Dreadful set with unknown affliction (4)
I believe the answer is:
stye
'affliction' is the definition.
(stye is a kind of health problem)
'dreadful set with unknown' is the wordplay.
'dreadful' is an anagram indicator.
'with' indicates putting letters inside.
'unknown' becomes 'y' (algebra).
'set' with letters rearranged gives 'ste'.
'ste' placed around 'y' is 'STYE'.
(Other definitions for stye that I've seen before include "dump" , "Eyelid sore" , "Red eye" , "producing eyesore" , "Ocular inflammation" .)