Direct immunofluorescence studies may be performed on skin biopsies (submitted fresh on saline soaked gauze), to look for an immune basis to the pathology.　 They should be marked urgent, and ideally sent during "business hours".

Common clinical situations include vesiculobullous lesions, and leucocytoclastic vasculitis

Bullous pemphigoid – if this is part of the clinical differential diagnosis, direct immunofluorescence is an essential part of the diagnosis (basement membrane IgG +/- C3c)

Pemphigus vulgaris – intercellular IgG staining is the hallmark of this condition, again direct immunofluorescence is essential to confirm the diagnosis, including on oral mucosal biopsies

Dermatitis herpetiformis – again direct immunofluorescence is essential (normal histology often non specific).　 Granular IgA staining in dermal papillae.

Less common dermatological conditions eg. Linear IgA disease – consultation with Dermatology unit recommended

Vasculitis – if patient has leucocytoclastic vasculitis, direct immunofluorescence should be performed to diagnose or exclude IgA vasculitis.　 It is not recommended direct immunofluorescence be performed before vasculitis is confirmed by routing H&E sections, although this will vary with the prebiopsy diagnostic confidence.

Other situations – inspite of some textbooks/literature/standard dogma, direct immunofluorescence is not a useful test in cutaneous lupus.　 This is a morphological diagnosis, immunofluorescence is often negative or non specific.　 Discussion with a histopathologist prior to biopsy can often stop unnecessary biopsies and ensure correct procedure.　 In general, skin biopsies for direct immunofluorescence should be of perilesional tissue (particularly in vesiculobullous lesions).　 For vasculitic rash, the rash should be sampled.　 Ulcerated skin should not be biopsied.

Direct immunofluorescence on skin biopsies should be performed only in specific clinical settings where one of the immune mediated skin conditions above is suspected.