Cutaneous immunopathology: The diagnostic use of direct and indirect immunofluorescence techniques in dermatologic disease

Abstract

Direct and indirect immunofluorescence tests performed on skin biopsy specimens and serum have enriched the diagnostic skills of the practicing pathologist. Specific patterns of immunoglobulin and complement deposition have clarified the diagnostic entities within the group of vesiculobullous diseases. The pemphigus group of diseases is characterized by antibodies, usually IgG, directed against the intercellular substance of squamous epithelium. The pemphigoid group of bullous diseases is characterized by antibody, usually IgG, directed against the basement membrane zone. The basement membrane zone deposition of immunoglobulin or complement is linear and localized to the lamina lucida. In dermatitis herpetiformis, granular or speckled IgA deposition in the upper papillary dermis is characteristic; however, other patterns of deposition may occur. Abnormal microfibrillar bundles in the upper papillary dermis have recently been identified in patients with dermatitis herpetiformis. Immunofluorescence studies of patients with lupus erythematosus are important not only in diagnosis but also in prognosis. The diseased skin of lupus patients contains deposits of immunoglobulin, usually IgG or IgM, at the basement membrane zone in more than 90 per cent of the cases. In discoid lupus erythematosus, clinically normal skin does not contain such deposits. However, in systemic lupus erythematosus, normal sun exposed skin contains these deposits in approximately 80 per cent of the cases and normal nonsun exposed skin contains them in 50 per cent of the cases. Direct immunofluorescence of normal skin may demonstrate basement membrane zone deposition of immunoglobulin in mixed connective tissue disease and other autoimmune diseases with anti-DNA antibodies. The skin of psoriatic patients may demonstrate in vivo bound IgG within the stratum corneum. Similar circulating antistratum corneum antibodies are found in normal subjects; however, these antibodies do not appear to have access to epidermal binding sites. Patients with lichen planus characteristically have large globular deposits of immunoglobulin and complement in the epidermis and dermis in diseased skin. Granular deposition of IgM and IgG at the basement membrane zone in lichen planus may lead to confusion with lupus erythematosus. Deposition of immunoglobulin and complement is found in and about vessels in early lesions of cutaneous vasculitis. Negative findings in older lesions may be due to immune complex degradation and removal. Further information has accrued concerning the possible role of humoral immunity in graft versus host disease. Granular or linear deposition of immunoglobulin, primarily IgM, has been identified in the skin of patients with acute and chronic graft versus host disease. Identification of infectious agent antigen in tissue using modified direct immunofluorescence techniques promises rapid diagnosis in certain infectious diseases such as Rocky Mountain spotted fever and gonococcemia. The direct and indirect immunofluorescence findings in the foregoing diseases as well as others are discussed in detail along with considerations of pathogenesis. A brief review of methodology is given.