Atopický ekzém / dermatitida

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Synonyma

Atopický ekzém
Prurigo Besnier [6]
Neurodermatitis atopica [6]
AD

Historie

„atopos“ = řecky podivný, nezvyklý
1982 Besnier

Souvislost mezi AD, alergickou rinitidou a astmatem [6]

Coca a Cooke

Charakterizaci triády symptomů: ekzém, alergická rinitida a astma = atopie [6]

1930 Hill a Sulzberger

Kritéria pro diagnózu AD
Koncept této kožní choroby [6]

Epidemiologie

Převážně kojeneckého a dětského věku
Světová prevalence AD

U dětí do 5 let 3 - 5 % [6]

Vznik do 6. měsíce u 49 - 75 % dětí
Vznik do 5. roku věku u 80-90 % [6]

V dospělé populaci 2-10 % [6]

Celková prevalence AD

Ve střední Evropě cca 10 %
Celosvětová 15-30 % [6]

S mírnou převahou dívek [6]

Prevalence rapidně vzrůstá

Chov domácích zvířat v bytě
Dieta typu „fast food“

Druhů koření, chemických aditiv, barviv [6]

Pokud by nárůst atopie pokračoval stávajícím tempem, tak se předpokládá, že v roce 2015 bude každý druhý Evropan alergikem.

současná data ?

ČR 2010

AD 16 % dětí do 1 roku života
AD 12 % dětí do 15 let věku
AD 3 % nad 16 let

Symptomy

Charakteristická triáda projevů:

Dermatitida
Xeróza
Pruritus

Klinický obraz

Velmi variabilní
Mění se v závislosti na věku pacienta
3 klinické formy choroby:

Kojeneckou
Dětskou
Dospělou [6]

Kojenecká - Infants

Typically erythematous papules and vesicles on the cheeks, forehead, or scalp
Intensely pruritic
Velmi plynule navazuje na seboroické dermatitidy
Obličej s bilaterálním postižením tváří

Silně svědivé papulky, občas i puchýřky
Mokvání
Povrch se pokrývá stroupky a šupinami
Odsud se nález může šířit na celý obličej, trup a končetiny
Na vlasaté části hlavy se často objevují mastné šupiny bílé barvy

„crusta lactea“

Bývá dáván do souvislosti s přechodem na mléčnou stravu [6]

Kdy kojenec začíná lézt

Ložiska ekzému na předloktích, kolenou a na bércích

V místech stálého, mechanického dráždění [6]

Často dochází k bakteriální superinfekci a impetiginizaci ložisek [6]
Průběh onemocnění je nepředvídatelný co do rozsahu a dalšího vývoje
Může během 2. roku života zcela zhojit
Plynule přejít do další vývojové fáze

Dětská - 2 years - puberty [3] od 3 do 10 let [6]

Méně mokvající charakter
Sklon k lichenifikaci
Nejčastěji ohybové partie končetin:

Kubitální a popliteální jamky
Krk
Zápěstí
Nárty
často i prsty rukou a nohou

I onychodystrofie [6]

Kůže je zhrubělá, místy až lichenifikovaná
S výraznými hlubokými kožními rýhami
Asteatóza [6]

Místy až jkao zvrásnělá, např. na očních víčkách

V akutním stadiu

červená
S mnohočetnými exkoriacemi po škrábání [6]

Kůže obličeje charakteristický vzhled

Bývá bledá
Tmavší a zhrubělou kůží očních víček
Zdvojením záhybu pod očima (tzv. Dennieho-Morganiho infraorbitální řasa) [6]

Less likely to have the exudative lesions
More lichenified papules and plaques
Hands, feet, wrists, ankles, and antecubital and popliteal regions

Nejčastějšími provokačními faktory tohoto věku

Vzdušné alergeny, např. prach, roztoči, peří, plísně, zvířecí anebo pylové alergeny
Stres

Se školou
Změnou prostředí dítěte

S těžkou formou AD, často i s potravinovou alergií

V předškolním věku

Ev. i astma či polinóza

Charakteristický měnlivý průběh
Exacerbace

V jarních a podzimních měsících

Zlepšování

V létě

S věkem dochází u většiny pacientů ke zlepšování
Zvratovým momentem pro průběh AD

Začátek školní docházky
Start puberty

Průběh se zmírňuje nebo nastává dlouhodobá až celoživotní remise až u 75 % případů

Dospělá - Adult

Flexural folds, the face and neck, the upper arms and back, and the dorsa of the hands, feet, fingers, and toes
Eruption is characterized by dry, scaling erythematous papules and plaques
Formation of large lichenified plaques from lesional chronicity
Obvykle předchází kojenecká a dětská forma choroby či astma
Nejčastěji ve stejné lokalizaci jako u dětské formy nebo s predilekcí v:

Obličeji
Na šíji, horní části hrudníku
Na ramenou
Nad velkými klouby končetin
Na hřbetech rukou
I kštice

Výrazným pruritem, šupením, vlasy jsou řídké a suché [6]

Kůže je více lichenifikovaná a pruritus je intenzívnější
Nejčastější provokační faktory v dospělém věku jsou:

Hormonální změny (menses, gravidita) [6]
Potravinové alergie [6]
Psychické vlivy [6]

Dieferenciální diagnostika

Other forms of eczema, especially in adulthood

Combination forms are prevalent with components of

Atopic
Contact
Irritative eczema [4]

Atopic eczema of the hands and feet

Must be differentiated from

Psoriasis in the palms and soles
Tinea [4]

Scabies

Must always be considered [4]

Acute Atopic Dermatitis

Intense erythema of the skin
Together with exudation or blistering [4]

Chronic lichenified forms of AD

Late-onset AD

Vzniknout de novo v dospělosti
Mezi těmito pacienty je část

Bez prokázané senzibilizace zprostředkované IgE protilátkami
Negativní rodinnou anamnézu
žádné další známky atopie
Průběh AD je mírnější [6]

Recalcitrant cases

In children genodermatoses

Netherton syndrome

Recently described immune dysregulation
Polyendocrinopathy
Enteropathy X-linked syndrome [4]

In both children and adults

Vitamin deficiencies
Malignancies

Cutaneous T cell lymphoma/mycosis fungoides [4]

Larvované nebo frustní formy AD

Kožní projevy ohraničené na jednu část těla
Charakter je dosti odlišný od typických projevů AD
„malé příznaky AD“ - „stigmata AD“

Pityriasis alba

Neostře ohraničené
Hypopigmentované skvrny
S mírným olupováním
Hlavně na obličeji a na končetinách

Xeróza kůže

Abnormální suchost kůže
U 80 až 98 % pacientů s AD

Keratosis pilaris

Projevem folikulární hyperkeratózy na: [6]

Zevních plochách paží
Na hýždích
Předních plochách stehen
U dětí i na tvářích [6]

Drobné papulky barvy kůže folikulárně vázané

S mírným erytémem okolí
Bez pruritu

Palmoplantární hyperlinearita

Zmnoženou kresbu rýh na dlaních a na ploskách

Dennieho-Morganiho rýha

Zvýrazněnou rýhou pod dolním víčkem
Symetricky pod oběma očima

Hlavně u kojenců a dětských pacientů

Ev. i periorbitální edém, lichenifikace a tmavé kruhy pod očima [6]

Hertoghovo znamení

Chyběním laterálního okraje obočí

Cheilitida

Představuje suché, popraskané rty a nebo koutky
častější u dětí než u dospělých pacientů

Dermatitida bradavek

Dermatitida bříšek prstů rukou (pulpitis sicca)

Nohou a ušních boltců

Bílý dermografismus

Paradoxní vazokonstrikční reakce na tlak

Oční komplikace

Katarakta [6]
Keratokonus [6]

Rizikové faktory

Hygienická teorie (David Štrachán, 1989)

Infekce prodělaná v raném dětství by mohla zabránit rozvoji AD
Další studie však tuto teorii neprokázaly
Některé infekce (např. spalničky) riziko vzniku AD zvyšují [6]

OA a RA

A personal or family history of eczema, allergies, hay fever or asthma [2]
Having attention-deficit/hyperactivity disorder (ADHD) [2]
Risk factor for persistent AD symptoms is the severity of disease in infancy [4]

Kojení

Incidence of infantile AD is reduced by breast-feeding for a least 4 months

Tends to disappear after 3 years of age [4]

Profese

Health care worker

Linked to hand dermatitis [2]

Životní prostředí

Living in urban areas [2]
Having parents with a high level of education [2]
Attending child care [2]
Tobacco smoke exposure in AD is inconclusive
Exposure to aeroallergens (pets, mites, and pollen) has been clearly shown to increase the risk factors for AD and AD severity

Ftaláty

Ostatní

DnBP, BBzP and DEHP

Significant associations between non-dietary exposures to DnBP, BBzP and DEHP in the indoor environment and allergic sensitization

Mass fractions in dust or daily indoor intakes from dust ingestion, inhalation and dermal absorption [17]

Alergeny

Sensitization to food allergens (cow's milk and hen's eggs) is associated with infantile AD and related to disease severity
Predictive for persistence of symptoms throughout childhood
Nejčastějším provokačním faktorem v kojeneckem věku potraviny

bílkoviny kravského mléka [6]
Vaječný bílek [6]
Pšeničná mouka [6]
Chlorovaná voda [6]
Nebavlněné, neprodyšné oblečení [6]
Virové anebo bakteriální infekce [6]

