A blister appears after minor skin damage when serum leaks from blood vessels in underlying skin. The serum is usually sterile, and the blister provides valuable protection to the damaged tissue. Blisters often appear after burns, sunburn, or friction (such as damage to the heel from wearing a poorly fitting shoe).

In addition, small blisters develop in the early stages of many viral infections, including chicken pox, shingles, and herpes simplex; these blisters contain infectious particles capable of spreading the infection.

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