The key is to realize none of the primes can be 2,3, or 5, or else we would have to use one of them twice. Hence p,q,r,s must lie among 7,11,13,17,19,23,29,…. These options give remainders of 1(mod2) (obviously), 1,−1,1,−1,1,−1,−1,… modulo 3, and 2,1,3,2,4,3,4,… modulo 5. We automatically have 2∣pq−rs, and we have 3∣pq−rs if and only if pqrs≡(pq)2≡1 (mod3), i.e. there are an even number of −1(mod3) 's among p,q,r,s. If {p,q,r,s}={7,11,13,17}, then we cannot have 5∣pq−rs, or else 12≡pqrs≡(pq)2(mod5) is a quadratic residue. Our next smallest choice (in terms of p+q+r+s ) is {7,11,17,19}, which works: 7⋅17−11⋅19≡22−4≡0(mod5). This gives an answer of 7+17+11+19=54.