Asociovaná rizika

Allergic rhinitis

Allergic asthma

AD during the first 2 years of life

50% will have asthma during subsequent years [4]

Severity of AD [4]
Early sensitization to food [4]

Increases the risk of asthma and allergic rhinitis [4]

In selected individuals sensitization to peanut allergen might occur through the skin [4]

Perzistence do dospělosti

Severity of AD [4]
Early sensitization to food [4]
Complex interaction of genetics, environmental exposure, and sensitization [4]

Rasa

Being African-American [2]

Genetika

Parental atopy, in particular AD

Significantly associated with the manifestation and severity of early AD in children [4]

European study of about 200 families

Region of highest linkage at human chromosome 3q21 [4]

Study of 148 nuclear families

Association with 5 regions, including 1q21, 17q25, 20p, 16q, and 5q31 [4]

Swedish study of 197 affected sib pairs

4 phenotypes, as well as 11 locations, associated with all of the different phenotypes that ranged from severity of AD, specific IgE, and direct diagnosis of AD [4]

Danish study

Association with 3 locations within the genome [4]

Candidate gene studies

TLR2 Toll-like receptor 2
IRF2 Interferon regulatory factor 2
CSF2 Colony-stimulating factor 2
3606
IL4
IL13
111C/T
IL5
IL18
CARD4 (12) Caspase recruitment domain-containing protein 4
Monocyte differentiation antigen CD14
IL12B Interleukin-12B
SPINK5 Serine protease inhibitor
FCER1B High-affinity IgE receptor, ß-chain
GSTP1 Glutathione S-transferase
PHF11 Plant homeodomain zink finger 11 protein
CMA1 Mast cell chymase
1903
IL4RA Interleukin 4 Receptor chain
CARD15 Caspase recruitment domain - containing protein 15
RANTES Regulated on activation
EOTAXIN
TGFß1 TGF-ß1
SCCE Stratum corneum chymotryptic enzyme [4]

Filaggrin (FLG)

Null mutations

Associated with severe and early onset of atopic dermatitis [15]
Increased the prevalence of foot dermatitis and persistent hand dermatitis only in participants with AD [15]

20–40% have an innate genetic filaggrin mutation
Confer a risk for allergen sensitization through the skin

Increased transepidermal water loss (TEWL)
Increased surface pH
Altered expression of antimicrobial peptides [16]

Příčiny

Defekt kožní bariéry se považuje za primární. [6]

Mutace genů pro

Filagrin
Ivolukrin
Lorikrin [6]

Mutace vedou k:

Poruše maturace keratinocytů
X integrity kožní bariéry
Změněný profil spektra ceramidů

Snížené funkci intercelulárních lipidů [6]

Vysoká koncentrace kožních serinových proteáz

Předčasné ztrátě soudržnosti keratinocytů a deskvamaci

Zvýšená náchylnost ke kolonizaci kmeny Staphylococcus aureus [6]

Kolonizace S. aureus

Přispívá ke vzniku, intenzitě a udržování atopického zánětu
K sensibilizaci [6]

V nepostižené kůži atopiků

Reziduální, minimální dermatitida vždy přítomna

Opodstatňuje význam udržovací léčby [6]

Porušená bariéra

Vstupní branou pro vznik senzibilizace
Vývoj atopického zánětu [6]

Psychogenní složka

Stresující životní události často předcházejí počátek exacerbace AD (Kodama et al., 1999, Pikardi et al., 2001) [6]
Psychická zátěž ovlivňuje AD interakcí centrálního nervového systému a imunitního systému [6]
Kolísání neurotransmiterů v neuroendokrinním a autonomním systému související se stresem

Ke změně imunologické reaktivity a rozvoji alergického zánětu [6]
Mohou ovlivňovat rovnováhu epidermální permeabilní bariéry, což následně vede k zánětu a svědění [6]

Dospělí pacienti s AD jsou více úzkostní a depresivní ve srovnání s kontrolními skupinami (Ehlers et al., 1995, Hashiro a Okumura, 1997) [6]

Přícina a následek ? Souvislost s metabolismem MK omega-3 ?

Dry, irritable skin

Reduces the skin's ability to be an effective barrier

A gene variation

Affects the skin's barrier function

Immune system dysfunction

Bacteria

Such as Staphylococcus aureus, on the skin
Creates a film that blocks sweat glands [2]

Environmental conditions

Histopathology

The skin

Dry
Greater irritant skin response
Sparse perivascular T-cell infiltrate in unaffected AD skin [4]

Not seen in normal healthy skin [4]

Atopické léze

Marked infiltration of CD41 activated memory T cells in acute AD
Antigen-presenting cells -APC (v menším rozsahu i v kůži bez lézí)

Langerhans cells [LCs]
Inflammatory dendritic epidermal cells [IDECs]
Macrophages
Bear IgE molecules [4]
Mast cell degranulation can be observed [4]

Chronic AD skin lesions

Tissue remodeling caused by chronic inflammation
Thickened plaques with increased skin markings (lichenification)
Increased collagen deposition in the dermis [4]
Dry fibrotic papules
Macrophages dominate the dermal mononuclear cell infiltrate
Eosinophils also contribute to the inflammatory response
T cells remain present [4]

In smaller numbers than seen in acute AD [4]

Cytokines and chemokines

Local tissue expression of proinflammatory cytokines and chemokines

TNF-alfa and IL-1 from resident cells

From keratinocytes, mast cells, and DCs
Binds to receptors on the vascular endothelium [4]
Activating cellular signaling [4]

Including the nuclear factor (NF) B pathway
Inducing expression of vascular endothelial cell adhesion molecules

Extravasation of inflammatory cells [4]

Once the inflammatory cells have infiltrated into the tissue

Respond to chemotactic gradients

Play a central role in defining the nature of the inflammatory infiltrate [4]

The onset of acute AD

Strongly associated with the production of TH2-produced cytokines [4]

IL-4 a IL-13

Significantly higher in AD individuals compared with control subjects
switching to IgE synthesis [4]
Upregulating expression of adhesion molecules on endothelial cells [4]
Implicated in the initial phase of tissue inflammation [4]

TH2 cytokine IL-5

Involved in eosinophil development and survival
Predominates in the chronic form [4]

GM-CSF

Increased production is reported to inhibit apoptosis of monocytes
Contributing to the chronicity - also:

TH1-like cytokines

IL-12
IL-18 [4]

Remodeling-associated cytokines (in chronic forms of the disease)

IL-11
TGF-beta 1 [4]

Increased expression of C-C chemokines

monocyte chemoattractant protein 4
eotaxin
RANTES [4]

Contributes to infiltration into acute and chronic AD skin lesions:

Macrophages
Eosinophils
T cells [4]

Cutaneous T cell–attracting chemokine (CCL27)

Highly upregulated in AD
Preferentially attracts cutaneous lymphocyte antigen–positive T cells into the skin [4]

Selective recruitment of CCR4-expressing TH2 cells

Mediated by macrophage-derived chemokine, thymus and activation-regulated cytokine

Increased in patients with AD

Severity of AD linked to magnitude of thymus and activation-regulated cytokine levels [4]

TH1 cell migration toward the epidermis

Strongly upregulated in keratinocytes

Fractalkine
IFN-gamma–inducible protein 10

IgE and IgE receptors

Cca 80% of adult patients with AD IgE levels >150 kU/L
sensitization against aeroallergens and food allergens
Concomitant allergic rhinitis and asthma
20% of adult patients with AD have normal serum IgE levels

Often has a late onset (>20 years of life)
Lack of IgE sensitization against inhalant or food allergens
Might have IgE sensitization against microbial antigens

Staphylococcus aureus enterotoxins
Candida albicans
Malassezia sympodialis - Pityrosporum ovale

Some have positive reactions on the atopy patch test (APT)

Transient form of AD

Low IgE serum levels in children
Without any detectable sensitizations
Develops into the extrinsic variant of AD with increasing IgE serum levels
Developing sensitizations against aeroallergens and food allergens later in life [4]

Expression of IgE receptors

high-affinity receptor for IgE [Fc RI]

Can be found in the epidermal skin lesions
Higher IgE-binding capacity of DCs in the skin and in the peripheral blood of patients with AD

Fc RI is regulated distinctly on DCs of atopic and non-atopic subjects [4]

Skin barrier dysfunction

dry skin

Even involving nonlesional skin [4]

Increased transepidermal water loss
reduced content of ceramides in the cornified envelope of both lesional and nonlesional skin

Major water-retaining molecules in the extracellular space of the cornified envelope [4]

Matrix of structural proteins

Bound to ceramides [4]

Changes in stratum corneum pH levels

Might impair lipid metabolism in the skin

Overexpression of stratum corneum chymotryptic enzyme

Likely to contribute to the breakdown of the AD epidermal barrier [4]

Penetration of irritants and allergens

Trigger an inflammatory response
Contributing to the cutaneous hyperreactivity [4]

T cells

Key role of immune effector
Primary T-cell immunodeficiency disorders frequently have increased serum IgE levels and eczematous skin lesions

Disappear after successful bone marrow transplantation [4]

In animal models of AD, the eczematous rash does not occur in the absence of T cells
treatment with topical calcineurin inhibitors (TCIs)

