Many users use the Lazy Approval Settings when they are designing a workflow.

Many of us don't know that when a user that receives an email that can be answered by replying it, and this user has set as Out of office, a loop of infinite emails begins.

To solve this issue is simple. Just go to Sharepoint Central Administration, navigate to the Nintex Workflow Management / Lazy Approval Settings and add a phrase to ignore. Ignore the phrase "Out of office"