Skin biopsies: their utility to allergists and immunologists

Skin biopsies are a commonly performed ancillary diagnostic test whose clinical utility may range from unnecessary to irreplaceably decisive, depending on the clinical setting and differential diagnosis. This chapter will review the diagnostic role of skin biopsy for eczematous and urticarial disorders most likely to be encountered by allergists/immunologists. The chapter is also a resource for rare autoinflammatory and immunodeficiency syndromes, and other skin disorders that may occasionally present to the allergy-immunology clinic.

Eczematous disorders include atopic dermatitis (eczema) but also other forms of eczematous dermatitis, including contact dermatitis, nummular dermatitis, seborrheic dermatitis, dyshidrosis, and others. On biopsy, these show a similar or identical appearance of spongiotic dermatitis, so clinical correlation is required to establish the final diagnosis.

Among urticarial disorders, the differential diagnosis of urticaria versus urticarial vasculitis represents a common indication for biopsy and may include direct immunofluorescence as an ancillary test that may increase diagnostic yield. Other urticarial disorders may include spongiotic/eczematous dermatitis, drug reactions, acquired immunobullous disorders, and a variety of rare autoinflammatory syndromes (chronic infantile neurologic cutaneous and articular disorder/neonatal-onset multisystem inflammatory disease, cryopyrin-associated periodic syndromes, familial cold autoinflammatory syndrome, hereditary angioedema, Muckle–Wells syndrome, NLRP12-associated autoinflammatory disease, Schnitzler syndrome). While histology alone can potentially establish a diagnosis of vasculitis or exclude a diagnosis of urticaria, in other cases, such as drug reactions, clinical correlation is always required.

Autoinflammatory and immunodeficiency are exceptionally rare. While histopathologic features alone are not diagnostic, recurring histologic reaction patterns have been observed and may be helpful in narrowing the differential diagnosis or supporting a suspected diagnosis. Noninfectious cutaneous granulomas may occur in ataxia-telangiectasia, Blau syndrome, chronic granulomatous disease, combined immunodeficiency, common variable immunodeficiency, Good syndrome, hemophagocytic lymphohistiocytosis, PLCγ2-associated antibody deficiency and immune dysregulation, primary biliary cirrhosis, severe CID, and X-linked agammaglobulinemia.