Use strace

Start by looking for ENOENT on your production servers. Then look for execessive stats and check your realpath_cache_size.

Smarty Modifier Example
access("/var/www/current/lib/plugins/modifier.json_encode.php", R_OK) = -1 ENOENT (No such file or directory)
access("/usr/lib/php5/plugins/modifier.json_encode.php", R_OK) = -1 ENOENT (No such file or directory)
access("/usr/share/php/plugins/modifier.json_encode.php", R_OK) = -1 ENOENT (No such file or directory)
access("./plugins/modifier.json_encode.php", R_OK) = -1 ENOENT (No such file or directory)
...
lstat("/var", {st_mode=S_IFDIR|0755, st_size=4096, ...}) = 0
lstat("/var/www", {st_mode=S_IFDIR|0755, st_size=4096, ...}) = 0
lstat("/var/www/current", {st_mode=S_IFDIR|0755, st_size=4096, ...}) = 0
lstat("/var/www/current/lib", {st_mode=S_IFDIR|0755, st_size=12288, ...}) = 0
lstat("/var/www/current/lib/Smarty", {st_mode=S_IFDIR|0755, st_size=4096, ...}) = 0
lstat("/var/www/current/lib/Smarty/plugins", {st_mode=S_IFDIR|0755, st_size=4096, ...}) = 0
lstat("/var/www/current/lib/Smarty/plugins/modifier.nl2br.php", {st_mode=S_IFREG|0644, st_size=649, ...}) = 0
open("/var/www/current/lib/Smarty/plugins/modifier.nl2br.php", O_RDONLY) = 33
Smarty/plugins/modifier.nl2br.php
<?php
function smarty_modifier_nl2br($string) {
    return nl2br($string);
}