Try adding
<lockingModel type="log4net.Appender.FileAppender+MinimalLock" />
to your <appender /> element. There is some performance impact because this means that log4net will lock the file, write to it, and unlock it for each write operation (as opposed to the default behavior, which acquires and holds onto the lock for a long time).
One implication of the default behavior is that if you’re using it under a Web site that is being executed under multiple worker processes running on the same machine, each one will try to acquire and hold onto that lock indefinitely, and two of them are just going to lose. Changing the locking model to the minimal lock works around this issue.
(When debugging, ungraceful terminations and spinning up lots of new worker processes is exactly the type of thing that’s likely to happen.)
Good luck!