Specifically target activated T cells
Significantly reduces the clinical skin rash present in AD [4]

TH1 and TH2 play

Transgenic mice with overexpress IL-4 in their skin

Inflammatory pruritic skin lesions similar to those seen in patients with AD
Local skin expression of TH2 cytokines may be a critical role in AD [4]

Allergen-sensitized skin from IL-5–deficient mice

No detectable eosinophils
Decreased thickening [4]

Skin from IL-4–deficient mice

Normal thickening of the skin layers
Reduction in eosinophil counts [4]

Patients with AD

activated T cells with skin-homing properties

Express high levels of IFN-gama
Predominantly undergo apoptosis in the circulation
Skewing the immune response to surviving TH2 cells
In the affected skin these T cells switch on effector cytokines

Induce the activation and apoptosis of keratinocytes [4]

T regulatory (TReg) cells

Further subtype of T cells
Immunosuppressive function
Cytokine profiles distinct from those of either TH1 or TH2
Able to inhibit the development of both TH1 and TH2 responses
Mutations in a nuclear factor expressed in TReg cells, Foxp3

Immune dysregulation polyendocrinopathy enteropathy X-linked syndrome

Hyper-IgE
Food allergy
Eczema [4]

staphylococcal superantigens

Subvert TReg cell function
Might thereby augment skin inflammation [4]

DCs

Two types of Fc RI-bearing myeloid DCs

Found in the lesional skin
LCs and IDECs [4]

LCs

Predominant role in the initiation of the allergic immune response
Prime naive T cells into T cells of the TH2 type with high IL-4–producing capacity

Predominate in the initial phase of AD

Stimulation of Fc RI on the surface of LCs by allergens

Induces the release of chemotactic signals
Recruitment of precursor cells of IDECs and T cells in vitro [4]

IDECs

Stimulation of Fc RI on IDECs leads to

Release of high amounts of proinflammatory signals

Contribute to the amplification of the allergic immune response [4]

Plasmacytoid DCs (pDCs)

In contrast to other inflammatory skin diseases

Allergic contact dermatitis
Psoriasis vulgaris

only very low numbers
Major role in the defense against viral infections
PDCs in the peripheral blood of patients with AD

Bear the trimeric variant of Fc RI on their cell surface
Occupied with IgE molecules

Modified immune function of pDCs in patients with AD after Fc RI-mediated allergen stimulation might contribute to

The deficiency of pDCs in patients with AD
Produce type I IFNs
High susceptibility of patients with AD toward viral skin infections

Herpes simplex–induced eczema herpeticum [4]

Undergoing apoptosis

Spongioform morphology in the epidermis

Hallmark of eczematous lesions

Suppression of keratinocyte activation and apoptosis

Potential target for the treatment of AD [4]

Eosinophils

Major role in AD
activated eosinophils in the peripheral blood and in the lesional skin
Psychosocial stress

Important trigger for the increase of eosinophil counts in the peripheral blood [4]

Inhibition of eosinophil apoptosis in AD

Autocrine release of IL-5 and GM-CSF

Recruited to, and activated at, tissue sites by TH2 cytokines

IL-5
IL-13 [4]

Chemokines (eotaxin and RANTES)

Contribute to eosinophil chemotaxis and activation

eosinophil extravasation and activation

Eosinophil surface molecules
Endothelial cells vascular cell adhesion molecule 1
Intercellular adhesion molecule 1 [4]

switching the TH1 response in AD

Production of significant amounts of IL-12 on activation

Activated

Releasing an armory of potent cytotoxic granule proteins and chemical mediators

Role in neuroimmunologic interactions

Pathophysiology of pruritus in AD

Mediátory pruritu

Zároveň mediátory zánětu i vazoaktivními látkami
Působí na volná nervová zakončení

Mohou vyvolávat až pocity bolesti [6]

Reduced threshold for pruritus
Cutaneous hyperreactivity
Scratching after exposure to allergens, changes in humidity, excessive sweating, and low concentrations of irritants

Usually worse at night
Frequently disrupting the patient's sleep and overall quality of life

Allergen-induced release of histamine from skin mast cells

Not an exclusive cause of pruritus in AD
Antihistamines are not effective in controlling the itch of AD unless there is associated urticaria

TCIs and corticosteroids

Effective at reducing pruritus

Inflammatory cells play an important role in driving pruritus

Cytokines
Neuropeptides
Proteases
Eicosanoids
Eosinophil-derived proteins

Dysbalance of skin microbiota

Resident flora

Constantly present on body surfaces
May prevent colonization by pathogens and possible disease
Restoring the ecological skin niches [16]

Commensal microorganisms

Mutualistic symbiosis
Contribute to human health and welfare

Production of defense molecules
Natural antibiotics [16]

Transient skin flora

Temporarily colonize the skin
Unable to remain in the body for a long period of time

Due to competition from resident microbes [16]

Meconium microbes

Presence of enterobacteria

Associated with a history of atopic eczema in the mother [16]

Presence of lactobacilli

Was associated with respiratory disorders in the baby [16]

Infant skin microbiome

Different from that of an adult

Differences in skin structure and function [16]

Early colonization is dominated by Staphylococci

Stratum corneum is better hydrated than that of an adult
Site specific [16]

Firmicutes

Predominate on infant skin [16]

Similar to an adult organism by the age of 12–18 months [16]

Kožní oblasti a různá mikroflora

Density of sebaceous glands
Dry, moist, or sebaceous

High density of sebaceous glands

Face, chest, and back

Encourage the growth of lipophilic microorganisms [16]

Near the top of hair follicles - sebum

Promotes the growth of facultative anaerobes

Propionibacterium acnes

Hydrolyzing the triglycerides present in sebum, releases free fatty acids

Maintenance of the acidic epidermal pH

Anoxic environment

Hosts anaerobic microorganisms
Cathelicidin LL37
Defensin (HBD-2)

Eccrine sweat glands - main sweat glands

water and NaCl
Natural antibiotic, dermcidin [16]

Apocrine sweat glands

Larger than eccrine sweat glands

Underarms (axillae)
Under the breasts
Around the nipples
In the groin and genital region [16]

Secretions into the hair follicles

Thick, milky fluid
Can easily be turned into smelly body odour by germs
Contains pheromones

Respond to adrenaline
Related to sexual attractiveness [16]

Komáři

Individuals that are highly attractive to Anopheles gambiae s.s.

Higher abundance, but lower diversity, of bacteria on their skin
Volatile metabolites released by Staphylococcus spp. are attractive to A. gambiae females [16]

Antimicrobial peptides (AMPs)

Z kůže

Cathelicidin LL37
Beta-defensins [16]

AMPs from commensal microbes

-able to increase the production of AMPs by keratinocytes [16]

Staphylococcus epidermidis

AMPs

Phenol-soluble modulin (PSM)gamma

Could be beneficial to the host

Additional AMPs on normal skin surface [16]

Exhibited bactericidal activity against skin pathogens

Staphylococcus aureus
Group A Streptococcus (GAS)
Escherichia coli [16]

Gram-positive bacterium
More than 90% of the aerobic resident flora
Mutualistic organism
Many strains of S. epidermidis produce lantibiotics

Lanthionine containing antibacterial peptides

Bacteriocins

Epidermin
Epilancin K7
Epilancin 15X
Pep5
Staphylococcin 1580 [16]

Host-bacterium relationship one of mutualism
Produce antibacterial peptides that amplify the keratinocyte response to pathogens via TLR2

Influencing the innate immune response of keratinocytes through Toll-like receptors (TLRs) signaling

Activation of TLR-2 by S. epidermidis

Enhances the expression of tight junctions [16]
Decreases the production of proinflammatory cytokines via TLR3 in the keratinocyte cultures [16]
Keratinocytes are able to respond more effectively and efficiently to pathogenic insults [16]

Colonization of body surfaces (especially in the nose) by S. epidermidis

Impairs the establishment of S. aureus [16]

Two different strains of S. epidermidis

Strain JK16

Inhibits biofilm formation by S. aureus
Esp-secreting S. epidermidis

Eliminates S. aureus nasal colonization [16]
serine protease Esp inhibits biofilm formation and nasal colonization by S. aureus
Correlates with the absence of S. aureus [16]
Destroys preexisting S. aureus biofilms [16]
Enhances the susceptibility of S. aureus in biofilms to immune system components through human beta-defensin-2 (hBD2) [16]

Strain JK11

Noninhibitory type

S. aureus

Nonmotile
Nonspore forming
Catalase and coagulase positive
Typical colonies

Yellow to golden yellow
Smooth, entire, slightly raised
Hemolytic on 5% sheep blood agar [16]

Extremely prevalent in people with atopic dermatitis.
Predominantly localized in the anterior nares (vestibulum nasi)

20% of individuals are persistent S. aureus carriers
60% are intermittent carriers
20% are persistent noncarriers [16]

Activates local inflammatory processes through the release of delta-toxin [16]
There is a strong association between worsening disease severity and lower skin bacterial diversity [16]
S. aureus is observed during disease flares [16]
Increases in the proportion of Staphylococcus and reductions in microbial diversity precede the worsening of AD disease severity as observed in no-treatment flares [16]

Glucocorticoid receptor (GR) gene polymorphisms

Associated also with variation in glucocorticoid sensitivity
Changes in glucocorticoid sensitivity

