How did the smallpox rash change from flat spots into pustules?

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Smallpox vaccination — smallpox Edward Jenner vaccinating his child against smallpox; colored engraving.

The progression of the smallpox rash follows a distinct sequence as the virus manifests on the skin. Initially, the rash appears as flat spots known as macules. Over the course of several days, these spots undergo a transformation: they first develop into raised bumps called papules, then evolve into clear blisters known as vesicles, and finally mature into infected pustules.1

This process typically occurs after the initial flulike symptoms of the disease have abated, often coinciding with a return of the fever. In nonfatal cases, these pustules eventually dry up and form scabs, which leave behind characteristic pockmarked scars once they separate from the skin.1