darker, stiffen, peel, or bleed.There are two main types of pellagra, primary and secondary. Primary pellagra is due to a diet that does not contain enough niacin and tryptophan. Secondary pellagra is due to a poor ability to use the niacin within the diet. This can occur as a result of alcoholism, long-term diarrhea, carcinoid syndrome, Hartnup disease, and a number of medications such as isoniazid. Diagnosis is typically based on symptoms and may be assisted by urine testing.Treatment is with either niacin or nicotinamide supplementation. Improvements typically begin within a couple of days. General improvements in diet are also frequently recommended. Decreasing sun exposure via sunscreen and proper clothing is important while the skin heals. Without treatment death may occur. The disease occurs most commonly in the developing world, often as a disease of poverty associated with malnutrition, specifically sub-Saharan Africa. Signs and symptoms
The classic symptoms of pellagra are diarrhea, dermatitis, dementia, and death ("the four Ds"). A more comprehensive list of symptoms includes:

Sensitivity to sunlight
Dermatitis (characteristic "broad collar" rash known as casal collar)
Hair loss
Swelling
Smooth, beefy red glossitis (tongue inflammation)
Trouble sleeping
Weakness
Mental confusion or aggression
Ataxia (lack of coordination), paralysis of extremities, peripheral neuritis (nerve damage)
Diarrhea
Dilated cardiomyopathy (enlarged, weakened heart)
Eventually dementiaJ.
Interactions
Only in vitro interaction studies are available. In these, trifluridine used the concentrative nucleoside transporter 1 (CNT1) and equilibrative nucleoside transporters 1 (ENT1) and 2 (ENT2), and tipiracil was transported by the solute carrier proteins SLC22A2 and SLC47A1. Drugs that interact with these transporters could influence blood plasma concentrations of trifluridine and tipiracil. Trifluridine, being a thymidine phosphorylase inhibitor, could also interact with substrates of this enzyme such as zidovudine. Pharmacology
Mechanism of action
The drug consists of the cytotoxin trifluridine and the thymidine phosphorylase inhibitor (TPI) tipiracil. Trifluridine is incorporated into DNA during DNA synthesis and inhibits tumor cell growth. Trifluridine (TFT) is incorporated into DNA by phosphorylation by thymidylate kinase (TK) to TF-TMP;  TF-TMP then covalently binds to tyrosine 146 of the active site of thymidylate synthase (TS) inhibiting the enzymes activity. TS is vital to the synthesis of DNA because it is an enzyme involved in the synthesis of the deoxynucleotide, thymidine triphosphate (dTTP). Inhibition of TS depletes the cell of dTTP and causes accumulation of deoxyuridine monophosphate (dUMP), which increases the likelihood that uracil gets misincorporated into the DNA. Also, subsequent phosphorylations of TF-TMP cause an increased level of TF-TTP within the cell, which results in it being incorporated into DNA. Even though the exact mechanism of how TFT causes DNA damage is not completely understood, it is hypothesized that the incorporation TF-TTP in DNA leads to DNA strand break formation.Tipiracil prevents the degradation of trifluridine via thymidine phosphorylase (TP) when taken orally and also has antiangiogenic properties.