Skin lesions are important clues to systemic diseases and, conversely, host factors make patients susceptible to skin infections caused by certain organisms. The skin has a limited response to insults from the microbial world, forming vesicles and pustules that eventually rupture and leave exposed dermis. Accurate diagnosis and appropriate treatment depend on a detailed history that includes systemic complaints, history of exposure and travel, and the initial appearance of the skin lesions. Sound diagnosis of difficult cases also depends on appropriate cultures and histopathology. When possible, cultures should be obtained by aspirating pus or blister fluid from under intact skin; cultures from ulcerated skin are less reliable because of colonization by nonpathogenic skin flora. A Gram stain and routine culture should be done first; if the ulcer persists despite a course of antibiotics, a skin biopsy with histopathology and cultures for routine agents, acid-fast organisms, and fungal pathogens is appropriate. If the lesion has multiple thin-walled vesicles with interspersed shallow ulcers and crusts or is on a mucus membrane, a direct fluorescent antibody (DFA) test or Tzank smear for herpes and viral culture should be considered.

Most superficial skin infections and ulcers can be treated empirically according to the typical clinical presentation of the lesions. A workup is required for lesions that do not respond to routine therapy, that are rapidly progressive, or that occur in an immunocompromised host.