LABORATORY EVALUATION If there is no clear etiology of what led to the blister, the laboratory tests described next can be helpful Gram Stain The Gram stain of fluid from an intact blister will be positive in impetigo and in a secondarily infected lesion It will be negative, however, in all other conditions Tzanck Smear Multinucleated giant cells will be present on a Tzanck smear of material scraped from the base of an intact, freshly opened vesicle caused by herpes simplex, herpes zoster, and primary varicella The Tzanck smear is not sensitive so additional testing is required if negative Rapid Slide Test for Direct Immunofluorescence Fluorescent-tagged monoclonal antibody is applied to cells scraped from the blister base and can differentiate HSV-1, HSV-2, or varicella-zoster virus Results can be available in to hours Bacterial or Viral Cultures Cultures help confirm an etiologic diagnosis when Gram stain, Tzanck smears, and DIF are negative or indeterminate Polymerase Chain Reaction An alternative or adjunct to traditional culture techniques, polymerase chain reaction techniques allow for amplification of DNA or RNA present within a specimen and rapid identification of the etiologic pathogen, including HSV, VZV, and enterovirus The technique is useful even when the pathogen present is no longer viable Skin Biopsy For perplexing cases undiagnosed by clinical and/or simple laboratory evaluation, dermatologic consultation and skin biopsy are required If the picture on histology is compatible with erythema multiforme, DIF should be considered DIF will be negative in erythema multiforme but will be positive in bullous pemphigoid (linear IgG and C3 on the basement membrane), DH (granular IgA at tips of dermal papillae of uninvolved perilesional skin), and CBDC (linear IgA on the basement membrane) though DIF can occasionally be negative in CBDC