May predispose to or protect from microbial colonization or infection

Novel environmental factor can influence

The ability of S. aureus to bind to nasal mucosa

Biocide triclosan

Commonly found in the nasal secretions of healthy adults
Presence of triclosan has a positive trend with nasal colonization by S. aureus [16]

Imunita kůže a Th2 reakce

Microorganisms are recognized by innate immune receptors such as Toll-like receptors on the keratinocyte surface
Keratinocytes produce antimicrobial molecules

HBD-2, HBD-3, and NO
IL-8 (neutrophil chemokine) is also produced

Drive neutrophils from the bone marrow pool into inflamed skin [16]

In a Th2 environment

IL-4 and IL-13

Induce the phosphorylation of STAT6

Inhibits INF-gamma and TNF-alpha

Inhibits the production of HBD-2 and HBD-3

Reduction of IL-8

Defective neutrophil accumulation in the skin

Contribute to allowing microbes to grow in the Th2 environment of AD skin [16]

Allergic immune reactions

Globally attenuated
Differentially polarized in patients with AD

Significant decreases in levels of TH1 products
Some increases in levels of TH17 products
Inconsistent upregulation in levels of TH2 products
The overall hyporesponsiveness in skin from patients with background AD might be explained

Baseline immune abnormalities

Increased TH2, TH17
Negative regulator levels

AD kontra psoriaza

T-cell infiltration characterizes both diseases
T-cell polarization differs
Psoriasis

IL-23/TH17 polarized

Testing of targeted therapeutics against various immune axes

TH2, TH22, and IL-23/TH17 [18]

Triggers of AD

Stress-induced immunomodulation - neuroimmunologic factors

Epidermal nerve fibers in close association with epidermal LCs-

neuropeptides

Increased levels in the plasma:

nerve growth factor
substance P
Correlate positively with the disease activity

brain-derived growth factor

Reduce eosinophil apoptosis
Enhancing chemotaxis of eosinophils in vitro [4]

Allergens

Food allergens

Can induce eczematoid skin rashes in a subset of infants and children with AD
Positive immediate skin test responses
Or serum IgE directed to various foods, particularly:

Egg
milk
Wheat
Soy
Peanut [4]

Food allergen– specific T cells

Cloned from the skin lesions
Direct evidence [4]

Food can exacerbate AD

Through allergic
Nonallergic hypersensitivity reactions [4]

Direct contact with the skin

Preparation of meals or when feeding infants
Might be an important factor for the aggravation of eczema [4]

Aeroallergens

Pruritus and skin lesions after intranasal or bronchial inhalation
Epicutaneous application of

House dust mites, weeds, animal danders, and molds, Dermatophagoides pteronyssinus (Der p 1)
Eczematoid reactions in a subset of patients
Effective house dust mite reduction measures has been reported to improve AD [4]

Microorganisms

Colonized with S. aureus
Exacerbation of their skin disease after infection with this organism
Antistaphylococcal antibiotics can result in reduction of skin disease
Secreting toxins called superantigens

Stimulate activation of T cells and macrophages [4]

Most patients with AD make specific IgE antibodies directed against staphylococcal superantigens

Correlate with skin disease severity [4]

Superantigens

Induce corticosteroid resistance [4]

Deficient in antimicrobial peptides needed for host defense against bacteria, fungi, and viruses

Underexpressed

Because of the upregulation of TH2 cytokines [4]

lower levels of proinflammatory cytokines, such as TNF-alfa and IFN-gamma

Increased susceptibility to skin infections [4]

Disseminated infections with herpes simplex or vaccinia virus
Susceptibility to severe viral infections

Smallpox vaccination is contraindicated in patients with AD unless there is imminent danger of exposure to smallpox [4]

Binding of S. aureus to skin

Enhanced by AD skin inflammation
Treatment with topical corticosteroids or tacrolimus reduces S. aureus counts in AD [4]

Yeasts

Opportunistic yeast Malassezia species

Contributing factor in AD
Presence of specific serum IgE
Positive skin prick test (SPT) response
Positive APT response against Malassezia species in adults with AD [4]

IgE sensitization to Malassezia species

Specific for patients with AD [4]
Not seen in patients with asthma or allergic rhinitis [4]

Autoantigens

Autoreactivity of patients with AD to human proteins
IgE against autoantigens could stimulate type 1 hypersensitivity reactions and DCs
Induce the proliferation of autoreactive T cells
IgE against manganese superoxide dismutase (MnSOD) from the skin-colonizing yeast M sympodialis cross-reacts with human MnSOD
Patients reacting to human MnSOD were sensitized against the M sympodialis MnSOD
Sensitization most likely occurs primarily by exposure to the environmental fungal MnSOD [4]

Irritant factors

Rough or woolly clothing

Mechanical irritation [4]

Chemical irritants [4]

Zhoršující faktory atopické dermatitidy

Alergeny

Ve vzduchu

V jídle

Eggs, milk, peanuts, soybeans, fish and wheat, in infants and children [2]

Dráždivé prostředí

Mýdla
Detergenty
Rozpouštědla
Wool in clothing, blankets and carpets
Dust
Pollen
Tobacco smoke
Air pollution
Hot water temperature during showering or bathing [4]

Změny počasí

Especially dry and cold

Psychika

Stress

Stav kůže

Sucuhá kůže

Long, hot baths or showers
Detergenty

Infekce kůže

Škrábání se

Further skin damage

Pocení se

Stres
Changes in heat and humidity

Terapie

Základní a nepostradatelnou léčbou jsou:

Emoliencia
V akutních stadiích lokálně aplikované kortikosteroidy a topické imunomodulátory [6]

Pomoc dietou

No universally recommended diet for patients with AD [4]
Restrictions only in cases of an established diagnosis of food hypersensitivity [4]
International guidelines for the diagnosis of food hypersensitivity have been published [4]
Predictive value of a positive case history is lower than that for food-induced immediate reactions [4]

Snížení střevní propustnosti

Zlepšeno - vhodné

Zhoršeno - nevhodné

Potraviny s lepkem

Potraviny obsahující lektiny

Rajče

Tomatin

Brambory

Solanin

Černý bez

Některé saponiny

Kontaminanty životního prostředí / potravin

Přídatné látky - E-čka v potravinách

Jiné látky v potravinách se schopností narušit střevní bariéru

Rucolla ve vyšším množství

Probiotika

Inulin

Laktobacily

3x v kapslích [9]
Bacterial products may induce an immune response of the Th 1 series instead of Th 2

Therefore inhibit the development of allergic IgE antibody production [9]

Limited benefit in preventive and therapeutic roles [9]
Prenatal and postnatal administration of probiotics

Reduced IgE levels in infants

May protect against sensitization to hereditary allergies [9]
But may not protect against asthma or wheezing [9]

January 2015, the World Allergy Organization

Recommend the use of probiotics by pregnant and lactating women and their breastfed infants to prevent the development of AD [9]

Based on a meta-analysis of 29 studies [9]
Probiotic use by pregnant women reduced the incidence of eczema by 9% during a 1- to 5-year follow-up [9]
Use by lactating women was associated with a 16% reduction in eczema during a 6-month follow-up period [9]
Probiotic consumption by breastfeeding infants was associated with a 5% reduction in eczema during the 6-month to 6-year follow-up period [9]

Administration of heat-killed L-92

Effective for AD symptoms in japanese adults
May contribute to the suppression of Th2-dominant inflammation [14]

Protizánětlivě ev. "antimikrobně" působící potraviny

Kurkuma

Nibma

Vyšší poměr omega-3 MK

Konopná semínka [9]
Lněná semínka
Fish oil [10]
Evening primrose oil [10]
Ryby high in EPA and DHA and lower in mercury

Salmon
Anchovies [11]
Herring [11]
Sardines [11]
Pacific oysters [11]
Trout [11]
Atlantic mackerel [11]
Pacific mackerel [11]

Rutin

Pohanka aj. mnohé rostliny, byliny a ovoce

Antihistaminová dieta

Eliminace alergenu

Assess for sensitization to a food

SPTs

Measurement of specific IgE

Diagnostic sensitivity and specificity varies considerably

Among different foods
Reading systems
Age groups

Discriminating between clinical relevance of sensitization

Lymphocyte cytotoxicity tests

Nepouziva se [4]

Basophil degranulation test

Nepouziva se [4]

Measurement of serum IgG (or subclasses)

Nepouziva se [4]

APT

An elimination diet should not be recommended solely on the basis of a positive APT response to a food [4]

Physician-supervised food challenges

Most accurate diagnostic tool
Patients can present with reactions at least 24 hours after a food challenge
In case of a negative challenge response

The skin of the patient should be examined the following day [4]

After a diagnosis has been established, a tailor-made education program for the patient should be initiated [4]

Mezi časté alergeny a dráždivé potraviny patří

Vaječný bílek [6]
Kravské mléko [6]
lepek [6]
Ořechy [6]
Soja [6]
Ryby [6]
Sýry [6]
Jahody [6]
Mák [6]
Citrusy [6]
čokoláda [6]

Režimová opatření

Teplota

Avoiding extreme temperatures [2]

Neškrabat se

Cover the itchy area if you can't keep from scratching it [2]
Trim nails and wear gloves at night [2]
Apply cool, wet compresses, bandages and dressings

Protect the skin and prevent scratching [2]

Warm bath

With baking soda
Uncooked oatmeal
Colloidal oatmeal
Ground oatmeal for the bathtub (Aveeno)
10 to 15 minutes

Dry
Medicated lotions, moisturizers

Behavioural therapy

Can be helpful to develop strategies to reduce scratching [3]

Mýdla

Mild soaps without dyes or perfumes
Rinse the soap completely off your body
Mild syndets with an adjusted pH value

Acidified to pH 5.5–6.0 in order to protect the acid mantle of the skin [4]

Vlhkost vzduchu

Use a humidifier

Hot, dry indoor air can parch sensitive skin and worsen itching and flaking [2]

Keep your humidifier clean

Prevent the growth of bacteria and fungi [2]

Oblečení, povlečení

Cool, smooth-textured cotton clothing [2]
Avoiding clothing that's rough, tight, scratchy or made from wool [2]
Prevent excessive sweating [2]

Treat stress and anxiety

Emotional disorders can worsen atopic dermatitis [2]

Pracovní podmínky

Používejte ochranné rukavice

Zvenku gumové a zevnitř bavlněné

Pracovní prostředí

Bezprašné
S minimem dráždivých látek
Bez většího znečištění a nutnosti častého mytí

Nevhodné např.

