The fact that I'm sure is :
- they have exactly the same nginx/proxy config files.
- this morning, I update from v5.6.20 to v5.6.21 the first server; reverse proxy stopped just after (<1 min).
- this afternoon, I updated the second server, reverse proxy stopped just after (<1 min).
If you have not pressed the Apply button in the UI then nothing should have happened. The latest version 5.6.21 has marked the nginx, host and postfix modules as dirty, thus their configuration is re-deployed on pressing Apply. But there are no changes in the code, except that the IPv6 detection has been improved/fixed, thus it can happen that now only IPv4 configuration is generated if IPv6 is not configured.