{"doi":"10.1016/j.jaad.2023.04.016","title":"C3d immunohistochemistry in the diagnosis of bullous pemphigoid: A comparative diagnostic test accuracy and cost analysis study","abstract":"To the Editor: Bullous pemphigoid (BP) is characterized by urticarial plaques that may evolve overlying tense bullae. BP can mimic other bullous, urticarial or eczematous dermatoses,1Della Torre R. Combescure C. Cortés B. et al.Clinical presentation and diagnostic delay in bullous pemphigoid: a prospective nationwide cohort.Br J Dermatol. 2012; 167: 1111-1117https://doi.org/10.1111/j.1365-2133.2012.11108.xCrossref PubMed Scopus (84) Google Scholar necessitating the use of histopathology and adjunct diagnostic tests. Direct immunofluorescence (DIF) demonstrating linear IgG and/or C3 deposits along the dermal-epidermal junction (DEJ) on perilesional skin biopsy constitutes the current diagnostic gold standard. However, DIF requires a dedicated fresh tissue specimen and has a relatively high cost. Recent evidence suggests C3d immunohistochemistry (IPOX) applied to paraffin-embedded, formalin-fixed tissue similarly identifies complement deposits along the DEJ.2Magro C.M. Dyrsen M.E. The use of C3d and C4d immunohistochemistry on formalin-fixed tissue as a diagnostic adjunct in the assessment of inflammatory skin disease.J Am Acad Dermatol. 2008; 59: 822-833https://doi.org/10.1016/j.jaad.2008.06.022Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar, 3Pfaltz K. Mertz K. Rose C. Scheidegger P. Pfaltz M. Kempf W. C3d immunohistochemistry on formalin-fixed tissue is a valuable tool in the diagnosis of bullous pemphigoid of the skin.J Cutan Pathol. 2010; 37: 654-658https://doi.org/10.1111/j.1600-0560.2009.01450.xCrossref PubMed Scopus (38) Google Scholar, 4Glauser S. Rutz M. Cazzaniga S. Hegyi I. Borradori L. Beltraminelli H. Diagnostic value of immunohistochemistry on formalin-fixed, paraffin-embedded skin biopsy specimens for bullous pemphigoid.Br J Dermatol. 2016; 175: 988-993https://doi.org/10.1111/bjd.14686Crossref PubMed Scopus (20) Google Scholar We hypothesize that C3d IPOX, when combined with serological studies (enzyme-linked immunosorbent assay [ELISA] 180/230), may have practical and cost advantages for BP diagnosis. We reviewed 1094 DIF reports from University of California San Francisco between February 2015 and February 2020, and analyzed 194 cases from 186 unique patients. The median age (range) was 71 (24-98) years. Fifty-six percent (n = 109) identified as female and 44% (n = 85) as male. Using final clinical diagnosis of BP as the gold standard, test characteristics were calculated for each diagnostic test (Table I).Table IDiagnostic performance of C3d IPOX, DIF, and ELISA in patients with suspected bullous and nonbullous/urticarial pemphigoidDiagnostic testNumber (pemphigoid/not pemphigoid)% (95% CI)Likelihood ratio (95% CI)Diagnostic odds ratio (95% CI)SensitivitySpecificityPostive predictive valueNegative predictive valuePositiveNegativeDIF194 (65/129)80.0 (68.2-88.9)100.0 (97.2-100.0)100.0 (93.2-100.0)90.9 (84.9-95.0)-0.2 (0.1-0.3)-C3d IPOX194 (65/129)64.6 (51.8-76.1)86.8 (79.7-92.1)71.2 (57.9-82.2)83.0 (75.5-88.9)4.9 (3.0-7.9)0.4 (0.3-0.6)12.0 (5.5-26.4)ELISA 180 and/or 230112 (51/61)76.5 (62.5-87.2)91.8 (81.9- 97.3)88.6 (75.4-96.2)82.4 (71.2-90.5)9.3 (4.0-21.9)0.3 (0.1-0.4)36.4 (10.8-137.1)ELISA 180112 (39/73)68.6 (54.1-80.9)93.4 (84.1- 98.2)89.7 (76.9-95.8)78.1 (70.3-84.3)10.5 (4.0-27.5)0.3 (0.2-0.5)31.2 (9.6-100.8)ELISA 230100 (25/75)48.9 (34.1-63.9)96.2 (87.0-99.5)92.0 (74.1-97.9)68.0 (61.5-73.9)13.0 (3.2-52.1)0.5 (0.4-0.7)24.4 (5.3-112.2)C3d IPOX and ELISA112 (51/61)92.2 (81.1-97.8)86.9 (75.8-94.2)85.5 (73.3-93.5)93.0 (83.0-98.1)7.0 (3.7-13.5)0.1 (0.04-0.2)77.8 (19.7-354.0)DIF and ELISA112 (51/61)94.1 (83.8-98.8)91.8 (81.9-97.3)90.6 (79.3-96.9)94.9 (85.9-98.9)11.5 (4.9-26.7)0.1 (0.02-0.2)179.2 (35.4-1097.3)DIF and C3d IPOX194 (65/129)90.8 (81.0-96.5)86.8 (79.7-92.1)77.6 (66.6-86.4)94.9 (89.3-98.1)6.9 (4.4-10.8)0.1 (0.1-0.2)64.8 (22.7-204.9)C3d IPOX, C3d immunohistochemistry; DIF, direct immunofluorescence; ELISA, enzyme-linked immunosorbent assay. Open table in a new tab C3d IPOX, C3d immunoh","journal":"Journal of the American Academy of Dermatology","year":2023,"id":381788,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1147716,"name":"Rebecca S. 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North","orcid":"0000-0003-3973-5314","position":6,"is_corresponding":false},{"id":519395,"name":"Lily Guo","orcid":"0000-0002-3777-0039","position":0,"is_corresponding":true}],"reference_count":5,"raw_metadata":null,"created_at":"2026-07-19T01:17:12.933204Z","pmid":"37080338","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}