Vaření
Chov zvířat
Práce na zahradě, atd.

Dovolená

Vhodné jsou pobyty u moře
Na horách ve vysokých nadmořských výškách

Praní prádla - vhodné při atopickém ekzému

Půl hrnku sody do vodní lázně, ve které namáčíte pleny nebo utěrky [1]
Lázeň ze sody a vody

Silně znečištěné prádlo
Mastné skvrny
Skvrny od krve

Nechejte prádlo namočené nejlépe přes noc a pak normálně vyperte [1]

Mýdlový sliz

Mýdlo na praní

Jádrové mýdlo
Marseilleské mýdlo se 72% olivového oleje aj.

Prášková prací soda (ne jedlá soda)

Rozpouští tuk
Změkčuje vodu
Odstraňuje skvrny
Desinfikuje

Recept 1

Poměr mýdla a prací sody cca 1:1

250 g mýdla : 250 g sody : 5 l vařící vody, dolít na 10 l vody

Celkem cca 10,5 litrů slizu do cca 12l nádoby

Recept 2

Mýdlo 175 g : Soda 150 g : 1 l horké vody, dolít dalšími 9 l

Celkem cca 10,3 l slizu

Recept 3

200 g mýdla : 100 g - 150 g prací sody : 5-10 l vody [8]

Postup

Mýdlo nastrouháme na běžném struhadle

Víc na jemno, tím lépe
Do cca 1l horké vody
Za stálého míchání necháme rozpustit
Přidáme sodu, s mícháním necháme rozpustit
Celý kyblík dolijeme další horkou vodou dle návodů

Sliz vychladne - gelovou až pudinkovou konzistenci [3]

Použití

Dávkujeme přímo do bubnu pračky
Cca 250 ml na jedno praní
Dávka závisí na koncentraci Vašeho slizu a také na stupni znečištění [3]

Rizika

Ucpání filtrů v pračce

Příliš hustým slizem

Málo vody
Nedostatečně rozpuštěné mýdlo

Málo změkčující sody
Sraženiny

Kombinace - soda s octem

Prevence

čas od času nechat pračku propláchnout na prázdno na 90 °C [5]
Eroze gumových haidček pračky

Použití příliš koncentrovaného octa

Zaprané prádlo

Pobledlé barvy
Pozor na překročení množství sody

Mohlo by dojít k zašesnutí prádla

Skvrny na prádle

žlučové mýdlo
Sůl na skvrny - perkarbonát sodný

Rozpadá na bělicí a desinfekční kyslík a sodu [3]
Krásně vybělí například látkové pleny [3]

Aviváž

žádnou

Ekologické důvody
Zdravotní důvody

Na dětské prádlo je přímo nevhodná a na ostatní prádlo zbytečná [3]
Prádlo vyprané v mýdlovém slizu je měkké a má jemnou mýdlovou vůni [3]

Náhrada

Kápnout trošku 100% éterického oleje

žádné olejové směsi
Např. éterické oleje od firmy Eoné nebo Nobilis Tilia [6]
Pro atopickou pokožku se doporučuje

Levandule [6]
Mandarinka (od 6-ti měs.) [6]
Eukalypt polybractea [6]

Lze přidat již do slizu [7]
Do zásobníku na aviváž lze dát ocet smíchaný s vodou

Prádlo změkčuje [7]

Ekologická bezpečnost pracích slizů

Zasolení prostředí

Na pražskou čistírnu odpadních vod by muselo denně přitéci 213 tun uhličitanu sodného denně, aby byl překročen limit

V přepočtu by to bylo víc jak 21 milionů pracích dávek

Opět zcela nereálná cifra... [5]

Použití sody v čistících a pracích prostředcích v domácnostech nemá nepříznivý vliv na vodní ekosystémy [5]

Prací soda a ocet - ještě šetrnější praní při atopické ekzému

Praní

Dlouhý cyklus 60°
Cyklus „jemné prádlo" / hodinový cyklus – 40 - 60°
1 pytlíku jedlé sody + půl decilitru octa

Funguje dobře i na fleky [6]
Dobré reference stran snášenlivosti při akutní exacerbaci atopického ekzému [6]

Alternativa s kyselinou citronovou

Místo octu lze použít i k. citronovou
Obojí zároveň odvápňuje pračku [6]

Vysoká teplota vody a delší prací cyklus

Dokážou běžně zašpiněné prádlo vyprat bez jakýchkoliv potřebných přísad [6]

Redukce roztočů v ložním prádle

Matrace

Denně vysávejte vysavačem

Odstranit odumřelé roztoče a prach

Chránič matrace a chránič polštáře

Na polštář postačí každý den čistý ručník

Zachytí veškerý pot a odpadávající kůži

Chránič matrace

Sníží množství živých roztočů během měsíce o více než 90%

Peřiny

Ven pouze ve velkém mrazu

Spolehlivě zabije roztoče
Nejlépe přes noc, aby pořádně promrzly
Pokud lze, ta vyprat

Větrání

Před spaním a také ráno v pokoji pořádně vyvětrejte
5 - 10 minut otevřená okna
Vlhkost v místnosti okolo 40%

Roztoči

Prachoví roztoči

0,250 - 0,3 mm
Příbuzní pavouků
1694 holanďan Anton van Leeuwenhoek objevil pod mikroskopem
Dermatophagoides farinae (americký)
Dermatophagoides pteronyssinus (evropský)
žijí 3 - 4 měsíce
Samička zvýší populaci o 25 - 30 roztočích miminek týdně
Alergii způsobuje

protein v jejich trusu
Rozpadlá, mrtvá těla

Literatura [prani pradla]:

[1] www.prozeny.cz/magazin/bydleni-a-zahrada/poradme-si/37388-tohle-vsechno-umi-jedla-soda-vypere-vycisti-mycku-a-odkyseli-telo
[2] www.nazeleno.cz/bydleni/domacnost/cisty-domov-bez-chemie-jak-vyuzit-jedlou-sodu-pri-uklidu.aspx
[3] www.ekozivot.cz/ekodomacnost/navod-na-vyrobu-mydloveho-slizu/
[4] www.rozpad.cz/forum/viewtopic.php?f=23&t=1506
[5] ekolist.cz/cz/zelena-domacnost/rady-a-navody/jeleni-sliz-praci-prostredek-z-mydla-a-sody-pro-opravdove-ekonadsence
[6] www.proalergiky.cz/magazin/uzivatelske-clanky/clanek/atopicky-ekzematik-v-cem-nejlepe-prat-ecover-ci-mydlove-orechy
[7] www.eshop.ekokoza.cz/Navod-na-vyrobu-domaciho-praciho-prasku/
[8] www.mydloteka.cz/mydloteka/eshop/2-1-mydla-na-prani/0/5/1670-Soda-na-prani-uhlicitan-sodny-1-kg

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Deprecated: Function split() is deprecated in /home/users/dana/medicinman.cz/web/csf/kf.inc.php on line 67

Koupele a očista kůže

Po koupeli se ručníkem jen „oplácat“ a ne stírat

Non-soap cleansers

Colloidal oatmeal

Aveeno [1]

Desinfekční koupele - antiseptic solutions

Bleach baths

Half a cup of household bleach (6% sodium hypochlorite solution) to a full bath and soak for 10 minutes [3]
Decreases bacteria on the skin and related infections [2]
May not be helpful for everyone who has atopic dermatitis [2]
Too much bleach in the water can cause severe skin irritation [2]
Even diluted bleach baths may cause dryness or skin irritation [2]
Can be taken 2 or 3 times a week [2]
Do not use bleach baths if you have an allergy to chlorine [2]

Lukewarm water [2]

Clorox liquid bleach [2]

Condy's crystals (potassium permanganate)

In weak concentration - light rose pink colour

Cetrimide

Chlorhexidine

Chloroxylenol

Dibromopropamidine

Polynoxylin

Povidone iodine

Triclosan

Alterantivní koupele

Koupele se solí z Mrtvého moře - Osmóza

Ponoříte lidské tělo (kožní buňky) do slané vody, začne vylučovat vodu

S vodou ale odcházejí také iritanty aj. nečistoty z atopické pokožky

V prvních dnech se ekzém může na pohled zhoršit a dokonce i objevit tam, kde dosud viditelný nebyl

V dalších dnech se začne stav zlepšovat [9]

Idealně soli s vysokým obsahem hořčíku [9]
Vysušují

Šampóny

Exomega (a-derma)

Dětský šampón v pumpičce

Měsíčkový šampón (weleda)

Podpora regenerace kůže a kožní bariery

Ceramides, cholesterol and fatty acids

Mimic the lipids naturally found in the horny layer of the skin [3]
May reduce the need for anti-inflammatory medications [3]

Zvlhčování a promašťování kůže - emoliencia - Emollients

Key feature of AD is severe dryness of the skin

Increased transepidermal water loss
Typically accompanied by intense pruritus and inflammation [4]

Regular use of emollients together with skin hydration

The mainstay of the general management of AD [4]

Moisturize your skin at least twice a day
Prevent further water loss
Attempt to restore skin barrier function
Clothing soaked in paraffin-based emollients becomes a fire hazard [3]
Emollients should be applied continuously

Even if no actual inflammatory skin lesions are obvious

"Water-in-oil" or "oil-in-water" emulsions
Ideálně do 3 minut po koupeli

Největší schopnost pokožky absorbovat lipidy v krému

Test snášenlivosti

Po 3 dny malé množství na malý okrsek kůže

Před ucho nebo na zápěstí ap.

