What is the frequency of immunoreactant positivity in direct immunofluorescence specimens associated with skin biopsies?
In this quality improvement study spanning 8 years, including 2050 direct immunofluorescence biopsies, immunoglobulin G, immunoglobulin A, and C3 antibodies identified all primary immunobullous disease cases, and immunoglobulin A, C3, and fibrin antibodies identified all vasculitis cases. A total of 247 samples were submitted for clinical diagnoses not optimally supported by direct immunofluorescence.
The findings of this study suggest that reflexive use of a 6-antibody direct immunofluorescence panel is likely not necessary to diagnose diseases associated with positive findings; pathologists may tailor antibodies used, and clinicians their decision to use direct immunofluorescence, to the suspected clinical diagnosis, which may result in more cost-conscious care.
Dermatologists submit direct immunofluorescence (DIF) biopsies on a daily basis, using an assay detecting immunoreactant deposition with a panel that has traditionally comprised immunoglobulin (Ig) G, IgA, IgM, C3, and fibrin, with or without albumin antibodies.
To evaluate and compare the frequency of immunoreactants in DIF biopsies submitted over an 8-year period and assess use by dermatologists based on clinical impression.
Design, Setting, and Participants
A quality improvement study was conducted in a community outreach reference laboratory associated with a large academic medical center. Results of 2050 consecutive DIF skin biopsies submitted to the laboratory between April 1, 2012, and June 12, 2020, were analyzed by final pathologic diagnosis and antibody subtype positivity, in comparison with clinical impression. Biopsies in which the submitting physician had not performed the biopsy were excluded.
Main Outcomes and Measures
Histopathologic findings and the results of DIF biopsies using the standard 6-antibody panel were evaluated in correlation with the submitted clinical diagnosis to assess immunoreactivity of the assay.
Of 2050 DIF biopsies submitted, 367 (17.9%) were positive; IgG, IgA, and C3 alone identified all primary immunobullous disease cases (pemphigoid, pemphigus, linear IgA, and dermatitis herpetiformis), and IgA, C3, and fibrin antibodies alone identified all vasculitis cases. A panel of IgG, IgA, IgM, and fibrin identified all cases of lupus erythematosus. DIF results were positive in less than half of cases of hematoxylin and eosin biopsy-confirmed lupus erythematosus (23 of 47 [49%]). A total of 247 biopsies were submitted for clinical diagnoses not optimally supported on DIF: lichen planus, porphyria, and connective tissue disease.
Conclusions and Relevance
The findings of this study suggest that there is a knowledge gap among dermatologists relating to the opportunity for high-value, cost-conscious use of DIF. The practice of reflexive antibody testing using a 6-antibody panel for all DIF biopsies is likely unnecessary. DIF protocols tailored to the clinical diagnosis may enhance cost-effectiveness without loss of test sensitivity or specificity.
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Reimann JDR, Moynihan SP, Horn TD. Assessment of Clinical and Laboratory Use of the Cutaneous Direct Immunofluorescence Assay. JAMA Dermatol. Published online October 06, 2021. doi:10.1001/jamadermatol.2021.3892
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