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26 CLINICAL REPORT Direct Immunofluorescence of Mechanobullous Epidermolysis Bullosa Acquisita, Porphyria Cutanea Tarda and Pseudoporphyria Heleen J. DE GROOT, Marcel F. JONKMAN, Hendri H. PAS and Gilles F. H. DIERCKS Center for Blistering Diseases, Department of Dermatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands Mechanobullous epidermolysis bullosa acquisita (mEBA) can have a clinical presentation that is very similar to other blistering diseases, such as porphyria cutanea tarda (PCT) and pseudoporphyria. Direct im- munofluorescence is an important feature in the diag- nosis of mEBA, although features that overlap with PCT and pseudoporphyria have been reported. This retro- spective observational study investigated whether di- rect immunofluorescence can discriminate mEBA from PCT and pseudoporphyria. Biopsies of 13 patients with mEBA, 10 with PCT and 10 with pseudoporphyria were included. In 7 cases of PCT and 4 of pseudopor­phyria, direct immunofluorescence showed a pattern at the dermal–epidermal junction that appeared similar to the u-serrated pattern in mEBA. Vessel wall deposi- tions were observed in all 3 diseases, but were more frequent and more intense in PCT and pseudoporphy- ria than in mEBA. Careful examination of direct immu- nofluorescence of mEBA vs. PCT and pseudoporphyria revealed different staining patterns, although overlap- ping features were present. Therefore, integrating all clinical and laboratory data is essential to differentiate between mEBA, PCT and pseudoporphyria. Key words: mechanobullous epidermolysis bullosa acquisita; porphyria cutanea tarda; pseudoporphyria; direct immunofluo- rescence microscopy. Accepted Aug 29, 2018; Epub ahead of print Sep 3, 2018 Acta Derm Venereol 2019; 99: 26–32. Corr: Gilles F. H. Diercks, Center for Blistering Diseases, Department of Dermatology, University Medical Center Groningen, Hanzeplein 1, NL- 9700 RB Groningen, The Netherlands. E-mail: [email protected] E pidermolysis bullosa acquisita (EBA) is a rare sub- epidermal autoimmune bullous disease. The classic mechanobullous subtype (mEBA) may mimic porphyria cutanea tarda (PCT) and pseudoporphyria. Clinically these diseases are characterized by acral blisters that heal with atrophic scarring and milia, whereas histological examination shows cell-poor subepidermal blistering in all 3 entities. Although higher sensitivities have been reported (1, 2), in our experience serology has a sensi- tivity of only 40% for salt-split skin (SSS) and 45% for NC1/NC2 type VII collagen enzyme-linked immunoas- say (ELISA) in patients with EBA (3), serration pattern analysis by direct immunofluorescence microscopy (DIF) is considered of the utmost importance for diagnosis. In EBA in vivo depositions of immunoglobulins at the doi: 10.2340/00015555-3021 Acta Derm Venereol 2019; 99: 26–32 SIGNIFICANCE Mechanobullous epidermolysis bullosa acquisita, porphyria cutanea tarda and pseudoporphyria are mechanobullous di- seases that have many clinical similarities, but have a different pathogenesis and need different treatment. It is therefore important to separate these entities. We performed a retro­ spective observational study to compare clinical and labora- tory data, in particular direct immunofluorescence, of these patient groups in order find discriminatory features. Careful examination of these data revealed (subtle) differences, alt- hough many overlapping features are present. There­fore, integrating all clinical and laboratory data is essential to dif- ferentiate between mechanobullous epidermolysis bullosa acquisita, porphyria cutanea tarda and pseudoporphyria. epidermal basement membrane zone (BMZ) are usually in a u-serrated linear pattern (4), whereas in PCT and pseudoporphyria homogenous depositions of fibrinogen, complement and immunoglobulins are found in the BMZ of epidermis and vessel walls (5, 6). However, in daily practice mEBA, PCT and pseudoporphyria can show very similar epidermal BMZ staining patterns. DIF pat- terns of mEBA, PCT and pseudoporphyria have never been compared systematically. The aim of this study is to re-evaluate clinical information and histopathology of confirmed mEBA, PCT and pseudoporphyria cases and to repeat DIF on archived frozen biopsies in order to re-examine features that may differentiate between these diseases. METHODS Patients Patients were selected from the biobank of the Center for Blistering Diseases of the University Medical Center Groningen (UMCG) for the period 1990 to 2016. Inclusion criteria for mEBA were: (i) mechanobullous blisters, (ii) a u-serrated pattern of linear im- munodeposits of IgG at the epidermal BMZ by DIF of skin tissue, and/or (iii) dermal staining on SSS substrate and/or autoantibodies to type VII collagen established by NC1/NC2 type VII collagen ELISA and/or reactivity to the 290-kDa band by immunoblot on dermal extract. The mEBA patients have been reported previously (7), but do not represent our total mEBA population, since only those patients with positive serological results were included in this study. Inclusion criteria for PCT were: (i) blisters on sun- exposed skin, with (ii) elevated porphyrin levels in urine and/or serum. Inclusion criteria for pseudoporphyria were: (i) blisters on sun-exposed skin, with (ii) no elevation of porphyrin levels This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica.