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 $7,11,13,17,19,23,29, \ldots$. These options give remainders of $1(\bmod 2)$ (obviously), $1,-1,1,-1,1,-1,-1, \ldots$ modulo 3, and $2,1,3,2,4,3,4, \ldots$ modulo 5. We automatically have $2 \mid p q-r s$, and we have $3 \mid p q-r s$ if and only if $p q r s \equiv(p q)^{2} \equiv 1$ $(\bmod 3)$, i.e. there are an even number of $-1(\bmod 3)$ 's among $p, q, r, s$. If $\{p, q, r, s\}=\{7,11,13,17\}$, then we cannot have $5 \mid p q-r s$, or else $12 \equiv p q r s \equiv(p q)^{2}(\bmod 5)$ is a quadratic residue. Our next smallest choice (in terms of $p+q+r+s$ ) is $\{7,11,17,19\}$, which works: $7 \cdot 17-11 \cdot 19 \equiv 2^{2}-4 \equiv 0(\bmod 5)$. This gives an answer of $7+17+11+19=54$.