I'm not at all familiar with Skype, but I will suggest the following:
Many applications provide the option of "port 80 tunneling" as an alternative to using their native port assignment (to get through firewalls).
If you establish appropriate interface ACLs (restrict transiting traffic to specific applications permitted by security policy), and combine it with Granular Protocol Inspection (GPI), and the APPFW inspection feature, I believe you would succeed.
We have eliminated use of generic TCP and UDP inspection with GPI, and have used the APPFW feature to eliminate P2P, IM, and port 80 tunneling (with HTTP compliance verification).
Some of the other application-specific inspections also perform compliance checks.
I'd start with verifying which protocols and ports Skype can utilize, and configure accordingly.
Table of ContentsIntroductionVersion HistoryPossible Future
UpdatesDocuments PurposeNAT Operation in ASA 8.3+ SectionsRule Types
Network Object NATTwice NAT / Manual NATRule Types used per SectionNAT
Types used with Twice NAT / Manual NAT and Network Obje...
Table of Contents Introduction:This document describes details on how
NAT-T works. Background: ESP encrypts all critical information,
encapsulating the entire inner TCP/UDP datagram within an ESP header.
ESP is an IP protocol in the same sense that TCP an...