Pokud se neobjeví svědění či pálení, začervenání, pupínky atp., pak teprve lze aplikovat na ostatní místa

Skupiny přípravků

Lotions

Easy to apply but evaporate quickly and may not be oily enough [3]

Creams

Oil in water emulsion (fatty cream)
PHARMAC subsidises urea cream

Very good for dryness but can sting active eczema [3]

3% wool fat with mineral oil lotion [3]
Cetomacrogol

Nonionic cream

Cetomacrogol with 10% glycerol
Aqueous cream and emulsifying ointment

Oleje k promazávání kůže

Oleje do koupele

Léčebné koupelové oleje
Navíc detergentní účinky - i mycí schopnosti
Linola, Oilatum Balneum Hermal, Balmandol [5]
U dospělých

Vhodnější přímo nanést na kůži
Nechat chvilku působit
Pak lehce osprchovat [5]

Léčebnou koupel max. 10 minut

Jinak kůže nabobtnává a přesušuje se [5]

Masti

More effective than creams in very dry skin [3]
Hard to rub in and leave a greasy surface [3]
Can also encourage folliculitis by blocking the hair follicles [3]

Protizánětlivé pasty

Mohou i přesušovat [5]
Jen na ekzémová ložiska a ne k běžnému promazávání
Tak často během dne, jak je třeba

žádná bezpečnostní omezení [5]

Endiaron pasta
Ichthyo Care
Ictamo pasta
Tanno-Hermal lotio [5]

Další blíže neurčené nálezy

Lipikar (La Roche Posay)

Dobra reference

Multilind, Exomega, Atoderm
Lipobase

Dobrá reference

Excipial
Balneum, Linola, Oilatum, Physiogel, Trixera, Leciderm
Konopné prostředky Cutis Help a Cannaderm [5]
Linola

Aktivní substance

Ceramidy [1]

Vhodne i u eczema, allergic contact dermatitis, and radiation dermatitis [1]
CeraVe, TriCeram, Atopiclair, MimyX [1]

Polidocanol

Effective in reducing pruritic symptoms [4]

Urea

Intensive hydration of the skin [4]

Salicyl acid

Can be added to an emollient for the treatment of chronic hyperkeratotic lesions [4]

Zinek

Zinková pasta
Zinková mast

Kamenouhelný dehet

Ichtamol

Tanin

St. John's wort

Vitamin B12

Nevhodná topika

Parfémované

Heřmánek

Vedou často k alergii

Ekzém kontaktní [7]

Propolis

Vedou často k alergii

Ekzém kontaktní [7]

Topické kortikoidy - glucocorticosteroids

Vlastnosti

Anti-inflammatory effect
Reduction of skin colonization with S. aureus [4]

Might affect a further trigger factor of AD [4]

Indikace

Treatment of acute flare-ups AD

NÚ

Absorbce kůží a NÚ

Max. v místech tenké kůže

Eyelids
Genitals
Body folds
Skin of infants

Systemic absorption and adrenal suppression

Large amounts of potent topical steroids

More than 100g/week over months [3]

Can further reduce the skin barrier function

Best applied as intermittent courses

Kůže zregeneruje

Lowest strength and smallest quantity of topical steroid that is effective should be used

To all areas affected

No benefit from applying them more than once daily [3]

Oční víčka

Topical corticosteroids for atopic dermatitis on the eyelids and periorbital region
Is safe with the respect to induction of glaucoma or cataracts [9]

Redukce NÚ

Risk of adverse effects can be reduced by

Optimizing application protocols [4]
Using new steroid preparations with lower atrophogenic potential [4]

Prednicarbate
Mometasone furoate
Fluticasone
Methylprednisolone aceponate

Zásady užívání

Jen 1x denně
Obvykle na noc
Jako poslední prostředek

Až po promazávání [7]

Stav akutní

Lze nárazově 2x denně
Obvykle po 3 dny [7]

Po zlepšení, obvykle do týdne

Postupně snižujte
Ob 1 den, ob 2 dny, ob 3 dny až do úplného vysazení

Prevence relapsu
Cílem je stabilizace stavu [7]

Pokud se po počátečním zlepšení již ekzém dále neustupuje

Zůstaňte na intervalu ob 3 dny
Nebo individuálně i delší, který stačí udržet ekzém pod kontrolou

Intervalová léčba [7]

Používejte kortikoidy pouze bodově, na postižené partie [7]
Jen nezbytně nutné množství léku
Nemají účinky preventivní

Nemohou zabránit opětovnému propuknutí ekzému [7]

V akutní fázi na krátkou dobu silnější kortikoid

Po zklidnění (cca do 3 - 5 dnů) se nahradí slabším [7]

Intermittent use

Might be as effective as an initial therapy with a high potent steroid
Followed by a time-dependent dose reduction or change over to a lower potent preparation [4]

Application of fluticasone on unaffected skin twice weekly [4]

Prevents further flare-ups of AD [4]

Topical steroid preparations should be applied no more than twice daily as short-term therapy for acute eczematous lesions
Only mild to moderately potent preparations should be used on

Genital
Facial
Intertriginous skin areas [4]

In children only mild to moderately potent steroid preparations should be used [4]

Návod na e-medicine

Initial therapy

Hydrocortisone 1% powder in an ointment base

2 times daily
To lesions on the face and in the folds [9]

Midstrength steroid ointment: triamcinolone or betamethasone valerate

2 times daily
To lesions on the trunk until the eczematous lesions clear [9]

Terapeutická odpověď

Mild eczema

Respond to low potency topical steroids within a few days
Complete clearance of eczema within one or two weeks
Intermittent treatment works very well

Moderate eczema

May require more potent topical steroids for at least two weeks before improving
May require several weeks of treatment before clearing

Severe eczema

May show only partial improvement with potent topical steroids alone even after several months of use
Can often be maintained with emollients alone [3]
Gradually reducing the number of days the stronger topical steroid is used

F.e.: potent topical steroid at weekends and an emollient on weekdays

The oral corticosteroids prednisone and prednisolone are often used in the short-term management

Gain rapid control
Cannot be continued for more than a few weeks without significant side effects [3]

Tachyphylaxis

If used continuously topical steroids may lose their effectiveness after a few weeks [3]
Can be avoided by reducing the strength and frequency of the topical steroid as the eczema comes under control [3]
Changing to a different topical steroid of the same strength can be helpful [3]
Treatment of infection, if present, may again make the topical steroid effective [3]
A stronger topical steroid or an additional treatment such as phototherapy may be required [3]

Druhy kortikoidů

Prednison

Hydrocortizon

At least 1 % hydrocortisone [2]
Can temporarily relieve the itch [2]
To the affected area before you moisturize [2]

Prednicarbate

Mometasone furoate

Fluticasone

Methylprednisolone aceponate

Topical immunomodulators - TCIs

Steroid-free
Anti-inflammatory
Immunomodulatory activity

NÚ

Observed side effect

Transient burning sensation of the skin [4]
Pimecrolimus achieved better local tolerability than tacrolimus in children [4]

Not associated with a risk of skin atrophy
Useful alternative for the treatment of sensitive skin areas

Face [4]
Intertriginous regions [4]

Generalized viral infections observed during TCI treatment

Eczema herpeticum [4]
Eczema molluscatum [4]

No evidence of a causal link of cancer and the use of TCIs, but black-box warning for

Pimecrolimus (Elidel; Novartis, Basel, Switzerland)
Tacrolimus (Protopic; Astellas, Deerfield, Ill)
Lack of long-term safety data
Recommended as second-line treatments
Use in children younger than 2 years of age is currently not recommended

Užívání

V akutní fázi mohou imunomodulátory dráždit

Při výrazném zhoršení ekzému 1 - 3 dny kortikoidy
Pak přejít na imunomodulátory

První měsíc se aplikují 2x denně
Pak 1x denně
S přechodem na intervalovou léčbu 2 - 3x týdně
Hodinu před a po aplikaci imunomodulátorů se nesmí aplikovat jiný krém či mast [7]

KI

Virová či bakteriální infekce (opar, impetigo atp.)

