A systemic disease is one that affects a number of organs and tissues, or affects the body as a whole.igns of a systemic disease may be evident on the outer surface of the eye (eyelids, conjunctiva and cornea), middle of the eye and at the back of the eye (retina).. Since 500 B.C., some researchers have also believed that the physical condition of the fingernails and toenails can indicate various systemic diseases.