The Ospreys full-back joins Scarlets flanker Rob McCusker in missing out on the autumn internationals while there are currently clouds hanging over both Ryan Jones and Leigh Halfpenny.
Warren Gatland's initial concerns were only surrounding Cardiff's Jamie Roberts but despite the dramatic change Howley is playing down the importance of Wales' absentees.
"Lee will be missed. I think you full-back is your best defender and he is disappointed to have that injury but it gives an opportunity to someone else," said Howley - who has seen Cardiff full-back Chris Czekaj drafted in to replaces Byrne.
"At this moment in time Lee and Rob are the two who probably won't be available for the autumn internationals and it is an important week in terms of preparation.
"It will be a waiting game over the next couple of days and hopefully the likes of Ryan and Leigh will pull through."