Calcineurin inhibitors affect your immune system

Used only when other treatments have failed or if someone can't tolerate other treatments [2]
Approved for children older than 2 and for adults [2]
Useful for mild to moderate atopic dermatitis
Antiinflammatory but do not thin the skin or affect its barrier function
Main side effect is initial burning, feeling of warmth or itching [3]
Useful for eczema in thin-skinned areas (face, genitals and body folds) [3]

Tacrolimus (Protopic) v masti

More potent and may have greater immunosuppressive activity
Tacrolimus ointment (0.03%)

Approved for the treatment of children aged 2 years and older [4]

Tacrolimus ointment (0.1%)

Only approved for use in adults

Anti-inflammatory potency of ointment is similar to a corticosteroid with moderate potency
Good safety profile for a treatment period of up to 4 years with tacrolimus

Pimecrolimus (Elidel) v krému

Most effective when used at the earliest sign of eczema (such as redness or itching) to prevent flares
Pimecrolimus cream (1%)

Approved for the treatment of children aged 2 years and older [4]
Pimecrolimus cream is less antiinflammatory active than moderate corticoids

Good safety profile for a treatment period of up to 2 years with pimecrolimus

Tar preparations

Creams, bandages and bath additives
Reducing itch and inflammation
Smelly and messy
Do not appear as effective as topical steroids

Coal tar

Pine tar

Ichthammol preparations

Topical antimicrobial therapy

Toxins secreted by the majority of S. aureus on the skin behave as superantigens

Can directly influence the disease activity
Clinical signs of bacterial superinfection might be absent

Can be used in emollients
Part of an additional wet-wrap dressing therapy
AD seems not to be associated with a higher risk of sensitization against topical antimicrobials [4]

Triclosan (2,4,4’-trichloro-2’-hydroxydiphenyl ether)

Low sensitizing potential [4]
Low resistance rate [4]
Effective in significantly reducing skin colonization with S. aureus and skin symptoms [4]
Irritative, photoallergenic, phototoxic, mutagenic, or carcinogenic potential of triclosan has not been observed [4]

Chlorhexidine

Low sensitizing potential [4]
Low resistance rate [4]

Silvercoated textiles

Can reduce S. aureus colonization and eczema severity [4]

Silk fabric with a durable antimicrobial finish

Can reduce S. aureus colonization and eczema severity [4]

Erythromycin

Fusidic acid

High resistance rates of S. aureus to erythromycin have resulted in a preferential use of fusidic acid
Proved to be very effective against S. aureus [4]
Low minimal inhibitory concentration [4]
Good tissue penetration
Long-term therapy with fusidic acid is suspected to be responsible for increasing resistance [4]
Restricted topical application for only 2 weeks is advisable [4]

Mupirocin topical

Intranasal eradication of methicillin-resistant S. aureus - shown to be effective [4]:

Terapie mokvavých ložisek

Wet dressings / wraps - Wet-wrap therapy

Bandages applied over emollients +/- topical steroids [3]
In acute red, hot, weeping eczema and usually require admission to hospital [3]
Wrapping the affected area with topical corticosteroids and wet bandages [2]
Effective, intensive treatment for severe atopic dermatitis [2]
Control signs and symptoms within hours to days [2]
They can be repeated for several days or longer, reapplied as they dry out. [3]
Wet layer of cotton dressing

Then covered with tubular bandages
Applied over emollients
In combination with antiseptics or topical steroids [4]

Beneficial in cases of exacerbated AD skin lesions
More practical alternative approach using clothing rather than bandages [4]

Odpařující obklady

S borovou vodou
S Jarischovým roztokem
Studený obklad jen na několik minut
Pak tekutinu s povrchu kůže odpařit
Několikrát opakovat

Spray

Aplikace termální léčebné vody

La Roche Possay, Avéne [5]

Kůže se ochlazuje, zmírňuje se zánět i mokvání [5]

Phototherapy

If the eczema has failed to respond to topical treatments or is too severe for topical treatment alone [3]
Phototherapy may aggravate dryness [3]
KI: transport problems, very fair skin or a history of photosensitivivity [3]

Standard second-line treatment for adults [4]
In phases of acute flares, a combination with corticosteroids is often practiced [4]

-UV therapy should be restricted to adolescents older than 12 years [4]

Broad-band UVB (280–320 nm) [4]

Narrow-band UVB (311–313 nm) [4]

UVA (320–400 nm) [4]

UVA1 (340–400 nm) [4]

PUVA [4]

Balneo-PUVA [4]

UVB and topical glucocorticosteroids [4]

UVB with UVA [4]

UVA1 medium- and high-dose therapy [4]

Natural sunlight

Controlled amounts [2]

Artificial ultraviolet A (UVA) and narrow band UVB

Controlled exposure to UV-B and/or UV-A for a few minutes two to three times each week
Treatment course may continue for several months
Alone or with medications
Reserved for severe eczema

Expensive [3]
Time-consuming
Potential side effects [3]

Photochemotherapy

Psoralen plus ultraviolet light therapy (PUVA)

Long-term light therapy has harmful effects, including premature skin aging and an increased risk of skin cancer [2]

Not used for infants and young children [2]

Celková terapie

Antihistamines

Sedative properties
Short-term adjuvant to topical treatment during relapses associated with severe pruritus
Nonsedating antihistamines

Only very modest value in atopic eczema [4]

There are no large controlled studies to date [4]

Cetirizine

Zyrtec
Several months theraphy may be helpful

May have disease-modifying effects in adults and children [3]

Fexofenadine

Allegra

Diphenhydramine

Benadryl etc.

Ospalost [2]

Další protisvědivé medikamenty

Hydroxyzine

Certain degree of relief from itching [9]
Not effective without other treatments [9]

Diphenhydramine hydrochloride

Certain degree of relief from itching [9]
Not effective without other treatments [9]

Ketotifen

calcium channel blocker
May be effective [9]

Oil of evening primrose

Was believed to be effective
In a randomized controlled study

No benefit in children [9]
Little improvement in adults [9]

Neúspěšná terapeutické pokusy

Everolimus [9]
Rapamycin-derived macrolide [9]

Combination therapy with either prednisone or cyclosporine A was not effective [9]

Thymopentin [9]
Gamma interferon [9]
Chinese herbs [9]

Kortikoidy

Interferon

Sometimes used in adults if other treatment doesn't work [1]

Cyclosporin A - (CyA)

Inhibits calcineurin-dependent pathways
Reduced levels of proinflammatory cytokines

IL-2
IFN-gamma [4]

Effective treatment for adult and childhood AD
Relapse after discontinuation of therapy is often observed [4]
Posttreatment disease severity often does not return to baseline levels [4]
Renal toxicity
Limited to patients with severe refractory disease
Blood pressure and laboratory parameters must be monitored closely
Short- or long-term therapy

High-dose (3–5 mg/kg/d)
Low-dose (2.5 mg/kg/d)

Aim for the lowest effective dose
Shortest treatment period
Vaccinations might not be effective during immunosuppression

Azathioprine

Affecting purine nucleotide synthesis and metabolism
Efficient for many dermatologic conditions [4]
As monotherapy in nonlicensed indications, including AD [4]
Accumulating evidence for its efficacy in severe recalcitrant AD [4]
Number of side effects

Myelosuppression
Hepatotoxicity
Gastrointestinal disturbances
Increased susceptibility for infections
Possible development of skin cancer [4]

Metabolized by the thiopurine methyltransferase

Deficiency of this enzyme should be excluded before starting oral immunosuppression with azathioprine [4]

Recommended dosage of azathioprine for dermatologic indications

1 to 3 mg/kg daily
Determined based on thiopurine methyltransferase levels
Regular blood tests must be performed [4]

Onset of action is usually slow
Benefit might not be apparent until 2 to 3 months after starting treatment [4]

Methotrexate - MTX

Mycophenolate mofetil

Immunotherapy

Hyposensitization is not an established instrument for the treatment of AD [4]
Case reports suggest clinical benefit from allergen-specific desensitization in AD [4]
Double-blinded controlled trials have failed to show consistent efficacy [4]
Allergen-specific immunotherapy of house dust mite preparations in patients with AD sensitized to house dustmite allergens for 1 year [4]

Dose-dependent effect on disease symptoms [4]

Zkoumané možnosti terapie AD

Rituximab

B-cell antibody, shows promise [3]
Has severe side effects [3]
Not effective in every case [3]

Omalizumab

Monoclonal antibody that blocks IgE function
Case reports suggest that it may be an effective
got the indication in Europe for the treatment of chronic spontaneous urticaria after escapement to antihistamines [12]
Randomized, placebo-controlled trial did not demonstrate improvement in the clinical course [9]

Dupilumab

Monoclonal antibody that blocks the IL-4 receptor
Randomized, double-blind, placebo-controlled trials have demonstrated marked and rapid improvement in AD disease activity
Drug remains to be FDA-approved for AD [9]

Corynebacterium bovis

Induced robust T helper 2 cell responses in mice skin
Langerhans cells were required for eliciting immune responses against S. aureus inoculation [13]
Possible target for future therapeutics in eczematous dermatitis [13]

Oficiální prohlášení

Insufficient evidence exists to recommend:

Probiotics
Leukotriene inhibitors
Essential fatty acids
Traditional Chinese medicines
Allergen immunotherapy

May be useful in a small number of individuals with proven sensitisation to inhalant allergens [3]

Komplikace

Asthma and hayfever

Neurodermatitis - lichen simplex chronicus

Starts with a patch of itchy skin
Scratch the area, which makes it even itchier
Affected skin become discolored, thick and leathery

Skin infections

Penicillin derivatives flucloxacillin or dicloxacillin [3]

Usually prescribed

Erythromycin

In those allergic to penicillin

Another drug active against staphylococcus and streptococcus may be preferred
On discontinuing the oral antibiotic, the patient may suffer another flare

Occurs repeatedly
Antibiotics may be prescribed for several weeks or months
Low risk of side effects from such treatment

Main concern is the development of MRSA [3]

Antibiotic creams and ointments are not recommended for use in extenisve atopic dermatitis

Not as effective as oral antibiotics
May also cause contact allergic dermatitis [3]
May promote the development of bacterial resistance [3]

Intranasal mupirocin ointment and diluted bleach (sodium hypochlorite) baths

Improved atopic dermatitis symptoms in patients with clinical signs of secondary bacterial infection [9]

Celková ATB terapie - Systemic antibiotic treatment

Widespread bacterial secondary infection (primarily S. aureus)
First- or second-generation cephalosporins

7 to 10 days are usually effective [4]

Semisynthetic penicillins

7 to 10 days are usually effective [4]

Erythromycin-resistant organisms

Fairly common [4]
Macrolides less useful alternatives [4]

Penicillin or cephalosporin allergy

Clindamycin
Oral fusidic acid [4]

Recolonization after a course of antistaphylococcal therapy occurs rapidly
Maintenance antibiotic therapy

Should be avoided [4]
Might result in colonization by methicillin-resistant organisms [4]

Eczema herpeticum - Kaposi's varicelliform eruption

Severe and possibly life-threatening complication
Systemic antiviral treatment

Acyclovir [4] [9]
Valacyclovir [4]

Eye problems

Severe itching around the eyelids, eye watering
Inflammation of the eyelid - blepharitis and conjunctivitis

Irritant hand dermatiti

Exposed to harsh soaps, detergents and disinfectants

Allergic contact dermatitis

Common in patients with atopic dermatitis
Including corticosteroids
To topical medications frequently occurs, especially in adults [4]
Cases of worsening eczema despite treatment

Needs to be ruled out by means of patch testing [4]

Sleep problems

Itch-scratch cycle

Behavioral problems

Link between atopic dermatitis and attention-deficit/hyperactivity disorder

Especially if a child is also losing sleep [2]

Omezení pracovní činnosti
Psychosociální problémy

Časté exacerbace či kontinuální průběh bez remisí

Nedostatečná odpověď na léčbu

Přechod do dospělosti

Silná dědičná zátěž [5]
Přítomnost alergie na mnohé látky (tzv. polyvalentní alergie) [5]
Nedostatečně zvládání zánětu/ekzému v dětském věku [5]
„early onset AD“

Přetrvává do dospělosti až u 30 % případů [6]

Prognosticky špatné ukazatele

Pozitivní rodinná anamnéza
Těžší průběh AD v dětství
Přítomnost respirační atopie
Vysoké hodnoty IgE v pupečníkové krvi
Nulová alela genu pro filagrin

Literatura:

[1] Atopic Dermatitis (Eczema) - Treatment Overview, Last Updated: March 12, 2014 www.webmd.com/skin-problems-and-treatments/eczema/tc/atopic-dermatitis-treatment-overview
[2] www.webmd.com/skin-problems-and-treatments/bleach-baths-for-atopic-dermatitis
[3] Treatment of atopic dermatitis. Is there a cure for atopic dermatitis? DermNet NZ www.dermnetnz.org/dermatitis/treatment.html
[4] Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report, C. A. Akdis1, M. Akdis1, T. Bieber2, C. Bindslev-Jensen3, M. Boguniewicz4,5, P. Eigenmann6, Q. Hamid7, A. Kapp8, D. Y. M. Leung4, J. Lipozencic9, T. A. Luger10, A. Muraro11, N. Novak2, T. A. E. Platts-Mills12, L. Rosenwasser4, A. Scheynius13, F. E. R. Simons14, J. Spergel15, K. Turjanmaa16, U. Wahn17, S. Weidinger18, T. Werfel19, T. Zuberbier17 andthe European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Group†, Article first published online: 28 JUN 2006, DOI: 10.1111/j.1398-9995.2006.01153.x onlinelibrary.wiley.com/doi/10.1111/j.1398-9995.2006.01153.x/full
[5] www.ordinace.cz/clanek/atopicky-ekzem-atopicka-dermatitida/?chapter=1
[6] Jiráková, A., Slavíková, Š., Vojáčková, N., Hercogová, J. Atopic dermatitis, Atopická dermatitida; 7.4.2010 zdravi.e15.cz/clanek/postgradualni-medicina/atopicka-dermatitida-450827
[7] www.ordinace.cz/clanek/atopicky-ekzem-atopicka-dermatitida/?chapter=4
[8] Atopický ekzém (atopická dermatitida) a jeho léčba? Jak léčit atopický ekzém? 15. 08. 2014 www.solnajeskyneletnany.cz/novinky/atopicka-dermatitida-atopicky-ekzem-jak-lecit-a-vylecit-atopicky-ekzem/
[9] Atopic Dermatitis Treatment & Management; Brian S Kim, MD; Chief Editor: William D James emedicine.medscape.com/article/1049085-treatment
[10] Atopic Dermatitis (Eczema) - Other Treatment www.webmd.com/skin-problems-and-treatments/eczema/tc/atopic-dermatitis-other-treatment
[11] Essential Fatty Acids (Omega-3 and Omega-6 Fatty Acids) www.webmd.com/hw-popup/essential-fatty-acids
[12] www.ncbi.nlm.nih.gov/pubmed/26021140
[13] Immunity. 2015 Apr 21;42(4):756-66. doi: 10.1016/j.immuni.2015.03.014. Dysbiosis and Staphylococcus aureus Colonization Drives Inflammation in Atopic Dermatitis. Kobayashi T1, Glatz M2, Horiuchi K3, Kawasaki H4, Akiyama H5, Kaplan DH6, Kong HH2, Amagai M4, Nagao K7. www.ncbi.nlm.nih.gov/pubmed/25902485
[14] www.ncbi.nlm.nih.gov/pubmed/25660281
[15] www.ncbi.nlm.nih.gov/pubmed/25659224
[16] Microbiota in Healthy Skin and in Atopic Eczema; Giuseppe Baviera, 1 , 2 ,* Maria Chiara Leoni, 2 , 3 Lucetta Capra, 2 , 4 Francesca Cipriani, 2 , 5 Giorgio Longo, 2 , 6 Nunzia Maiello, 2 , 7 Giampaolo Ricci, 2 , 5 and Elena Galli www.ncbi.nlm.nih.gov/pmc/articles/PMC4122000/
[17] www.ncbi.nlm.nih.gov/pubmed/25625823
[18] www.ncbi.nlm.nih.gov/pubmed/25541257
[11]
[11]
[11]
[11]
[11]
[11]
[11]

MUDr. Dana Maňasková

Atopický ekzém / dermatitida

Synonyma

Historie

Epidemiologie

Prevalence rapidně vzrůstá

ČR 2010

Symptomy

Kojenecká - Infants

Dětská - 2 years - puberty [3] od 3 do 10 let [6]

Dospělá - Adult

Dieferenciální diagnostika

Combination forms are prevalent with components of

Atopic eczema of the hands and feet

Acute Atopic Dermatitis

Chronic lichenified forms of AD

Late-onset AD

Recalcitrant cases

Larvované nebo frustní formy AD

Pityriasis alba

Xeróza kůže

Keratosis pilaris

Palmoplantární hyperlinearita

Dennieho-Morganiho rýha

Hertoghovo znamení

Cheilitida

Dermatitida bradavek

Dermatitida bříšek prstů rukou (pulpitis sicca)

Bílý dermografismus

Oční komplikace

Rizikové faktory

Hygienická teorie (David Štrachán, 1989)

OA a RA

Kojení

Profese

Životní prostředí

Ftaláty

Ostatní

DnBP, BBzP and DEHP

Alergeny

Asociovaná rizika

Allergic rhinitis

Allergic asthma

Perzistence do dospělosti

Rasa

Genetika

Filaggrin (FLG)

Příčiny

Dry, irritable skin

A gene variation

Immune system dysfunction

Bacteria

Environmental conditions

Histopathology

The skin

Atopické léze

Chronic AD skin lesions

Cytokines and chemokines

TNF-alfa and IL-1 from resident cells

The onset of acute AD

IL-4 a IL-13

TH2 cytokine IL-5

GM-CSF

Increased expression of C-C chemokines

Cutaneous T cell–attracting chemokine (CCL27)

Selective recruitment of CCR4-expressing TH2 cells

TH1 cell migration toward the epidermis

IgE and IgE receptors

Transient form of AD

Expression of IgE receptors

Skin barrier dysfunction

T cells

TH1 and TH2 play

DCs

LCs

IDECs

Plasmacytoid DCs (pDCs)

Eosinophils

Pathophysiology of pruritus in AD

Dysbalance of skin microbiota